September 01, 2024
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Mpox Resurgence: Need for Global Coordination and Vaccine Equity

S Krishnaswamy

MPOX, formerly known as monkeypox until the WHO renamed it in November 2022 to avoid stigma, is resurging, particularly in Africa. On August 14, 2024, WHO declared a Public Health Emergency of International Concern (PHEIC) due to a sharp rise in cases in the Democratic Republic of the Congo (DRC) and neighbouring countries, including Burundi, Kenya, Rwanda, and Uganda. This is the second time in history (the first being in 2022 also for mpox) that a PHEIC has been declared for a DNA virus outbreak, highlighting the urgent need for coordinated global efforts to control the virus. Mpox has long been a concern in Central and West Africa, but global attention has only recently intensified as the disease spread to non-endemic regions.

WHAT IS MPOX?

Mpox is a viral zoonotic disease (i.e., transmitted from animals to humans) that spreads through close contact with infected individuals, contaminated materials and, less commonly, animals. While not classified as a sexually transmitted disease, it has spread among certain populations due to close physical and sexual interactions. Symptoms include fever, rash, and swollen lymph nodes, lasting two to four weeks. Though usually self-limiting, severe cases can lead to complications like secondary skin infections, septicemia, encephalitis, or corneal ulceration. The incubation period is 5 to 21 days, and the disease is contagious from the onset of fever until scabs form and fall off. Despite its earlier name, monkeys are not the natural hosts of the virus. Instead, African rodents like Gambian pouched rats, dormice, and African squirrels are believed to be the reservoirs, though the original reservoir is unknown.

MPXV, a large, enveloped, double-stranded DNA virus, has a lower pandemic potential than RNA viruses like COVID-19 due to its lower mutation rate. First identified in 1958 during an outbreak among laboratory monkeys,  The disease  was initially called "monkeypox." To reduce stigma, WHO recommended using the term "mpox" instead in November 2022, although the term "monkeypox" remains for the virus itself (MPXV). The first human case emerged in 1970 in the DRC. MPXV has two genetic clades (or groupings having a common ancestor and its descendents): Clade I (Central African or Congo Basin) and Clade II (West African). Clade I historically causes more severe disease and is thought to be more transmissible. Cameroon is the only country where both clades co-exist.

Orthopoxviruses (referring to a genus of viruses) that have infected humans include vaccinia, monkeypox, cowpox, buffalopox, and camelpox. Mpox is related to the more lethal smallpox virus, which killed over 300 million people in the 20th century before being declared eradicated in 1980.

EPIDEMICS

The 2022 mpox epidemic, involving Clade II, was a major global outbreak, with over 99,176 cases and 208 deaths reported in 116 countries, according to WHO. The outbreak mainly affected gay, bisexual, and other men who have sex with men (MSM), spreading through sexual networks. In May 2022, cases were identified in several non-endemic countries. India detected 30 cases from mid-July 2022. The epidemic peaked in July 2022 and gradually declined, leading to the end of the PHEIC declaration on May 11, 2023. In 2022, the Indian government issued guidelines to healthcare professionals and set up testing centres nationwide.

The global mpox outbreak in 2022 had a case fatality rate of about 0.03 per cent, varying by region and strain. Comparing fatality rates must be done cautiously due to other influencing factors.  WHO reported a 3–6 per cent fatality rate in Africa, higher in Central Africa and endemic areas. From January to May 2022, Cameroon, the Central African Republic, the DRC, and Nigeria reported 1,405 cases and 62 deaths, a 4.4 per cent fatality rate. Clade I, endemic to Central Africa, causes more severe illness with a 1–10 per cent fatality rate, around 5.5 per cent in the Congo province. Clade II, responsible for the 2022 global outbreak, is endemic to West Africa and less severe, with a 0.1–4 per cent fatality rate. The reproduction number (R0 or R-zero) for mpox is about 2.4, lower than 3.5 to 6 for smallpox, but still significant.

The current resurgence of mpox in Africa, especially in the DRC, shows a shift in the virus's behaviour, with Clade Ib becoming more prominent over the previously dominant Clade II. Since early 2023, over 22,000 mpox cases and 1,200 deaths have likely occurred in the DRC, driven by Clade Ib, which has also spread to Burundi, Kenya, and Rwanda. Clade II continues to circulate, with over 1,000 cases detected in the U.S. in the first half of 2024. India reported one Clade II case in March 2024.

VACCINES

Smallpox vaccination with first-generation vaccinia virus was 85 per cent effective in preventing mpox. In January 2022, the European Medicines Agency approved tecovirimat, an antiviral for smallpox, for treating monkeypox. However, experience with these treatments during mpox outbreaks is limited.

WHO recommends the use of MVA-BN or LC16 vaccines for mpox, with ACAM2000 as an alternative if the other two are unavailable. MVA-BN, or Modified Vaccinia Ankara-Bavarian Nordic, is a third-generation vaccine based on a live, attenuated orthopoxvirus called Modified Vaccinia Ankara (MVA). This live virus does not replicate well in humans, and the JYNNEOS vaccine, a specific MVA-BN formulation, contains an altered virus that cannot multiply within the human body. The vaccine is administered in two doses, at least 28 days apart, for individuals aged 18 and older. As of June 2024, a study found that a single dose of MVA-BN had vaccine effectiveness (VE) of 76 per cent, while two doses had a VE of 82 per cent. ACAM2000, a second-generation vaccine containing a live vaccinia virus, is primarily intended to prevent smallpox, but experts believe that it could also produce immunity against mpox due to the similarities between the viruses. LC16, approved for mpox in 2022 alongside Russia's OrthopoxVac, is produced by Japan's KM Biologics and can be administered to children, though it is more complex to administer than other vaccines.

INEQUITIES

Vaccine distribution has been slow and marked by significant inequities, particularly in Africa. The first 10,000 doses are expected to arrive soon, not in Congo where it is needed urgently but in Nigeria due to political considerations. But these are donations from the United States, not from the UN system. This delay in vaccine availability highlights ongoing global healthcare inequities, reminiscent of those seen during the COVID-19 pandemic. WHO has only recently initiated the necessary process to provide poor countries with access to large quantities of the vaccine through international agencies. This delay has compelled individual African governments and the Africa CDC to request vaccine donations from wealthier nations, a process that is often unreliable.

Although WHO is working to expedite access to vaccines for poorer countries, the cost of directly purchasing these vaccines is prohibitive for many low-income nations. For instance, Bavarian Nordic's vaccine costs $100 per dose, while the price of KM Biologics' vaccine remains unknown.  WHO's slow approval process has been another significant barrier. While vaccines have been widely available in high- and middle -income countries since 2022, availability in Africa outside clinical trials has been minimal.

The Africa CDC estimates that 10 million doses are needed across the continent. However, there are substantial challenges in ensuring proper storage and handling of the vaccines, which must be kept at -20 degrees C. The situation is further complicated by the fact that Bavarian Nordic's vaccine is only approved for adults, while LC16, although approved for use in children, presents a more complex administration process.

As the situation evolves, the urgent need is to improve access to mpox vaccines, diagnostics, and treatments, not only in wealthier regions but especially in low-income countries where the disease has been endemic for decades. During the 2022 epidemic which warranted a PHEIC declaration from WHO, vaccines were cornered by the rich countries leaving nothing for the African continent which needed them the most. Results of the greed of the global North are now biting back two years later.

The resurgence of mpox, particularly in Africa, underscores the need for urgent global action to address vaccine inequities and ensure that effective prevention and treatment measures are available to all affected regions. The ongoing challenges in vaccine distribution and access, primarily due to patents, IPR issues and the callousness of rich countries, highlight the broader issue of global health inequities that have been exacerbated by the Covid-19 pandemic and now by the mpox outbreaks (2022 and 2024).