A review and a case study illustrate the challenges of monkeypox

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With the onset of an epidemic of monkeypox in various parts of the developed world, international attention has focused on this disease. A new article published in Travel Medicine and Infectious Diseases reviews the history of this disease in Africa and outside Africa, with particular reference to its clinical difficulties.

Study: New challenges in human monkeypox outside of Africa: A review and case report from Italy. Image Credit: Corona Borealis Studio/Shutterstock

Introduction

Monkeypox is a neglected tropical zoonotic disease endemic to the rainforest regions of Central and West Africa. The virus that causes it, Monkeypoxvirus (MPXV), is so called because it was first found in Cynomolgus monkeys, Denmark, in 1958. However, primates, including humans, are now believed to be only incidental hosts, although 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, primarily in the Democratic Republic of Congo and Nigeria, with more than 19,000 cases documented over the two decades from 2000 to 2019. Since then, nearly 16,000 cases were reported between 2021 and 2022. This indicates the increasing extent of the infection.

This could be due to many different reasons: better monitoring and reporting, felling of forests and therefore greater contact with animal reservoirs, loss of immunity to poxviruses as the current generation is not immune to smallpox and monkeypox virus mutations that cause higher rates of spread among humans. Currently, the reproductive number is calculated to be above 2, up from earlier estimates of 0.8 and 0.6 from the 1980s and again from the first decade of this millennium.

Mode of infection

Infection occurs through direct contact with an infected animal but also between humans. High-risk contacts include hunting and slaughtering animals, with saliva, respiratory droplets, skin lesions, and fomites being the agents of transmission.

The secondary attack rate varies by area, time, extent of contact, and history of previous smallpox vaccination. It ranges from just over 3% to nearly 8%, although half of contacts in a recent outbreak in Congo were found to be infected.

In contact with an infected human being, 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 can be 10 to 14 days, although in three quarters of a recent Nigerian outbreak it appears to be between 7 and 21 days.

Clinical features

The virus is a brick-shaped virus with double-stranded deoxyribonucleic acid (DNA) and comprises two clades, the Central African (Congo Basin) and West African clades. The latter seems softer. Symptoms include a smallpox-like rash, although the distribution is changing as more cases are reported in HIV patients. Many cases of chickenpox can be misdiagnosed as monkeypox, and the two occur together in more than a tenth of cases.

The monkeypox rash is primarily on the face and trunk, involving the palms and soles of the feet, with nearly 70% of patients also having genital involvement. The plaques and papules progress to vesicles and pustules, then develop a central cavity before forming scabs. Up to 66% of patients have more than a hundred lesions indicating serious disease, and almost one in five have more than a thousand lesions.

The scars are variable, but recent studies report their disappearance within two months. A secondary bacterial infection can occur in half of the cases. Fever may or may not precede the rash, although enlarged lymph nodes are thought to be a distinguishing feature of the disease. Recent research indicates that it can occur in as few as 40% but up to 87% of cases, however.

The case fatality rate (CFR) is about 11% and 5% for the Central and West African clades, respectively.

While most cases outside of Africa have been imported via infected animals from that continent, cases have been reported from May 7, 2022, with no history or travel history to Africa. Such cases have now been reported in 13 European countries.

Outbreaks outside Africa

Most of the 48 cases outside the monkeypox endemic area through 2021 occurred in the United States in 2003 via rodents imported from Ghana that infected humans or other animals who then transmitted it to the man. Most cases were mild, but in five cases serious illness set in. One child required mechanical ventilation for two days due to encephalitis with seizures, but all cases made a full recovery.

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

To date, more than a thousand cases have arisen in nearly 30 countries, making it the largest outbreak on record outside of Africa. Most of the cases for which relevant information is available were men who have sex with men (MSM), possibly due to genital lesions that prompted them to seek medical attention. This suggests that the virus can be transmitted sexually, especially since cases of monkeypox in Nigeria frequently show genital lesions and cowpox is transmitted through this route.

Diagnosis and treatment

Infection is diagnosed by PCR of a swab from a lesion, although genomic sequencing is also useful to follow its phylogenetic development. Virology and serology are currently limited, one for reference laboratory use and the other for surveillance or public health studies, especially since antibodies are crossed at multiple Orthopoxvirus.

Without specific antiviral treatments for this disease, brincidofovir and tecovirimat are two effective investigational oral agents that have been approved by the Food and Drugs Administration (FDA) against smallpox in animal studies. The latter has also been approved in its intravenous form, where available. Their effectiveness against monkeypox remains to be established.

A case report

In this article, researchers present the case of a young Italian man who presented with a perianal lesion lasting a few days 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 his elbows, in the week before his presentation at the clinic.

Following these first symptoms, he developed new lesions accompanied by a sore throat and sneezing. However, he tested negative for COVID-19.

He had been in Lisbon, Portugal, since January 2022, with a week-long trip 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 series of primary and booster vaccines against the coronavirus disease 2019 (COVID-19) pandemic.

He had enlarged lymph nodes in both groins, with a few lesions scattered all over his 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 solitary confinement and sent home to remain isolated until all lesions were healed. The last oropharyngeal swab was positive, but all other swabs were negative.

Conclusion

While it is difficult to diagnose this disease in non-endemic areas, a higher index of suspicion is needed given the increasing number of cases outside Africa. Such a presentation is evidenced here, with few lesions and other atypical features. Contact tracing presents a challenge given the multiple casual sexual encounters reported by many of these patients.

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