Global Advisory Committee on Vaccine Safety (GACVS) review of latest evidence of rare adverse blood coagulation events with AstraZeneca COVID-19 Vaccine (Vaxzevria and Covishield)

16 Apr

A very rare new type of adverse event called Thrombosis with Thrombocytopenia Syndrome (TTS), involving unusual and severe blood clotting events associated with low platelet counts, has been reported after vaccination with COVID-19 Vaccines Vaxzevria and Covishield. A specific case definition for TTS is being developed by the Brighton Collaboration1. This will assist in identifying and evaluating reported TTS events and aid in supporting causality assessments.

The biological mechanism for this syndrome of TTS is still being investigated. At this stage, a ‘platform specific’ mechanism related to the adenovirus-vectored vaccines is not certain but cannot be excluded. Ongoing review of TTS cases and related research should include all vaccines using adenoviral vector platforms. The GACVS noted that an investigation has been initiated into the occurrence of TTS following the Johnson & Johnson vaccine administered in the United States. The TTS syndrome has not been linked to mRNA-based vaccines (such as Comirnaty or the Moderna mRNA-1273 vaccine).

Based on latest available data, the risk of TTS with Vaxzevria and Covishield vaccines appears to be very low. Data from the UK suggest the risk is approximately four cases per million adults (1 case per 250 000) who receive the vaccine, while the rate is estimated to be approximately 1 per 100 000 in the European Union (EU). Countries assessing the risk of TTS following COVID-19 vaccination should perform a benefit-risk analysis that takes into account local epidemiology (including incidence and mortality from COVID-19 disease), age groups targeted for vaccination and the availability of alternative vaccines.

Work is ongoing to understand risk factors for TTS. Some investigators have looked into rates of TTS by age2.  GACVS supports further research to understand age-related risk because while available data suggest an increased risk in younger adults, this requires further analysis. On the issue of sex-related risk, although more cases have been reported in females, it is important to underscore that more women have been vaccinated and that some TTS cases have also been reported in men. Therefore, further analysis is required to determine any sex-related risk. GACVS recommends further epidemiological, clinical and mechanistic studies to fully understand TTS. 

Thrombosis in specific sites (such as the brain and abdomen) appears to be a key feature of TTS. Clinicians should be alert to any new, severe, persistent headache or other significant symptoms, such as severe abdominal pain and shortness of breath, with an onset between 4 to 20 days after adenovirus vectored COVID-19 vaccination.

At a minimum, countries should encourage clinicians to measure platelet levels and conduct appropriate radiological imaging studies as part of the investigation of thrombosis.  Clinicians should also be aware that although heparin is used to treat blood clots in general, administration of heparin in TTS may be dangerous, and alternative treatments such as immunoglobulins and non-heparin anticoagulants should be considered.

There may be a geographic variation in the risk of these rare adverse events. It is therefore important to evaluate potential cases of TTS in all countries. Countries are encouraged to review, report and investigate all cases of TTS following COVID-19 vaccinations. Countries should assess cases according to the presence of thrombosis with thrombocytopenia and the time to onset following vaccination, using the Brighton Case Definition of TTS.

Whilst we have some information on Comirnaty, Moderna (mRNA-1273), Vaxzevria and Covishield vaccines, there is limited post-market surveillance data on other COVID-19 vaccines and from low- and middle-income countries. GACVS highly recommends that all countries conduct safety surveillance on all COVID-19 vaccines and provide data to their local authorities and to the WHO global database of individual case safety reports. This is urgently needed to support evidence-based recommendations on these life-saving vaccines. 

Open, transparent, and evidence-based communication about the potential benefits and risks to recipients and the community is essential to maintain trust. WHO is carefully monitoring the rollout of all COVID-19 vaccines and will continue to work closely with countries to manage potential risks, and to use science and data to drive response and recommendations.

Update of the WHO guidance on the treatment of drug susceptible tuberculosis

16 Apr

The World Health Organization (WHO) is convening a Guideline Development Group (GDG) to advise on updates needed to its recommendations on the treatment of drug susceptible tuberculosis (TB).

Drug susceptible TB affects approximately 7 million people annually. It is currently treated with four first line TB medicines for a period of six months. Approximately 85% of patients who take the six-month regimen will have a successful treatment outcome. Ensuring access to effective treatment is a key component of the End TB Strategy, which includes a priority indicator that 90% or more of patients should have a successful treatment outcome.

Despite its effectiveness, the current treatment regimen of six months remains too long for many patients. In recent years, research efforts have been directed towards finding safe and effective shorter regimens. New evidence from a randomized controlled trial on a 4-month treatment regimen containing a fluoroquinolone and high dose rifapentine has recently become available to WHO. This will be the evidence that will be reviewed and considered by the GDG.

WHO last updated its guidance on the treatment of drug susceptible TB in 2017. At this time WHO issued a recommendation against the use of shorter fluoroquinolone containing regimens as the evidence did not support that these regimens were more effective than the six-month regimen. However, it is now time to review the evidence on shorter regimens again, to provide users worldwide with the most up to date evidence-informed guidance on how to treat drug susceptible TB.

The GDG meeting will be held online in late April 2021, in accordance with WHO requirements for the development of evidence-informed policy guidance. The updated recommendations will be released in 2021, as part of the treatment module of the WHO consolidated guidelines on tuberculosis. More details of the process, inclusive of brief biographies of the experts invited to serve in the current GDG, are available here.

 

 

Digital technologies for health financing:

15 Apr

Digital innovation for health care and illness prevention with its potential to transform health-service delivery has received strong public attention over the past decade in both high-income and low- and middle-income countries. However, the use of digital technologies and their role in enhancing health financing, and their implications for health systems transformation, are less well known, especially in LMICs. 

This paper is particularly focused on digital technologies that significantly change “business as usual” – i.e. technologies that substantially transform the way in which health-financing tasks are undertaken by stewards, purchasers, providers, users and citizens in general. These technologies include mobile telephone applications, webpage interaction platforms, blockchain, big data analytics, and artificial intelligence including machine learning. 

A key premise of this paper is that digital technologies for health financing should contribute to universal health coverage (UHC). To achieve progress towards UHC, digital technologies should support the achievement of widely agreed health-financing principles and desirable attributes – i.e. largely relying on public finance, reducing out-of-pocket expenditure and expanding prepaid and pooled funding, and making purchasing more strategic. Nevertheless, digital technologies may pose risks to health financing and the application and implementation of digital technologies face various challenges that could jeopardize their health-financing benefits. These specific risks for health financing need to be explored.

This paper outlines potential benefits and seeks to anticipate and explore possible risks and challenges on the basis of a scoping literature review, including published and grey literature, with a focus on LMICs. It provides initial conclusions and reflections on how to reap the benefits, and mitigate the risks and challenges, in relation to health financing.

New WHO Global Compact to speed up action to tackle diabetes

14 Apr

The World Health Organization’s  new Global Diabetes Compact aims to bring a much-needed boost to efforts to prevent diabetes and bring treatment to all who need it  ̶  100 years after the discovery of insulin.

The Compact is being launched today at the Global Diabetes Summit, which is co-hosted by WHO and the Government of Canada, with the support of the University of Toronto. During the event, the President of Kenya will join the Prime Ministers of Fiji, Norway and Singapore; the WHO Global Ambassador for Noncommunicable Diseases and Injuries, Michael R. Bloomberg; and ministers of health from a number of countries as well as diabetes experts and people living with diabetes, to highlight the ways in which they will support this new collaborative effort. Other UN agencies, civil society partners and representatives of the private sector will also attend.

The risk of early death from diabetes is increasing

“The need to take urgent action on diabetes is clearer than ever,” said Dr Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization. “The number of people with diabetes has quadrupled in the last 40 years.  It is the only major noncommunicable disease for which the risk of dying early is going up, rather than down. And a high proportion of people who are severely ill in hospital with COVID-19 have diabetes. The Global Diabetes Compact will help to catalyze political commitment for action to increase the accessibility and affordability of life-saving medicines for diabetes and also for its prevention and diagnosis.”

“Canada has a proud history of diabetes research and innovation. From the discovery of insulin in 1921 to one hundred years later, we continue working to support people living with diabetes,” said the Honourable Patty Hajdu, Minister of Health, Canada. “But we cannot take on diabetes alone. We must each share knowledge and foster international collaboration to help people with diabetes live longer, healthier lives — in Canada and around the world.”

Urgent action needed on increasing access to affordable insulin

One of the most urgent areas of work is to increase access to diabetes diagnostic tools and medicines, particularly insulin, in low- and middle-income countries.

The introduction of a pilot programme for WHO prequalification of insulin in 2019 has been an important step. Currently the insulin market is dominated by three companies. Prequalification of insulin produced by more manufacturers could help increase the availability of quality-assured insulin to countries that are currently not meeting demand. In addition, discussions are already underway with manufacturers of insulin and other diabetes medicines and diagnostic tools about avenues that could help meet demand at prices that countries can afford.

Insulin is not the only scarce commodity:  many people struggle to obtain and afford blood glucose metres and test strips as well.   

In addition, about half of all adults with type 2 diabetes remain undiagnosed and 50% of people with type 2 diabetes don’t get the insulin they need, placing them at avoidable risk of debilitating and irreversible complications such as early death, limb amputations and sight loss.

Innovation will be one of the core components of the Compact, with a focus on developing and evaluating low-cost technologies and digital solutions for diabetes care. 

Global targets to be agreed on

The Compact will also focus on catalyzing progress by setting global coverage targets for diabetes care. A “global price tag” will quantify the costs and benefits of meeting these new targets. The Compact will also advocate for fulfilling the commitment made by governments to include diabetes prevention and treatment into primary health care and as part of universal health coverage packages. 

“A key aim of the Global Diabetes Compact is to unite key stakeholders from the public and private sectors, and, critically, people who live with diabetes, around a common agenda, to generate new momentum and co-create solutions,” said Dr Bente Mikkelsen, Director of the Department of Noncommunicable Diseases at WHO. “The “all hands on deck” approach to the COVID-19 response is showing us what can be achieved when different sectors work together to find solutions to an urgent public health problem.”

People watching the Summit will hear from people living with diabetes from India, Lebanon, Singapore, the United Republic of Tanzania, the USA and Zimbabwe about the challenges they face in managing their diabetes and how these could be overcome. Part of the Summit has been co-designed with people who live with diabetes and will give them a global platform to explain what they are expecting from the Compact and how they would like to be involved in its further development and implementation. 

“It is time to create momentum not just for living with diabetes, but thriving with it,” said Dr Apoorva Gomber, a diabetes advocate living with type 1 diabetes who is taking part in the Summit. “We must grab the opportunity of the Compact with both hands and use it to ensure that we can look back in a few years’ time and say that, finally, our countries are equipped to help people with diabetes live healthy and productive lives.”

Note for journalists:

The Global Diabetes Summit has three segments:

  1. a first segment primarily for governments, donors, non-state actors and people living with diabetes;
  2. a second segment on operationalizing meaningful engagement of people living with diabetes; and
  3. a third segment for people living with diabetes entitled ‘100 Years of Insulin  ̶  Celebrating Its Impact on Our Lives’ organized by the University of Toronto

Segment 1

Join the WHO Director-General and world leaders for the launch of the Global Diabetes Compact, a collective effort to prevent diabetes and bring the right care to all who need it.

Moderated by awarding-winning journalist Femi Oke

11:00-13:00 - New York, 17:00-19:00 - Geneva, 20.30-22.30 - New Delhi

Segment 2

Organized in collaboration with a consultative group of people living with diabetes, this segment will discuss how people with lived experience of diabetes will meaningfully engage in all phases of the Global Diabetes Compact.

13:00-15:00 - New York, 19:00-21:00 - Geneva time, 22:30-00:30 - New Delhi

Join us for both segments at www.youtube.com/who

Segment 3

100 Years of Insulin  ̶  Celebrating Its Impact on Our Lives

This segment, organized by the University of Toronto, will focus on the latest approaches to using insulin, the experiences of people living with diabetes, and how research on insulin is changing.

Starting at 16:30 Toronto time, 22:30 Geneva time

WHO calls for comprehensive, equitable access to healthcare for every Chagas disease patient

14 Apr

 

Today on World Chagas Disease Day, the World Health Organization (WHO) has called for comprehensive and equitable access to health care and services to everyone affected by Chagas disease. An estimated 6 to 7 million people worldwide are infected by Trypanosoma cruzi - the parasite that causes the disease.

 “It is sad to note that despite progress, millions of people still remain undiagnosed, with limited or no access to healthcare” said Dr Ren Minghui, Assistant Director-General, Division for Universal Health Coverage/Communicable and Non-Communicable Diseases. “We need to improve detection and diagnosis rates which currently are at unacceptably low levels1 and we need to provide equitable access to treatment and health services to everyone.”

Chagas disease remains a public health problem in several endemic areas of continental Latin America where the burden on the health system is high. Over the past decades, Chagas disease has been detected in several countries outside Latin America, including the United States, Canada and in many European and some African, Eastern Mediterranean and Western Pacific countries.

Chagas Disease is curable if treatment is initiated soon after infection. Left undiagnosed and untreated in its chronic phase Chagas disease can result in arrythmias, dilated cardiomyopathy, leading to sudden death or heart failure, with relatively frequent digestive clinical manifestations and thrombotic vascular accidents and neurological sequela.

“The NTD road map for 2021-2030 provides for a series of objectives to accelerate progress in the prevention and control of Chagas disease, including the elimination of its congenital form and providing 75% coverage of antiparasitic treatment to eligible populations everywhere” said Dr Mwelecele Ntuli Malecela, Director, Department of Control of Neglected Tropical Diseases. “We are confident that this day will boost activities that will help to improve visibility and awareness of the disease.”

Silent and silenced disease

Chagas disease is mostly asymptomatic, either in the acute phase after infection or in the life-lasting chronic phase, without a successful antiparasitic treatment.

It can take decades before an infected person develops chronic clinical manifestations.

More than ever, with the current pandemic and the risk of presenting severe COVID-19 clinical manifestations, detection of people with Chagas disease should be prioritized and provided with access to vaccination.

Potential of integrated interventions

Already, integrated interventions with malaria and other haemoparasites, maternal and child health programmes, HIV/AIDS and other communicable and noncommunicable health programmes are improving implementation in a cost-effective manner.

Monitoring and verification of achievements through data exchange and information sources2 have opened possibilities to share and make accessible information, monitor advances and verify achievements. Better research and diagnosis tools can accelerate the screening of patients (including blood transfusion, organ transplant, screening of girls and women of childbearing age, and pregnant women and their newborns and children).

In 2019, the 72nd World Health Assembly endorsed the designation of a World Chagas Disease Day to raise public awareness and information about what is often termed as a ‘silent and silenced disease’.

The disease

Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi (T. cruzi).

It is found mainly in endemic areas of 21 continental Latin American countries and regions3

For centuries, the disease was strictly a Latin American problem of rural populations, but movement of people from rural to urban areas and to other continents expanded the reach of disease transmission channels towards non vectorial routes, such as blood transfusion, congenital and oral transmission, organ transplant and contaminated food.

There is no vaccine against Chagas disease. Domiciliary vectorial control and transfusional control, together with congenital transmission, remain the most effective methods of preventing transmission in Latin America.

Chagas disease was named after Carlos Ribeiro Justiniano Chagas, a Brazilian physician and researcher who discovered the disease in 1909.

-------------------------------------------------

 

1Depending on the areas, under-diagnosis of Chagas disease cases can be as high as 90% or even more, and this includes congenital and paediatric cases.

2The open-source WHO information system to control/eliminate Chagas disease and other NTDs is contributing to gather and analyze real-time data/information on Chagas disease.

3Argentina, Belize, Bolivia (Plurinational State of), Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela (Bolivarian Republic of)

 

WHO and the International Organisation of the Francophonie (IOF) sign Memorandum of Understanding to strengthen access to health in Francophone countries

13 Apr

The World Health Organization and the International Organisation of the Francophonie (IOF) today signed a memorandum of understanding to scale up collaboration and boost access to health services in Francophone countries. 

The agreement, finalized at a ceremony held at the WHO Headquarters in Geneva, focuses on advancing universal health coverage, fighting malaria and collaborating on the development of the WHO Academy, which aims to train millions of health workers worldwide. It will also support COVID-19 response efforts, including on promoting equitable access to vaccines.

"Our actions, supported by this memorandum of understanding, must contribute to the development of social protection and universal access to public health services in the French-speaking countries,” said Ms. Louise Mushikiwabo, IOF Secretary General. “This is a fundamental right for individuals and an essential condition for the socio-economic progress of our countries.”

Ms Mushikiwabo added: “This memorandum of understanding aims to bring IOF political and diplomatic support to some of WHO’s priorities.”

WHO Director-General Dr Tedros Adhanom Ghebreyesus said the MoU signing further bolstered an already strong partnership with IOF, and would play a vital role in promoting and protecting people’s health, including in the response to COVID-19.

“Strengthening the relationship between WHO and the IOF comes at a crucial time, when the world needs even closer collaboration to fight COVID-19 and address existing health challenges, from malaria to inequitable access to health services,” said Dr Tedros. “Expanding universal health coverage and equipping current and future health systems with highly trained health workers are essential steps that WHO and IOF will continue working on together.”

Under the MoU, the IOF will work through advocacy actions, to promote and protect people’s access to the fundamental human right to health, in doing so supporting WHO’s work with national, regional and global authorities to advance access to universal health coverage. The MoU will, in particular, promote multilingualism, including use of the French language, in health promotion and training materials. Another key focus is promoting health education for young women and girls, including on sexual and reproductive health.

With 88 Member States and governments, the International Organization of the Francophonie (IOF) counts among its missions the promotion and protection of fundamental rights, among which the right to Health. Several Resolutions on this subject were adopted at the Francophonie by its governing bodies, the latest of which was approved by the Francophonie Ministerial Conference in November 2020, on "Living together during the COVID-19 pandemic and in the post-COVID world.”

 

Benefits of continuing to provide life-saving HIV services outweigh the risk of COVID-19 transmission by 100 to 1

13 Apr

UNAIDS and WHO have supported mathematical modelling to establish the benefits of continuing HIV services compared to the potential harm of additional COVID-19 transmission. The analysis shows that maintaining HIV services would avert between 19 and 146 AIDS-related deaths per 10 000 people over a 50-year time horizon, while the additional COVID-19-related deaths from exposures related to HIV services would be 0.002 to 0.15 per 10 000 people. The analysis demonstrates that the benefits of continuing to provide HIV services during the COVID-19 pandemic far outweigh the risk of additional COVID-19-related deaths.

“The world should make investments now that don’t leave it with such stark trade-offs in the future,” said Peter Ghys, Director, Strategic Information and Evaluation, UNAIDS. “We need to build robust future systems for health that recognize community-led contributions as part and parcel of a resilient system, not as an afterthought.”

“Ministries of health take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic,” said Meg Doherty, Director of WHO’s Global HIV, Hepatitis and Sexually Transmitted Infections Programmes. “This work shows that taking the longer view, the benefits of continuing key HIV services are far larger than the risks of additional COVID-19 transmission; innovative and safe delivery of services must continue as the pandemic is brought under control.”

The analysis looked at disruptions to four key HIV services, voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programmes to prevent mother-to-child transmission of HIV. It compared COVID-19 deaths in 2020 and 2021 among health workers and clients due to keeping HIV services open with averted AIDS-related deaths occurring now and over the next 50 years due to maintenance of services. The models were applied to countries with a range of HIV and COVID-19 epidemics.

The COVID-19 pandemic has caused widespread disruption to health services with restrictions in population movements and health services suspended or limited in many countries. The analysis shows that the potential harm of additional COVID-19 transmission occurring in HIV health services need to be carefully balanced against the benefits of those services, which, the analysis shows, include fewer AIDS-related deaths. These results may seem intuitive, but it is important to realize that some services have been closed to protect people living with HIV from exposure to COVID-19 and its potential lethal outcomes. However, the risk of not keeping those essential HIV services open entails a greater overall risk of death related to lack of prevention of HIV, access to diagnosis and eventual treatment — these trade-offs are unacceptable.

While there is some additional short-term risk of COVID-19 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the AIDS-related deaths averted by continuing those services. Additional effort to encourage health care seeking for HIV services during the ongoing COVID-19 pandemic may be needed.

The full analysis can be found on medrxiv at: https://doi.org/10.1101/2021.03.01.21252663


UNAIDS

The Joint United Nations Programme on HIV/AIDS (UNAIDS) leads and inspires the world to achieve its shared vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. UNAIDS unites the efforts of 11 UN organizations—UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, UN Women, ILO, UNESCO, WHO and the World Bank—and works closely with global and national partners towards ending the AIDS epidemic by 2030 as part of the Sustainable Development Goals. Learn more at unaids.org and connect with us on Facebook, Twitter, Instagram and YouTube.

WHO

WHO’s department of Global HIV, Hepatitis and Sexually Transmitted Infections (HHS) programmes works across all three levels of WHO: headquarters; regional offices and country offices, and with countries and partners, to drive progress towards the elimination of HIV, viral hepatitis and STIs as public health threats by 2030. Find us at www.who.int/teams/global-hiv-hepatitis-and-stis-programmes

US$ 1.4 trillion lost every year to tobacco use – New tobacco tax manual shows ways to save lives, money and build back better after COVID-19

9 Apr

WHO’s new technical manual on tobacco tax policy and administration shows countries ways to cut down on over US$1.4 trillion in health expenditures and lost productivity due to tobacco use worldwide.

Improved tobacco taxation policies can also be a key component of building back better after COVID-19, where countries need additional resources to respond and to finance health system recovery.

“We launched this new manual to provide updated, clear, and practical guidance for policymakers, finance officials, tax authorities, customs officials and others involved in tobacco tax policy to create and implement the strongest tobacco taxation policies for their specific countries,” said Jeremias N. Paul Jr, Unit Head for the Fiscal Policies for Health team in the Health Promotion Department at WHO.

“We hope this document sheds light on the significant advantages to raising tobacco taxation. The data and insights provided here should be an eye opener for policymakers worldwide,” he said.

The ‘best buy’ highlighted in the manual not only saves money, but saves lives. The human and economic costs of tobacco are on the rise - 8 million people died because of tobacco last year.

Only 14% of the world has enough tax on tobacco

In 2018 only 38 countries, covering 14% of the global population had sufficiently high tobacco taxes - which means taxing at least 75% of the price of these health-harming products. By implementing proven policies like tobacco taxes, the costs created by the tobacco industry to local communities and nations can be avoidable.  It is a win for population health, revenue and for development and equity.

Raising tobacco taxes is SMART

Tobacco taxes Save lives, Mobilize resources, Address health inequities, Reduce health system burdens and costs, and Target noncommunicable risk factors for the achievement of Sustainable Development Goals (SDGs).

 

Meeting of the Guidelines Development Group (GDG) for the update and consolidation of guidelines for safe abortion care

9 Apr

WHO has released new details regarding membership of the Guidelines Development Group (GDG) for the update and consolidation of the following guidelines: 

Safe Abortion: technical and policy guidance for health systems, 2012

Health worker roles in providing safe abortion care and post-abortion contraception, 2015) and

Medical Management of Abortion, 2019

The meeting of the GDG will be held on 27-30 April 2021 and will focus on reviewing the latest evidence relating to the epidemiological, clinical, service delivery, legal and human rights aspects of providing safe abortion care. The purpose of the meeting is to review the evidence, then provide recommendations and guidance on safe abortion care.

List of experts with biographies

See list of experts

NOTE: The GDG members are participating in the meeting on their individual capacity. Affiliations are presented only as a reference. The participation of experts in a WHO meeting does not imply that they are endorsed or recommended by the WHO nor does it create a binding relationship between the experts and WHO. The biographies have been provided by the experts themselves and are the sole responsibility of the individuals concerned. WHO is not responsible for the accuracy, veracity and completeness of the information provided. In accordance with WHO conflict of interest assessment policy, expert’s biographies are published for transparency purposes. Comments and perceptions are brought to the knowledge of WHO through the public notice and comment process. Comments sent to WHO are treated confidentially and their receipt will be acknowledged through a generic email notification to the sender.

Please send any comments to the following email: srhpua@who.int. WHO reserves the right to discuss information received through this process with the relevant expert with no attribution to the provider of such information. Upon review and assessment of the information received through this process, WHO, in its sole discretion, may take appropriate management of conflicts of interests in accordance with its policies.

Global shortage of innovative antibiotics fuels emergence and spread of drug-resistance

8 Apr

The world is still failing to develop desperately needed antibacterial treatments, despite growing awareness of the urgent threat of antibiotic resistance, according to report by the World Health Organization. WHO reveals that none of the 43 antibiotics that are currently in clinical development sufficiently address the problem of drug resistance in the world’s most dangerous bacteria.

“The persistent failure to develop, manufacture, and distribute effective new antibiotics is further fueling the impact of antimicrobial resistance (AMR) and threatens our ability to successfully treat bacterial infections,” says Dr. Hanan Balkhy, WHO Assistant Director General on AMR.

Almost all the new antibiotics that have been brought to market in recent decades are variations of antibiotic drugs classes that had been discovered by the 1980s.

The impact of AMR is most severe in resource-constrained settings and among vulnerable groups such as new-borns and young children. Bacterial pneumonia and bloodstream infections are among the major causes of childhood mortality under the age of 5. Approximately 30% of neonates with sepsis die due to bacterial infections resistant to multiple first-line antibiotics. https://doi.org/10.1016/S2214-109X(17)30362-5

Report findings:

WHO’s annual Antibacterial Pipeline Report, reviews antibiotics that are in the clinical stages of testing as well as those in early product development. The aim is to assess progress and identify gaps in relation to urgent threats of drug resistance, and to encourage action to fill those gaps.

The report evaluates the potential of the candidates to address the most threatening drug-resistant bacteria outlined in the WHO Bacterial Priority Pathogens List (WHO PPL). This list, which includes 13 priority drug-resistant bacteria, has informed and guided priority areas for research and development since its first publication in 2017.

The 2020 report reveals a near static pipeline with only few antibiotics being approved by regulatory agencies in recent years.  Most of these agents in development offer limited clinical benefit over existing treatments, with 82% of the recently approved antibiotics being derivatives of existing antibiotic classes with well-established drug-resistance. Therefore, rapid emergence of drug-resistance to these new agents is expected.

The review concludes that “overall, the clinical pipeline and recently approved antibiotics are insufficient to tackle the challenge of increasing emergence and spread of antimicrobial resistance”.

Novel solutions outside the traditional development pathway:

The lack of progress on antibiotic development highlights the need to explore innovative approaches to treat bacterial infections. The 2020 WHO pipeline report for the first time includes a comprehensive overview of non-traditional antibacterial medicines.  It highlights 27 non-traditional antibacterial agents in the pipeline ranging from antibodies to bacteriophages and therapies that support the patient’s immune response and weaken the effect of the bacteria.

High failure rates and impact on market dynamics: 

The report notes that there are some promising products in different stages of development. However, only a fraction of these will ever make it to the market due to the economic and inherent scientific challenges in the drug development process. This, along with the small return on investment from successful antibiotic products, has limited the interest of major private investors and most large pharmaceutical companies.

The report confirms that the preclinical and clinical pipeline continue to be driven by small- and medium-sized companies. These enterprises often struggle to finance their products to the late stages of clinical development or until regulatory approval is obtained.

The COVID-19 opportunity:

The COVID-19 crisis has deepened the global understanding of the health and economic implications of an uncontrolled pandemic. It also accentuated the gaps in sustainable funding to address these risks, including investments in R&D of antimicrobial medicines and vaccines, whilst revealing what rapid progress can be made when there is enough political will and enterprise.

“Opportunities emerging from the COVID-19 pandemic must be seized to bring to the forefront the needs for sustainable investments in R&D of new and effective antibiotics,” said Haileyesus Getahun, Director of AMR Global Coordination at WHO.  “Antibiotics present the Achilles heel for universal health coverage and our global health security.  We need a global sustained effort including mechanisms for pooled funding and new and additional investments to meet the magnitude of the AMR threat.”

Global Initiatives:

To address gaps in funding and drive sustainable investments in antibiotics development, WHO and its partner Drugs fro Neglected Diseases intitive (DNDi) have set up the Global Antibiotic R&D Partnership (GARDP) to develop some of the innovative treatments that are included in the report. In addition, the WHO has been working closely with other non-profit funding partners such as the CARB-X to “push” and accelerate antibacterial research.

Another important new initiative is the AMR Action Fund, a partnership that was set up by a coalition of pharmaceutical companies, philanthropies, the European Investment Bank, with the support of the WHO, that aims to strengthen and accelerate antibiotic development through global pooled funding. The Fund is expected to play an important role in ensuring that the most innovative and promising products receive the required funding.