A study in The Lancet Global Health sought to provide counterfactual scenarios to evaluate the short-term effects of different vaccination strategies on mpox cases and deaths in the Democratic Republic of the Congo (DRC). The researchers used a dynamic transmission model to simulate mpox transmission, stratified by age and province; this was used to assess potential vaccination strategies and their effects on deaths and cases in an epidemic year. The results indicate that vaccinating children aged 15 years or younger, or younger than 5 years, in endemic regions, would be the “most efficient use of vaccines” when resources are limited.
Mpox in DRC
Mpox was first identified in the Democratic Republic of the Congo (DRC) in 1970; it is a zoonotic infectious disease caused by the monkeypox virus (MPXV), which is endemic in “numerous regions” of west and central Africa. MPXV has two clades:
- Clade I is endemic in central Africa with an estimated case fatality rate of up to 10% and mainly affecting children. It is divided into two subclades, Ia and Ib.
- Clade II was historically found in west Africa, with an estimated case fatality rate of up to 1%-3%. It is also divided into two subclades, IIa and IIb. Clade IIb was responsible for the global mpox epidemic in 2022.
The authors state that, until 2022, MPXV was not associated with large outbreaks; most cases were related directly to sylvatic transmission from animals to humans via hunting, wild game preparation, and consumption. Increases in human-to-human transmission were identified in 2017.
The researchers suggest that the low likelihood of transmission in the early decades after the virus’ discovery could be related to smallpox eradication programmes, which offered cross-immunity via vaccination against a related orthopoxvirus. Indeed, since the cessation of the smallpox vaccination programme in the DRC, there has been a “concurrent increase in mpox cases and outbreak frequency”. There is an ongoing, “unprecedentedly large” outbreak of clade I mpox in the DRC, with more than 14,000 reported suspected cases by the end of 2023 and a 4.6% case fatality rate. Over 70% of the deaths are in children younger than 15 years.
Genetic analyses of clade Ia MPXV genomes indicate that in this outbreak, multiple, independent zoonotic introductions into the human population have occurred from one or more reservoir species. An increasing burden of clade Ib MPXV infections have been identified in eastern DRC with evidence of “sustained” human-to-human transmission and many cases in women aged 15-29 years, but clade Ia infections continue to comprise most mpox cases in the DRC.
The study
Bavarian Nordic’s modified vaccinia Ankara vaccine (JYNNEOS) is protective against mpox. It was approved by the US FDA in 2019 but was not widely used against mpox until the 2022 outbreak, when it was “quickly mobilised to vaccinate people at high risk of infection in the USA and Europe”. Despite its high efficacy at two doses, it is “largely unavailable” outside the USA and Europe.
The authors aimed to inform policy and decision makers on the “potential benefits of, and resources needed,” for mpox vaccination campaigns in the DRC. They used an approach based on models from operations research and decision science to offer a robust analysis of policy choices “even in the context of incomplete and uncertain data”. The study uses mathematical modelling to simulate the spread of mpox in the DRC during 2023.
Without vaccination, the model predicted 14,700 cases of mpox and 700 deaths from mpox in the DRC over 365 days, consistent with reported estimates. Almost 50% of the cases and deaths came from the province of Equateur. Cases were evenly split between the three age groups: 34% in children under 5 years, 32% in children aged 5-15 years, and 34% in people older than 15 years. However, deaths were “predominantly” seen in children younger than 5 years (51%).
Vaccinating 80% of children younger than 5 years in all provinces or provinces with a history of mpox cases decreased the outbreak to 10,500 cases and 400 deaths. Vaccinating in endemic provinces increased cases to 10,700 and deaths remained the same. The numbers of vaccine doses needed for the strategies were 41.4 million (all provinces), 33.8 million (provinces with a history of mpox), and 13.2 million (endemic provinces only).
Vaccinating 80% of children younger than 15 years in all provinces or provinces with a history of mpox cases decreased the outbreak to 6,400 cases and 200 deaths. Vaccinating in endemic provinces increased cases to 6,800 and deaths remained the same. The numbers of vaccine doses required for these strategies were 81.6 million (all provinces), 67.1 million (provinces with a history of mpox), and 26.6 million (endemic provinces only).
Vaccinating 80% of all ages in all provinces or only non-endemic provinces with a history of cases decreased the case burden to 1,400 cases and 100 deaths, and 2,000 cases and 100 deaths when vaccinating in provinces endemic for mpox. The numbers of doses required for these strategies were 170.8 million (all provinces), 142.0 million (provinces with a history of mpox), and 56.8 million (endemic provinces only).
Managing resources
The paper finds that vaccinating all ages leads to the “largest impact on magnitude of cases and deaths”, but that vaccinating only children aged 15 years or younger provides “nearly the same effect with fewer vaccine doses required”. Although vaccinating only children younger than 5 years showed a “drop-off” in averted cases and deaths, it provides the most efficiency.
“This analysis shows the effectiveness of focussing an mpox vaccination campaign specifically in the provinces endemic for mpox in the DRC. This targeted strategy prevents nearly as many cases and deaths as broader approaches but uses fewer vaccine doses and thus would be less costly to implement.”
Alexandra Savinkina, fourth year PhD student in the Yale School of Public Health (YSPH) Department of Epidemiology (Microbial Diseases), commented that this study could influence vaccination policy.
“My hope is that it could help inform policy for vaccination in the country and potentially the region and move the needle forward on getting vaccines to the people who need them most in the DRC.”
Savinkina hopes that “we can learn from the global mpox outbreak that we can’t ignore disease in other places”.
“If the resources to help people exist, I think we should be using them, whether in the U.S. or in Africa.”
Dr Gregg Gonsalves, associate professor of epidemiology at YSPH, acknowledged barriers to access.
“We take it for granted that we can get a vaccination for COVID or a flu shot at our local CVS, but the infrastructure to deliver vaccines in DRC is far less robust.”
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