There was considerable relief on 22 June 2022 when mandatory mask-wearing regulations were repealed at the end of the fifth COVID-19 wave.(1) Masks were uncomfortable and claustrophobic, constantly reminding one of the potential dangers lurking in the environment. Most people had until recently, perhaps because of lingering post-pandemic stress, completely ignored the World Health Organization (WHO) declaration on 23 June 2022 that mpox was an ‘evolving threat of moderate public health concern’.(2) In that year in South Africa (SA), there were only five confirmed cases of mpox, without evidence of community transmission, which allayed any fears the public might have had. Subsequent events have caused health authorities to re-evaluate the risk and have employed measures to contain and prevent the spread. There is, however, still confusion as to the degree of risk to healthcare workers (HCWs) and the general public.
Mpox is caused by the monkeypox virus of the genus Orthopoxvirus, as is the variola virus, which causes smallpox. It is a zoonotic virus transmitted from animals to humans through close contact. It was first identified in 1958.(3) The first human infection was reported in 1970 in a 9-year-old boy from the Democratic Republic of the Congo (DRC), and subsequently, it has become endemic in Central and West Africa.(3) There are two genetic clades: clade 1, endemic to Central Africa, and clade 2, endemic to West Africa. Clade 1 has historically caused more severe disease and has a higher case fatality rate (CFR) and transmissibility.(4,5)
Originally, transmission was zoonotic, through contact with bodily fluids or cutaneous/mucosal lesions of infected animals. Although the natural reservoir has not been definitively identified, rodents are the most likely culprits.(3) Human-to-human transmission occurs through close contact with respiratory secretions, skin/mucosal lesions from an infected individual, or contaminated items in the environment, such as bedding and surfaces. Transmission via respiratory droplets requires a prolonged period of face-to-face contact. Because of this, HCW, household, and other close contacts are at the most significant risk of contracting the infection through this route.(3) Although monkeypox virus DNA has been isolated from the seminal fluid of infected persons, it appears not to be sexually transmitted but rather through close physical contact with an infected person as occurs with sexual activity.(2)
Patients typically present with a viral prodrome, including fever, myalgia, sore throat, lymphadenopathy, and skin lesions. The latter often begin at the inoculation site and progress from a macule or papule to vesicles or pustules, which eventually ulcerate and crust.(4) The diagnosis is confirmed by a polymerase chain reaction, with samples preferably taken from any skin lesions, including fluid, crust, or roof.(6,7)
The mainstay of treatment is supportive, and most patients do not require hospitalisation.(2,3) Patients with severe disease, however, which occurs most often in children, pregnant women, or the immunocompromised, and in whom complications related to the infection may develop, such as eye infections, pneumonia, or encephalitis, may require hospitalisation. Deaths may occur in this group, too.(4) Antivirals, specifically tecovirimat, were considered the treatment of choice. However, it has proved disappointing in a randomized controlled trial.(8) Data, however, shows that it is well tolerated and safe.(9–11)
There are currently three licensed vaccines; the modified vaccinia Ankara-BN (MVA-BN or JYNNEOS) vaccine, which SA will have access to, is a third generation, live attenuated smallpox vaccine which is safe and effective at preventing infection. If the disease is still contracted despite vaccination, it reduces the severity and may prevent hospitalisation.(12–14)
Several outbreaks of mpox have occurred since 1970, mostly in endemic countries. Outbreaks outside of Africa have all been related to travelers from an endemic region or the importation of infected animals.(2,3) The worldwide outbreak in 2022 resulted from human-to-human transmission and has involved all continents except Antarctica.(15) Clade 2 was mainly responsible for this outbreak and predominantly affected men who have sex with men (MSM). This was the first time that mpox had been described as a sexually transmitted disease, albeit through close contact rather than sexual transmission.(16) This outbreak has primarily subsided, but there continues to be low-level transmission in countries where monkeypox was not previously endemic.(17)
The current outbreak has been declared a public health emergency by the Africa Centres for Disease Control and Prevention (CDC) and the WHO. This announcement by two international health organisations has engendered anxiety in both HCW and the public. In contrast to the 2022 outbreak, this outbreak has been driven by clade 1 and originated in the DRC.(16) Although not fully understood, there appear to be two outbreaks occurring in the DRC.(10) One is driven by subclade 1a, which is endemic to the region, predominantly causes infection in children under 15 years of age, and is concentrated in the northwest of the country. Transmission in this setting is likely to be a combination of zoonotic and household and, less frequently, sexual contact.(16) In Eastern DRC, subclade 1b, a new variant which is likely to have emerged sometime between June and September 2023, is responsible for the concurrent outbreak.(16,18) Unlike the subclade 1a strain, 1b seems to be transmitted predominantly by sexual contact. Also different from the global clade 2 outbreak, which has predominantly affected the MSM community, this clade has primarily involved heterosexual men and women (a third of whom are sex workers).(16)
The reasons for international concern are the rapidly increasing numbers of infections, particularly in Africa, and the potential for a higher CFR based on historical evidence, which has demonstrated that clade 1a has a higher CFR than clade 2. CFR estimates for clade 1a infections are 1-10% and for clade 2, 0.1-4%.(16) It has been challenging to identify whether the higher CFR of 1a is due to increased transmissibility and inherent virulence or that most of these infections have occurred in rural areas with limited access to healthcare.(19) In support of the latter theory are studies showing a lower CFR with hospitalization and provision of primary care.(16)
The true virulence of clade 1b is mainly unknown, but data suggest it may be lower than 1a. When sequenced, the 1b genome was found to have a large deletion, including a gene also missing from clade 2, possibly contributing to the lower CFR as seen in animal studies of monkeypox virus with this gene deletion.(16) Despite evidence of less virulence and lower mortality, mpox cases in Africa have increased by 160% compared to 2023, with 5,265 confirmed cases, 18,737 suspected cases, and 617 deaths (CFR: 2.57%) since the start of 2024.(20,21) Although 90% of these infections were reported from the DRC, four neighboring countries (Burundi, Kenya, Rwanda, and Uganda), which have not previously had mpox infections, have reported new clade 1b infections within the last month.(10) In addition, the first cases of clade 1b infections outside of Africa were reported in August 2024, with one case in Sweden and another in Thailand, both in individuals who had traveled to areas in Africa experiencing a mpox outbreak.(10)
South Africa is currently experiencing an outbreak of the clade 2 mpox.(22) As of 9 September 2024, there have been 25 confirmed cases with 3 deaths (CFR: 12%). All patients were men aged between 17 and 44, most identifying as MSM. The majority have, in addition, been people living with human immunodeficiency virus (HIV) with uncontrolled or recently diagnosed HIV contributing to severe mpox infection and requiring hospitalisation.(7,23) The only antiviral available in SA, although in minimal quantities, is tecovirimat, accessed through a Section 21 South African Health Products Regulatory Authority approval on a named patient basis and supplied by a limited WHO donation program.(9) As discussed earlier, the efficacy of this agent is questionable. Vaccines have not yet been secured by the Department of Health, although discussions to procure them are underway. SA is one of the African countries that the Africa CDC and the WHO financially support in the mpox response.(7,24)
How concerned should we be in SA?
Firstly, the SA outbreak involves the historically less transmissible, less deadly clade 2 virus with a low probability of introducing the clade 1 virus. Evidence for this is the fact that the relative risk [RR (%)] for the importation of cases both globally and for the 13 African countries experiencing outbreaks into SA is less than 1.(25) The WHO has also assessed the risk of acquiring the disease as low for the general public. Still, the risk increases to moderate in those that engage in high-risk sexual behaviour, especially in the MSM community.(7,10)
The CFR in SA is high, which is concerning and is probably due to an initial lack of awareness amongst patients and healthcare providers and the high proportion of people living with HIV who have contracted the disease. Fortunately, awareness has improved, and there are plans to acquire vaccines that will initially be distributed to the most high-risk individuals, as described above. Mpox is not as contagious as COVID-19. In contrast, there is no need for travel restrictions or bans, and efforts must be made to continue the overall educational process for all role players, particularly concerning prevention and personal protection.(10,26,27) Ongoing, appropriate investigations with reporting, contact tracing, and surveillance are also essential and should be upscaled. Planning for a vaccine rollout when they become available, and preparations to manage a potentially larger outbreak should it occur should be developed now.
Should we worry? Yes, but not to the same extent as we did with COVID-19 and not to the same extent as we currently do for the possibility of future pandemics, particularly those due to influenza.