m Monkeypox: Transmission, Clinical Features, Diagnosis, Treatment, and Prevention

Monkeypox: Transmission, Clinical Features, Diagnosis, Treatment, and Prevention

Dr. Charmi Bhanushali 1, Vidhi Bhanushali 2

Abstract

Monkeypox is a zoonotic disease that is caused by the Monkeypox virus (MPX). MPX is similar to the virus that causes smallpox. It was endemic to central and west regions of Africa but has recently been reported in different parts of the globe. The primary reservoirs of MPX are wild animals particularly primates (Mangabey monkeys), Gambian pouched rats, and squirrels. Most cases of Monkeypox are due to the transmission of the virus from animals to humans. In addition, there have also been instances of human-to-human spread through respiratory droplets, fomites, and sexual contact. Monkeypox has a varied presentation ranging from mild symptoms to severe disabling complications. Real time PCR is used to diagnose orthopoxvirus. Retrospective diagnosis is done using serological tests. Symptomatic management and prevention of secondary infection are the mainstay aim of treatment. Antiviral drugs like cidofovir, brincidofovir, and tecovirimat seem to work against MPX even though there is no specific treatment against the virus. Health education of masses, prophylactic vaccination, quarantining the exposed, appropriate personal protective equipment for health care workers, etc. is some of the preventive measures to curb the disease. The newer-generation smallpox vaccine, JYNNEOS and the older-generation ACAM20, can also be used for prevention of Monkeypox. Keywords: monkeypox virus, smallpox, orthopoxvirus, skin lesions, antiviral medications, ring vaccination

Introduction

Monkeypox (MPX) is a zoonotic disease caused by a double-helix DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family.[1] It was first reported in the Democratic Republic of Congo in 1970 and is closely related to the virus that causes smallpox.[2] In the past, there have been sporadic outbreaks in Africa, particularly in the Central and West regions where it is endemic. However, the recent surfacing of MPX in several nonendemic areas outside Africa has caused great concern. This could be due to the waning of population immunity after the discontinuation of smallpox vaccination in 1980.[3] Other plausible causes are the worldwide growth of trade, travel, cultural and diplomatic rela-

1 General Medicine, TNMC & Nair Hospital, Mumbai 2 Final Year Medical Student, Seth GS Medical College and KEM Hospital, Mumbai Corresponding Author: Dr. Charmi Bhanushali, General Medicine, TNMC & Nair Hospital, Mumbai. Email: charmi.bhan@gmail.com tions.[4] Climate change is another possible factor as deforestation and flooding have driven animals, which are reservoirs of MPX into human populations. On June 23, 2022, the World Health Organization declared Monkeypox as an “evolving threat of moderate public health concern” after more than 3000 cases was identified in more than 50 countries since May 2022.[2]

Transmission

Most cases of Monkeypox are due to the transmission of the virus from animals to humans.[5] The primary reservoirs of MPX are wild animals particularly primates (Mangabey monkeys), Gambian pouched rats, and squirrels.[6] Infection occurs by bites of infected fauna and through direct contact with blood, body fluids, and MPX lesions of diseased animals. Eating undercooked infected animals can also spread the virus.[7] Since the eradication of smallpox, there has been a reduction in the population immunity to Orthopoxvirus, leading to instances of human-to-human spread. This can occur through respiratory droplets, direct contact with skin lesions of infected individuals, and possibly

through contaminated fomites. The recent outburst has exceedingly affected men who have sex with men. This points out to the transmission of the virus through sexual contact. The mother can also spread the virus to the fetus via the placenta.[6]

Clinical features

The incubation period of MPX is 4–21 days.[3] MPX causes mild symptoms in immunocompetent individuals. However, immunocompromised individuals like children, the elderly, pregnant women, and individuals with co-morbidities such as HIV/AIDS and diabetes, can present with severe disease.[3] Human Monkeypox shares many clinical features with smallpox. The presence of lymphadenopathy classically differentiates Monkeypox from smallpox.

Monkeypox has a varied presentation. It can present with a prodrome of fever, fatigue, myalgia, and headaches. This is followed by the appearance of a rash which may be accompanied by lymphadenopathy. An individual can have cervical, maxillary, or inguinal lymphadenopathy. On examination, the enlarged lymph nodes are firm and tender.[8] The rash that follows the prodrome begins on the face and spreads on the body in a centrifugal manner. The rash progresses through the following stages- macular, papular, vesicular, and then pustular. The lesions may be present in the mouth and can interfere with eating and drinking.[9,10] Fever subsides on or within 3 days of rash onset. The skin lesions can also become secondarily infected with bacteria.

Another presentation is the occurrence of skin lesions due to MPX in the following anatomical regions in the order of decreasing frequency- the anogenital area (73%); the trunk, arms, or legs (55%); the face (25%); and the palms and soles (10%). The involvement of the anogenital region can present with pain, proctitis, tenesmus, and/or diarrhea.[2]

Immunocompromised patients can present with severe symptoms. The case fatality rate of Monkeypoxis about 1%–10%.[5] There can be secondary infection of the lungs leading to bronchopneumonia and respiratory distress. There have been instances of the virus causing diarrhea, resulting in dehydration.[8] In extreme cases, it can cause encephalitis and septicemia. [10] Corneal scarring and permanent vision loss may occur due to the virus attacking the eye or due to secondary bacterial infections.[11] Other serious complications that can occur due to MPX are- epiglottitis, myocarditis, and acute kidney injury.

Diagnosis

The clinical presentation of Monkeypox overlaps with that of many other rash causing viruses like varicella and HSV, therefore it is important to differentiate them using laboratory methods. Testing should be done on any individual that meets the criteria laid down by WHO 2022.[12]

The specimen is mostly collected from skin lesions in the form of vesicular lesions, exudate, or crusts. Vigorous swabbing is done from the surface, floor, corners, and exudate of the lesion for obtaining an adequate amount of viral DNA.[13] Nasopharyngeal swab is collected for viral culture.

Two swabs from skin lesions are collected using a sterile, dry, polyester or Dacron swab. The sample is laid down in a sterile and dry container or in a viral transport medium and transported at the temperature of 4°C. One swab is used for screening and another for additional testing.[14,15]

Screening is done using nucleic acid amplification testing (NAAT) - real-time polymerase chain reaction (PCR) that detects viral DNA. The advantage of this test is that it is highly sensitive and provides quick results. [16] Once the test comes positive for Orthopoxvirus, it is sent further to test specifically for Monkeypox virus. Several MPX generic PCR based tests have been developed having high specificity for Monkeypox virus to differentiate it from other Orthopoxviruses. In addition, there are also tests available that can differentiate between strains of MPV like Congo Basin and West African strain. [17,18]

Electron microscopy (round-to-oval inclusions with sausage-shaped structures) and immunohistochemistry was carried out earlier but are no longer in use as they are not specific and cannot distinguish between Orthopoxviruses.

Retrospective diagnosis is done using serological tests. Anti-Orthopoxvirus IgG tests for the presence of Orthopoxvirus antibodies but is not specific due to cross-reactivity among Orthopoxviruses. There is also a chance of getting false positive results in people who are vaccinated against smallpox.[14,15] Instead, Orthopoxvirus immunoglobulin M (IgM) can be used to determine the infectious agent in a recently retrospective infection or one with previous history of vaccination against smallpox.[19]

Treatment

The course of infection by Monkeypox virus is mostly self-limiting and resolves on its own. There is as such no specific treatment for the Monkeypox virus. Symptomatic treatment is the prime focus in management along with the prevention of secondary bacterial infection by early diagnosis and prompt treat-

ment using appropriate antibiotics.[20] Usage of antiviral medications may be necessitated in immunocompromised people, pregnant or breastfeeding women, and children. One of the antiviral medications is Tecovirimat which acts by inhibiting the envelope protein of Orthopoxvirus.[21] Other medications include Cidofovir and brincidofovir which prevent the action of viral DNA polymerase thus blocking viral replication. [22] Tecovirimat was found to be more efficient and was associated with fewer adverse effects than brincidofo-

vir.[23]

Vaccine Protection

All people exposed to Monkeypox or likely to get exposed in the future are vaccinated. These include all the people who have been identified to have been in contact with a person having Monkeypox by a public health officer, those who have multiple sexual partners in Monkeypox endemic areas or got notified that one of their sexual partners was diagnosed with Monkeypox in past 2 weeks.[24] It is also given to service providers that may come in contact with these patients like researchers, health care workers, field investigators, animal control personnel, andveterinarians. Prophylactic use of the vaccine either aborts the infection or significantly decreases the severity of the clinical course.[25]

The concept of ring vaccination is used to confer protection against both smallpox and Monkeypox using ACAM2000.[20] It is administered in a single dose and its protective effect starts after 4 weeks. The disadvantage of this vaccine is that it cannot be used in immunocompromised as it is a live virus vaccine. Moreover, vaccination leads to the formation of skin lesions that can spread the virus to those that come in contact with it.[26]

To overcome these disadvantages, the newer vaccine JYNNEOS is used. It is administered in two doses and confers immunity 14 days after the second dose. [24] It is used as post-exposure prophylaxis in immunocompromised patients and in whom ACAM2000 is contraindicated.

Usage of vaccine immunoglobulin is still under research.

Prevention

Prevention includes preventing contact with rodents and primates and consumption of inappropriately cooked meals. Health education about the virus, its transmission, and means of control should be made known to the masses.

In case of an outbreak, infected animals need to be identified and those who came in contact with them should be traced. These individuals are quarantined for around 6 weeks and given a prophylactic vaccine. Isolation of the diseased and proper transport or care of secretions using gloves, protective clothing, and surgical masks is imperative to prevent accidental exposure to the virus. The patient should be kept in a negative air pressure isolation room. Standard, contact, and droplet precautions should be taken.[1]

Acknowledgments:

We would like to express our appreciation to Dr. Shah for his guidance and support throughout the process of writing this article. We would also like to thank our families for their continued support.

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