Monkey poxB04.x0

Since monkeypox was first diagnosed in humans in the Democratic Republic of Congo (DRC) in 1970, it has spread to other regions of Africa (mainly West and Central Africa). Since 2003, import- and travel-related spread outside Africa has occasionally led to outbreaks. Interactions/activities with infected animals or people are risk behaviors associated with the acquisition of monkeypox. Recent research shows an escalation of monkeypox cases, particularly in the highly endemic Democratic Republic of Congo, a spread to other countries and an increase in the mean age of onset from young children to young adults. According to the RKI, the increase in infections observed in Germany in 2022 mainly affected men who have sex with men (RKI communication 2022).

Zoonosis that used to occur sporadically in rural areas of the tropical rainforest (Cameroon, Liberia, Nigeria, Sierra Leone, Gabon, Democratic Republic of Congo, Ivory Coast, Central African Republic) and is caused by an orthopoxvirus that leads to a smallpox-like disease in humans.

Orthopoxvirus that has evolved independently of the variola virus.

Incubation period: 5-21 days, usually 10-14 days.

Transmission occurs through direct contact or aerosol. 28% human-to-human transmission (the chain of infection breaks down quickly), otherwise through contact with sick animals. Approx. 65 reported infections per year. 30% of infections are subclinical. Lethal outcome possible. Presumably protected by smallpox vaccination. In 2022, an increased incidence of infection was observed in men with homosexual contact.

By 25.8.2022, the percentage of reported monkeypox cases was distributed as follows:

• 52% (24,172 cases in 29 countries and territories) reported in the WHO Region of the Americas
• 46% (21,246 cases in 43 countries) in the WHO European Region
• < 1% (445 cases in 9 countries) in the WHO African Region
• < 1 percent (135 cases in 8 countries) in the WHO Western Pacific Region
• < 1 percent (36 cases in 7 countries) in the WHO Eastern Mediterranean Region
• < 1 percent (14 cases in 3 countries) in the WHO South-East Asia Region

Of the confirmed cases with known information (n=22,154), 98.2% (21,757) are male.

The average age is 36 years.

Regarding sexual orientation, of the 10,785 cases with available information, 96% of males reported same-sex sexual contact (MSM). Of the 10,963 cases with available information on HIV infection, 44 percent were HIV-positive.

The clinical picture is similar to variola infection. Incubation period is about 12 days. The clinical picture begins with fever, a patchy exanthema, severe headache and back pain, and a severe feeling of illness. Almost simultaneously, there is an outbreak of typical smallpox exanthema. Papules become pustules with typical central indentation. A high percentage of patients also develop mucosal involvement. The disease lasts 2-4 weeks. The efflorescences heal with scarring. After the efflorescences have completely dried up, the lesions are no longer contagious.

Monkeypox can be confirmed by polymerase chain reaction (PCR) (lesional smear) or immunohistochemistry. Pustule contents with electron microscopic evidence of the 300x200nm monkeypox virus. A skin biopsy of the vesiculopustular rash or from the roof of an intact vesiculopustule can be analyzed for this purpose.

A Tzanck smear can be helpful in distinguishing monkeypox from other non-viral diseases, but not from smallpox or herpes infections.

CBC, CRP, ESR, liver and kidney function. Of importance would be testing for syphilis, HIV or other STDs, especially in MSM patients.

Risk of scarring. Secondary bacterial infections may occur.

Mortality in Africa ranges from 1% to 10.6% in high-risk individuals (e.g., immunocompromised, malnourished).

Quarantine (applies to the Federal Republic of Germany): according to the RKI, isolation is required for 3 weeks, as infected persons are infectious for the entire duration of the disease.

In immunocompetent patients, the disease is usually self-limiting after 2-4 weeks. Symptomatic and supportive measures (e.g. analgesia, topical antiseptic therapy - prevention of bacterial superinfection). Disinfection of surfaces and objects, appropriate washing of textiles.
Examination of partners. Vaccinations are available after risk exposure.
Special attention to HIV infection, immunosuppressed and malnourished patients. There is currently no specific treatment approved for monkeypox virus infections. However, antivirals developed for use in patients with smallpox may prove beneficial. The following medical countermeasures are currently available.

• Tecovirimate (also known as ^TPOXX®) is an antiviral medication approved by the United States Food and Drug Administration (FDA).
• Cidofovir(also known as Vistide®) is an antiviral drug approved by the FDA.
• Brincidofovir (also known as Tembexa) is an antiviral drug that was approved by the FDA on June 4, 2021 for the treatment of human smallpox disease in adult and pediatric patients, including newborns. Brincidofovir has been extended compared to cidofovir by a lipid that is cleaved inside the cell and metabolized to the active ingredient cidofovir diphosphate. There are no findings on its use in monkeypox. Although data from in-vitro studies suggest efficacy in monkeypox, animal or human data are still lacking. Brincidofovir was originally developed for the treatment and prophylaxis of cytomegalovirus infections in patients following stem cell transplantation. The broad-spectrum antiviral was also used during the Ebola epidemic in West Africa between 2014 and 2016.

The overall mortality rate was 8.7%, with a significant difference between the regional collectives:

• Central Africa 10.6% (95% CI: 8.4% - 13.3%) vs.
• West Africa 3.6% (95% CI: 1.7% - 6.8%).

The live vaccine (Imvanex®, 3rd generation) is available for the prophylaxis of monkeypox (from the age of 18). Imvanex® has been approved by the EMA for the prophylaxis of smallpox since 2013; the indication was extended in 2022 following an increased incidence of monkeypox in Europe. Complete vaccination protection is achieved after two doses (at least 28 days apart).

Post-exposure prophylaxis: Vaccination with Imvanex® should be offered after a high-risk contact with close physical contact. In particular, this should be offered to patients with a severe course (e.g. HIV-infected patients).

For monkeypox virus, there is both a medical notification requirement and a laboratory notification requirement under the Infection Protection Act (IfSG).

1. Bunge EM et al. (2022) The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis 16:e0010141.
2. Mukinda VB et al (1997) Re-emergence of human monkeypox in Zaire in 1996. monkeypox Epidemiologic Working Group. Lancet 349: 1449-50
3. Mukinda VB et al. (1997) Re-emergence of human monkeypox in Zaire in 1996. dermatologist 48:598.
4. Meyer H et al. (2002) Outbreaks of disease suspected of being due to human monkeypox virus infection in the democratic republic of congo in 2001. J Clin Microbiol 40: 2919-2921.