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)
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.
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.
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:
- a first segment primarily for governments, donors, non-state actors and people living with diabetes;
- a second segment on operationalizing meaningful engagement of people living with diabetes; and
- 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
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 DelhiSegment 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/whoSegment 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