Measles Resurgence, Polio Persistence & HPV Vaccine Shortages Concern Health Experts

Measles is undergoing a worrisome worldwide resurgence, and it has killed more people in the Democratic Republic of Congo than the current Ebola outbreak – which is finally showing signs of decline, said a panel of vaccine experts in a WHO press briefing on Thursday.

A child gets vaccinated against measles during the outbreak in the DRC.

Meanwhile, a worldwide shortage of human papillomavirus (HPV) vaccine, which protects girls and women from cervical cancer, is confounding efforts to expand coverage, warranting a temporary change in vaccine strategy to focus more exclusively on pre-adolescent girls, said the experts who spoke just after the close of a biannual meeting of the Strategic Advisory Group of Experts on Immunization (SAGE), the principal expert advisory group to WHO for vaccines and immunization.

And Pakistan and Afghanistan are seeing a worrisome resurgence of the wild polio virus, serotype 1. Vaccine-derived polio cases seen in some countries also continue to thwart global eradication efforts – although experts are hopeful that a novel oral polio vaccine (nOPV2) under expedited development and production will demonstrate far greater efficacy in preventing vaccine-derived cases. The new polio vaccine could be ready for deployment as early as June 2020.

Coming the day after donors finalized commitments of US$ 14 billion to the Global Fund to Fight AIDS, Tuberculosis and Malaria, the SAGE briefing was a sober reminder that vaccine-preventable diseases including measles/rubella, polio and HPV remain major challenges for health systems in both affluent countries as well as some of the most underserved regions of the world.

On a more positive note, the Commission of the Global Polio Eradication Initiative will meet next week in Geneva to determine if the world can be certified as free of the wild polio virus serotype 3 – which has not been detected anywhere in the world since 2012.  Africa might be eligible for certification as free of all wild polio viruses by 2020, the group said.

“There is bad and good news on polio,” declared Michel Zaffran, director of WHO’s Polio Eradication Initiative. “The good news is that Serotype 3 of wild polio virus, has not been detected anywhere in the world since 2012. The Global Certification Commission will be reviewing the data  next week, and might be in a position to certify that Serotype 3 of the wild polio virus has been eradicated from the world.

“The [other] good news is that the wild polio virus has not been detected on the African continent for over 3 three years, that is why the region of Africa might be eligible for certification next year,” Zaffran added, noting that Serotype 2 of the wild virus was already eradicated some years ago.

A girl receives an oral polio vaccine in India.

On the downside, serotype 1 of the wild polio virus remains a challenge in Afghanistan and Pakistan, where vaccine coverage is spotty in some regions, and Pakistan has seen a significant upsurge this year with over 70 cases.

In terms of tackling persistent cases of vaccine-derived polio, Zaffran said that the Initiative is working with an Indonesian manufacturer to produce over 100 million doses of the new oral formulation (nOPV2) even while clinical trials are ongoing in parallel.

He said that if the clinical trial results, due to be released in February, show it to be efficacious, “at best case scenario we will have over 100 million doses available for use in June of next year”.

Below is a wrap-up of details on other vaccine issues covered at the SAGE meeting. A new draft global immunization strategy for the coming decade is also currently being finalized and should be released soon for review followed by final approval at the May 2020 World Health Assembly, the experts said.

“Strategy 2020 aims to address the challenges of reaching everyone, with a focus on those who remain left out. It is a people, country and data-focused strategy, with an emphasis on strengthening primary health care,” said Kate O’Brien, WHO Director, Department of Immunization, Vaccines and Biologicals, of the new ten-year strategic plan.

HPV Supply Shortage Warrants Change in Vaccine Strategy  

To address the HPV vaccine shortage, Alejandro Cravioto, SAGE Chairman, said that the expert group would recommend that immunization of teenage boys be temporarily suspended in order to redirect available supplies and efforts on girls, who are directly vulnerable to cervical cancer.

A young girl gets vaccinated against HPV in Sao Paulo, Brazil.

He said that the strategic change would allow countries to “focus use of the vaccine on the groups that would profit more from the vaccination,” adding that current evidence shows that “postponing vaccination of boys is not a public health problem” although the evidence supports vaccinating boys at a later stage, when there is more vaccine available – insofar as boys/men can also transmit the virus to unvaccinated girls/women through sexual contact.

He also noted that many countries with a high level of cervical cancer are not getting the vaccine at all.

“Constraints in the supply of the vaccine have made us think about how can we improve the access to this vaccine, start protecting women in countries that have a high level of cervical cancer,” he said. “We need to use the vaccine that is available in the most efficient way, and to start vaccinating as many girls as possible, whether by age 9 or 11, we need to immunize them before the age of 14, which is before the age of sexual activity.”

But he also stressed that the SAGE recommendations are made to the WHO Director General, “and it is up to the countries to decide if they take on the recommendations made.”

He said that the SAGE panel was also recommending that WHO support the creation of a Global Access Forum specifically for vaccines, where global health officials could interact with the producers, and with other stakeholders on improving access to vaccines whose availability is constrained. “How do we provide a system of access that protects everyone in need and allows us to use vaccines in a more effective way? This Forum is something to be created that would allow us to move not only in the HPV field, but other vaccines.”

Measles, a Worldwide Epidemic

“The world is facing an alarming upsurge in measles cases and deaths in all regions,” said O’Brien. She noted that the epidemic is driven by incomplete coverage of children with the two-dose vaccine, particularly in areas where healthy systems are weak and in conflict zones. But in affluent countries there are pockets of vaccine resistance where fears about vaccine safety or religious beliefs are driving epidemics.

A young girl receives a measles vaccination in Ukraine, which has consistently suffered from vaccine shortages.

“Some 80 countries have achieved and are maintaining the elimination, it is technically feasible to do, with the tools we have, but it requires day and day out vigilance so that coverage remains high,” she emphasized.  “If you don’t keep your eye on the ball, it can slip back.

So far only one WHO region, the Americas, had achieved measles elimination, meaning that there is no transmission and circulation of the virus within or between countries.

“Unfortunately the Americas region lost its elimination status as a result of the ongoing transmission in Brazil and Venezuela,” she noted. In Europe, the UK and the Czech Republic have also lost elimination status.

“The reasons vary from country to country and situation to situation, but the the majority reason is lack of access to the vaccine; the vaccine not available, services insufficient. In high income countries there are sub pockets of the population where immunization is very low. In the US, where coverage is extremely high, there are communities that have very low coverage, and when the virus is introduced in the community, that virus is going to move from child to child.”

A large measles outbreak in the DRC has already “claimed more lives than Ebola, disrupting families, livelihoods and economies,” she added. Along with the deployment of Ebola vaccines, however, campaigns to vaccinate measles have been accelerated “children and adults been vaccinated evermore against a range of diseases.”

Joachim Hombach, SAGE executive secretary, stressed that given the current resurgence of measles, the final “eradication” of the disease remains a distant goal, and countries should focus on ramping up efforts to “eliminate” transmission within and across their borders.

“To have a defined goal for eradication in the measles situation is really not obtainable but what we are proposing is that everyone should go back to the elimination goals and look at the prospect of how we can ramp up the elimination and control of the outbreak and then decide in the long run of how we are going to tackle other [eradication],” he said.

Second Ebola Vaccine is Valuable Tool in Arsenal Even as Outbreak Finally Declines

O’Brien also said that a much-discussed second Ebola vaccine, a two-stage vaccine produced by Johnson & Johnson is soon to be deployed in areas of DRC where there is no direct Ebola transmission.  This decision was taken insofar as the first Ebola vaccine to be deployed, produced by Merck, offers more immediate coverage and has already demonstrated high efficacy in the active transmission zones where some 230,000 people have been immunized.

Response worker prepares an Ebola vaccine in the DRC.

However, even as the current DRC Ebola outbreak seems to be finally in a pattern of decline – with just 14 cases reported in the past week, the Johnson & Johnson vaccine could be useful in offering additional protection to recipients against  future Ebola outbreak risks.

Notably, the Johnson & Johnson formula is intended to offer protection against different Ebola strains that commonly circulate in the region, while the Merck vaccine only offers protection against the  strain of the virus that prompted the current outbreak, ongoing since August 2018.

“Is it worth continuing with this investigating product? The answer is absolutely yes,” said Hombach, ”because we cannot assure at some point that there will not be a surge, as you know this product has different characteristics, there might be value for this type of product, and it is important to have choice of product available as well as a broader supply base.

“We need to look forward to preventive vaccination approaches in the future, this is something where we think this vaccine could play a significant role.

“It [Johnson&Johnson vaccine] is also a vaccine that is composed of non-replicating viruses, in contrast to the Merck vaccines, so may come with less concerns for contraindications. This would need to be evaluated over time, whether the vaccine is effective against the different strains, but if so, it could provide significant additional interest in this product.”

Image Credits: WHO DRC Office Twitter, CDC Global, WHO PAHO, UN Ukraine, WHO Twitter.

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