Tips for physicians: Recognising and treating monkeypox

Monkeypox is currently spreading worldwide. In the process, the virus may be adapting more to humans, and a majority of cases are sexually transmitted.

MPX 2022 - The most important facts at a glance

New characteristics of the MPXV

Monkeypox virus (MPXV) is originally a classical zoonotic virus that can pass from animals to humans. In the past, there have often been smaller outbreaks in the African endemic areas, with rather short chains of transmission from human to human.

It is assumed that changes in the virus, as well as global travel that has restarted during the COVID-19 pandemic, have contributed to human-to-human transmissions outside the endemic areas. It is striking that MPXV is now spread through sexual contact in the majority of cases outside Africa.

In addition, the World Health Organisation (WHO) recently reported some new symptoms, particularly in people with severe courses of infection. These include severe proctitis, urethritis and urinary retention.

It is very likely that MPXV has been spreading unnoticed for some time and has since continued to adapt to humans through mutations. Currently, it seems to be occupying the ecological niche of the already eradicated small pox.

MPX - from asymptomatic to complex symptoms

Currently, the population of men who have sex with men (MSM) is the most frequently affected, with about 99% of reported cases. The median age of onset in the UK, for example, is 39 years. Since the virus is transmitted primarily by sexual means, the sexual history associated with the cases often indicates changing partners or new sexual contact within the past 12 weeks.

The average incubation period is about 8.5 days. In the majority of cases, there are only mild symptoms of the disease, which disappear by themselves after a few days. Non-specific symptoms described for the prodromal stage in MPX include:

In 17% of the cases, there were no symptoms at all in a British study. About two-thirds of patients with prodromal symptoms also develop the characteristic skin lesions. Due to sexual transmission within the current outbreak, the skin lesions occur predominantly in the anogenital area, orally and on the hands and extremities. Two out of three affected persons also suffer from concomitant bilateral lymphadenopathy.

Complications and co-infections

Those affected can develop severe forms of progression and complications comparatively often. For example, severe proctitis can occur in about one in five patients. This is associated with severe pain and defecation problems. In addition, up to 25% of patients require antibiotic therapy to treat abscesses and bacterial superinfections. In the UK, there have also been cases of lesions in the pharynx causing difficulty in swallowing, and vision may also be impaired due to involvement of the cornea.

Due to the sexual transmissibility of MPXV, other sexually transmitted infections (STI) should be considered, some of which develop similar symptoms, such as syphilis, gonorrhoea, chlamydial infections, HIV and others.

Therapy options for MPXV infection

Currently, there is no approved causal therapy for MPX, so treatment is primarily symptomatic and only in severe cases off-label. Symptomatic therapy focuses in particular on pain and fever in the prodromal stage and on sufficient fluid intake.

If symptoms occur or complications arise, symptomatic treatment is extended accordingly. Painkillers help to relieve the symptoms of proctitis. Laxatives can help with defecation. Antibiotics are given for bacterial superinfections. Patients with urinary dysfunction can be catheterised for support.

Selected antiviral drugs are available, but these are only intended for very severe courses and most of them are not currently approved for MPX. These include Tecovirimat, which was active against orthopoxvia in animal studies and could possibly reduce the viral load and the duration of the disease. Cidofovir and brincidofovir are viral DNA polymerase inhibitors that have shown activity against orthopoxviruses. Brincidofovir currently has a CDC recommendation for the treatment of human smallpox in children and adults.

Alternatively, post-exposure vaccination should also be considered. This is best given within 4 days of possible MPX contact to prevent disease, or within the first 14 days of exposure to reduce symptoms.

Vaccination recommendation for selected groups of people

In Germany, for example, the Standing Committee on Vaccination (German acronym: STIKO), part of the country's biomedical center Robert Koch Institute (RKI)  published the recommendation for post-exposure prophylaxis (PEP) and indication vaccination against monkeypox (MPX) with the vaccine Imvanex (Modified Vaccinia Ankara, Bavarian-Nordic [MVA-BN]) for ≥18-year-olds on 21 June 2022. For complete basic immunisation, the vaccine is administered 2 times at intervals of at least 28 days in accordance with the approval.

Currently, vaccination is recommended especially for men who have sex with men and frequently change partners, as they are particularly at risk due to the increased risk of exposure and infection. In addition, there are persons with an increased risk of a severe course of the disease, such as immunodeficient patients, but also personnel from diagnostic laboratories with a high frequency of contact with corresponding risk material.

As there is currently not enough vaccines available in the German healthcare system, the STIKO recommends providing suitable persons with a 1st vaccination dose and postponing the 2nd immunisation for the time being. Results from animal experiments and human studies have shown that the 1st vaccine dose already provides basic protection against monkeypox and that the 2nd vaccine dose mainly serves to prolong the duration of the vaccination protection. Immunological studies have shown that the immune protection mediated by a 1st Imvanex vaccination decreases from 2 years after vaccination and then a 2nd vaccine dose is required for lasting vaccination protection.

The STIKO therefore urgently advises to use all available vaccines for the first vaccination and to postpone the administration of the second vaccine dose to a later time when sufficient vaccine is available. This applies to both PEP and indication vaccination. If the 2nd vaccine dose is postponed to a later date, the vaccination series does not have to be restarted.
 

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