world health organization assignment

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What Does the World Health Organization Do?

• The WHO is the UN agency responsible for coordinating international health efforts.
• The agency has undergone some reforms in recent years, but still faces criticism over budget constraints and slow responses to health emergencies.
• President Biden reversed his predecessor’s move to withdraw the United States from the WHO amid the COVID-19 pandemic.

Introduction

The World Health Organization (WHO) is the UN agency charged with spearheading international public health efforts. Over its nearly seventy-five years, the WHO has logged both successes, such as eradicating smallpox, and perceived failures, such as its delayed response to the Ebola outbreak in 2014.

In response, the WHO has undertaken reforms to improve its ability to fight future epidemics and boost the health of the hundreds of millions of people still living in extreme poverty. However, the WHO is in an uphill battle to loosen its rigid bureaucracy and it faces an increasingly troublesome budget. The COVID-19 pandemic has proved to be another monumental challenge for the health agency, sparking fresh debate over its effectiveness.

Why was the WHO established?

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Created in 1948 as part of the United Nations, the WHO has a broad mandate to guide and coordinate international health policy. Its primary activities include developing partnerships with other global health initiatives, conducting research, setting norms, providing technical support, and monitoring health trends around the world. Over the decades, the WHO’s remit has expanded from its original focus on women’s and children’s health, nutrition, sanitation, and fighting malaria and tuberculosis.

What does the WHO do?

Daily news brief, a summary of global news developments with cfr analysis delivered to your inbox each morning.  weekdays., the world this week, a weekly digest of the latest from cfr on the biggest foreign policy stories of the week, featuring briefs, opinions, and explainers. every friday., think global health.

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Today, the WHO monitors and coordinates activities concerning many health-related issues, including genetically modified foods, climate change, tobacco and drug use, and road safety. The WHO is also an arbiter of norms and best practices. Since 1977, the organization has maintained a list of essential medicines it encourages hospitals to stock; it has since made a similar list of diagnostic tests. The agency also provides guidance on priority medical devices, such as ventilators and X-ray and ultrasound machines.

Some of the WHO’s most lauded successes include its child vaccination programs, which contributed to the eradication of smallpox in 1979 and a 99 percent reduction in polio infections in recent decades, and its leadership during the 2003 severe acute respiratory syndrome (SARS) epidemic. The agency has the exclusive authority to declare global health emergencies, which it has done several times since its members granted it the power in 2007. At present, the WHO’s work includes combating the COVID-19 pandemic and other emergencies, as well as promoting refugees’ health.

In its 2019 strategy, the WHO identified three priorities [PDF] for its work over the next five years:

• providing health coverage to one billion more people;
• protecting one billion more people from health emergencies such as epidemics; and
• ensuring another one billion people enjoy better health and well-being, including protection from non-infectious diseases such as cancer.

The WHO’s strategic priorities are rooted in the United Nations’ Sustainable Development Goals , a set of seventeen objectives for ending poverty by 2030.

How is the WHO governed?

The WHO is headquartered in Geneva and has six regional and 150 country offices. It is controlled by delegates from its 194 member states, who vote on policy and elect the director general. Tedros Adhanom Ghebreyesus, previously Ethiopia’s foreign minister, was elected to a five-year term in 2017 and reelected in 2022. He is the WHO’s first leader from Africa , and his election was the first time all WHO countries had an equal vote.

WHO delegates set the agency’s agenda and approve an aspirational budget each year at the World Health Assembly. The director general is responsible for raising the lion’s share of funds from donors.

What is the WHO’s budget?

The current two-year goal (2022–23) is about $6.1 billion [PDF], with a sharp focus on managing consequences of the COVID-19 pandemic. Roughly 16 percent of the budget comes from mandatory dues paid by members; the rest is made up of voluntary donations from governments and private partners. In recent years, the top voluntary contributors have included Germany, the United States, the United Kingdom, and the Bill and Melinda Gates Foundation. Unlike dues, voluntary contributions are often earmarked for specific initiatives, which can complicate the WHO’s ability to set its own course.

The WHO has become increasingly dependent on voluntary contributions, which puts pressure on the organization to align its goals with those of its donors.

Over the past decade, the WHO has become increasingly dependent on voluntary contributions, which puts pressure on the organization to align its goals with those of its donors. For instance, President Donald Trump reportedly threatened to cut U.S. contributions in 2018 if other member states proceeded with a resolution to encourage breastfeeding. And in 2020, amid the COVID-19 pandemic, Trump announced he would cut all U.S. ties with the WHO, arguing it failed to take steps to reduce China’s influence over the body. Usually the top contributor, the United States fell to the second-largest donor, providing $680 million in 2020–21, or about 12 percent of the WHO’s budget. However, upon taking office in 2021, President Joe Biden issued an executive order to halt the withdrawal and reengage with the agency.

Some experts argued that the Trump administration’s moves seriously threatened the body’s effectiveness and cited budget cuts as a major factor in the WHO’s slow response to outbreaks. The eradication of polio could also place financial stress on the WHO, whose budget has for decades been bolstered by polio funding, and on lower-income countries that rely on international funding to keep up surveillance and immunization efforts.

How does the WHO fight global health emergencies?

Under the International Health Regulations (IHR), a legally binding framework drawn up in 2005 to prevent and mitigate health emergencies, WHO member states are required to monitor and report potential crises. Countries have historically been hesitant to report outbreaks, often because they’re fearful of economic repercussions. In 2003, for example, China denied for months that it was suffering an outbreak of the infectious disease that was eventually identified as SARS . Before the WHO declared China free of SARS in 2004, the disease killed more than three hundred people. In Ethiopia, Tedros himself was accused of downplaying cholera outbreaks while he was the country’s health minister; he denied these claims.

In an extraordinary crisis, the WHO can declare a public health emergency of international concern (PHEIC), which it has done six times: during the 2009 swine flu (H1N1) epidemic; in reaction to a reversal of progress in eradicating polio in 2014; amid the 2014 Ebola outbreak in West Africa; during the 2016 Zika virus outbreak in the Americas; once the ongoing Ebola epidemic reached the city of Goma in the Democratic Republic of Congo in 2019; and amid the global outbreak of the new coronavirus in 2020.

During a PHEIC, the WHO issues nonbinding guidance to its members on how they should respond to the emergency, including on potential travel and trade restrictions. It seeks to prevent countries in the surrounding region and beyond from overreacting and inflicting undue economic harm on the country in crisis. The WHO has hoped this would encourage affected countries to report outbreaks in a timely manner. However, experts say that, despite the WHO’s guidance, many countries continue to impose damaging travel and trade restrictions, a problem that was laid bare during the Ebola and COVID-19 crises. In an emergency, the WHO also spells out treatment guidelines and acts as a global coordinator , shepherding scientific data and experts to where they are most needed.

Additionally, the WHO provides guidance and coordination for emergencies that don’t rise to the level of a PHEIC. But declaring a PHEIC can help speed up international action and often encourages research on the disease in question, even if there is little risk of a pandemic. This was particularly true for the 2014 declaration for polio. At the same time, PHEIC declarations are contentious, and some argue that they can exacerbate ongoing outbreaks.

How has the WHO responded to COVID-19?

China alerted WHO officials of a growing outbreak in the city of Wuhan on December 31, 2019. The WHO declared a PHEIC one month later and drew up a strategic preparedness and response plan that initially called for $675 million in funding from donors, though it struggled to get contributions at first. (By late 2020, it had received $1.5 billion for its pandemic response fund, close to 90 percent of its goal for the year.) In March, after the virus had spread to more than one hundred countries, Tedros announced that the outbreak had reached pandemic levels. While such a designation generally does not affect how the WHO addresses a crisis, it amplifies the call for countries to develop their own emergency response plans.

As it has done in past health crises, the WHO has provided medical and technical guidance as its experts investigate the virus, particularly new variants, as well as coordinated with world leaders on their national responses. It has also distributed critical supplies to member states, including millions of diagnostic tests and personal protective equipment for health-care workers. Additionally, it has helped to lead the global vaccination effort: the WHO partnered with the Coalition for Epidemic Preparedness Innovations (CEPI) and Gavi, the Vaccine Alliance, to launch COVAX, a global initiative aimed at providing equitable access to COVID-19 vaccines. By mid-2022, COVAX had delivered about 1.5 billion doses , falling short of its goal to distribute 2 billion by the end of 2021.

However, the WHO’s response has been the subject of controversy. Many experts have raised concerns about the agency’s deference to Beijing and increasing Chinese influence over the institution. Among other criticisms, they say WHO officials accepted misinformation from the Chinese government as the outbreak unfolded, waited too long to declare an emergency, and have shunned Taiwan because of bias toward China. Trump was particularly critical of the agency and in May 2020 he announced an end to the U.S. relationship with the WHO. (Biden reversed course on the U.S. exit immediately after taking office.) In January 2021, a delegation of WHO scientists traveled to Wuhan to investigate the virus’s origin , though its findings were inconclusive and critics say Beijing constrained the group’s work. The WHO has since established a new advisory group to continue research on the issue.

What reforms has the WHO made?

Many critics have faulted the WHO for slow and poorly coordinated responses to outbreaks. That includes the 2014 Ebola outbreak, in which it waited five months before declaring a PHEIC, despite pleas from groups such as Doctors Without Borders. Responding to these criticisms, the organization instituted several reforms intended to improve its responses, including the creation of a reserve force of public health workers and a $100 million emergency fund. The WHO also added an incident management system that allows it to place medical responders, equipment, and supplies such as medicines on the ground right away while it coordinates a broader response.

Under Tedros, the WHO has tackled another of its most enduring problems: political friction between its headquarters and its six regional offices, which critics say have enjoyed too much autonomy. Some say that tension between Geneva and the WHO’s Africa office, in Brazzaville, Republic of Congo, contributed to the agency’s poor response to the 2014 Ebola outbreak. To assert its authority over these regional power bases, the WHO has begun requiring staff to rotate among posts around the world, similar to a policy at UNICEF. While some observers paint this and other changes as merely cosmetic, others have applauded the reforms. “There is much greater cooperation than there was in the past,” global health expert Ilona Kickbusch said at a 2020 CFR meeting .

More recently, the COVID-19 crisis has prompted calls for major reforms. In a rare special session of the WHO’s World Health Assembly in 2021, delegates initiated the drafting of a global treaty on pandemic prevention, preparedness, and response. The proposal for a pandemic treaty has sparked debate , however, and the deliberation process could take years. At the 2022 assembly, countries agreed on a U.S.-led proposal to strengthen the IHR by increasing member states’ accountability around disease outbreaks, though no changes have been formally approved.

“Pleas for strengthening the WHO have remained prominent,” writes CFR’s David P. Fidler for Think Global Health. “However, this goal faces serious obstacles ,” Fidler says, namely resistance from China, Russia’s war in Ukraine, and a lack of strong U.S. support for expanding the body’s authority and funding.

Recommended Resources

On The President’s Inbox podcast, CFR’s Stewart M. Patrick lays out what the WHO can and cannot do .

For Think Global Health, CFR’s David P. Fidler looks at the World Health Assembly’s slow steps toward global health reforms.

This CFR Independent Task Force report argues that the WHO has an important leadership role in public health emergencies but lacks the geopolitical heft to address their broader implications.

In Foreign Affairs , Laurie Garrett examines the WHO’s mishandling of the 2014 Ebola outbreak .

Plagues and the Paradox of Progress , a 2018 book by CFR’s Thomas J. Bollyky, discusses the WHO’s attempts to improve itself after the Ebola crisis.

This CFR Backgrounder describes ongoing global efforts  to eradicate polio.

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Mia Speier contributed to this report.

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Lesson Plan: Role of the World Health Organization

Role of the World Health Organization

Christian McMillen talked about the origin of the World Health Organization and its role throughout history.

Description

The World Health Organization was started after World War II as an endeavor to coordinate efforts to combat infectious diseases as they spread around the world. Over the decades, other organizations have stepped into this role as well. The World Health Organization (WHO) declared COVID-19 a pandemic but was also criticized for its response. President Trump withdrew support from WHO, but President Biden renewed support his first day in office. In this lesson, students investigate the role of the organization and decide if they think the United States should support WHO.

This lesson offers several options for you to use with your students whether you are teaching in class, using a hybrid model, or engaging through distance learning. It can be completed in steps as a class or students can move at their own pace and complete the activities independently.

You can post links to the videos in the lesson along with the related handouts and engage in discussion to share responses on a discussion board or learning management system.

You can also save and share the following documents for students to use with this lesson.

Handout; World Health Organization Vocabulary Chart (Google Doc)

Handout with Questions: The Role of the World Health Organization (Google Doc)

In Google, choose "File" then "Make a Copy" to get your own copy. You can make any needed adjustments in the instructions such as which activities students need to complete, when it is due, etc. and then make it available to them via Google.

Discuss the following questions with students:

What makes a disease a pandemic?

In what ways could a global organization that addresses pandemics be helpful?

• What could be some potential shortcomings?

INTRODUCTION:

As a class, watch the video clip below and use the guiding questions for class discussion.

Video Clip 1: Role of the World Health Organization (3:22)

What is the purpose of the World Health Organization?

What are examples of what the WHO has done?

• Why is the role of the WHO less involved now than at its origin?

EXPLORATION:

Have students view the following video clips and respond to the accompanying questions on the handout. They can watch each video independently or view a video with a partner.

Video Clip 2: WHO Director General declares COVID-19 a Pandemic (2:55)

Dr. Tedros Adhanom Gebreyesus, Director-General of the World Health Organization, 'sounds the alarm bell' that COVID-19 can be characterized as a pandemic.

Why did WHO declare COVID-19 a pandemic?

• What difference do you think it makes if the WHO labels a disease as a ‘pandemic’?

Video Clip 3: The National Institute of Allergy and Infectious Diseases and the Federal Bureaucracy (5:52)

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases since 1984 talked about the role of the NIAID and how the institute works with other parts of the US government and organizations like the World Health Organization.

How does the United States Government approach preparation for infectious diseases?

What specific diseases has this part of the government dealt with in the past?

• How do the different health organizations work together?

Video Clip 4: China and the World Health Organization (4:01)

After President Trump announced that the United States would cut funding for the World Health Organization (WHO), Brett Schaefer of the Heritage Foundation talked about the decision and China's role in the organization. He also discussed the structure of the organization and the events that led to the current coronavirus outbreak.

How does the World Health Organization work?

• According to Brett Schaeffer of the Heritage Foundation, how was this a problem with China?

Video Clip 5: Misinformation during Public Health Emergencies (2:47)

Reid Wilson, author of "Epidemic: Ebola and the Global Scramble to Prevent the Next Killer Outbreak" talked about how misinformation can impact the spread of pandemics. He talked about examples of misinformation during the Ebola outbreak in Africa and COVID-19 in the United States.

What are infomedics during pandemics?

What are some examples of infodemics?

• According to Reid Wilson, how do we combat the dangers of misinformation during pandemics?

CONCLUDING ACTIVITY:

After discussing the information presented in the videos, students will prepare an argument for increasing or decreasing the U.S. government’s current level of support using evidence from the videos and additional outside resources.

Students will respond to the following prompt:

President Trump cut funding to the WHO and President Biden renewed our membership. Should the United States increase or decrease our support of the World Health Organization? What makes you say that?

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World Health Organization

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• National Public Radio - What Does The World Health Organization Do?
• Official Site of the World Health Organization

Recent News

World Health Organization (WHO) , specialized agency of the United Nations (UN) established in 1948 to further international cooperation for improved public health conditions. Although it inherited specific tasks relating to epidemic control, quarantine measures, and drug standardization from the Health Organization of the League of Nations (set up in 1923) and the International Office of Public Health at Paris (established in 1907), WHO was given a broad mandate under its constitution to promote the attainment of “the highest possible level of health” by all peoples. WHO defines health positively as “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.” Each year WHO celebrates its date of establishment, April 7, 1948, as World Health Day.

With administrative headquarters in Geneva , governance of WHO operates through the World Health Assembly, which meets annually as the general policy-making body, and through an Executive Board of health specialists elected for three-year terms by the assembly. The WHO Secretariat , which carries out routine operations and helps implement strategies, consists of experts, staff, and field workers who have appointments at the central headquarters or at one of the six regional WHO offices or other offices located in countries around the world. The agency is led by a director general nominated by the Executive Board and appointed by the World Health Assembly. The director general is supported by a deputy director general and multiple assistant directors general, each of whom specializes in a specific area within the WHO framework, such as family, women’s, and children’s health or health systems and innovation . The agency is financed primarily from annual contributions made by member governments on the basis of relative ability to pay. In addition, after 1951 WHO was allocated substantial resources from the expanded technical-assistance program of the UN.

WHO officials periodically review and update the agency’s leadership priorities. Over the period 2014–19, WHO’s leadership priorities were aimed at:

1. Assisting countries that seek progress toward universal health coverage

2. Helping countries establish their capacity to adhere to International Health Regulations

3. Increasing access to essential and high-quality medical products

4. Addressing the role of social, economic, and environmental factors in public health

5. Coordinating responses to noncommunicable disease

6. Promoting public health and well-being in keeping with the Sustainable Development Goals, set forth by the UN.

The work encompassed by those priorities is spread across a number of health-related areas. For example, WHO has established a codified set of international sanitary regulations designed to standardize quarantine measures without interfering unnecessarily with trade and air travel across national boundaries. WHO also keeps member countries informed of the latest developments in cancer research, drug development, disease prevention, control of drug addiction, vaccine use, and health hazards of chemicals and other substances.

WHO sponsors measures for the control of epidemic and endemic disease by promoting mass campaigns involving nationwide vaccination programs, instruction in the use of antibiotics and insecticides , the improvement of laboratory and clinical facilities for early diagnosis and prevention, assistance in providing pure-water supplies and sanitation systems, and health education for people living in rural communities . These campaigns have had some success against AIDS , tuberculosis , malaria , and a variety of other diseases. In May 1980 smallpox was globally eradicated , a feat largely because of the efforts of WHO. In March 2020 WHO declared the global outbreak of COVID-19 , a severe respiratory illness caused by a novel coronavirus that first appeared in Wuhan, China, in late 2019, to be a pandemic . The agency acted as a worldwide information centre on the illness, providing regular situation reports and media briefings on its spread and mortality rates; dispensing technical guidance and practical advice for governments, public health authorities, health care workers, and the public; and issuing updates of ongoing scientific research. As pandemic-related infections and deaths continued to mount in the United States , Pres. Donald J. Trump accused WHO of having conspired with China to conceal the spread of the novel coronavirus in that country in the early stages of the outbreak. In July 2020 the Trump administration formally notified the UN that the United States would withdraw from the agency in July 2021. The U.S. withdrawal was halted by Trump’s successor, Pres. Joe Biden , on the latter’s first day in office in January 2021.

In its regular activities WHO encourages the strengthening and expansion of the public health administrations of member nations, provides technical advice to governments in the preparation of long-term national health plans, sends out international teams of experts to conduct field surveys and demonstration projects, helps set up local health centres, and offers aid in the development of national training institutions for medical and nursing personnel. Through various education support programs, WHO is able to provide fellowship awards for doctors, public-health administrators, nurses, sanitary inspectors, researchers, and laboratory technicians.

The first director general of WHO was Canadian physician Brock Chisholm, who served from 1948 to 1953. Later directors general of WHO included physician and former prime minister of Norway Gro Harlem Brundtland (1998–2003), South Korean epidemiologist and public health expert Lee Jong-Wook (2003–06), and Chinese civil servant Margaret Chan (2007–17). Ethiopian public health official Tedros Adhanom Ghebreyesus became director general of WHO in 2017.

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World Health Organisation (WHO) - UPSC Notes

The World Health Organisation (WHO) is a specialized agency of the United Nations that looks into matters of public health. Established on April 7th, 1948, its headquarters is located in Geneva, Switzerland. WHO is an important topic for the IAS exam , as it is keeping in news concerning the Covid-19 outbreak. On 9th July, 2020, WHO created an Independent Panel for Pandemic Preparedness and Response (IPPR) to evaluate the world’s response to the COVID-19 pandemic.

World Health Organisation (WHO)

Recent Update:

To evaluate the world’s response to Coronavirus pandemic, Independent Panel for Pandemic Preparedness and Response (IPPR) has been created by the World Health Organisation. The main points related to it are:

• New Zealand former President Helen Clark and Liberia former President Ellen Johnson Sirleaf are co-chairs of  the IPPR, as announced by the WHO Director-General Tedros Adhanom Ghebreyesus
• The IPPR comes on the heels of the Landmark Resolution related to Covid-19 that was adopted in the 73rd World Health Assembly in May 2020.
• On 7 July 2020, President Trump formally notified the UN of his intent to withdraw the United States from the WHO. However, in January 2021, President Joe Biden announced plans to rejoin, and signed an executive order to that effect after his inauguration.
• In February 2021, the WHO team visited China in order to investigate the origins of the COVID-19 virus that allegedly had its origin in the Wuhan Virology Institute. The team will publish its findings in mid-march.
• WHO chief Tedros Adhanom Ghebreyesus on February 26, 2021 had lauded Prime Minister Narendra Modi’s commitment for supporting vaccine equity and sharing COVID-19 vaccines with over 60 countries across the world, hoping that other nations will follow his example.

Facts about WHO for UPSC

At the 1945 United Nations Conference on International Organization (also known as the San Francisco Conference), Szeming Sze, a delegate from the Republic of China (modern-day Taiwan), proposed the creation of an international health organization under the auspices of the new United Nations . Alger Hiss, the Secretary-General of the conference, recommended using a declaration to establish such an organization. 

As a result of these proceedings, the World Health Organisation came to be established in 1948. It became the first specialized agency of the United Nations to which every member subscribed.

• The WHO is headed by its Director-General and is headquartered in Geneva. Currently, the WHO has 194 member countries. 
• Full membership of the WHO is only guaranteed with the ratifying of the treaty known as the Constitution of the World Health Organisation.  To know more about Important Headquarters of International Organisations , visit the linked article.
• The member states of the WHO appoint delegates to the World Health Assembly, which is the supreme decision-making body. The World Health Assembly is attended by delegations from all Member States and determines the policies of the Organisation.
• On May 19, 2020, India was elected by the 73rd World Health Assembly to the Executive Board of the World Health Organisation for three years. Union Health Minister Harsh Vardhan took charge as the chairman of the WHO Executive Board on May 22. He succeeds Dr. Hiroki Nakatani of Japan.
• The WHO celebrates World Health Day annually on its formation day (7 April). The theme for 2020 was “Y ear of the Nurse and Midwife”.

WHO UPSC Notes:- Download PDF Here

What is the Overall Focus of the WHO?

The WHO Constitution states that the organization’s objective “is the attainment by all people of the highest possible level of health”.

The WHO fulfills this objective through the following functions:

• By playing a role as the directing and coordinating authority on international health work.
• Maintaining and establishing collaboration with the UN and any other appropriate bodies.
• Assisting governments, upon request, in strengthening their health services.
• Giving appropriate technical assistance and in case of emergencies, required aid upon the request or acceptance of governments.

What is the Health Policy of the WHO?

The WHO addresses government health policy with the following two aims:     

• To address the social and economic determinants of health through policies and programs “that enhance health equity and integrate pro-poor, gender-responsive, and human rights-based approaches”.
• To promote a healthier environment, intensify primary prevention, and influence public policies in all sectors to address the root causes of environmental threats to health”.

Contribution of WHO

The WHO has been instrumental in eradicating the suffering of millions all over the world through its assistance to various governments. Some of the important milestones include:

• Eradication of smallpox in 1980.
• The organization is close to eradicating Polio, a disease that affects mainly infants and young children. Due to eradication programs by the WHO, polio cases have come down by 99% since 1988. As of 2019, only three nations are suffering from polio – Nigeria, Afghanistan, and Pakistan.
• In 2008, the WHO initiated the observance of the ‘World Malaria Day’. This day is observed annually on April 25. Read more about this day in This Day in History dated April 25 .
• It focuses on infectious diseases like HIV, influenza, malaria, tuberculosis , and Ebola; and also other non-communicable diseases such as heart disease and cancer.
• It also takes efforts in the direction of maternity and infant healthcare, old-age care, and hygienic food and water for all.

Contributions of the WHO in India

India is a member of the WHO and the organization has its offices in various parts of the country. The WHO Country Office (WCO) is headquartered in New Delhi.

The WHO Country Cooperation Strategy (CCS) – India has been jointly developed by the Ministry of Health and Family Welfare of the GOI and the WCO. 

• Its chief aim is to contribute to improving health and equity in the country. 

The National Strategic Plan for Elimination of Malaria (2017-2022) was launched by the Union Minister for Health and Family Welfare. 

• Its chief aim is to eliminate Malaria by 2027. 
• The National Strategic Plan has formulated year wise elimination targets in various parts of the country. 
• It is formulated with the support of the World Health Organization’s Global Technical Strategy for Malaria (2016-2030).

What are the current challenges of WHO?

As an international organization, WHO has its fair share of challenges. Some of them are as follows:

• The WHO is largely dependent on funds from donors – usually from economically well-developed countries and organizations such as Melinda Gates Foundation – rather than a secured channel of funding.
• As a result, most of the WHO’s funding for crucial programs remain on the back burner as some of these programs also clash with the interests of the donors. 
• The effectiveness of the organization has come under question especially due to its disastrous handling of the Ebola outbreak in West Africa and the very recent coronavirus outbreak in 2019-20.
• Consequently, the WHO’s role as a leader in global health has been supplanted by other intergovernmental bodies such as the World Bank, and increasingly by big foundations.
• Initial concerns included the observation that while the WHO relies upon data provided and filtered by member states, China has had a “historical aversion to transparency and sensitivity to international criticism”. US President Donald Trump has been the most vocal of all the critics of the organization. This has led to the US’s withdrawal from the WHO.

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Explainer: what does the world health organization do.

World Health Organization leaders at a press briefing on COVID-19, held on March 6 at WHO headquarters in Geneva. Here's a look at its history, its mission and its role in the current crisis. Fabrice Coffrini/AFP via Getty Images hide caption

World Health Organization leaders at a press briefing on COVID-19, held on March 6 at WHO headquarters in Geneva. Here's a look at its history, its mission and its role in the current crisis.

Updated on May 19 at 8:51 a.m. ET

The World Health Organization describes its job as "the global guardian of health."

It is now possibly facing the most devastating global health threat in its 72-year history: the coronavirus pandemic. WHO is devoting hundreds of millions of dollars and an all-hands-on-deck approach to the effort to vanquish the virus.

And it is being accused of failing to uphold its mission.

On April 14, President Trump put a temporary halt on U.S. funding for the agency, pending an investigation to see if WHO is "severely mismanaging and covering up the spread of the coronavirus."

On May 18, Trump sent a letter to the agency's director-general, Tedros Adhanom Ghebreyesus, vowing to end U.S. funding for and participation in the world body if WHO fails to "commit to major substantive improvements in the next 30 days."

Here's a look at the agency at the eye of the storm.

How did it start?

The newly inaugurated World Health Organization building in Geneva in May 1966. AP Photo/PhotoPress Bilderdienst hide caption

As World War II was winding down, countries came together to form the United Nations and voted to create a global health agency as a U.N. arm.

And so in 1948 the World Health Organization was founded for "the attainment by all peoples of the highest possible level of health." As a specialized agency of the U.N., WHO has as its directive "to act as the directing and coordinating authority on international health work," according to the agency's constitution .

WHO replaced several regional health authorities that had been established in Europe and the Americas in the early 1900s to help prevent the spread of diseases such as smallpox and typhus . WHO started with 55 member states and has now grown to include 194 member states and two associate members (Puerto Rico and Tokelau).

The member states form the World Health Assembly , which sets WHO policy, approves and supervises its budget, and elects a director-general to lead WHO for five-year terms. Its budget is set for two-year periods and stood at $6.3 billion for 2018 and 2019. The money comes from dues and voluntary contributions from member states as well as money from nonprofit groups such as the Bill and Melinda Gates Foundation (which is also a funder of NPR and this blog) and Rotary International.

For its COVID-19 response, WHO initially requested $675 million from donors and plans to significantly increase the amount to fund its services providing "advice, supplies and leadership" in the pandemic.

WHO has a staff of 7,000 that includes scientists, medical doctors and public health specialists, as well as experts in economics, statistics and emergency relief. The agency is headquartered in Geneva and has offices in more than 150 countries around the world.

The current director-general is Tedros Adhanom Ghebreyesus , a former minister of health in Ethiopia. He is WHO's first leader from Africa and its first director-general who is not a physician — Tedros has a Ph.D. in community health. He started his term in 2017.

What is WHO's mission?

At a press conference on April 22 , Michael Ryan, director of WHO's Health Emergencies program, summed up the organization's overarching mission: "The mandate we have [is] to establish global standards and to give strong advice to countries regarding rational public health measures."

To achieve these goals, WHO does not typically give out grants or loans or send doctors and others from its staff to countries to provide hands-on medical treatments.

Rather, "what it does do is get on the ground to provide direction, advice, help trace disease outbreaks and provide additional support when needed," says Jennifer Kates , director of global health and HIV policy at the Kaiser Family Foundation.

One of WHO's primary roles is to provide countries with science-based recommendations for health policy, which are often published on its website. "There will be guidelines on what kind of essential medicines there should be, what kind of essential diagnostics there should be, what might be the regimens to use in relation to HIV in different countries, taking into account the resources available," says Rifat Atun , professor of global health systems at Harvard University, "Countries are not under any obligation legally to follow these guidelines, but many do in relation to epidemics."

WHO is governed by its member states — it does not have legal authority to enter countries without permission or to force countries to take its advice.

For instance, in February, WHO sent international experts to China on a " joint mission " with Chinese researchers to look into the steps the country was taking to prevent and control the spread of COVID-19. WHO emphasized that the mission was agreed to by both parties, and that the members were invited by both WHO and China.

"The power that we have is the power to persuade through science, persuade through evidence, persuade by demonstrating what other countries are doing and showcasing good examples of good practice," Ryan said on April 22. "Beyond that, WHO has no power to enforce, no power to put any form of pressure on the country to change what is their sovereign will."

What is WHO's role in the COVID-19 pandemic?

Under the International Health Regulations , a global legal agreement revised in 2005 and signed by all WHO members, countries are required to report to WHO any disease outbreaks that are unexpected or of unknown cause and have significant risk of international spread.

China reported a cluster of pneumonia cases to WHO on Dec. 31, 2019. "Based on the [International Health Regulations], what is expected from WHO is declaring the Public Health Emergency of International Concern as early as possible," Tedros said on April 22.

That PHEIC designation is an official alert that triggers a set of responses. WHO can help guide the country and gauge whether its response is effective. And it can bring in international assistance for training, surveillance and other measures. But all of this can only be done "at the request of a State Party."

Timing is tricky. "It's partly a technical decision. It's partly a political decision," Atun says. "If you act too early, you may contain the epidemic but people may say, 'There was no need [to act so early].' But if you act too late countries will say, 'You are too late and we're now facing the consequences.' "

WHO declared the coronavirus a PHEIC on Jan. 30 , when there were no reported deaths outside of China but a sharp increase in the number of countries reporting cases.

"Looking back, I think we declared the emergency at the right time, and when the world had enough time to respond," Tedros said on April 22.

Weeks later, in its role as an international standard-bearer, WHO officially named the disease COVID-19.

In the months since, WHO has requested information that countries are bound to provide under international health regulations — for instance, explanations of why travel bans are needed to stop disease spread. WHO has also asked countries — including China — for timely and accurate outbreak data that they're required to provide under the international health regulations.

Drawing from publications and discussions with researchers globally, WHO has published reams of COVID-related public health advice on topics ranging from diagnostic tests and the public use of masks to how religious leaders can assess the risks of holding social and religious gatherings during Ramadan and how countries can manage risks as they lift their lockdowns . The agency has also developed online courses to train health care workers to diagnose and treat COVID-19 patients.

WHO has sent more than 70 teams of response coordinators, epidemiologists and other advisers into countries to help guide COVID-19 responses. It is also raising money for and organizing a global COVID-19 supply chain to get diagnostic tests, medical equipment and aid workers to places that need them. "We estimate this supply chain may need to cover more than 30% of the world's needs in the acute phase of the pandemic," Tedros said at a press conference April 10 , calling on donors to support the initiative.

And the agency is helping to organize global research into treatment drugs and potential coronavirus vaccines . In February, WHO brought medical doctors, virologists, modelers and epidemiologists together in a global research forum to establish a unified set of priorities and timelines for COVID-19 research. On April 24, WHO announced a pledge campaign for global collaboration asking researchers, donors and manufacturers to agree to work together and commit to equitable distribution of vaccines and medicines.

Performance over the years

WHO's handling of the SARS (severe acute respiratory syndrome) outbreak in 2003 was considered a success. "WHO acted fairly quickly and issued guidance to restrict travel. The epidemic did not extend to all countries in the world," Atun says. Effects of the SARS outbreak were concentrated in Asia; 8,000 people were sickened, and around 800 died before the epidemic ended in 2004.

But the concerns raised over WHO's current performance are not the first criticisms for a WHO response to a health emergency.

In the 2009 H1N1 swine flu pandemic, WHO received mixed reviews. In post-pandemic analysis requested by WHO, an international committee found that, while WHO provided useful guidance to countries on how to slow pandemic flu transmission and helped monitor the virus's spread, its messaging around the severity of the pandemic was unclear and its failure to coordinate effective vaccine distribution led to countries receiving them too late to be truly helpful.

And the WHO response to the 2014 Ebola outbreak in West Africa was widely panned. "[In] the Ebola outbreak, the WHO was criticized for not responding quickly enough in declaring a public health emergency of international concern," says Raphael Lencucha , a global health researcher at McGill University. WHO initially dismissed the scale of the problem, then lacked the staff and funds to lead an effective response, NPR reported in 2015 .

"[Back then,] the focus was on the WHO in responding in a timely way," Lencucha says. "And in the case of COVID, similar criticisms are being waged."

Now, U.S. officials say WHO was too trusting of China in the beginning stages of the COVID-19 pandemic and slow to sound the alarm. On April 15, President Trump said the organization's earlier "objections" to travel bans from China was "a horrible, tragic mistake" that resulted in "quickly unleashing the contagion around the world." Secretary of State Mike Pompeo says China withheld timely information about the outbreak from WHO, which means to him that "the World Health Organization's regulatory arm clearly failed during this pandemic."

WHO officials say they welcome "after-action" assessments of their performance in emergencies. "We do them for every outbreak response and I'll look forward ... to look and see where we can learn to do better, where we can improve our response," WHO official Michael Ryan said on April 15 .

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The World Health Organization (WHO)

By Michael Marshall

The World Health Organization is the international body responsible for public health. Known as the WHO, it is part of the United Nations and was established in 1948. It is involved in many aspects of health policy and planning.

The WHO has played a major role in many of the public health successes of the last few decades. It was instrumental in the global eradication of smallpox , which used to be one of the world’s biggest killers. It has also run a campaign that has achieved the near-eradication of polio , and has worked for decades to reduce the threat from malaria .

When major disease outbreaks occur, the WHO coordinates the international response. It was front-and-centre in the 2014 Ebola outbreak , which it declared an international emergency. Similarly, it coordinated the response to the 2015-16 Zika outbreak . In 2020 it declared the outbreak of the covid-19 coronavirus a pandemic and urged governments to take strong measures to control the spread of the disease.

The WHO also sets international standards for diagnosing diseases and disorders. It maintains a catalogue called the International Classification of Diseases (ICD), which lists all the known conditions and the symptoms by which they should be diagnosed. The ICD is used around the world. It is regularly updated as medical knowledge advances, which often takes the WHO into tricky territory. In recent years the WHO has had to decide whether video gaming disorder and sex addiction are real disorders that could be diagnosed and treated.

Finally, the WHO promotes healthy lifestyles that reduce the risk of cancer , heart disease and other slow killers. It has mounted campaigns against smoking tobacco, and more recently against alcohol abuse . It also has a key role in maintaining healthy environments, for example setting standards for safe levels of air pollution. In recent years it has even begun measuring wellbeing – going beyond basic health measures to determine whether people are happy.

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• v.96(1); Jan 2006

The World Health Organization and the Transition From “International” to “Global” Public Health

Theodore m. brown.

Theodore M. Brown is with the Department of History and the Department of Community and Preventive Medicine, University of Rochester, Rochester, NY. Marcos Cueto is with the Facultad de Salud Pública, Universidad Peruana Cayetano Heredia, Lima, Peru. Elizabeth Fee is with the History of Medicine Division, National Library of Medicine, National Institutes of Health, Bethesda, Md.

Marcos Cueto

Elizabeth fee.

The term “global health” is rapidly replacing the older terminology of “international health.” We describe the role of the World Health Organization (WHO) in both international and global health and in the transition from one to the other. We suggest that the term “global health” emerged as part of larger political and historical processes, in which WHO found its dominant role challenged and began to reposition itself within a shifting set of power alliances.

Between 1948 and 1998, WHO moved from being the unquestioned leader of international health to being an organization in crisis, facing budget shortfalls and diminished status, especially given the growing influence of new and powerful players. We argue that WHO began to refashion itself as the coordinator, strategic planner, and leader of global health initiatives as a strategy of survival in response to this transformed international political context.

EVEN A QUICK GLANCE AT THE titles of books and articles in recent medical and public health literature suggests that an important transition is under way. The terms “global,” “globalization,” and their variants are everywhere, and in the specific context of international public health, “global” seems to be emerging as the preferred authoritative term. 1 As one indicator, the number of entries in PubMed under the rubrics “global health” and “international health” shows that “global health” is rapidly on the rise, seemingly on track to overtake “international health” in the near future (Table 1 ▶ ). Although universities, government agencies, and private philanthropies are all using the term in highly visible ways, 2 the origin and meaning of the term “global health” are still unclear.

TABLE 1—

Number of Articles Retrieved by PubMed, Using “International Health” and “Global Health” as Search Terms, by Decade: 1950 Through July 2005

a Picks up variant term endings (e.g. “international” also picks up “internationalize” and “internationalization”; “global” also picks up “globalize” and “globalization”).

b Number for 55 months only.

We provide historical insight into the emergence of the terminology of global health. We believe that an examination of this linguistic shift will yield important fruit, and not just information about fashions and fads in language use. Our task here is to provide a critical analysis of the meaning, emergence, and significance of the term “global health” and to place its growing popularity in a broader historical context. In particular, we focus on the role of the World Health Organization (WHO) in both international and global health and as an agent in the transition from one concept to the other.

Let us first define and differentiate some essential terms. “International health” was already a term of considerable currency in the late 19th and early 20th century, when it referred primarily to a focus on the control of epidemics across the boundaries between nations (i.e., “international”). “Intergovernmental” refers to the relationships between the governments of sovereign nations—in this case, with regard to the policies and practices of public health. “Global health,” in general, implies consideration of the health needs of the people of the whole planet above the concerns of particular nations. The term “global” is also associated with the growing importance of actors beyond governmental or intergovernmental organizations and agencies—for example, the media, internationally influential foundations, nongovernmental organizations, and transnational corporations. Logically, the terms “international,” “intergovernmental,” and “global” need not be mutually exclusive and in fact can be understood as complementary. Thus, we could say that WHO is an intergovernmental agency that exercises international functions with the goal of improving global health.

Given these definitions, it should come as no surprise that global health is not entirely an invention of the past few years. The term “global” was sometimes used well before the 1990s, as in the “global malaria eradication program” launched by WHO in the mid-1950s; a WHO Public Affairs Committee pamphlet of 1958, The World Health Organization: Its Global Battle Against Disease 3 ; a 1971 report for the US House of Representatives entitled The Politics of Global Health 4 ; and many studies of the “global population problem” in the 1970s. 5 But the term was generally limited and its use in official statements and documents sporadic at best. Now there is an increasing frequency of references to global health. 6 Yet the questions remain: How many have participated in this shift in terminology? Do they consider it trendy, trivial, or trenchant?

Supinda Bunyavanich and Ruth B. Walkup tried to answer these questions and published, under the provocative title “US Public Health Leaders Shift Toward a New Paradigm of Global Health,” their report of conversations conducted in 1999 with 29 “international health leaders.” 7 Their respondents fell into 2 groups. About half felt that there was no need for a new terminology and that the label “global health” was meaningless jargon. The other half thought that there were profound differences between international health and global health and that “global” clearly meant something transnational. Although these respondents believed that a major shift had occurred within the previous few years, they seemed unable clearly to articulate or define it.

In 1998, Derek Yach and Douglas Bettcher came closer to capturing both the essence and the origin of the new global health in a 2-part article on “The Globalization of Public Health” in the American Journal of Public Health . 8 They defined the “new paradigm” of globalization as “the process of increasing economic, political, and social interdependence and integration as capital, goods, persons, concepts, images, ideas and values cross state boundaries.” The roots of globalization were long, they said, going back at least to the 19th century, but the process was assuming a new magnitude in the late 20th century. The globalization of public health, they argued, had a dual aspect, one both promising and threatening.

In one respect, there was easier diffusion of useful technologies and of ideas and values such as human rights. In another, there were such risks as diminished social safety nets; the facilitated marketing of tobacco, alcohol, and psychoactive drugs; the easier worldwide spread of infectious diseases; and the rapid degradation of the environment, with dangerous public health consequences. But Yach and Bettcher were convinced that WHO could turn these risks into opportunities. WHO, they argued, could help create more efficient information and surveillance systems by strengthening its global monitoring and alert systems, thus creating “global early warning systems.” They believed that even the most powerful nations would buy into this new globally interdependent world system once these nations realized that such involvement was in their best interest.

Despite the long list of problems and threats, Yach and Bettcher were largely uncritical as they promoted the virtues of global public health and the leadership role of WHO. In an editorial in the same issue of the Journal, George Silver noted that Yach and Bettcher worked for WHO and that their position was similar to other optimistic stances taken by WHO officials and advocates. But WHO, Silver pointed out, was actually in a bad way: “The WHO’s leadership role has passed to the far wealthier and more influential World Bank, and the WHO’s mission has been dispersed among other UN agencies.” Wealthy donor countries were billions of dollars in arrears, and this left the United Nations and its agencies in “disarray, hamstrung by financial constraints and internal incompetencies, frustrated by turf wars and cross-national policies.” 9 Given these -realities, Yach and Bettcher’s promotion of “global public health” while they were affiliated with WHO was, to say the least, intriguing. Why were these spokesmen for the much-criticized and apparently hobbled WHO so upbeat about “global” public health?

THE WORLD HEALTH ORGANIZATION

The early years.

To better understand Yach and Bettcher’s role, and that of WHO more generally, it will be helpful to review the history of the organization from 1948 to 1998, as it moved from being the unquestioned leader of international health to searching for its place in the contested world of global health.

WHO formally began in 1948, when the first World Health Assembly in Geneva, Switzerland, ratified its constitution. The idea of a permanent institution for international health can be traced to the organization in 1902 of the International Sanitary Office of the American Republics, which, some decades later, became the Pan American Sanitary Bureau and eventually the Pan American Health Organization. 10 The Rockefeller Foundation, especially its International Health Division, was also a very significant player in international health in the early 20th century. 11

Two European-based international health agencies were also important. One was the Office Internationale d’Hygiène Publique, which began functioning in Paris in 1907; it concentrated on several basic activities related to the administration of international sanitary agreements and the rapid exchange of epidemiological information. 12 The second agency, the League of Nations Health Organization, began its work in 1920. 13 This organization established its headquarters in Geneva, sponsored a series of international commissions on diseases, and published epidemiological intelligence and technical reports. The League of Nations Health Organization was poorly budgeted and faced covert opposition from other national and international organizations, including the US Public Health Service. Despite these complications, which limited the Health Organization ’s effectiveness, both the Office Internationale d’Hygiène Publique and the Health Organization survived through World War II and were present at the critical postwar moment when the future of international health would be defined.

An international conference in 1945 approved the creation of the United Nations and also voted for the creation of a new specialized health agency. Participants at the meeting initially formed a commission of prominent individuals, among whom were René Sand from Belgium, Andrija Stampar from Yugoslavia, and Thomas Parran from the United States. Sand and Stampar were widely recognized as champions of social medicine. The commission held meetings between 1946 and early 1948 to plan the new international health organization. Representatives of the Pan American Sanitary Bureau, whose leaders resisted being absorbed by the new agency, were also involved, as were leaders of new institutions such as the United Nations Relief and Rehabilitation Administration (UNRRA).

Against this background, the first World Health Assembly met in Geneva in June 1948 and formally created the World Health Organization. The Office Internationale d’Hygiène Publique, the League of Nations Health Organization, and UNRRA merged into the new agency. The Pan American Sanitary Bureau—then headed by Fred L. Soper, a former Rockefeller Foundation official—was allowed to retain autonomous status as part of a regionalization scheme. 14 WHO formally divided the world into a series of regions—the Americas, Southeast Asia, Europe, Eastern Mediterranean, Western Pacific, and Africa—but it did not fully implement this regionalization until the 1950s. Although an “international” and “intergovernmental” mindset prevailed in the 1940s and 1950s, naming the new organization the World Health Organization also raised sights to a worldwide, “global” perspective.

The first director general of WHO, Brock Chisholm, was a Canadian psychiatrist loosely identified with the British social medicine tradition. The United States, a main contributor to the WHO budget, played a contradictory role: on the one hand, it supported the UN system with its broad worldwide goals, but on the other, it was jealous of its sovereignty and maintained the right to intervene unilaterally in the Americas in the name of national security. Another problem for WHO was that its constitution had to be ratified by nation states, a slow process: by 1949, only 14 countries had signed on. 15

As an intergovernmental agency, WHO had to be responsive to the larger political environment. The politics of the Cold War had a particular salience, with an unmistakable impact on WHO policies and personnel. Thus, when the Soviet Union and other communist countries walked out of the UN system and therefore out of WHO in 1949, the United States and its allies were easily able to exert a dominating influence. In 1953, Chisholm completed his term as director general and was replaced by the Brazilian Marcolino Candau. Candau, who had worked under Soper on malaria control in Brazil, was associated first with the “vertical” disease control programs of the Rockefeller Foundation and then with their adoption by the Pan American Sanitary Bureau when Soper moved to that agency as director. 16 Candau would be director general of WHO for over 20 years. From 1949 until 1956, when the Soviet Union returned to the UN and WHO, WHO was closely allied with US interests.

In 1955, Candau was charged with overseeing WHO’s campaign of malaria eradication, approved that year by the World Health Assembly. The ambitious goal of malaria eradication had been conceived and promoted in the context of great enthusiasm and optimism about the ability of widespread DDT spraying to kill mosquitoes. As Randall Packard has argued, the United States and its allies believed that global malaria eradication would usher in economic growth and create overseas markets for US technology and manufactured goods. 17 It would build support for local governments and their US supporters and help win “hearts and minds” in the battle against Communism. Mirroring then-current development theories, the campaign promoted technologies brought in from outside and made no attempt to enlist the participation of local populations in planning or implementation. This model of development assistance fit neatly into US Cold War efforts to promote modernization with limited social reform. 18

With the return of the Soviet Union and other communist countries in 1956, the political balance in the World Health Assembly shifted and Candau accommodated the changed balance of power. During the 1960s, malaria eradication was facing serious difficulties in the field; ultimately, it would suffer colossal and embarrassing failures. In 1969, the World Health Assembly, declaring that it was not feasible to eradicate malaria in many parts of the world, began a slow process of reversal, returning once again to an older malaria control agenda. This time, however, there was a new twist; the 1969 assembly emphasized the need to develop rural health systems and to integrate malaria control into general health services.

When the Soviet Union returned to WHO, its representative at the assembly was the national deputy minister of health. He argued that it was now scientifically feasible, socially desirable, and economically worthwhile to attempt to eradicate smallpox worldwide. 19 The Soviet Union wanted to make its mark on global health, and Candau, recognizing the shifting balance of power, was willing to cooperate. The Soviet Union and Cuba agreed to provide 25 million and 2 million doses of freeze-dried vaccine, respectively; in 1959, the World Health Assembly committed itself to a global smallpox eradication program.

In the 1960s, technical improvements—jet injectors and bifurcated needles—made the process of vaccination much cheaper, easier, and more effective. The United States’ interest in smallpox eradication sharply increased; in 1965, Lyndon Johnson instructed the US delegation to the World Health Assembly to pledge American support for an international program to eradicate smallpox from the earth. 20 At that time, despite a decade of marked progress, the disease was still endemic in more than 30 countries. In 1967, now with the support of the world’s most powerful players, WHO launched the Intensified Smallpox Eradication Program. This program, an international effort led by the American Donald A. Henderson, would ultimately be stunningly successful. 21

The Promise and Perils of Primary Health Care, 1973–1993

Within WHO, there have always been tensions between social and economic approaches to population health and technology-or disease-focused approaches. These approaches are not necessarily incompatible, although they have often been at odds. The emphasis on one or the other waxes and wanes over time, depending on the larger balance of power, the changing interests of international players, the intellectual and ideological commitments of key individuals, and the way that all of these factors interact with the health policymaking process.

During the 1960s and 1970s, changes in WHO were significantly influenced by a political context marked by the emergence of decolonized African nations, the spread of nationalist and socialist movements, and new theories of development that emphasized long-term socioeconomic growth rather than short-term technological intervention. Rallying within organizations such as the Non-Aligned Movement, developing countries created the UN Conference on Trade and Development (UNCTAD), where they argued vigorously for fairer terms of trade and more generous financing of development. 22 In Washington, DC, more liberal politics succeeded the conservatism of the 1950s, with the civil rights movement and other social movements forcing changes in national priorities.

This changing political environment was reflected in corresponding shifts within WHO. In the 1960s, WHO acknowledged that a strengthened health infrastructure was prerequisite to the success of malaria control programs, especially in Africa. In 1968, Candau called for a comprehensive and integrated plan for curative and preventive care services. A Soviet representative called for an organizational study of methods for promoting the development of basic health services. 23 In January 1971, the Executive Board of the World Health Assembly agreed to undertake this study, and its results were presented to the assembly in 1973. 24 Socrates Litsios has discussed many of the steps in the transformation of WHO’s approach from an older model of health services to what would become the “Primary Health Care” approach. 25 This new model drew upon the thinking and experiences of nongovernmental organizations and medical missionaries working in Africa, Asia, and Latin America at the grass-roots level. It also gained saliency from China’s reentry into the UN in 1973 and the widespread interest in Chinese “barefoot doctors,” who were reported to be transforming rural health conditions. These experiences underscored the urgency of a “Primary Health Care” perspective that included the training of community health workers and the resolution of basic economic and environmental problems. 26

These new approaches were spearheaded by Halfdan T. Mahler, a Dane, who served as director general of WHO from 1973 to 1988. Under pressure from the Soviet delegate to the executive board, Mahler agreed to hold a major conference on the organization of health services in Alma-Ata, in the Soviet Union. Mahler was initially reluctant because he disagreed with the Soviet Union’s highly centralized and medicalized approach to the provision of health services. 27 The Soviet Union succeeded in hosting the September 1978 conference, but the conference itself reflected Mahler’s views much more closely than it did those of the Soviets. The Declaration of Primary Health Care and the goal of “Health for All in the Year 2000” advocated an “intersectoral” and multidimensional approach to health and socioeconomic development, emphasized the use of “appropriate technology,” and urged active community participation in health care and health education at every level. 28

David Tejada de Rivero has argued that “It is regrettable that afterward the impatience of some international agencies, both UN and private, and their emphasis on achieving tangible results instead of promoting change . . . led to major distortions of the original concept of primary health care.” 29 A number of governments, agencies, and individuals saw WHO’s idealistic view of Primary Health Care as “unrealistic” and unattainable. The process of reducing Alma-Ata’s idealism to a practical set of technical interventions that could be implemented and measured more easily began in 1979 at a small conference—heavily influenced by US attendees and policies—held in Bellagio, Italy, and sponsored by the Rockefeller Foundation, with assistance from the World Bank. Those in attendance included the president of the World Bank, the vice president of the Ford Foundation, the administrator of USAID, and the executive secretary of UNICEF. 30

The Bellagio meeting focused on an alternative concept to that articulated at Alma-Ata—“Selective Primary Health Care”—which was built on the notion of pragmatic, low-cost interventions that were limited in scope and easy to monitor and evaluate. Thanks primarily to UNICEF, Selective Primary Health Care was soon operationalized under the acronym “GOBI” (Growth monitoring to fight malnutrition in children, Oral rehydration techniques to defeat diarrheal diseases, Breastfeeding to protect children, and Immunizations). 31

In the 1980s, WHO had to reckon with the growing influence of the World Bank. The bank had initially been formed in 1946 to assist in the reconstruction of Europe and later expanded its mandate to provide loans, grants, and technical assistance to developing countries. At first, it funded large investments in physical capital and infrastructure; in the 1970s, however, it began to invest in population control, health, and education, with an emphasis on population control. 32 The World Bank approved its first loan for family planning in 1970. In 1979, the World Bank created a Population, Health, and Nutrition Department and adopted a policy of funding both stand-alone health programs and health components of other projects.

In its 1980 World Development Report , the Bank argued that both malnutrition and ill health could be countered by direct government action—with World Bank assistance. 33 It also suggested that improving health and nutrition could accelerate economic growth, thus providing a good argument for social sector spending. As the Bank began to make direct loans for health services, it called for more efficient use of available resources and discussed the roles of the private and public sectors in financing health care. The Bank favored free markets and a diminished role for national governments. 34 In the context of widespread indebtedness by developing countries and increasingly scarce resources for health expenditures, the World Bank’s promotion of “structural adjustment” measures at the very time that the HIV/AIDS epidemic erupted drew angry criticism but also underscored the Bank’s new influence.

In contrast to the World Bank’s increasing authority, in the 1980s the prestige of WHO was beginning to diminish. One sign of trouble was the 1982 vote by the World Health Assembly to freeze WHO’s budget. 35 This was followed by the 1985 decision by the United States to pay only 20% of its assessed contribution to all UN agencies and to withhold its contribution to WHO’s regular budget, in part as a protest against WHO’s “Essential Drug Program,” which was opposed by leading US-based pharmaceutical companies. 36 These events occurred amidst growing tensions between WHO and UNICEF and other agencies and the controversy over Selective versus Comprehensive Primary Health Care. As part of a rancorous public debate conducted in the pages of Social Science and Medicine in 1988, Kenneth Newell, a highly placed WHO official and an architect of Comprehensive Primary Health Care, called Selective Primary Health Care a “threat . . . [that] can be thought of as a counter-revolution.” 37

In 1988, Mahler’s 15-year tenure as director general of WHO came to an end. Unexpectedly, Hiroshi Nakajima, a Japanese researcher who had been director of the WHO Western Pacific Regional Office in Manila, was elected new director general. 38

Crisis at WHO, 1988–1998

The first citizen of Japan ever elected to head a UN agency, Nakajima rapidly became the most controversial director general in WHO’s history. His nomination had not been supported by the United States or by a number of European and Latin American countries, and his performance in office did little to assuage their doubts. Nakajima did try to launch several important initiatives—on tobacco, global disease surveillance, and public–private partnerships—but fierce criticism persisted that raised questions about his autocratic style and poor management, his inability to communicate effectively, and, worst of all, cronyism and corruption.

Another symptom of WHO’s problems in the late 1980s was the growth of “extrabudgetary” funding. As Gill Walt of the London School of Hygiene and Tropical Medicine noted, there was a crucial shift from predominant reliance on WHO’s “regular budget”—drawn from member states’ contributions on the basis of population size and gross national product—to greatly increased dependence on extrabudgetary funding coming from donations by multilateral agencies or “donor” nations. 39 By the period 1986–1987, extrabudgetary funds of $437 million had almost caught up with the regular budget of $543 million. By the beginning of the 1990s, extra-budgetary funding had overtaken the regular budget by $21 million, contributing 54% of WHO’s overall budget.

Enormous problems for the organization followed from this budgetary shift. Priorities and policies were still ostensibly set by the World Health Assembly, which was made up of all member nations. The assembly, however, now dominated numerically by poor and developing countries, had authority only over the regular budget, frozen since the early 1980s. Wealthy donor nations and multilateral agencies like the World Bank could largely call the shots on the use of the extrabudgetary funds they contributed. Thus, they created, in effect, a series of “vertical” programs more or less independent of the rest of WHO’s programs and decisionmaking structure. The dilemma for the organization was that although the extrabudgetary funds added to the overall budget, “they [increased] difficulties of coordination and continuity, [caused] unpredictability in finance, and a great deal of dependence on the satisfaction of particular donors,” 40 as Gill Walt explained.

Fiona Godlee published a series of articles in 1994 and 1995 that built on Walt’s critique. 41 She concluded with this dire assessment: “WHO is caught in a cycle of decline, with donors expressing their lack of faith in its central management by placing funds outside the management’s control. This has prevented WHO from [developing] . . . integrated responses to countries’ long term needs.” 41

In the late 1980s and early 1990s, the World Bank moved confidently into the vacuum created by an increasingly ineffective WHO. WHO officials were unable or unwilling to respond to the new international political economy structured around neoliberal approaches to economics, trade, and politics. 42 The Bank maintained that existing health systems were often wasteful, inefficient, and ineffective, and it argued in favor of greater reliance on private-sector health care provision and the reduction of public involvement in health services delivery. 43

Controversies surrounded the World Bank’s policies and practices, but there was no doubt that, by the early 1990s, it had become a dominant force in international health. The Bank’s greatest “comparative advantage” lay in its ability to mobilize large financial resources. By 1990, the Bank’s loans for health surpassed WHO’s total budget, and by the end of 1996, the Bank’s cumulative lending portfolio in health, nutrition, and population had reached $13.5 billion. Yet the Bank recognized that, whereas it had great economic strengths and influence, WHO still had considerable technical expertise in matters of health and medicine. This was clearly reflected in the Bank’s widely influential World Development Report , 1993: Investing in Health , in which credit is given to WHO, “a full partner with the World Bank at every step of the preparation of the Report.” 44 Circumstances suggested that it was to the advantage of both parties for the World Bank and WHO to work together.

WHO EMBRACES “GLOBAL HEALTH”

This is the context in which WHO began to refashion itself as a coordinator, strategic planner, and leader of “global health” initiatives. In January 1992, the 31-member Executive Board of the World Health Assembly decided to appoint a “working group” to recommend how WHO could be most effective in international health work in light of the “global change” rapidly overtaking the world. The executive board may have been responding, in part, to the Children’s Vaccine Initiative, perceived within WHO as an attempted “coup” by UNICEF, the World Bank, the UN Development Program, the Rockefeller Foundation, and several other players seeking to wrest control of vaccine development. 45 The working group’s final report of May 1993 recommended that WHO—if it was to maintain leadership of the health sector—must overhaul its fragmented management of global, regional, and country programs, diminish the competition between regular and extrabudgetary programs, and, above all, increase the emphasis within WHO on global health issues and WHO’s coordinating role in that domain. 46

Until that time, the term “global health” had been used sporadically and, outside WHO, usually by people on the political left with various “world” agendas. In 1990, G. A. Gellert of International Physicians for the Prevention of Nuclear War had called for analyses of “global health interdependence.” 47 In the same year, Milton and Ruth Roemer argued that further improvements in “global health” would be dependent on the expansion of public rather than private health services. 48 Another strong source for the term “global health” was the environmental movement, especially debates over world environmental degradation, global warming, and their potentially devastating effects on human health. 49

In the mid-1990s, a considerable body of literature was produced on global health threats. In the United States, a new Centers for Disease Control and Prevention (CDC) journal, Emerging Infectious Diseases , began publication, and former CDC director William Foege started using the phrase “global infectious disease threats.” 50 In 1997, the Institute of Medicine’s Board of International Health released a report, America’s Vital Interest in Global Health: Protecting Our People, Enhancing Our Economy, and Advancing Our International Interests . 51 In 1998, the CDC’s Preventing Emerging Infectious Diseases: A Strategy for the 21st Century appeared, followed in 2001 by the Institute of Medicine’s Perspectives on the Department of Defense Global Emerging Infections Surveillance and Response System . 52 Best-selling books and news magazines were full of stories about Ebola and West Nile virus, resurgent tuberculosis, and the threat of bioterrorism. 53 The message was clear: there was a palpable global disease threat.

In 1998, the World Health Assembly reached outside the ranks of WHO for a new leader who could restore credibility to the organization and provide it with a new vision: Gro Harlem Brundtland, former prime minister of Norway and a physician and public health professional. Brundtland brought formidable expertise to the task. In the 1980s, she had been chair of the UN World Commission on Environment and Development and produced the “Brundtland Report,” which led to the Earth Summit of 1992. She was familiar with the global thinking of the environmental movement and had a broad and clear understanding of the links between health, environment, and development. 54

Brundtland was determined to position WHO as an important player on the global stage, move beyond ministries of health, and gain a seat at the table where decisions were being made. 55 She wanted to refashion WHO as a “department of consequence” 55 able to monitor and influence other actors on the global scene. She established a Commission on Macroeconomics and Health, chaired by economist Jeffrey Sachs of Harvard University and including former ministers of finance and officers from the World Bank, the International Monetary Fund, the World Trade Organization, and the UN Development Program, as well as public health leaders. The commission issued a report in December 2001, which argued that improving health in developing countries was essential to their economic development. 56 The report identified a set of disease priorities that would require focused intervention.

Brundtland also began to strengthen WHO’s financial position, largely by organizing “global partnerships” and “global funds” to bring together “stakeholders”—private donors, governments, and bilateral and multilateral agencies—to concentrate on specific targets (for example, Roll Back Malaria in 1998, the Global Alliance for Vaccines and Immunization in 1999, and Stop TB in 2001). These were semiautonomous programs bringing in substantial outside funding, often in the form of “public–private partnerships.” 57 A very significant player in these partnerships was the Bill & Melinda Gates Foundation, which committed more than $1.7 billion between 1998 and 2000 to an international program to prevent or eliminate diseases in the world’s poorest nations, mainly through vaccines and immunization programs. 58 Within a few years, some 70 “global health partnerships” had been created.

Brundtland’s tenure as director general was not without blemish nor free from criticism. Some of the initiatives credited to her administration had actually been started under Nakajima (for example, the WHO Framework Convention on Tobacco Control), others may be looked upon today with some skepticism (the Commission on Macroeconomics and Health, Roll Back Malaria), and still others arguably did not receive enough attention from her administration (Primary Health Care, HIV/AIDS, Health and Human Rights, and Child Health). Nonetheless, few would dispute the assertion that Brundtland succeeded in achieving her principal objective, which was to reposition WHO as a credible and highly visible contributor to the rapidly changing field of global health.

We can now return briefly to the questions implied at the beginning of this article: how does a historical perspective help us understand the emergence of the terminology of “global health” and what role did WHO play as an agent in its development? The basic answers derive from the fact that WHO at various times in its history alternatively led, reflected, and tried to accommodate broader changes and challenges in the ever-shifting world of international health. In the 1950s and 1960s, when changes in biology, economics, and great power politics transformed foreign relations and public health, WHO moved from a narrow emphasis on malaria eradication to a broader interest in the development of health services and the emerging concentration on smallpox eradication. In the 1970s and 1980s, WHO developed the concept of Primary Health Care but then turned from zealous advocacy to the pragmatic promotion of Selective Primary Health Care as complex changes overtook intra-and interorganizational dynamics and altered the international economic and political order. In the 1990s, WHO attempted to use leadership of an emerging concern with “global health” as an organizational strategy that promised survival and, indeed, renewal.

But just as it did not invent the eradicationist or primary care agendas, WHO did not invent “global health”; other, larger forces were responsible. WHO certainly did help promote interest in global health and contributed significantly to the dissemination of new concepts and a new vocabulary. In that process, it was hoping to acquire, as Yach and Bettcher suggested in 1998, a restored coordinating and leadership role. Whether WHO’s organizational repositioning will serve to reestablish it as the unquestioned steward of the health of the world’s population, and how this mission will be effected in practice, remains an open question at this time.

“War on the Malaria Mosquito!” Poster produced by the Division of Public Information, World Health Organization, Geneva, 1958. Courtesy of the World Health Organization. Source: Prints and Photographs Collection of the National Library of Medicine.

Smallpox Vaccination Program in Togo, 1967. Courtesy of the Centers for Disease Control and Prevention. Source: Public Health Image Library, CDC.

Alma Ata Conference, 1978. Courtesy of the Pan American Health Organization. Source: Office of Public Information, PAHO.

Current Director General Jongwook Lee with three former Directors-General at the celebration to mark the 25th Anniversary of the Alma Ata Declaration. From left: G. H. Brundtland, H. Mahler, H. Nakajima, Lee JW. Courtesy of the World Health Organization. Source: Media Center, WHO.

Acknowledgments

The authors are grateful to the Joint Learning Initiative of the Rockefeller Foundation, which initially commissioned this article, and to the Global Health Histories Initiative of the World Health Organization, which has provided a supportive environment for continuing our research.

Peer Reviewed

Contributors All authors contributed equally to the research and writing.

The Challenges of the World Health Organization: Lessons from the Outbreak of COVID-19

• First Online: 29 January 2021

Cite this chapter

• Virdzhiniya Petrova Georgieva 23  

Part of the book series: Balkan Yearbook of European and International Law ((BYEIL,volume 2020))

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The decisions adopted by the World Health Organization and the responses of its member states to the pandemic provoked by COVID-19 have revealed some of the challenges of this intergovernmental organization in its ability to provide efficient solutions to the health and health security problems of the international community at the beginning of the twenty-first century. WHO’s normative deficit has negatively affected the organization’s fight against the outbreak of the novel coronavirus. The chronic financial deficit of this institution has also determined its failures to control and eradicate the COVID-19 pandemic. Finally, the persistent violations of the rules and recommendations, adopted under WHO’s auspices, and the lack of control and accountability mechanisms in its legal framework have induced the little success of the institution’s intents to contain the global COVID-19 crisis. WHO could only surmount these challenges and continue to play a crucial role as a leader forum for states’ international cooperation in health and health security matters, if its members accept to reform the organization’s legal and institutional design.

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The Breathing Catastrophe: COVID-19 and Global Health Governance

Global Public Health Security: Three Vital Lessons

Introduction: Governance Challenges in the Management of the COVID-19 Pandemic in Africa

Preamble of WHO Constitution.

By virtue of article 2 of the WHO Constitution, the organization’s functions encompass the following: “to promote maternal and child health and welfare and to foster the ability to live harmoniously in a changing total environment; (m)to foster activities in the field of mental health, especially those affecting the harmony of human relations; (n) to promote and conduct research in the field of health; (o) to promote improved standards of teaching and training in the health, medical and related professions; (p) to study and report on, in co-operation with other specialized agencies where necessary, administrative and social techniques affecting public health and medical care from preventive and curative points of view, including hospital services and social security; (q) to provide information, counsel and assistance in the field of health; (r) to assist in developing an informed public opinion among all peoples on matters of health; (s) to establish and revise as necessary international nomenclatures of diseases, of causes of death and of public health practices; (t) to standardize diagnostic procedures as necessary; (u) to develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products; (v) generally to take all necessary action to attain the objective of the Organization.”

In this sense, article 21 of the WHO’s Constitution states: “Each Member undertakes that it will, within eighteen months after the adoption by the Health Assembly of a convention or agreement, take action relative to the acceptance of such convention or agreement. Each Member shall notify the Director-General of the action taken, and if it does not accept such convention or agreement within the time limit, it will furnish a statement of the reasons for non-acceptance. In case of acceptance, each Member agrees to make an annual report to the Director-General in accordance with Chapter XIV.”

Namely: “a) sanitary and quarantine requirements and other procedures designed to prevent the international spread of disease; b) nomenclatures with respect to diseases, causes of death and public health practices; (c) standards with respect to diagnostic procedures for international use; (d) standards with respect to the safety, purity and potency of biological, pharmaceutical and similar products moving in international commerce; (e) advertising and labelling of biological, pharmaceutical and similar products moving in international commerce” (article 2-k of WHO’s Constitution).

Many of these soft law instruments influenced the adoption of national legislation and international measures in health protection related matters. See Velasques ( 2012 ).

Examples of that kind of norms can be found in WHO’s Global Strategy on Diet, Physical Activity and Health (2010), Global Strategy to Reduce the Harmful Use of Alcohol (2008), Global Strategy for Women’s, Children’s and Adolescent’s Health (2016), Road Safety Strategies and Action Plans, Guide-lines for the Prevention of Maternal Diseases, etc.

Ostin ( 2015 ), p. 5.

The Tobacco Convention is aimed to control and regulate the cross-border effects of the tobacco epidemic.

The Nomenclature Regulations unify the standards for compilation and publication of the statistics of mortality and morbidity for the international classification of diseases. The last modification of the instrument was adopted in 2013.

The first International Sanitary Regulations were adopted at the end of the nineteenth century, in order to improve the international response against communicable diseases. In 1969, the instrument was named International Health Regulations (IHR) and was intended to control six infectious diseases: cholera, plague, yellow fever, smallpox, relapsing fever and typhus. After the spread of the Severe Acute Respiratory Syndrome (SARS), the World Health Assembly adopted the last modification of the IHR, in 2005.

In particular, states have the duty to notify to WHO detailed public health information “including case definitions, laboratory results, source and type of the risk, number of cases and deaths, conditions affecting the spread of the disease and the health measures employed” (article 6 of the IHR). This information is then shared by the WHO to all the other member states, who can entail consultation with each other and with the organization, in order to improve the measures adopted in response to the control and eradication of the disease.

According to this provision: “In determining whether an event constitutes a public health emergency of international concern, the Director-General shall consider: (a) information provided by the State Party; (b) the decision instrument contained in Annex 2; (c) the advice of the Emergency Committee; (d) scientific principles as well as the available scientific evidence and other relevant information; and (e) an assessment of the risk to human health, of the risk of international spread of disease and of the risk of interference with international traffic. 5. If the Director-General, following consultations with the State Party within whose territory the public health emergency of international concern has occurred, considers that a public health emergency of international concern has ended, the Director-General shall take a decision in accordance with the procedure set out in Article 49.”

These recommendations may include: “health measures (…) regarding persons, baggage, cargo, containers, conveyances, goods and/or postal parcels (…)” (Article 15-2 of the IHR), such as the application of medical exams, the requirement of additional documents and information concerning travelers destination, the disinfection and decontamination of conveyances, etc.

Article 13 of the IHR provides: “Each State Party shall develop, strengthen and maintain (…), the capacity to respond promptly and effectively to public health risks and public health emergencies of international concern as set out in Annex 1.”

According to article 13 of the IHR: “WHO shall publish, in consultation with Member States, guidelines to support States Parties in the development of public health response capacities.”

By virtue of this document: “The strengthening of national health systems and public health functions, based on the principles of primary health care and universal coverage, underpins many aspects of the Organization’s work – not just in terms of technical content but by providing a set of guiding values. In the last few years, the Organization’s work has focused on the building blocks of health systems (health service delivery, health workforce, health information systems, access to essential medicines, health systems financing, and leadership and governance). Now WHO’s focus will be to put those building blocks together into an integrated framework at community, district and national levels.” (WHO 2011 , p. 7).

Reuters ( 2020a ), New York Times ( 2020a ), and Euronews ( 2020 ).

New York Times ( 2020b ) and WHO ( 2020g ).

By virtue of WHO’s Constitution’s Preamble: “The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition.”

For example in article 5 (e) (iv) of the International Convention on the Elimination of All Forms of Racial Discrimination of 1965, in articles 11.1 (f) and 12 of the Convention on the Elimination of All Forms of Discrimination against Women of 1979 and in article 24 of the Convention on the Rights of the Child of 1989. The right to health is also recognized in the European Social Charter of 1961 as revised (art. 11), the African Charter on Human and Peoples’ Rights of 1981 (art. 16) and the Additional Protocol to the American Convention on Human Rights in the Area of Economic, Social and Cultural Rights of 1988 (art. 10).

According to this provision: “1. The States Parties to the present Covenant recognize the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. 2. The steps to be taken by the States Parties to the present Covenant to achieve the full realization of this right shall include those necessary for: (a) The provision for the reduction of the stillbirth-rate and of infant mortality and for the healthy development of the child; (b) The improvement of all aspects of environmental and industrial hygiene; (c) The prevention, treatment and control of epidemic, endemic, occupational and other diseases; (d) The creation of conditions which would assure to all medical service and medical attention in the event of sickness.”

The commentary states: “3.The right to health is closely related to and dependent upon the realization of other human rights, as contained in the International Bill of Rights, including the rights to food, housing, work, education, human dignity, life, non-discrimination, equality, the prohibition against torture, privacy, access to information, and the freedoms of association, assembly and movement.” It also “acknowledges that the right to health embraces a wide range of socio-economic factors that promote conditions in which people can lead a healthy life, and extends to the underlying determinants of health, such as food and nutrition, housing, access to safe and potable water and adequate sanitation, safe and healthy working conditions, and a healthy environment.”

According to article 32 of the IHR: “In implementing health measures under these Regulations, States Parties shall treat travellers with respect for their dignity, human rights and fundamental freedoms and minimize any discomfort or distress associated with such measures.”

Human Rights Watch ( 2020 ).

Tzeng ( 2020 ), pp. 1346–1351.

The CITES subjects the international trade of certain species to strict controls and includes them in three Appendices. CITES’ Appendices 1 includes 600 animal and 300 plant species, whose traffic is prohibited with very few exceptions. Appendices 2 covers 48,000 animal and 30,000 plant species, whose traffic is permitted but subject to strict controls, and Appendices 3 lists 135 animal and 15 plant species, the traffic of which is permitted under some control.

Challender et al. ( 2015 ), pp. 129–148.

WHO ( 2020a ).

According to article 16 of the Convention: “1. Each Contracting Party, recognizing that technology includes biotechnology, and that both access to and transfer of technology among Contracting Parties are essential elements for the attainment of the objectives of this Convention, undertakes subject to the provisions of this Article to provide and/or facilitate access for and transfer to other Contracting Parties of technologies that are relevant to the conservation and sustainable use of biological diversity or make use of genetic resources and do not cause significant damage to the environment.”

Toebes ( 2015 ), p. 300.

As stated by the Director-General of the WHO in 2011—Margaret Chan—in its Proposal for Reforms, the organization’s future work should “increasingly be concerned with building the capacity needed in countries to monitor and act on the environmental, economic and social determinants of health.” (Retrieved April 27, 2020 from https://apps.who.int/gb/ebwha/pdf_files/EBSS/EBSS2_2-en.pdf , p. 6).

Toebes (2015), p. 300.

Ostin ( 2015 ), p. 7.

In the first place, inspiring itself from the example of the global environmental treaties, the convention has created a COP (conference of parties), where states’ officials meet periodically to discuss subjects related to the interpretation and application of the Convention. The COP has adopted an additional Protocol to the convention, which is a treaty itself. Both the Convention and the Protocol have produced an important impact in states’ domestic legal system, as 80% of the members have adopted new legislation to implement their provisions at the national level (Nikogosian 2016 , p. 684).

WHO ( 2020b ).

US Department of Health and Human Services ( 2020 ).

According to the same document: “Voluntary contributions are the major source of the Organization’s funding2 and are expected to remain so. Voluntary contributions are often highly specified and not fully aligned with the programme budget. The majority of WHO’s funding is not sufficiently predictable or sustainable. There is an imbalance of funding for different programmes between technical cooperation and normative work, and between staff costs and activities.” See WHO ( 2011 ), p. 25.

In this sense, the initiative envisaged the “institution of a collective financing approach designed to secure a shared commitment by Member States and other donors to fully finance the Organization’s priorities as agreed by Member States in the programme budget” and “proposed that Member States and other donors increase the proportion of WHO’s income that is flexible by providing voluntary contributions that are less specified i.e. linked to higher level strategic components of the programme Budget”. See WHO ( 2011 ), p. 41.

WHO ( 2011 ), p. 27.

Ostin ( 2015 ), p. 8.

WHO ( 2011 ), p. 41.

Ostin ( 2015 ). p. 8.

Reuters ( 2014 ).

Wenham ( 2017 ), p. 1721.

New York Times ( 2014 ).

Wenham ( 2017 ).

WHO ( 2020c ).

WHO ( 2020d ).

WHO ( 2020i ).

WHO ( 2020e ).

CNBC ( 2020a ).

CNBC ( 2020b ).

Dupret ( 2014 ), p. 9.

Peterson ( 2019 ).

Ikenberry ( 2012 ).

For example, this country has a veto power in the UN Security Council and special voting rights at the two Bretton Woods institutions (the International Monetary Fund and the World Bank). In the same sense, the Director of the World Bank has to be an American citizen, NATO is dependent on the American military (super) power and the United States is the principal contributor to the budget of most of these organizations, including the UN.

BBC ( 2020a ).

DW ( 2020 ).

BBC ( 2020b ).

According to article 6: “The Director-General shall determine, on the basis of the information received, in particular from the State Party within whose territory an event is occurring, whether an event constitutes a public health emergency of international concern in accordance with the criteria and the procedure set out in these Regulations. (…) In determining whether an event constitutes a public health emergency of international concern, the Director-General shall consider: (a) information provided by the State Party; (b) the decision instrument contained in Annex 2; (c) the advice of the Emergency Committee; (d) scientific principles as well as the available scientific evidence and other relevant information; and (e) an assessment of the risk to human health, of the risk of international spread of disease and of the risk of interference with international traffic.” By virtue of article 7: “If a State Party has evidence of an unexpected or unusual public health event within its territory, irrespective of origin or source, which may constitute a public health emergency of international concern, it shall provide to WHO all relevant public health information. In such a case, the provisions of Article 6 shall apply in full.”

Burci ( 2020 ).

By virtue of this article: “Each State Party shall assess events occurring within its territory by using the decision instrument in Annex 2. Each State Party shall notify WHO, by the most efficient means of communication available, by way of the National IHR Focal Point, and within 24 hours of assessment of public health information, of all events which may constitute a public health emergency of international concern within its territory in accordance with the decision instrument, as well as any health measure implemented in response to those events.”

BBC ( 2020c ).

WHO ( 2020f ).

Aljazeera ( 2020a ).

Articles 42 and 43 of the IHR.

WHO ( 2020h ).

Burci ( 2019 ), p. 233.

According to article 61: “Each Member shall report annually to the Organization on the action taken and progress achieved in improving the health of its people.” In the same sense, in conformity with article 62: “Each Member shall report annually on the action taken with respect to recommendations made to it by the Organization and with respect to conventions, agreements and regulations.” Article 63 provides: “Each Member shall communicate promptly to the Organization important laws, regulations, official reports and statistics pertaining to health which have been published in the State concerned.”

Other treaties, establishing international organizations, set up mechanisms and sanctions that can be applied in such cases. Thus, for example, the Statute of the International Monetary Fund includes the imposition of sanctions against member States that do not respect the obligations incumbent on them by virtue of this agreement. The sanctions include the publication of public reports with sensible information on countries’ economic situation, the negative to afford financial assistance and credits to the State that has failed to fulfil its international obligations, the suspension of its voting rights, and, ultimately, its expulsion from the organization.

As mentioned above, article 43 of the regulations permits to the organization’s member states to implement additional measures to those provided by the Director-General’s recommendations after the declaration of a health emergency of international concern. However, the IHR do not include any negative consequences of the possible incompatibility between the measures adopted by the member states and those recommended by the Director-General. According to article 43-4: “After assessing information provided pursuant to paragraph 3 and 5 of this Article and other relevant information, WHO may request that the State Party concerned reconsider the application of the measures.” This “request” to “reconsider” the application of the measure does not include any duty to “put an end” to the inconsistent measures and exhorts state parties to the IHR to cooperate with the WHO, on a completely voluntary (and not compulsory) basis. State’s only binding obligation regarding their compliance with the IHR “is to report to the Health Assembly on the implementation of these Regulations” (article 54 of the IHR).

According to article 56 of the IHR: “in the event of a dispute between two or more States Parties concerning the interpretation or application of these Regulations, the States Parties concerned shall seek in the first instance to settle the dispute through negotiation or any other peaceful means of their own choice, including good offices, mediation or conciliation (…). In the event that the dispute is not settled by the means described under paragraph 1 of this Article, the States Parties concerned may agree to refer the dispute to the Director-General, who shall make every effort to settle it. 3. A State Party may at any time declare in writing to the Director-General that it accepts arbitration as compulsory with regard to all disputes concerning the interpretation or application of these Regulations to which it is a party or with regard to a specific dispute in relation to any other State Party accepting the same obligation. The arbitration shall be conducted in accordance with the Permanent Court of Arbitration Optional Rules for Arbitrating Disputes between Two States applicable at the time a request for arbitration is made. The States Parties that have agreed to accept arbitration as compulsory shall accept the arbitral award as binding and final. The Director-General shall inform the Health Assembly regarding such action as appropriate. 4. Nothing in these Regulations shall impair the rights of States Parties under any international agreement to which they may be parties to resort to the dispute settlement mechanisms of other intergovernmental organizations or established under any international agreement. 5. In the event of a dispute between WHO and one or more States Parties concerning the interpretation or application of these Regulations, the matter shall be submitted to the Health Assembly.”

Reuters ( 2020b ).

The Guardian ( 2020 ).

According to article 56: “A State Party may at any time declare in writing to the Director-General that it accepts arbitration as compulsory with regard to all disputes concerning the interpretation or application of these Regulations to which it is a party or with regard to a specific dispute in relation to any other State Party accepting the same obligation.”

Tzeng ( 2020 ).

By virtue of article 2 of the International Law Commission’s Draft Articles on Responsibility of States for Internationally Wrongful Acts: “There is an internationally wrongful act of a State when conduct consisting of an action or omission: (a) is attributable to the State under international law; and (b) constitutes a breach of an international obligation of the State.”

International Court of Justice, Declarations recognizing the jurisdiction of the Court as compulsory, Retrieved May 4, 2020 from https://www.icj-cij.org/en/declarations .

By virtue of this provision: “Any question or dispute concerning the interpretation or application of this Constitution which is not settled by negotiation or by the Health Assembly shall be referred to the International Court of Justice in conformity with the Statute of the Court, unless the parties concerned agree on another mode of settlement.”

According to article 62: “Each Member shall report annually on the action taken with respect to recommendations made to it by the Organization and with respect to conventions, agreements and regulations.” However, the obligation to report annually on the measure taken according to the IHR is different from the one established in the IHR regarding events that might constitute health emergencies of international concern. Consequently, it will be difficult to held China responsible for the violation of article 62 of the Constitution because of the delay of its reports to the WHO on the spread of COVID-19. In the same sense, article 63 of WHO’s constitutive statute provides: “Each Member shall communicate promptly to the Organization important laws, regulations, official reports and statistics pertaining to health which have been published in the State concerned.” The scope of this obligation is too general to fit with China’s response to COVID-19 and only covers published official reports and statistics. As noted above, China is accused to maintain secret and confidential relevant information on the novel virus, not only from the WHO, but also from the public opinion, in general.

Infobae ( 2020 ).

By virtue of article 12: “A State which becomes a Party to this Statute thereby accepts the jurisdiction of the Court with respect to the crimes referred to in article 5. 2. In the case of article 13, paragraph (a) or (c), the Court may exercise its jurisdiction if one or more of the following States are Parties to this Statute or have accepted the jurisdiction of the Court in accordance with paragraph 3: (…) (b) The State of which the person accused of the crime is a national.”

A situation, implicating the commission of international crimes can be referred to the ICC, directly, by the UN Security Council, even in relation to States that are not parties to the Rome Statute. However, the paradox of this procedure is that the Council can refer the nationals of other states to the ICC, but never the nationals of its five permanent members (the United States, France, the United Kingdom, Russia and China) because of their veto power during the referral.

In fact, article 12 of the Rome Statue establishes the possibility to determine the international criminal responsibility of nationals of a State non-signatory of the Statute, if “the State on the territory of which the conduct in question occurred or, if the crime was committed on board a vessel or aircraft, the State of registration of that vessel or aircraft” has ratified the treaty.

Aljazeera ( 2020b ).

The investigation will cover international crimes committed by nationals of a State that is not party to the Rome Statute (the United States) on the territory of other States parties to the convention (Afghanistan, Poland or Lithuania).

According to article 12-3 of the Rome Statute: “If the acceptance of a State which is not a Party to this Statute is required under paragraph 2, that State may, by declaration lodged with the Registrar, accept the exercise of jurisdiction by the Court with respect to the crime in question. The accepting State shall cooperate with the Court without any delay or exception in accordance with Part 9.”

The WHO’s officials enjoys a special legal status under the UN Convention on the Privileges and Immunities of the Specialized Agencies. According to article VI of this treaty: “Officials of the specialized agencies shall: (a) Be immune from legal process in respect of words spoken or written and all acts performed by them in their official capacity;” The broader scope of the term “legal process” seems to include immunity from jurisdiction in cases brought before domestic and international tribunals, such as the ICC. The question of the immunity from jurisdiction of the UN specialized agencies and/or other international organizations officials is not settled in the Rome Statute. Article 27 of the Statute provides: “1. This Statute shall apply equally to all persons without any distinction based on official capacity. In particular, official capacity as a Head of State or Government, a member of a Government or parliament, an elected representative or a government official shall in no case exempt a person from criminal responsibility under this Statute, nor shall it, in and of itself, constitute a ground for reduction of sentence.” However, the WHO is not a party to the Rome Statute and is not bound by this article. Even if its officials are nationals of a State that is party to the treaty, the special legal status of the officials derives from the organization’s own international personality, and is not related to the rights and duties of the organization’s member states. The UN and the ICC celebrated a Special Relationship Agreement in 2014. According to this agreement, if the ICC requests the testimony of a UN official, or wishes to exercise criminal jurisdiction over a person, who enjoys immunity under the UN Convention on Privileges and Immunities, the UN undertakes to cooperate and to waive the immunity. See Higgins et al. ( 2017 ), pp. 617–618. Thus, in the present case, the ICC could only hear a case related to the international criminal responsibility of a WHO’s official in relation to the outspread of COVID-19, if the UN Secretary-General expressly authorizes a waiver of its immunity from jurisdiction.

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Georgieva, V.P. (2021). The Challenges of the World Health Organization: Lessons from the Outbreak of COVID-19. In: Meškić, Z., Kunda, I., Popović, D.V., Omerović, E. (eds) Balkan Yearbook of European and International Law 2020. Balkan Yearbook of European and International Law, vol 2020. Springer, Cham. https://doi.org/10.1007/16247_2020_21

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• Published: 22 June 2022

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

• Joseph D. Khoury   ORCID: orcid.org/0000-0003-2621-3584 1 ,
• Eric Solary   ORCID: orcid.org/0000-0002-8629-1341 2 ,
• Oussama Abla 3 ,
• Yassmine Akkari   ORCID: orcid.org/0000-0002-3072-7388 4 ,
• Rita Alaggio 5 ,
• Jane F. Apperley   ORCID: orcid.org/0000-0002-1710-1794 6 ,
• Rafael Bejar   ORCID: orcid.org/0000-0002-5603-4598 7 ,
• Emilio Berti 8 ,
• Lambert Busque   ORCID: orcid.org/0000-0002-5375-3749 9 ,
• John K. C. Chan 10 ,
• Weina Chen   ORCID: orcid.org/0000-0001-5638-4371 11 ,
• Xueyan Chen 12 ,
• Wee-Joo Chng 13 ,
• John K. Choi   ORCID: orcid.org/0000-0002-2861-0180 14 ,
• Isabel Colmenero   ORCID: orcid.org/0000-0001-6859-187X 15 ,
• Sarah E. Coupland 16 ,
• Nicholas C. P. Cross   ORCID: orcid.org/0000-0001-5481-2555 17 ,
• Daphne De Jong 18 ,
• M. Tarek Elghetany 19 ,
• Emiko Takahashi   ORCID: orcid.org/0000-0001-8284-567X 20 ,
• Jean-Francois Emile   ORCID: orcid.org/0000-0002-6073-4466 21 ,
• Judith Ferry 22 ,
• Linda Fogelstrand 23 ,
• Michaela Fontenay 24 ,
• Ulrich Germing 25 ,
• Sumeet Gujral 26 ,
• Torsten Haferlach   ORCID: orcid.org/0000-0003-0196-2837 27 ,
• Claire Harrison 28 ,
• Jennelle C. Hodge 29 ,
• Shimin Hu   ORCID: orcid.org/0000-0001-7110-3814 1 ,
• Joop H. Jansen 30 ,
• Rashmi Kanagal-Shamanna   ORCID: orcid.org/0000-0001-7829-5249 1 ,
• Hagop M. Kantarjian   ORCID: orcid.org/0000-0002-1908-3307 31 ,
• Christian P. Kratz   ORCID: orcid.org/0000-0003-4120-5873 32 ,
• Xiao-Qiu Li 33 ,
• Megan S. Lim 34 ,
• Keith Loeb 35 ,
• Sanam Loghavi   ORCID: orcid.org/0000-0001-8980-3202 1 ,
• Andrea Marcogliese 19 ,
• Soheil Meshinchi 36 ,
• Phillip Michaels 37 ,
• Kikkeri N. Naresh   ORCID: orcid.org/0000-0003-3807-3638 35 ,
• Yasodha Natkunam   ORCID: orcid.org/0000-0002-9816-1018 38 ,
• Reza Nejati 39 ,
• German Ott 40 ,
• Eric Padron   ORCID: orcid.org/0000-0002-4707-7916 41 ,
• Keyur P. Patel 1 ,
• Nikhil Patkar   ORCID: orcid.org/0000-0001-9234-2857 42 ,
• Jennifer Picarsic 43 ,
• Uwe Platzbecker   ORCID: orcid.org/0000-0003-1863-3239 44 ,
• Irene Roberts 45 ,
• Anna Schuh   ORCID: orcid.org/0000-0002-3938-8490 46 ,
• William Sewell 47 ,
• Reiner Siebert 48 ,
• Prashant Tembhare   ORCID: orcid.org/0000-0002-9030-0415 42 ,
• Jeffrey Tyner   ORCID: orcid.org/0000-0002-2133-0960 49 ,
• Srdan Verstovsek   ORCID: orcid.org/0000-0002-6912-8569 31 ,
• Wei Wang   ORCID: orcid.org/0000-0001-6821-4556 1 ,
• Brent Wood 50 ,
• Wenbin Xiao   ORCID: orcid.org/0000-0001-8586-8500 51 ,
• Cecilia Yeung   ORCID: orcid.org/0000-0001-6799-2022 35 &
• Andreas Hochhaus   ORCID: orcid.org/0000-0003-0626-0834 52  

Leukemia volume  36 ,  pages 1703–1719 ( 2022 ) Cite this article

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The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

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Introduction.

The World Health Organization (WHO) classification of tumours is an evidence-based classification of cancers occurring within various organ systems. It is a standard for diagnosis, research, cancer registries, and public health monitoring worldwide. For the first time since the inception of the classification over 60 years ago, the current series (5th edition) has been developed within a unified relational database framework that encompasses the entirety of human cancers. Tumours of each organ system and across volumes (blue books) are classified hierarchically within this novel framework along taxonomy principles and a set of non-negotiables that include process transparency, bibliographic rigor, and avoidance of bias [ 1 , 2 ]. The development of the 5th edition is overseen by an editorial board that includes standing members —representatives from major medical and scientific organizations around the world—who oversee the entire series, in addition to expert members appointed for their leadership and contemporaneous expertise relevant to a particular volume [ 3 ]. The editorial board, in turn, identifies authors through an informed bibliometry process, with an emphasis on broad geographic representation and multidisciplinary expertise. By design, multidisciplinary author/editor groups (a total of 420 contributors) shared overlapping coverage of disease categories to ensure conceptual continuity and content harmonization. This approach reflects the ways in which the classification is meant to be implemented, with multidisciplinary input that emphasizes a holistic approach to patient management from diagnosis through disease monitoring.

The aim of this paper is to provide an overview of the new edition of the WHO classification for myeloid and histiocytic/dendritic tumours. The last edition of the haematolymphoid classification dates back to 2008 and was revised in 2017. An overview of the lymphoid tumours is provided in a companion manuscript [ 4 ].

The classification structure follows a lineage-based framework, flowing broadly from benign to malignant and branching down to category, family, type (disease/tumour), and subtype. Where possible, a triad of attributes was systematically applied and included: lineage + dominant clinical attribute + dominant biologic attribute. Lineage attribution rests on immunophenotyping with flow cytometry and/or immunohistochemistry. Dominant clinical attributes are general features of the untreated disease and include descriptors such as acute, chronic, cytopenia(s) (myelodysplasia) and cytosis(es) (myeloproliferation). Most biologic attributes include gene fusions , rearrangements , and mutations . Fusions are part of the nomenclature of types/subtypes when the identities of both implicated genes are required or often desirable criteria for diagnosis (e.g., PML :: RARA ). Rearrangements, a broad term that encompasses a range of structural genomic alterations leading to gene fusions, are part of the nomenclature of types/subtypes when there are multiple possible fusion partner genes of a biologically dominant gene (e.g., KMT2A ). Of note, the use of the term rearrangements is maintained in the classification due to its wide usage across prior editions, although it is recognized that it is more appropriate for genomic modifications in genes consisting of various segments (e.g., immunoglobulin genes and T-cell receptor genes). A deliberate attempt is made to prioritize classifying tumour types based on defining genetic abnormalities where possible.

Emerging entities are listed as disease subtypes under a novel rubric of other defined genetic alterations . This is envisioned as a landing spot in the classification to incorporate new/rare entities whose recognition is increasing as high-throughput molecular diagnostic tools become more available. This approach replaces the assignment of provisional status to such entities. It is recognized that the diagnosis of such subtypes might not be feasible in all practice settings. A set of decision support guidelines was adopted to aid in determining what subtypes would qualify in this context; they include: (1) having distinct molecular or cytogenetic features driven by established oncogenic mechanisms; (2) not meeting subtype criteria under other tumour types with defining genetic abnormalities; (3) having distinct pathologic and clinical features, including - but not limited to - response to therapeutic interventions; and, (4) at least two quality peer-review publications by distinct investigator groups.

The application of this classification is predicated on integrating morphologic (cytology and histology), immunophenotypic, molecular and cytogenetic data. This is in line with previous editions, with expanded numbers of disease types and subtypes that are molecularly defined. It is hoped that the genetic underpinnings of the classification will prompt the provision of health resources to ensure that the necessary genetic testing platforms are available to peruse the full potential of the classification. Notwithstanding, the full published classification will include listing of essential diagnostic criteria that have the broadest possible applicability, particularly in limited resource settings. A further aid to broader applicability is the improved hierarchical structure of the classification, which permits reverting to family (class)-level definitions when detailed molecular genetic analyses may not be feasible; this approach is further elaborated on in the introduction of the blue book.

In line with the rest of the WHO 5th edition series, the classification of myeloid and histiocytic/dendritic neoplasms follows the Human Genome Organization Gene Nomenclature Committee recommendations, including the new designation of gene fusions using double colon marks (::) [ 5 ].

Clonal haematopoiesis

Clonal haematopoiesis (CH) refers broadly to the presence of a population of cells derived from a mutated multipotent stem/progenitor cell harbouring a selective growth advantage in the absence of unexplained cytopenias, haematological cancers, or other clonal disorders. The incidence of CH increases with age [ 6 ]. Substantial advances in understanding the molecular genetics and public health implications of CH took place since the last classification, including recognition of their association with increased overall mortality, cardiovascular diseases, and myeloid malignancies. More specific emerging associations, such as those characterizing the VEXAS ( v acuoles, E 1 enzyme, X -linked, a utoinflammatory, s omatic UBA1 mutations) syndrome [ 7 ], represent manifestations of the interplay between inflammation and CH/myeloid neoplasia that are being gradually uncovered. Inclusion of CH in the classification represents a key inaugural effort to define and codify such myeloid precursor lesions.

Clonal haematopoiesis of indeterminate potential (CHIP) is defined in the classification as a term referring specifically to CH harbouring somatic mutations of myeloid malignancy-associated genes detected in the blood or bone marrow at a variant allele fraction (VAF) of ≥ 2% (≥4% for X-linked gene mutations in males) in individuals without a diagnosed haematologic disorder or unexplained cytopenia [ 8 ]. (Supplemental Data Table  S1 ) The significance of variants detected at lower levels is unclear at present.

Clonal cytopenia of undetermined significance (CCUS) is defined as CHIP detected in the presence of one or more persistent cytopenias that are otherwise unexplained by haematologic or non-haematologic conditions and that do not meet diagnostic criteria for defined myeloid neoplasms. Cytopenia definitions are harmonized for CCUS, MDS, and MDS/MPN; they include Hb <13 g/dL in males and <12 g/dL in females for anaemia, absolute neutrophil count <1.8 ×10 9 /L for leukopenia, and platelets <150 × 10 9 /L for thrombocytopenia [ 9 ].

Summary Box:

CH is recognized as a category of precursor myeloid disease state.

CHIP and CCUS are formally defined.

Myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) are listed in Table  1 . The main types remain largely unchanged from the prior edition. Initial diagnostic evaluation of MPN continues to depend on close correlation between clinical features, molecular diagnostics, and usually morphologic evaluation of a trephine bone marrow biopsy. Most MPN patients are diagnosed in chronic phase (CP), which may progress into a blast phase (BP) associated with the accumulation of secondary cytogenetic and/or molecular aberrations.

Chronic myeloid leukaemia risk factors are refined, and accelerated phase is no longer required

Chronic myeloid leukaemia (CML) is defined by the BCR :: ABL1 fusion resulting from t(9;22)(q34;q11). The natural history of untreated CML before the introduction of targeted tyrosine kinase inhibitors (TKI) was biphasic or triphasic: an initial indolent CP followed by a blast phase (BP), with or without an intervening accelerated phase (AP). With TKI therapy and careful disease monitoring, the incidence of progression to advanced phase disease has decreased, and the 10-year overall survival rate for CML is 80–90% [ 10 , 11 ]. The designation of AP has thus become less relevant, where resistance stemming from ABL1 kinase mutations and/or additional cytogenetic abnormalities and the development of BP represent key disease attributes [ 12 , 13 ]. Accordingly, AP is omitted in the current classification in favour of an emphasis on high risk features associated with CP progression and resistance to TKI. Criteria for BP include: (1) ≥20% myeloid blasts in the blood or bone marrow; or (2) the presence of an extramedullary proliferation of blasts; or (3) the presence of increased lymphoblasts in peripheral blood or bone marrow. The optimal cutoff for lymphoblasts and the significance of low-level B-lymphoblasts remain unclear and require additional studies.

Minor changes in diagnostic criteria for BCR::ABL1 -negative myeloproliferative neoplasms

The classification retains an emphasis on distinguishing between polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) using diagnostic criteria established in previous editions, with minor refinements. Distinction between these types is based on integrating peripheral blood findings with molecular data and bone marrow morphologic evaluation findings, as none of these parameters alone provide sufficient diagnostic specificity.

Major diagnostic criteria for the diagnosis of PV include elevated haemoglobin concentration and/or haematocrit, accompanied by trilineage hyperplasia (panmyelosis), with pleomorphic mature megakaryocytes in the bone marrow, and NM_004972:JAK2 p.V617F or JAK2 exon 12 mutations. As the determination of increased red cell mass with 51 Cr-labeled red cells has become uncommon in routine clinical practice, it has been removed as a diagnostic criterion. The diagnostic criteria of ET are well-established and have not changed.

Primary myelofibrosis (PMF) is characterized by a proliferation of abnormal megakaryocytes and granulocytes in the bone marrow, which is associated in fibrotic stages with a polyclonal increase in fibroblasts that drive secondary reticulin and/or collagen marrow fibrosis, osteosclerosis, and extramedullary haematopoiesis. Recognizing prefibrotic PMF remains necessary to separate it not only from ET and PV but also from fibrotic PMF [ 14 ]. The importance of serial monitoring of bone marrow fibrosis and spleen size using reproducible and standardized criteria remain pertinent, especially for patients receiving JAK1/2 inhibitors. PV and ET progress to AP (10-19% blasts) and BP (≥20% blasts) in a minority of cases, but leukaemic transformation is more frequent in PMF, and leukaemia-free survival is shorter in fibrotic than prefibrotic PMF [ 15 , 16 ].

While JAK2 , CALR , and MPL mutations are considered driver events, mutations in other genes – particularly TET2 , ASXL1 , and DNMT3A – are found in over half of patients with MPN. Mutations affecting splicing regulators ( SRSF2, SF3B1, U2AF1, ZRSR2 ) and other regulators of chromatin structure, epigenetic functions and cellular signaling (e.g., EZH2, IDH1, IDH2, CBL, KRAS, NRAS, STAG2, TP53 ) are less common. These additional mutations are more frequent in PMF and advanced disease compared to PV and ET, and some are known to correlate with a poorer prognostic risk (e.g., EZH2, IDH1, IDH2, SRSF2, U2AF1 , and ASXL1 mutations in PMF).

Chronic neutrophilic leukaemia (CNL) is a BCR :: ABL1 -negative MPN characterized by sustained peripheral blood neutrophilia (white blood cell count (WBC) ≥ 25 × 10 9 / L, with ≥80% segmented neutrophils and bands), bone marrow hypercellularity due to neutrophilic granulocyte proliferation, and hepatosplenomegaly. CSF3R mutations are common in this disease and detected in >60% of cases [ 17 , 18 ].

Chronic eosinophilic leukaemia (CEL) is a multi-system disorder characterized by a sustained clonal proliferation of morphologically abnormal eosinophils and eosinophil precursors resulting in persistent hypereosinophilia in blood and bone marrow [ 19 , 20 , 21 ]. Several changes to the diagnostic criteria of CEL are introduced: (1) the time interval required to define sustained hypereosinophilia is reduced from 6 months to 4 weeks; (2) addition of requirement for both clonality and abnormal bone marrow morphology (e.g., megakaryocytic or erythroid dysplasia); and, (3) elimination of increased blasts (≥2% in peripheral blood or 5-19% in bone marrow) as an alternative to clonality. These criteria improve the distinction between CEL and entities such as idiopathic hypereosinophilic syndrome and hypereosinophilia of unknown significance [ 22 ]. As the criteria of CEL and its place relative to other disorders with eosinophilia have become well characterized, the qualifier “not otherwise specified” is no longer needed and has been omitted from the name.

As in prior editions, MPN, not otherwise specified (MPN-NOS) is a designation that should be reserved for cases with clinical, laboratory, morphologic, and molecular features of MPN but lacking diagnostic criteria of any specific MPN type or with features that overlap across distinct MPN types.

Juvenile myelomonocytic leukaemia is recognized as a myeloproliferative neoplasm of early childhood with frequent association with germline pathogenic gene variants

Juvenile myelomonocytic leukaemia (JMML) is a haematopoietic stem cell-derived myeloproliferative neoplasm of early childhood. The pathogenetic mechanism in at least 90% of cases involves unchecked activation of the RAS pathway. A diagnosis of JMML can be made by combining clinical, laboratory, and molecular criteria. Updates to diagnostic criteria include: (1) exclusion of KMT2A rearrangements; (2) elimination of monosomy 7 as a cytogenetic criterion; and, (3) emphasizing the significance of diagnostic molecular studies, particularly those aimed at demonstrating RAS pathway activation. The genetic background of JMML plays a major role in risk stratification and therapeutic approaches, with cases initiated by somatic mutations involving PTPN11 and germline pathogenic variants associated with neurofibromatosis type 1 being the most aggressive types, while some cases associated with pathogenic germline CBL variants undergoing occasionally spontaneous remission. The inclusion of JMML under MPN reflects its molecular pathogenesis and underscores the virtual absence of stigmata of bona fide myelodysplastic neoplasia in this disease.

CML phases consolidated into chronic and blast phases, with emphasis on risk features in chronic phase.

Diagnostic criteria of CEL are updated, and the qualifier NOS is omitted.

JMML is categorized under myeloproliferative neoplasms.

Mastocytosis

Mastocytosis comprises rare heterogeneous neoplasms characterized by an accumulation of abnormal mast cells in various organs or tissues, typically driven by constitutive activation of the KIT receptor. The pathology of mastocytosis is complex, and clinical features span a broad spectrum that may be modulated by the presence of comorbidities. Significant comorbidities include IgE-dependent allergies, vitamin D deficiency, and psychiatric, psychological or mental problems. The classification continues to recognize three disease types: systemic mastocytosis (SM), cutaneous mastocytosis (CM) and mast cell sarcoma (MCS) [ 23 ]. (Table  2 )

A somatic point mutation in the KIT gene at codon 816 is detected in >90% of patients with SM. Other rare activating KIT alterations include mutations in the extracellular (e.g., deletion of codon 419 on exon 8 or A502_Y503dup in exon 9), transmembrane (e.g., NM_000222:KIT p.F522C), or juxtamembrane (e.g., NM_000222:KIT p.V560G) domains, detected in <1% of advanced SM cases but enriched in cases of indolent SM. Most patients with advanced SM and NM_000222: KIT p.D816V have additional somatic mutations involving most frequently TET2, SRSF2, ASXL1, RUNX1 , and JAK2 . An associated haematologic (usually myeloid) neoplasm may be detected in these patients [ 24 ].

Diagnostic criteria for SM have been modified. Namely, expression of CD30 and the presence of any KIT mutation causing ligand-independent activation have been accepted as minor diagnostic criteria. Basal serum tryptase level >20 ng/ml, which should be adjusted in case of hereditary alpha-tryptasaemia, is a minor SM criterion [ 25 ]. In addition, bone marrow mastocytosis is now a separate subtype of SM characterized by absence of skin lesions and B-findings and a basal serum tryptase below 125 ng/ml. Classical B-findings (‘burden of disease’) and C-findings (‘cytoreduction-requiring’) have undergone minor refinements. Most notably, NM_000222: KIT p.D816V mutation with VAF ≥ 10% in bone marrow cells or peripheral blood leukocytes qualifies as a B-finding.

The classification recognizes well-differentiated systemic mastocytosis (WDSM) as a morphologic pattern that can occur in any SM subtype, characterized by round and well-granulated mast cells usually heavily infiltrating the bone marrow. In most patients with WDSM, KIT codon 816 mutation is not detected, and neoplastic mast cells are usually negative for CD25 and CD2 but positive for CD30 [ 26 ].

Diagnostic criteria for mastocytosis have been refined: CD30 and any KIT mutation are introduced as minor diagnostic criteria.

Bone marrow mastocytosis is a new SM subtype.

KIT D816V mutation with VAF ≥ 10% qualifies as a B-finding.

Myelodysplastic neoplasms

New terminology and grouping framework.

The classification introduces the term myelodysplastic neoplasms (abbreviated MDS) to replace myelodysplastic syndromes, underscoring their neoplastic nature and harmonizing terminology with MPN. These clonal haematopoietic neoplasms are defined by cytopenias and morphologic dysplasia. As indicated above, cytopenia definitions are adopted for consistency across CCUS, MDS, and MDS/MPN. Additionally, the recommended threshold for dysplasia is set at 10% for all lineages. MDS entities are now grouped as those having defining genetic abnormalities and those that are morphologically defined . (Table  3 ) It is posited that such reorganization enhances classification rigor by emphasizing genetically-defined disease types and ceding the prior emphasis on ‘risk-based’ grouping in the classification (based on blast percentage, ring sideroblasts, and number of lineages with dysplasia) in favour of more comprehensive risk-stratification schemes such as the Revised International Prognostic Scoring System for MDS (IPSS-R) [ 27 ]. An additional modification is a clarified terminology to distinguish between MDS with low blasts (MDS-LB) and MDS with increased blasts (MDS-IB), while retaining longstanding cutoffs.

MDS with defining genetic abnormalities

Myelodysplastic neoplasms with defining genetic abnormalities are grouped together and include: MDS with low blasts and isolated 5q deletion (MDS-5q), MDS with low blasts and SF3B1 mutation (MDS- SF3B1 ), and MDS with biallelic TP53 inactivation (MDS-bi TP53 ). The latter supersedes MDS-5q and MDS- SF3B1 .

The diagnostic criteria of MDS-5q have not changed. While recognized as factors that may potentially alter the biology and/or prognosis of the disease, the presence of SF3B1 or a TP53 mutation (not multi-hit) does not per se override the diagnosis of MDS-5q.

Recent studies have identified MDS- SF3B1 as a distinct disease type that includes over 90% of MDS with ≥5% ring sideroblasts [ 28 ]. The term MDS with low blasts and ring sideroblasts is retained as an acceptable alternative to be used for cases with wild-type SF3B1 and ≥15% ring sideroblasts. This permits inclusion of rare MDS cases harbouring driver mutations in other RNA splicing components.

Pathogenic TP53 alterations of any type (sequence variations, segmental deletions and copy neutral loss of heterozygosity) are detected in 7-11% of MDS [ 29 , 30 , 31 ]. Among these, about two-thirds of patients have multiple TP53 hits (multi-hit), consistent with biallelic TP53 alterations [ 29 ]. Biallelic TP53 (bi TP53 ) alterations may consist of multiple mutations or mutation with concurrent deletion of the other allele. This “multi-hit” mutational status results in a neoplastic clone that lacks any residual wild-type p53 protein. Clinical detection of biallelic TP53 alterations is based on sequencing analysis (covering at least exons 4 to 11) [ 29 , 32 ], often coupled with a technique to detect copy number status, usually fluorescence in situ hybridization with a probe set specific for the TP53 locus on 17p13.1 and/or array techniques (e.g., comparative genomic hybridization or single nucleotide polymorphism arrays) [ 33 ]. Loss of genetic material at the TP53 locus may also be inferred by next-generation sequencing [ 29 ]. A TP53 VAF ≥ 50% may be regarded as presumptive (not definitive) evidence of copy loss on the trans allele or copy neutral loss of heterozygosity when a constitutional TP53 variant can be ruled out. When two or more TP53 mutations are detected, they usually affect both alleles [ 29 ] and can be considered a multi-hit status. Over 90% of patients with MDS-bi TP53 have complex, mostly very complex (>3), karyotype [ 29 , 30 ] and thus are regarded as very high risk in IPSS-R [ 27 ]. Additional studies are needed to determine whether bi TP53 status is per se AML-defining, a point for consideration in future editions. Notwithstanding, published data suggests that MDS-bi TP53 may be regarded as AML-equivalent for therapeutic considerations [ 29 , 30 ].

MDS, morphologically defined

Hypoplastic MDS (MDS-h) is listed as a distinct MDS type in this edition. Long recognized as having distinctive features, MDS-h is associated with a T-cell mediated immune attack on haematopoietic stem and progenitor cells, along with oligoclonal expansion of CD8 + cytotoxic T-cells overproducing IFNγ and/or TNFα. Several features overlap across the triad of MDS-h, paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA), including an association with CH [ 34 , 35 , 36 ]. Many patients with MDS-h have sustainable responses to agents used in patients with AA (i.e., anti-thymocyte globulin, ATG). As such, an emphasis is placed on careful morphologic evaluation, typically requiring trephine biopsy evaluation in addition to evaluation of bone marrow smears and touch preparations, and detection of mutations and/or clonal cytogenetic abnormalities. Individuals with germline pathogenic variants in GATA2 , DDX41 , Fanconi anaemia (FA) or telomerase complex genes can have hypoplastic bone marrow and evolve to MDS and/or AML and do not respond to immunosuppressive treatment.

As the number of dysplastic lineages is usually dynamic and often represents clinical and phenotypic manifestation of clonal evolution – rather than per se defining a specific MDS type, the distinction between single lineage and multilineage dysplasia is now considered optional. The updated MDS classification scheme and the incorporation of CCUS in the classification obviates the need for “NOS” or “unclassifiable” attributes. Specifically, MDS, unclassifiable, which was present in the prior edition, is removed.

The boundary between MDS and AML is softened, but the 20% blast cutoff to define AML is retained

Reassessment of the bone marrow blast percentage defining the boundary of MDS-IB2 and AML has been advocated for several cogent reasons and in view of novel therapeutic approaches that show efficacy in patients currently classified as MDS or AML with 10-30% myeloid blasts [ 37 , 38 , 39 ]. Salient practical challenges underpinning arguments for such a reassessment include: (1) any blast-based cutoff is arbitrary and cannot reflect the biologic continuity naturally inherent in myeloid pathogenic mechanisms; (2) blast enumeration is subject to sampling variations/error and subjective evaluation; and, (3) no gold standard for blast enumeration exists, and orthogonal testing platforms can and often do produce discordant results. The pros and cons of merging MDS-IB2 with AML and adopting a 10% cutoff for what would be called MDS/AML were explored in multidisciplinary expert discussions and at editorial board meetings in the course of producing this classification. Lowering the blast cutoff to define AML was felt to suffer from the same challenges listed above and would merely replace one cutoff with another. Further, an arbitrary cutoff of 10% blasts to define AML (even if qualified as MDS/AML or AML/MDS) carries a risk of overtreatment. Accordingly, a balanced approach was adopted by eliminating blast cutoffs for most AML types with defining genetic alterations but retaining a 20% blast cutoff to delineate MDS from AML. Notwithstanding, there was broad agreement that MDS-IB2 may be regarded as AML-equivalent for therapeutic considerations and from a clinical trial design perspective when appropriate.

Childhood myelodysplastic neoplasms: Enhanced specificity of disease terminology introduced

Childhood MDS is a clonal haematopoietic stem cell neoplasm arising in children and adolescents (<18 years of age) leading to ineffective haematopoiesis, cytopenia(s), and risk of progression to AML. The annual incidence is 1-2 per million children, with 10-25% presenting with increased blasts. JMML, myeloid proliferations associated with Down syndrome, and MDS post cytotoxic therapy are excluded from this group and belong elsewhere in the classification. The qualifying term childhood MDS emphasizes that this category of myeloid neoplasms is biologically distinct from that seen in adults [ 40 , 41 ], underscoring the need to further elucidate its pathogenesis which remains incompletely understood

Childhood MDS with low blasts (cMDS-LB) replaces the former term “refractory cytopenia of childhood (RCC)”. It includes two subtypes: childhood MDS with low blasts, hypocellular; and, childhood MDS with low blasts, not otherwise specified (NOS). (Table  4 ) Exclusion of non-neoplastic causes of cytopenia such as infections, nutritional deficiencies, metabolic diseases, bone marrow failure syndromes (BMFS), and germline pathogenic variants remains an essential diagnostic prerequisite for childhood MDS with low blasts. Approximately 80% of cases show hypocellular bone marrow with features similar to severe aplastic anemia and other BMFS, requiring close morphologic examination to evaluate the distribution, maturation, and presence of dysplasia in haematopoietic lineages [ 42 ]. Some cytogenetic findings such as monosomy 7, 7q deletion, or complex karyotype are associated with an increased risk of progression to AML and typically treated with haematopoietic stem cell transplantation, while cases with normal karyotype or trisomy 8 can have an indolent course.

Childhood MDS with increased blasts (cMDS-IB) is defined as having ≥5% blasts in the bone marrow or ≥2% blasts in the peripheral blood. The genetic landscape of cMDS-IB and cMDS-LB is similar, and they both differ from MDS arising in adults. Acquired cytogenetic abnormalities and RAS-pathway mutations are more common in cMDS-IB compared to cMDS-LB [ 43 , 44 ].

Myelodysplastic syndromes renamed myelodysplastic neoplasms (abbreviated MDS).

MDS genetic types updated to include MDS-5q, MDS- SF3B1 and MDS-bi TP53

Hypoplastic MDS (MDS-h) is recognized as a distinct disease type.

MDS with low blasts (MDS-LB) is a new term that enhances clarity.

MDS with increased blasts (MDS-IB) is a new term that enhances clarity.

Terminology of childhood MDS types is updated.

Myelodysplastic/myeloproliferative neoplasms

This category of myeloid neoplasms is defined by overlapping pathologic and molecular features of MDS and MPN, often manifesting clinically with various combinations of cytopenias and cytoses. The definition of cytopenias is the same as that for MDS. The classification includes major revisions in the diagnostic criteria of CMML and terminology changes for other MDS/MPN types. (Table  5 )

Chronic myelomonocytic leukaemia diagnostic criteria, subtypes, and blast-based subgrouping criteria reflect diagnostic refinement and emphasize unifying characteristics

The prototype and most common MDS/MPN is chronic myelomonocytic leukaemia (CMML), which is characterized by sustained peripheral blood monocytosis and various combinations of somatic mutations involving epigenetic regulation, spliceosome, and signal transduction genes. Diagnostic criteria are revised to include prerequisite and supporting criteria. (Table  6 ) The first prerequisite criterion is persistent absolute (≥0.5 × 10 9 / L) and relative (≥10%) peripheral blood monocytosis. Namely, the cutoff for absolute monocytosis is lowered from 1.0 ×10 9 /L to 0.5 ×10 9 /L to incorporate cases formerly referred to as oligomonocytic CMML [ 45 , 46 , 47 ]. To enhance diagnostic accuracy when absolute monocytosis is ≥0.5 ×10 9 /L but <1.0 ×10 9 /L, detection of one of more clonal cytogenetic or molecular abnormality and documentation of dysplasia in at least one lineage are required. Abnormal partitioning of peripheral blood monocyte subsets is introduced as a new supporting criterion [ 48 , 49 ]. Additional studies are needed to determine the optimal approach to classifying individuals with unexplained clonal monocytosis [ 50 ] who do not fit the new diagnostic criteria of CMML.

Two disease subtypes with salient clinical and genetic features are now formally recognized based on WBC: myelodysplastic CMML (MD-CMML) (WBC < 13 × 10 9 /L) and myeloproliferative CMML (MP-CMML) (WBC ≥ 13 × 10 9 /L). MP-CMML is commonly associated with activating RAS pathway mutations and adverse clinical outcomes [ 51 ]. The blast-based subgroup of CMML-0 (<2% blasts in blood and <5% blasts in bone marrow) introduced in the previous edition has been eliminated in view of evidence that its addition provides no or limited prognostic significance [ 52 , 53 ].

Atypical chronic myeloid leukaemia is renamed MDS/MPN with neutrophilia, and other terminology updates

Diagnostic criteria for other MDS/MPN types were largely unchanged. The term MDS/MPN with neutrophilia replaces the term atypical CML. This change underscores the MDS/MPN nature of the disease and avoids potential confusion with CML. MDS/MPN with ring sideroblasts and thrombocytosis is redefined based on SF3B1 mutation and renamed MDS/MPN with SF3B1 mutation and thrombocytosis . The term MDS/MPN with ring sideroblasts and thrombocytosis has been retained as an acceptable term to be used for cases with wild-type SF3B1 and ≥15% ring sideroblasts. MDS/MPN, unclassifiable is now termed MDS/MPN, not otherwise specified ; this is in line with an intentional effort to remove the paradoxical qualifier “unclassifiable” from the entire classification.

CMML diagnostic criteria undergo major revisions, including lowering the cutoff for absolute monocytosis, adopting MD-CMML and MP-CMML subtypes, and eliminating CMML-0.

Atypical chronic myeloid leukaemia renamed MDS/MPN with neutrophilia.

MDS/MPN with ring sideroblasts and thrombocytosis redefined based on SF3B1 mutation and renamed MDS/MPN with SF3B1 mutation and thrombocytosis.

Acute myeloid leukaemia

Enhanced grouping framework permitting scalable genetic classification and deemphasizing blast enumeration where relevant.

The classification of AML is re-envisioned to emphasize major breakthroughs over the past few years in how this disease is understood and managed. Foremost is the separation of AML with defining genetic abnormalities from AML defined by differentiation. (Table  7 ) The latter eliminates the previously confusing use of the term AML NOS, under which types based on differentiation were listed. Another key change, as indicated above, is the elimination of the 20% blast requirement for AML types with defining genetic abnormalities (with the exception of AML with BCR :: ABL1 fusion and AML with CEBPA mutation). Removal of the blast cutoff requires correlation between morphologic findings and the molecular genetic studies to ensure that the defining abnormality is driving the disease pathology. This approach was deemed more appropriate than assigning another arbitrary lower bone marrow blast cutoff. A third component of the new structure is the introduction of a section on AML with other defined genetic alterations , a landing spot for new and/or uncommon AML subtypes that may (or may not) become defined types in future editions of the classification. As such, the overall AML classification structure continues to emphasize integration of clinical, molecular/genetic, and pathologic parameters and emphasis on clinicopathologic judgement.

AML with defining genetic abnormalities

While the classification retains much of the established diagnostic criteria for AML with PML :: RARA , AML with RUNX1 :: RUNX1T1 , and AML with CBF :: MYH11 , increased recognition of the importance of highly sensitive measurable residual disease (MRD) evaluation techniques, and the impact of concurrent molecular alterations reflect factors that impact patient management and therapeutic decisions in current practice. Namely, prognostic factors have expanded from KIT mutations, which are still relevant, to include additional cytogenetic features and MRD status post induction. The diagnostic criteria of AML with DEK :: NUP214 and AML with RBM15 :: MRTFA (formerly RBM15 :: MKL1 ) have also remained largely unchanged.

AML with BCR :: ABL1 and AML with CEBPA mutation are the only disease types with a defined genetic abnormality that require at least 20% blasts for diagnosis. The blast cutoff requirement is needed for the former to avoid overlap with CML. Distinguishing AML with BCR :: ABL1 from initial myeloid blast phase of CML can be challenging, and additional evidence continues to be needed to better characterize this AML type. There is insufficient data to support any change in the blast cutoff criterion for AML with CEBPA mutation [ 54 , 55 ].

Three AML types with characteristic rearrangements involving KMT2A, MECOM , and NUP98 are recognized. A blast count under 20% is acceptable based on studies demonstrating that patients with <20% blasts (MDS) and any of these rearrangements have clinical features that resemble those with higher blast counts. It is important to note that rearrangements involving these three genes, particularly NUP98 , may be cryptic on conventional karyotyping. AML with KMT2A rearrangement is the new term that replaces “AML with t(9;11)(p22;q23); KMT2A-MLLT3” . More than 80 KMT2A fusion partners have been described, with MLLT3, AFDN, ELL , and MLLT10 being most common. While not required, the identification of the fusion partner is desirable since it could provide prognostic information and may impact disease monitoring. Adult patients often present with high blast counts, usually with monocytic differentiation. In children particularly, AML with KMT2A :: MLLT3 and KMT2A :: MLLT10 show megakaryoblastic differentiation and/or low blast counts in bone marrow aspirate smears.

AML defined by mutations include AML with NPM1 and AML with CEBPA mutation. AML with NPM1 mutation can be diagnosed irrespective of the blast count, albeit again with emphasis on judicious clinicopathologic correlation. This approach aligns with data showing that cases previously classified as MDS or MDS/MPN with NPM1 progress to AML in a short period of time. Similar data have emerged from patients with CH who acquire NPM1 mutation. The definition of AML with CEBPA mutation has changed to include biallelic (biCEBPA) as well as single mutations located in the basic leucine zipper (bZIP) region of the gene (smbZIP- CEBPA ). The favourable prognosis associated with smbZIP- CEBPA has been demonstrated in cohorts of children and adults up to 70 years old. RUNX1 mutations in AML overlap with such a broad range of defining molecular features that it was determined to lack enough specificity to define a standalone AML type.

Several changes were introduced to the entity formerly designated AML with myelodysplasia-related changes, now called AML, myelodysplasia-related (AML-MR). This AML type is defined as a neoplasm with ≥20% blasts expressing a myeloid immunophenotype and harboring specific cytogenetic and molecular abnormalities associated with MDS, arising de novo or following a known history of MDS or MDS/MPN. Key changes include: (1) removal of morphology alone as a diagnostic premise to make a diagnosis of AML-MR; (2) update of defining cytogenetic criteria; and, (3) introduction of a mutation-based definition based on a set of 8 genes – SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, STAG2 , > 95% of which are present specifically in AML arising post MDS or MDS/MPN [ 56 , 57 ]. The presence of one or more cytogenetic or molecular abnormalities listed in Table  8 and/or history of MDS or MDS/MPN are required for diagnosing AML-MR.

AML with other defined genetic alterations represents a landing spot for new, often rare, emerging entities whose recognition is desirable to determine whether they might constitute distinct types in future editions. At present, subtypes under this heading include AML with rare genetic fusions.

AML defined by differentiation

This AML family includes cases that lack defining genetic abnormalities. (Table  9 ) It is anticipated that the number of such cases will diminish as discoveries provide novel genetic contexts for their classification. Notwithstanding, categorizing AML cases lacking defining genetic abnormalities based on differentiation offers a longstanding classification paradigm with practical, prognostic, and perhaps therapeutic implications.

The classification includes an updated comprehensive framework of differentiation markers and criteria, harmonized with those of mixed-phenotype acute leukaemia (MPAL) and early T-precursor lymphoblastic leukaemia/lymphoma (ETP-ALL) (see section below on acute leukaemia of ambiguous lineage). Indeed, the recent identification of BCL11B rearrangements in MPAL T/Myeloid, ETP-ALL, acute leukaemia of ambiguous lineage (ALAL) and a subset of AML with minimal differentiation suggests a biologic continuum across these entities, a finding with likely implications on future editions of the classification [ 58 , 59 , 60 , 61 ].

Acute erythroid leukaemia (AEL) (previously pure erythroid leukaemia, an acceptable related term in this edition) is a distinct AML type characterized by neoplastic proliferation of erythroid cells with features of maturation arrest and high prevalence of biallelic TP53 alterations. Diagnostic criteria include erythroid predominance, usually ≥80% of bone marrow elements, of which ≥30% are proerythroblasts (or pronormoblasts). The occurrence of AEL cases in which nucleated erythroid cells constitute less than 80% of bone marrow cellularity is recognized; such cases share the same clinicopathologic features of other AEL [ 62 , 63 ]. The central role that biallelic TP53 mutations play in this aggressive AML type is underscored [ 64 , 65 ]. The diagnosis of AEL supersedes AML-MR. De novo AEL and cases that arise following MDS or MDS/MPN share distinctive morphologic features, with prominent proerythroblast proliferation. Proerythroblast have been shown to play an important role in treatment resistance and poor prognosis in AML patients [ 66 , 67 ].

Several molecular drivers can give rise to acute megakaryoblastic leukaemia (AMKL), which arises within three clinical groups: children with Down syndrome, children without Down syndrome, and adults. Immunophenotyping and detection of markers of megakaryocytic differentiation are required to make a diagnosis of AMKL and detect the newly described “RAM immunophenotype”, which correlates with CBFA2T3 :: GLIS2 , a subtype of AML with other defined genetic alterations .

Myeloid sarcoma

Myeloid sarcoma represents a unique tissue-based manifestation of AML or transformed MDS, MDS/MPN, or MPN. Cases of de novo myeloid sarcoma should be investigated comprehensively, including cytogenetic and molecular studies, for appropriate classification and planning therapy. Molecular alterations in myeloid sarcoma and concurrent bone marrow disease are concordant in ~70% of patients, suggesting that myeloid sarcoma may be derived from a common haematopoietic stem cell or precursor [ 68 , 69 ]. Relevant gene mutations are detected in a subset of patients with morphologically normal-appearing bone marrow, suggesting low-level clonal myeloid disease or CH in the bone marrow [ 68 , 70 ].

AML is arranged into two families: AML with defining genetic abnormalities and AML defined by differentiation . AML, NOS is no longer applicable.

Most AML with defining genetic abnormalities may be diagnosed with <20% blasts.

AML-MR replaces the former term AML “with myelodysplasia-related changes”, and its diagnostic criteria are updated. AML transformation of MDS and MDS/MPN continues to be defined under AML-MR in view of the broader unifying biologic features.

AML with rare fusions are incorporated as subtypes under AML with other defined genetic alterations .

AML with somatic RUNX1 mutation is not recognized as a distinct disease type due to lack of sufficient unifying characteristics.

Secondary myeloid neoplasms

A newly segregated category encompassing diseases that arise in the setting of certain known predisposing factors.

Myeloid neoplasms that arise secondary to exposure to cytotoxic therapy or germline predisposition are grouped in this category. AML transformation of MPN is retained in the MPN category, while AML transformation of MDS and MDS/MPN is kept under AML-MR (see above). The framework of this disease category was redesigned with an eye towards two important areas: (1) providing a scalable structure for incorporating novel discoveries in the area of germline predisposition to myeloid neoplasia; (2) recognizing the dual importance of cataloguing myeloid neoplasms that arise following exposure to cytotoxic therapies for clinical purposes as well as population health purposes. The latter factor is gaining increased recognition as cancer survival is prolonged and the incidence of late complications of therapy such as secondary myeloid neoplasia increases. An overarching principle in this context is the requirement to consider “post cytotoxic therapy” and “associated with germline [gene] variant” as disease attributes that should be added as qualifiers to relevant myeloid disease types whose criteria are fulfilled as defined elsewhere in the classification, e.g. AML with KMT2A rearrangement post cytotoxic therapy or MDS with low blasts associated with germline RUNX1 variant .

Myeloid neoplasms post cytotoxic therapy: introduction of more precise terminology and novel associations with new cytotoxic drug classes

As in previous editions, this category includes AML, MDS, and MDS/MPN arising in patients exposed to cytotoxic (DNA-damaging) therapy for an unrelated condition. The terminology and definitions of this disease category have been modified slightly to reflect an improved understanding of the risk that CH plays as a risk factor for myeloid neoplasia related particularly to the expansion of pre-existing clones secondary to selection pressures of cytotoxic therapy agents in an altered marrow environment [ 71 ]. Thus, the diagnosis of myeloid neoplasms post cytotoxic therapy (MN-pCT) entails fulfilment of criteria for a myeloid neoplasm in addition to a documented history of chemotherapy treatment or large-field radiation therapy for an unrelated neoplasm [ 72 ]. This would exclude CCUS, which by definition lacks sufficient support for morphologic dysplasia. Cases with a ‘ de novo molecular signature’ such as NPM1 mutation and core-binding factor leukaemias should still be assigned to this category since the “ post cytotoxic therapy ” designation is based on the medical history, and the indication of the most specific diagnosis in the pathology report is recommended when possible. Exposure to PARP1 inhibitors is added as a qualifying criterion for MN-pCT, and methotrexate has been excluded. It is recommended that specification of the type of myeloid neoplasm is made when possible, with the appendix “post cytotoxic therapy” appended, e.g. CMML post cytotoxic therapy.

The majority of AML-pCT and MDS-pCT are associated with TP53 mutations. The outcomes of such patients are generally worse with biallelic (multi-hit) TP53 alterations, manifesting as ≥2 TP53 mutations, or with concomitant 17p/ TP53 deletion or copy neutral LOH. Less frequent mutations involve genes such as PPM1D and DNA-damage response genes that may require additional work-up for germline predisposition.

Myeloid neoplasms associated with germline predisposition: A novel scalable model is introduced

Myeloid neoplasms associated with germline predisposition include AML, MDS, MPN, and MDS/MPN that arise in individuals with genetic conditions associated with increased risk of myeloid malignancies. Myeloid neoplasms arising in individuals with Fanconi anemia, Down syndrome, and RASopathies are discussed in separate dedicated sections. These diseases are now classified using a formulaic approach that couples the myeloid disease phenotype with the predisposing germline genotype, e.g., AML with germline pathogenic variants in RUNX1 . The clinical manifestations of these diseases are grouped into three subtypes under which most germline predisposition conditions can be assigned. (Table  10 ) Genetic counseling and evaluation of family history is an expected component of the diagnostic evaluation of index patients. Myeloid proliferations associated with Down syndrome, typically associated with somatic exon 2 or 3 GATA1 mutation, continue to encompass two clonal conditions that arise in children with constitutional trisomy 21: transient abnormal myelopoiesis (TAM), which is confined to the first 6 months of life and myeloid leukaemia of Down syndrome (ML-DS).

Myeloid neoplasms (MDS, MDS/MPN, and AML) post cytotoxic therapy (MN-pCT) require full diagnostic work up; the term replaces therapy-related .

Exposure to PARP1 inhibitors is added as a qualifying criterion for MN-pCT.

The diagnostic framework for myeloid neoplasm associated with germline predisposition is restructured along a scalable model that can accommodate future refinement and discoveries.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are myeloid or lymphoid neoplasms driven by rearrangements involving genes encoding specific tyrosine kinases leading to fusion products in which the kinase domain is constitutively activated leading to cell signaling dysregulation that promotes proliferation and survival. (Table  11 ) These BCR::ABL1 -negative diseases have long been recognized in view of their distinctive clinicopathologic features and sensitivity to TKI. They encompass a broad range of histologic types, including MPN, MDS, MDS/MPN, AML, and MPAL, as well as B- or T- lymphoblastic leukaemia/lymphoma (ALL). Extramedullary disease is common. While eosinophilia is a common and salient feature, it may be absent in some cases. From a diagnostic hierarchy standpoint, the diagnosis of MLN-TK supersedes other myeloid and lymphoid types, as well as SM. In some instances, defining genetic abnormalities of MLN-TK are acquired during course of a myeloid neoplasm such as MDS or MDS/MPN or at the time of MPN BP transformation. MLN-TK must be excluded before a diagnosis of CEL is rendered.

The majority of MLN-TK cases associated with PDGFRA rearrangements have cytogenetically cryptic deletion of 4q12 resulting in FIP1L1 :: PDGFRA , but PDGFRA fusions involving other partners are also identified. Cases with PDGFRB rearrangement result most commonly from t(5;12)(q32;p13.2) leading to ETV6 :: PDGFRB ; however, more than 30 other partners have been identified. Cases with FGFR1 rearrangement may manifest as chronic myeloid neoplasms or blast-phase disease of B-cell, T-cell, myeloid or mixed-phenotype origin, typically with associated eosinophilia. The characteristic cytogenetic feature is an aberration of chromosome 8p11. Detection of JAK2 rearrangements leading to fusion products with genes other than PCM1 have been recognized, supporting MLN-TK with JAK2 rearrangement as a distinct type [ 73 , 74 ]. Cases with FLT3 fusion genes are particularly rare and result from rearrangements involving chromosome 13q12.2. They manifest as myeloid sarcoma with MPN features in the bone marrow or T-ALL with associated eosinophilia, but disease features and phenotypic presentation may be variable and diverse. MLN-TK with ETV6 :: ABL1 should be separated from B-ALL with ETV6 :: ABL1 [ 75 ].

The natural history of MLN-TK with PDGFRA or PDGFRB has been dramatically altered by TKI therapy, particularly imatinib. In contrast, patients with FGFR1 , JAK2 and FLT3 fusions and ETV6 :: ABL1 have more variable sensitivity to available newer generation TKIs [ 73 , 76 ]; in most cases, long-term disease-free survival may only be achievable with allogeneic haematopoietic stem cell transplantation.

Other less common defined genetic alterations involving tyrosine kinase genes have also been discovered, and these are listed as MLN-TK subtypes under MLN-TK with other defined tyrosine kinase fusions until further data is accrued [ 77 , 78 ].

Family renamed myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK).

Recognition of novel types with JAK2 rearrangements, FLT3 rearrangements, and ETV6 :: ABL1 fusion.

New scalable genetic framework introduced under MLN-TK with other defined tyrosine kinase fusions.

Acute leukaemias of mixed or ambiguous lineage

Acute leukemia of ambiguous lineage (ALAL) and mixed-phenotype acute leukaemia (MPAL) are grouped under a single category in view of their overlapping clinical and immunophenotypic features, which in recent studies have been shown to also share common molecular pathogenic mechanisms. Here too, a framework for a molecular classification is laid by separating ALAL/MPAL with defining genetic abnormalities from those that are defined based on immunophenotyping only. (Table  12 )

Two new subtypes of ALAL with defining genetic alterations are added. The first subtype is MPAL with ZNF384 rearrangement, which commonly has a B/myeloid immunophenotype and is identified in ~50% of pediatric B/myeloid MPAL with fusion partners including TCF3 , EP300 , TAF15 , and CREBBP. ZNF38 4-rearranged B/myeloid MPAL and B-ALL have similar transcriptional profile, suggesting a biological continuum [ 79 ]. The other subtype is ALAL with BCL11B rearrangement, which has a more heterogenous immunophenotype - identified in acute undifferentiated leukaemia (AUL) and ~20-30% of T/myeloid MPAL. BCL11B rearrangement is also identified in AML with minimal differentiation or without maturation and ~20-30% of ETP-ALL. [ 59 , 60 , 61 , 80 ] These different types of acute leukaemias with stem cell, myeloid, and T-ALL features having BCL11B rearrangement in common suggests a biological continuum. Other genomic findings such as PHF6 mutations and PICALM :: MLLT10 fusions are also enriched in MPAL, but more studies are needed.

The assignment of lineage by immunophenotyping is dependent on the strength of association between each antigen and the lineage being assessed. As a general principle, the closer the expression of an antigen is to either the intensity and/or pattern of expression seen on the most similar normal population, the more likely it reflects commitment to that lineage. For instance, variable myeloperoxidase expression with an intensity and pattern similar to that seen in early myeloid maturation is more strongly associated with myeloid lineage than uniform dim myeloperoxidase expression. In addition, demonstration of a coordinated pattern of expression of multiple antigens from the same lineage further improves the specificity of those antigens for lineage assignment, e.g. combined expression of CD19, CD22, and CD10 is more strongly associated with B lineage than each antigen individually. Given these principles, the immunophenotypic criteria to be used for lineage assignment in cases where a single lineage is not evident are revised. (Table  13 )

Assessment of myeloperoxidase expression by cytochemistry and/or flow cytometry immunophenotyping plays a key role intersecting AML with minimal differentiation, T/myeloid MPAL, and ETP-ALL. Various groups have proposed flow cytometry thresholds for positive myeloperoxidase expression in acute leukaemia, ranging from 3 to 28% of blasts [ 81 , 82 , 83 ]. The 3% cutoff for myeloperoxidase, historically used for cytochemistry, was determined to have high sensitivity but poor specificity for general lineage assignment in acute leukaemia by flow cytometry [ 82 , 83 ]. A threshold of >10% for myeloperoxidase positivity seems to improve specificity [ 81 ], but no consensus cutoff has been established.

Acute leukaemias of mixed or ambiguous lineage are arranged into two families: ALAL with defining genetic abnormalities and ALAL, immunophenotypically defined .

Novel genetic findings are listed as subtypes under ALAL with other defined genetic alterations as additional data accrues.

Lineage assignment criteria for MPAL are refined to emphasize principles of intensity and pattern.

Histiocytic/dendritic cell neoplasms

These neoplasms are positioned in the classification after myeloid neoplasms in recognition of their derivation from common myeloid progenitors that give rise to cells of the monocytic/histiocytic/dendritic lineages. (Table  14 ) Key changes in the current edition of the classification include: (1) inclusion of clonal plasmacytoid dendritic cell (pDC) diseases in this category; (2) moving follicular dendritic cell sarcoma and fibroblastic reticular cell tumor to a separate category; and, (3) addition of Rosai-Dorfman disease (RDD) and ALK-positive histiocytosis as disease types. Indeed, neoplasms that arise from lymphoid stromal cells such as follicular dendritic cell sarcoma and fibroblastic reticular cell tumor are now appropriately classified under the new chapter of “stroma-derived neoplasms of lymphoid tissues” as detailed in the companion manuscript [ 4 ].

Plasmacytoid dendritic cell neoplasms: recognition of clonal proliferations detected in association with myeloid neoplasms and refinement/update of the diagnostic criteria for blastic plasmacytoid dendritic cell neoplasm

Mature plasmacytoid dendritic cell proliferation (MPDCP) associated with myeloid neoplasm reflects recent data showing that these represent clonal proliferation of pDCs with low grade morphology identified in the context of a defined myeloid neoplasm. Clonal MPDCP cells accumulate in the bone marrow of patients with myeloproliferative CMML harbouring activating RAS pathway mutations [ 84 ]. Patients with AML can have clonally expanded pDCs (pDC-AML), which share the same mutational landscape as CD34 +  blasts, and frequently arise in association with RUNX1 mutations [ 85 , 86 ]. It is unknown whether the pathogenetic mechanisms leading to MPDCP in association with MDS or MDS/MPN and with AML are the same. The framework for diagnosing blastic plasmacytoid dendritic cell neoplasm remains largely the same, with emphasis on immunophenotypic diagnostic criteria. (Table  15 )

Dendritic and histiocytic neoplasms: Rosai-Dorfman disease and ALK-positive histiocytosis are new entities in the classification

Much has been learned about the molecular genetics of histiocytoses/histiocytic neoplasms in recent years. These neoplasms, in particular Langerhans cell histiocytosis/sarcoma, Erdheim-Chester disease, juvenile xanthogranuloma, RDD and histiocytic sarcoma, commonly show mutations in genes of the MAPK pathway, such as BRAF, ARAF, MAP2K1, NRAS and KRAS , albeit with highly variable frequencies, indicating a unifying genetic landscape for diverse histiocytoses and histiocytic neoplasms. ALK-positive histiocytosis furthermore converges on the MAPK pathway, which is one of the signaling pathways mediating ALK activation [ 87 , 88 ]. Insights on genetic alterations have significant treatment implications, because of availability of highly effective therapy targeting components of the activated signaling pathway, such as BRAF and MEK inhibitors [ 88 , 89 , 90 , 91 , 92 ].

For RDD, the distinctive clinicopathologic features with accumulation of characteristic S100-positive large histiocytes showing emperipolesis, coupled with frequent gain-of-function mutations in genes of the MAPK pathway indicating a neoplastic process, provides a rationale for this inclusion and offers opportunities for targeted therapy [ 92 , 93 , 94 , 95 ].

ALK-positive histiocytosis, which shows a broad clinicopathologic spectrum unified by the presence of ALK gene translocation (most commonly KIF5B :: ALK ) and remarkable response to ALK-inhibitor therapy, has been better characterized in recent studies [ 88 , 96 ]. The multisystem systemic form that typically occurs in infants, with involvement of liver, spleen and/or bone marrow, runs a protracted course but often resolves slowly, either spontaneously or with chemotherapy. Other multisystem and single-system cases occur in any age group, with involvement of two or more organs or one organ alone, respectively, most commonly central/peripheral nervous system and skin; the disease has a favourable outcome with systemic and/or surgical therapy [ 88 , 97 ]. The histiocytes in ALK-positive histiocytosis can assume variable appearances including large oval cells, foamy cells and spindle cells, some with multinucleation (including Touton giant cells) or emperipolesis. That is, morphology is not entirely diagnostic, and overlaps extensively with that of juvenile xanthogranuloma and rarely RDD. Thus, it is recommended that ALK immunostaining be performed for histiocytic proliferations not conforming to defined entities, to screen for possible ALK-positive histiocytosis.

In most circumstances, classification of a dendritic cell/macrophage neoplasm as Langerhans cell histiocytosis/sarcoma, indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma or histiocytic sarcoma is straightforward. Nonetheless, there are rare cases that show overlap or hybrid features, defying precise classification [ 98 , 99 ].

Among histiocytic neoplasms, a subset of cases occurs in association with or follow a preceding lymphoma/leukaemia, most commonly follicular lymphoma, chronic lymphocytic leukaemia and T- or B-ALL [ 100 ]. Since these histiocytic neoplasms usually exhibit the same clonal markers and/or hallmark genetic changes as the associated lymphoma/leukaemia, a “transdifferentiation” mechanism has been proposed to explain the phenomenon [ 99 , 100 , 101 ]. Furthermore, the histiocytic neoplasm and associated lymphoma/leukaemia often show additional genetic alterations exclusive to each component, suggesting that divergent differentiation or transdifferentiation occurs from a common lymphoid progenitor clone [ 100 , 102 , 103 ]. Histiocytoses are also sometimes associated with myeloproliferative neoplasms [ 104 ], sharing mutations with CD34 +  myeloid progenitors [ 105 ], and with CH [ 106 ].

Histiocytic/dendritic cell neoplasms are regrouped and positioned to follow myeloid neoplasms in the classification scheme in view of their close ontogenic derivation.

Mature pDC proliferation is redefined with an emphasis on recent data demonstrating shared clonality with underlying myeloid neoplasms. This framework is bound to evolve in future editions.

Diagnostic criteria of BPDCN are refined.

ALK-positive histiocytosis is introduced as a new entity.

Genetic tumor syndromes with predisposition to myeloid neoplasia

Fanconi anaemia is a heterogeneous disorder caused by germline variants in the BRCA-Fanconi DNA repair pathway (≥21 genes) resulting in chromosomal breakage and hypersensitivity to crosslinking agents used for diagnosis. Clinical features include congenital anomalies, bone marrow failure, and cancer predisposition [ 107 ]. The new classification distinguishes 5 haematologic categories depending on blast percentage, cytopenia and chromosomal abnormalities [ 108 ]. Dysgranulopoiesis and dysmegakaryopoiesis are histologic indicators of progression [ 109 ]. Allogenic haematopoietic stem cell transplantation is efficacious.

The term RASopathies encompasses a diverse group of complex, multi-system disorders associated with variants in genes involved in the RAS mitogen-activating protein kinase (MAPK) pathway. Myeloid neoplasms in RASopathies involve MAPK hyperactivation, leading to myeloid cell proliferation [ 110 ]. Genomic analysis of NF1 , NRAS , KRAS , PTPN11 , and CBL from myeloid neoplasms of patients suspected of having a RASopathy is important and aids in the diagnosis of JMML in the majority of cases [ 111 , 112 ]. Diagnostic criteria include pathogenic variants in genes associated with the RAS pathway and/or classic phenotype suggestive of a RASopathy [ 113 ].

The content of this article represents the personal views of the authors and does not represent the views of the authors’ employers and associated institutions. This work is intended to provide a preview and summary of content whose copyright belongs solely to the International Agency for Research on Cancer/World Health Organization. Any or all portions of the material in this work may appear in future International Agency for Research on Cancer/World Health Organization publications.

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Acknowledgements

We thank the leadership and staff of the International Agency for Research on Cancer (IARC), Lyon, France, especially Dr. Ian Cree and Ms. Asiedua Asante, for their tireless efforts.

The following colleagues are acknowledged for their expert contributions as authors in the WHO Classification of Haematolymphoid Tumours blue book on myeloid and histiocytic/dendritic cell topics:

Lionel Adès 53 , Iván Alvarez-Twose 54 , Lars Bullinger 55 , Andrey Bychkov 56 , Maria Calaminici 57 , Peter J Campbell 58 , Hélène Cavé 59 , Kenneth Tou En Chang 60 , Jorge E Cortes 61 , Immacolata Cozzolino 62 , Ian A Cree 63 , Sandeep S Dave 64 , Kara L Davis 65 , Rita De Vito 66 , Hans Joachim Deeg 67 , Elizabeth G. Demicco 68 , Ann-Kathrin Eisfeld 69 , Carlo Gambacorti-Passerini 70 , Francine Garnache Ottou 71 , Stephane Giraudier 72 , Lucy A Godley 73 , Peter L Greenberg 74 , Patricia T Greipp 75 , Alejandro Gru 76 , Sumeet Gujral 77 , Detlef Haase 78 , Claudia Haferlach 27 , Julien Haroche 79 , Xiao-Jun Huang 80 , Yin Pun Hung 22 , Ahmed Idbaih 81 , Masafumi Ito 82 , Thomas S Jacques 83 , Sidd Jaiswal 38 , Rhett P Ketterling 84 , Navin Khattry 85 , Rami S Komrokji 41 , Shinichi Makita 86 , Vikram Mathews 87 , L Jeffrey Medeiros 1 , Ruben Mesa 88 , Dragana Milojkovic 6 , Yasushi Miyazaki 89 , Valentina Nardi 22 , Gaurav Narula 86 , Seishi Ogawa 90 , Eduardo Olavarria 91 , Timothy S Olson 92 , Etan Orgel 93 , Sophie P Park 94 , Mrinal Patnaik 95 , Naveen Pemmaraju 31 , Mary-Elizabeth Percival 68 , Gordana Raca 94 , Jerald P Radich 96 , Sabrina Rossi 97 , Philippe Rousselot 98 , Felix Sahm 99 , David A Sallman 41 , Valentina Sangiorgio 100 , Marie Sebert 101 , Riccardo Soffietti 102 , Jamshid Sorouri Khorashad 103 , Karl Sotlar 104 , Karsten Spiekermann 105 , Papagudi Ganesan Subramanian 106 , Kengo Takeuchi 107 , Roberto Tirabosco 108 , Antonio Torrelo 109 , George S Vassiliou 110 , Huan-You Wang 111 , Bruce M Wenig 112 , David A Westerman 113 , David Wu 114 , Akihiko Yoshida 115 , Bernhard WH Zelger 116 , Maria Claudia Nogueira Zerbini 117

53 Hématologie Sénior Hôpital Saint Louis, and Université de Paris Cité, Paris, France. 54 Instituto de Estudios de Mastocitosis de Castilla La Mancha, CIBERONC, Hospital Virgen del Valle, Toledo, Spain. 55 Department of Hematology, Oncology and Tumor Immunology, Campus Virchow, Charité-Universitätsmedizin Berlin, Berlin, Germany. 56 Department of Pathology, Kameda Medical Center, Kamogawa, Chiba, Japan. 57 Department of Cellular Pathology, the Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. 58 Wellcome Sanger Institute, Hinxton, United Kingdom. 59 Institut de Recherche Saint-Louis, Paris University, Genetic Department, Molecular Genetic Unit, Robert Debré Hospital, Paris, France. 60 Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore. 61 Georgia Cancer Center, Augusta, GA, USA. 62 Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy. 63 International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France. 64 Duke Medical Center, Durham, NC, USA. 65 Department of Pediatrics, Center for Cancer Cellular Therapy, Cancer Correlative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA. 66 Department of Pathology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. 67 Clinical Research Division, Fred Hutchinson Cancer Center, Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA. 68 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 69 The Ohio State University, Columbus, OH, USA. 70 Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy. Hematology Division and Bone Marrow Unit, San Gerardo Hospital, ASST Monza, Monza, Italy. 71 Inserm UMR1098, Université de Franche-Comté, Laboratoire Hématologie, Etablissement Français du Sang Bourgogne Franche-Comté, Besançon, France. 72 Laboratoire UMRS-1131, Université de Paris, Hôpital Saint-Louis, Paris, France. 73 Section of Hematology/Oncology, Department of Medicine, Department of Human Genetics, The University of Chicago, Chicago, IL, USA. 74 Stanford Cancer Institute, Stanford, CA, USA. 75 Division of Laboratory of Genetics and Genomics, Mayo Clinic, Rochester, MN, USA. 76 Department of Pathology, E. Couric Clinical Cancer Center, University of Virginia, Charlottesville, VA, USA. 77 Hematopathology Laboratory, Tata Memorial Center, Homi Bhabha National Institute, University, Mumbai, India. 78 Department of Hematology and Medical Oncology, University Medicine Göttingen, Göttingen, Germany. 79 Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service de Médicine Interne 2, Centre National de Référence des Histiocytoses, Hôpital Pitié-Salpêtrière, Paris, France. 80 Peking University People’s Hospital, Peking University Institute of Hematology, Peking University, Beijing, China. 81 Sorbonne Université, Institut du Cerveau—Paris Brain Institute—ICM, Hôpital Universitaire La Pitié Salpêtrière, DMU Neurosciences, Paris, France. 82 Department of Pathology, Japanese Red Cross, Aichi Medical Centre Nagoya Daiichi Hospital, Nagoya, Japan. 83 Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health; Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 84 Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 85 Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India. 86 Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. 87 Department of Hematology, Christian Medical College, Vellore, India. 88 Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, TX, USA. 89 Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan. 90 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden. 91 Servicio de Hematologia, Hospital de Navarra, Pamplona, Spain. 92 Department of Pediatrics, Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 93 Children’s Hospital Los Angeles; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 94 Centre Hospitalier Universitaire de Grenoble, Grenoble, France. 95 Mayo Clinic, Hematology Division, Rochester, MN, USA. 96 Department of Medicine, University of Washington, Seattle, WA, USA. 97 Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom. 98 Centre Hospitalier de Versailles, Hematologie Oncologie, Le Chesnay, France. 99 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany. 100 Division of Hematopathology, Department of Cellular Pathology, The Royal London Hospital. Barts Health NHS Trust, London, United Kingdom. 101 3. Université de Paris, Unité 944/7212-GenCellDi, INSERM and Centre National de la Recherche Scientifique, Paris, France. 102 Division of Neuro-Oncology, Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy. 103 SIHMDS, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. 104 Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria. 105 Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital. LMU Munich, Munich, Germany. 106 Hematopathology Laboratory, Tata Memorial Center, Homi Bhabha National Institute University, Navi Mumbai, Maharashtra, India. 107 Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. 108 Department of Histopathology, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, United Kingdom. 109 Department of Dermatology, University Children’s Hospital Niño Jesús, Madrid, Spain. 110 University of Cambridge & Wellcome Sanger Institute, Cambridge, United Kingdom. 111 Division of Laboratory and Genomic Medicine, Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA. 112 Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA. 113 Department of Pathology, Peter MacCallum Cancer Centre, Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville; Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia. 114 Department of Laboratory Medicine and Pathology, School of Medicine, Seattle, WA, USA. 115 Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan. 116 Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria. 117 Faculdade de Medicina, Universidade de São Paulo, Departamento de Patologia, São Paulo, Brazil.

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Joseph D. Khoury, Shimin Hu, Rashmi Kanagal-Shamanna, Sanam Loghavi, Keyur P. Patel & Wei Wang

Department of Hematology, Gustave Roussy Cancer Center, Université Paris-Saclay, Villejuif, France

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Uwe Platzbecker

Department of Paediatrics, University of Oxford, Oxford, UK

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JDK and JCH are standing members of the WHO Classification of Tumours editorial board. ES, YA, RA, JKCC, WJC, SEC, DDJ, JF, SG, HMK, MSL, KNN, GO, AS, WS, RS, BW and AH are expert members of the Haematolymphoid Tumours 5th edition blue book editorial board. OA, JFA, RB, EB, LB, WC, XC, JKC, IC, NCPC, MTE, ET, JFE, LF, MF, UG, TH, CH, SH, JHJ, RKS, CPK, XQL, KL, SL, AM, SM, PM, YN, RN, EP, KPP, NP, JP, UP, IR, PT, JT, SV, WW, WX, and CY contributed as responsible authors in the book. All authors and editors contributed to discussions on the content of the book chapters. All listed authors edited and approved the manuscript.

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Khoury, J.D., Solary, E., Abla, O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36 , 1703–1719 (2022). https://doi.org/10.1038/s41375-022-01613-1

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DOI : https://doi.org/10.1038/s41375-022-01613-1

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How did atc/ddd start.

In order to analyze drug use, it is essential to have both a classification system and a unit of measurement. To address the drawbacks of traditional units of measurement, a technical unit of measurement called the Defined Daily Dose (DDD) was developed for use in drug utilization studies. International interests in the ATC/DDD methodology rapidly expanded, largely through the activity of the DURG. In 1981, the WHO Regional Office for Europe formally recognized the ATC/DDD system for drug utilization studies and recommended its use in Europe. In 1982 the WHO Collaborating Centre for Drug Statistics Methodology was established and assigned the responsibility to coordinate the development and use of the ATC/DDD methodology. In 1996, WHO recommended the global use of the ATC/DDD methodology. Several decades of experience have demonstrated its suitability in drug utilization monitoring and research. The increase in the number of users indicates the usefulness of the system.

1 .  Engel A, Siderius P. The consumption of drugs. Report on a study, 1966-1967. WHO Regional Office for Europe, Copenhagen 1968 (EURO 3101).

Responsible Organizations of ATC/DDD methodology

Who is who.

-  The World Health Organization : The WHO endorsed the ATC/DDD methodology for global use in 1996 as an international standard for drug utilization studies in an effort to ensure universal access to essential drugs and to stimulate rational use of drugs particularly in middle/low income countries.

-  The WHO Collaborating Centre for Drug Statistics Methodology  : The central body responsible for the development and maintenance of the ATC/DDD system. This Centre is located at the Norwegian Institute of Public Health (NIPH) and the main activities of the Centre are drawn up in an agreement between the WHO Headquarters and the Government of Norway. These activities are:

• To classify drugs according to the ATC system.
• To establish DDDs for drugs which have been assigned an ATC code.
• To review and revise as necessary the ATC classification system and DDDs.
• To stimulate and influence the practical use of the ATC system by cooperating with researchers in the drug utilization field.
• To organize training courses in the ATC/DDD methodology and to lecture such courses and seminars organized by others.
• To provide technical support to countries in setting up their national medicines classification systems and build capacity in the use of medicines consumption information.

-  WHO International Working Group for Drug Statistics Methodology  : This body includes 12 expert members selected by WHO Headquarters, who represent a wide range of geographical and professional backgrounds. All six WHO regions are represented in the group. This body gives expert advice to the WHO Collaborating Centre. The main terms of reference of the Working Group are:

• To continue the scientific development of the ATC/DDD system.
• To discuss and approve all new ATC codes, DDD assignments and alterations to existing ATC codes and DDDs.
• To develop further the use of the ATC/DDD system as an international standard for drug utilization studies.
• To revise as necessary the guidelines for assignment and change of ATC codes and DDDs.
• To revise as necessary the procedures for applications for assignment of and changes to ATC codes and DDDs to ensure they are consistent and transparent.
• To assess the sources and availability of statistics on drug use internationally, and to encourage the systematic collection of comprehensive drug use statistics in all countries and regions using the ATC/DDD system as the international standard.
• To develop methods, manuals and guidelines for the practical application and appropriate use of the ATC/DDD system in drug utilization studies in a variety of settings, particularly those applicable to developing countries.
• To work with groups involved in rational drug use initiatives to integrate methods for measurement of drug use in assessing needs and outcomes of interventions with the aim of improving drug use.

The International Working Group meets twice annually, and the WHO Collaborating Centre for Drug Statistics Methodology acts as secretariat for the group.

Guidance Material

The ATC/DDD guidelines and the Index were both published for the first time in the current format in 1990. The system has been in use for statistics since 1975. Both publications are updated annually and available electronically and in hard copies. English and Spanish versions of the publications are available.

Guidelines for ATC Classification and DDD assignment

A comprehensive guide regarding ATC and DDD can be found  here  . The Guidelines includes information on the ATC Classification system and general principles of DDDs assignment. Information necessary for allocating ATC codes and DDDs at a national or local level can be found in the Guidelines.

The ATC index with DDDs

The index includes all officially assigned ATC codes and DDDs at the time of issuing. Changes to the index are made annually and a cumulative list including all ATC and DDD alterations made since 1982 is available  here  .