With the onset of a monkeypox epidemic in various parts of the developed world, international attention has been focused on this disease. A new paper reviews the history of this disease in and outside Africa, with special reference to its clinical difficulties.
Introduction
Monkeypox is a neglected tropical zoonotic disease endemic in the tropical rainforest regions of Central and West Africa. The virus causing it, the Monkeypoxvirus (MPXV), is so-called because it was first found in Cynomolgus monkeys, in Denmark, back in 1958. However, primates, including humans, are now suspected to be only incidental hosts, though there is little evidence to support the hypothesis that small mammals, including rodents, are the natural hosts.
Since the first human case of monkeypox in 1970, several outbreaks have been reported, mostly in the Democratic Republic of Congo and Nigeria, with over 19,000 cases documented over the two decades from 2000-2019. Since then, almost 16,000 cases have been reported from 2021-22. This indicates the rapidly increasing scale of infection.
This could be due to many different reasons: better surveillance and reporting, cutting down of forests and thus greater contact with animal reservoirs, loss of poxvirus immunity as the present generation is not immunized against smallpox and mutations in the monkeypox virus that drive higher rates of spread among humans. At present, the reproductive number is calculated as being above 2, up from earlier estimates of 0.8 and 0.6 from the 80s and again from the first decade of this millennium.
Mode of Infection
The infection occurs through direct contact with an infected animal but also between humans. High-risk contacts include hunting and butchering animals, with saliva, respiratory droplets, skin lesions, and fomites being the agents of transmission.
The secondary attack rate varies with the area, period, extent of contact, and with a history of previous vaccination against smallpox. It ranges from just above 3% to almost 8%, though half the contacts in a recent Congo outbreak were found to be infected.
When in contact with an infected human, up to 12% of young children can be infected among unvaccinated people. Unvaccinated and vaccinated household contacts are four times and seven times more likely to be infected. The incubation period may be 10-14 days, though, in three-quarters of a recent Nigerian outbreak, it appeared to range between 7 and 21 days.
Clinical Features
The virus is a brick-shaped virus with double-stranded deoxyribonucleic acid (DNA) and comprises two clades, Central Africa (Congo basin) and West Africa clades. The latter appears to be milder. Symptoms include a rash similar to smallpox, though the distribution is changing as more cases are reported among HIV patients. Many chickenpox cases may be misdiagnosed as monkeypox instead, and the two occur together in over a tenth of cases.
The monkeypox rash is mostly on the face and trunk, involving palms and soles, with almost 70% of patients showing genital involvement as well. Patches and papules progress to vesicles and pustules, then develop a central cavity before crusting. Up to 66% of patients show more than a hundred lesions indicative of severe disease, and almost one in five have more than a thousand lesions.
Scarring is variable, but recent studies report their fading within two months. Secondary bacterial infection may occur in as many as half of the cases. Fever may or may not precede the rash, though lymph node enlargement was thought to be a distinguishing feature of the disease. Recent research indicates that it may occur in as few as 40% but as much as 87% of cases, however.
The case fatality rate (CFR) is about 11% and 5% for the Central African and West African clades, respectively.
While most cases outside Africa were imported via infected animals from this continent, cases have been reported beginning May 7, 2022, without such a history or history of travel to Africa. Such cases have now been reported from 13 European countries.
Diagnosis and Treatment
The infection is diagnosed by PCR of a swab from a lesion, though genomic sequencing is also useful to track its phylogenetic development. Virology and serology are limited at present, the one for use by reference laboratories and the other for public health surveillance or studies, especially since the antibodies are cross-reactive to multiple Orthopoxviruses.
Without specific antiviral treatments for this disease, brincidofovir and tecovirimat are two orally effective experimental agents that have been approved by the Food and Drugs Administration (FDA) against smallpox in animal studies. The latter received approval in its intravenous form also, where indicated. Their efficacy against monkeypox remains to be established.
Conclusion
While it is difficult to diagnose this disease in non-endemic areas, a higher index of suspicion is required in view of the increasing number of cases outside Africa. One such presentation is highlighted here, with few lesions and other atypical features. Contact tracing presents a challenge in view of the multiple casual sexual encounters reported by many of these patients.
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