New mpox clade Ib disproportionately affects children Premium

Ongoing global mpox outbreaks pose a significant threat, with over 97,000 cases and 203 deaths reported worldwide.

The ongoing multinational mpox (formerly known as monkeypox) outbreaks continue to be a significant threat to public health systems across the world. The outbreak that gained global attention in 2022 has persisted, and as of mid-2024, the WHO reports that over 97,000 laboratory-confirmed cases and 203 deaths have been recorded across 116 countries, including the recent one in South Africa, which affected over 20 patients, suggesting that the global outbreak which started in 2022 is continuing unabated. 

It is concerning that new massive outbreaks emerged last year in the Democratic Republic of the Congo (DRC), with significant human-to-human transmission. Over 14,000 cases and 500 deaths have been documented this year. Given the country’s ongoing struggle with internal conflict and health infrastructure challenges, this is a cause of global concern with cases now being reported from almost 10 African nations. The WHO has recently called an emergency meeting with experts in this context, to assess the situation and evaluate whether to declare it as a public health emergency of international concern.

The emergence of mpox in the DRC is caused by a new clade of the virus, clade Ib, which emerged late last year and is characterised by severe disease and higher mortality. Broadly, the monkeypox virus has two clades. Clade I has been present in the DRC for several years causing sporadic outbreaks, while clade II (previously the West African clade) and specifically IIb emerged during the global mpox outbreak that attracted global attention in 2022. The clades are also characterised by distinct disease severity, with clade I known to be associated with severe disease and mortality compared to clade II, which has a mortality rate of less than 4%.

The outbreak in the DRC is unique in many aspects. The unprecedented human-to-human transmission in a short period is in stark contrast with previous clade I infections, which were largely sporadic and potentially zoonotic in origin. While the initial spread was seemingly through sexual contact, the epidemiology of the disease rapidly shifted to affect children under 15 years who constitute over 60% of all cases and 80% of all deaths, with the largest case fatality rate in children aged less than one year. The rapid availability of whole genome sequencing of the virus from the outbreak could provide immense insights into the origin and spread of the outbreak.

A preprint has dated the emergence of the outbreak using a molecular clock to September 2023, apart from suggesting mutations in the binding site of primers used in diagnostics for clade I mpox. A recent preprint analysing 58 genome sequences of mpox suggests three potential clusters, driving the spread of infection in the DRC. Both analyses suggest a significant number of APOBEC3-induced mutations, confirming a significant human-to-human transmission.

The emerging situation in the DRC specifically and in Africa in general would potentially result in the declaration of a Public Health Emergency of Continental Security by Africa CDC with mpox spread across 16 countries in the continent. While there are many unanswered questions, including what drives the rapid spread and unprecedented emergence of clade I, the urgent need would be to enable the rollout of vaccines. With only two major vaccine producers for the smallpox vaccine which was repurposed for mpox, and with little emphatic support from global organisations to enable diagnosis and prevention, the world might be awaiting another global outbreak in the immediate future. Molecular surveillance could indeed be the best effort for countries like India, apart from international cooperation and developing indigenous capacity for vaccine manufacturing before it becomes too late. 

(Bani Jolly is a senior scientist at Karkinos Healthcare. Vinod Scaria is a senior consultant at Vishwanath Cancer Care Foundation and adjunct professor at IIT Kanpur)