Review and case study illustrates the challenges of monkeypox

By Dr. Liji Thomas, MDReviewed by Danielle Ellis, B.Sc.Jun 27 2022

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 published in Travel Medicine and Infectious Disease 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.

Outbreaks outside Africa

Most of the 48 cases outside the endemic zone for monkeypox until 2021 occurred in the USA in 2003 via imported rodents from Ghana that infected either humans or other animals that then transmitted it to humans. Most cases were mild, but in five severe disease set in. One child had to be mechanically ventilated for two days due to encephalitis with seizures, but all cases recovered completely.

A small outbreak occurred in the UK, with another two cases in the USA, and one each in Israel and Singapore, with either exposure to human hosts or infected animal meat.

As of now, over a thousand cases have cropped up in almost 30 countries, making it the largest ever outbreak outside Africa. Most cases on whom relevant information is available were men who had sex with men (MSM), perhaps because of the genital lesions which caused them to seek medical help. This suggests that the virus can be sexually transmitted, especially since monkeypox cases in Nigeria frequently have genital lesions, and cowpox is transmitted via this route.

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.

A case report

In the current paper, the researchers present the case of a young Italian man who presented with a perianal lesion of a few days’ duration on May 24, 2022. He had a history of casual anal sex on May 8, 2022. This was followed by weakness, malaise and loss of appetite, and two papules on the elbows, during the week before his presentation to the clinic.

Following these initial symptoms, he developed new lesions along with a sore throat and sneezing. However, he tested negative for COVID-19.

He had been in Lisbon, Portugal, since January 2022, with a week’s travel to Madrid. He had a history of human immunodeficiency virus (HIV) infection, diagnosed in 2016, and was being treated with a good response. He had taken a full primary plus booster series of vaccines against the coronavirus disease 2019 (COVID-19) pandemic.  

He had enlarged lymph nodes in both groins, with a few scattered lesions all over the body. No evidence of common sexually transmitted infections was found. However, he was diagnosed with monkeypox infection by swabs from multiple sites, tested by polymerase chain reaction (PCR).

He was treated in isolation and released home to remain in isolation until all lesions recovered. The last oropharyngeal swab was positive, though all other swabs were negative.

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.