The Epidemic of Monkeypox

Monkeypox is a rare zoonotic (animal-to-human) infection caused by the monkeypox virus (MPXV). It is a highly contagious infectious disease (HCID) spreading through close contact, and presenting with symptoms similar to smallpox, but with less clinical severity and contagiousness. Looking at the surge in 82 nonendemic countries, World Health Organization (WHO) has declared Monkeypox as a public health emergency of international concern (PHEIC, pronounced as feek). Earlier other diseases such as COVID-19, Zika, Polio, Ebola, and H1N1 had been declared PHEICs. It implies that the outbreak is serious, sudden, unusual, or unexpected. The condition is a public health risk beyond the borders of the countries requiring an urgent international response¹ . There is a decline in the new monkeypox cases by the end of August 2022.

Monkeypox was first recognized in 1958 in the colonies of monkeys kept in a research facility in Copenhagen, Denmark for polio-related experiments. Since they manifested blisters over the skin, the condition was labeled monkeypox. But the condition is not a monkey disease. Monkeys do not appear to be the main reservoir of the virus nor does this condition spreads among monkeys. Rodents and squirrels appear to be the reservoir of the virus. Humans have contracted the virus from rodents.

The first human case of monkeypox was reported in the Democratic Republic of the Congo (DRC, earlier called Zaire) in 1970 in a nine-month-old baby.² Another case of monkeypox was reported in the same year in Nigeria.

Two cases were reported from Nigeria in 1978. Between 1981 and 1986, 338 cases were reported from DRC with 10% mortality (Clade 1). Between 1991 and 99, 511 cases were reported in West Africa from another clade (clusters of genomes possessing common and shared mutations and a common origin) referred to as clade 2 and clade 3 of monkeypox virus with a case fatality rate of less than 1%.³

Monkeypox infection was noted regularly in Central and West Africa and nearly 2000 cases were reported annually.

There was a limited outbreak in 2003 in the United States (US) with over infected 71 people. It was due to direct exposure to imported animals without any humanto-human transmission. The monkeypox virus had crossed the species barrier from the rodents imported from Ghana.

There was a re-emergence of monkeypox infection in Nigeria in 2017 after a gap of nearly four decades. By the end of April 2022, 528 cases were reported from 43 sites belonging to 16 countries. Over the next five years, sporadic cases were reported around the World for travelers arriving from Nigeria.

A case of monkeypox was reported in the United Kingdom (UK) on May 6, 2022, in a person who came from Nigeria. Three more cases of monkeypox were diagnosed in May 2022 in the UK where the index case had traveled from Nigeria. Subsequently, many cases of monkeypox were reported in the UK whose origin remained undetermined. A large-scale outbreak of monkeypox then followed in other European countries, the US, Canada, the Middle East, Australia, Argentina, and Brazil. A total of 7896 cases of monkeypox were identified in the European Union till 18 July 2022. Most of the cases were from the UK, Spain, Germany, France, and Portugal.⁴ Europe became the epicenter of the current outbreak. The US reported nearly 460 cases.

Monkeypox infection was restricted to countries in Central and Western Africa since 1970 as an endemic disease. A large number of cases have been reported since May 2022 in regions in Europe and North America where the disease was not endemic. There are more than 51,257 probable and laboratory-confirmed cases of monkeypox across 82 countries including African countries according to WHO on 22 August 2022. The current monkeypox outbreak has reported 12 deaths. In Italy, a 36-years-old male simultaneously tested positive for monkeypox, COVID-19, and HIV-1 after returning from a trip to Spain.

The majority of the cases were between 31 and 40 years and were chiefly from urban areas. Men who had sex with men accounted for 98% of the cases.⁵ Of the ten cases reported from India, from July–August 2022, five males were from Kerala. Three patients aged 31, 35, and 35 years exhibited features of monkeypox who returned from the United Arab Emirates (UAE) to their native places in Kollem, Kannur, and Mallapuram, Kerala, respectively. The fourth case was a 22-years-old male who returned from UAE to Kerala and died from monkeypox. The fifth person was a 7-year-old boy who came from the UK to Kannur and showed features of monkeypox. Of the 5 cases reported from Delhi, the first case was a 34-yearold male without any history of foreign travel. Four African nationals aged 34, 32, 31, and 22 years showed the presence of monkeypox. There was a woman patient also. These patients did not have a recent travel history to Nigeria. All cases were mild and made a good recovery. There was no instance of sexual transmission.

Monkeypox is the result of an infection with the monkeypox virus. It is a double-stranded, enveloped, large DNA virus belonging to the genus Orthopoxvirus of the family Poxviridae.⁶ Variolar virus ( VARV causes smallpox), and Vaccinia virus (used in the smallpox vaccine) also belong to the family of Poxviridae. Unlike the smallpox virus and chickenpox virus, which affect humans, the monkeypox virus is found in rodents. Monkeypox virus possesses a very large genome of around 2,00,000 base pairs. The virus undergoes evolution by accumulating genetic errors, or mutations in its genome during its replication inside the host cell. The current outbreak has resulted from the virus imported from a country where monkeypox is endemic, potentially representing the continuous circuit and evolution of the virus that caused 2017–18 Nigerian outbreaks.⁷ Its mutation rate was low with two mutations in a year. But studies have yielded results contrary to that and the genetic changes in the virus appear to be about 50.

The virus is continuously evolving with sustained humanto-human transmission. Over 95% of the cases that have been reported have the genome sequence of the virus belonging to the B.1 (B refers to original parent lineage and 1 refers to sub-lineage) lineage. This has been linked to the rapid spread of infection encountered in Europe. There is an A.2 lineage of the virus encompassing six genomic sequences. This lineage appears to be responsible for the infection seen in the US, India, and Thailand. Two samples from Kerala showed A.2 lineage after studying the complete genome sequence and phylogenetic analysis. A.2 lineage was not detected earlier and the virus has made a cryptic transmission in many countries recently. This strain of monkeypox is different from the one that caused the outbreak in Europe, and it belonged to the lineage of clade 3 (West African clade).

WHO has given new names for monkeypox virus variants using Roman numerals such as Clade I, Clade IIa, and Clade IIb to align the names with current best practices.

The initial infection has been acquired from an infected animal. The reservoir of the virus and the route of transmission remain undetermined. The route of entry of the virus into the body appears to be through broken skin, respiratory tract, and the mucous membrane of the oral cavity, nose, and eyes. Contact with alive or dead wild animals such as small mammals including rodents, squirrels, pouched rats, dormice, and non-human primates (monkeys, apes) and eating or preparing bush meat make an individual susceptible to the virus.⁸ The infection subsequently spreads from one infected person to another. Skin contact plays an important role in the spread of the infection. Close physical and more intimate skin-to-skin contact or face-to-face contact can lead to the transmission of infection through direct contact with skin lesions. Direct contact with the body fluids or lesions or indirect contact with the material from the lesions through contaminated bedding, linen, bed sheets, clothes, and towels also facilitate the spread. The spread of the infection may be airborne entering through the respiratory tract through large respiratory droplets from an infected person. The virus is found in seminal fluid and vaginal secretions.

Most of the reported cases have been in homosexual or bisexual men and men who have sex with other men in urban areas. Close skin contact with lesions during sexual activities enables the spread of the virus. Though monkeypox can be transmitted during sexual activity, it is not a sexually transmitted disease as the virus can be acquired without having sex. It must be noted that the virus does not spread by casual contact. Monkeypox may also spread from those without exhibiting any symptoms.

Middle-aged people are more at risk from monkeypox. It should be noted that all outbreaks of infection in Africa were from animals and the current outbreak is spreading through human-to-human contact. Asymptomatic carriers with high viral loads in the anal mucosa can transmit the infection to those having anal sex.

The incubation period is from 6 to 13 days. However, it can range from 5 to 21 days. The period of communicability is one to two days before the appearance of the rash until the fall of all scabs. The illness typically lasts for 2–4 weeks of infection.

Monkeypox begins with prodromal symptoms such as fever, headache, muscle aches, fatigue, and asthenia. There may be a non-productive cough. There is lymphadenopathy in the region near the ear and jaw and groin. The presence of enlarged lymph nodes distinguishes the condition from that of smallpox or chickenpox. Lymphadenopathy precedes the appearance of rash; macular rash is noted on the face, palms of the hands, and soles of the feet which spreads in a centrifugal fashion. Skin eruptions begin 1–3 days after the appearance of fever. Rashes may be found in the oral cavity, genitalia, conjunctiva, and trunk. The macular eruptions pass through sequential stages of papule, vesicle, and pustule simulating the rash of smallpox. Within a week, the pustules get dried and undergo crusting. A person is considered contagious until all scabs have fallen and new skin is formed. All cases may not exhibit classical features and pustules may be noted before the appearance of fever and other constitutional symptoms. The condition may present with only a few or even a single lesion. The lesions may develop on the genital or perineal region. The condition may present with atypical features such as rectal pain, proctalgia, and penile edema.⁹ Some infected individuals may not exhibit any symptoms. The condition may appear in a severe form in children, pregnant women, and those with immune-compromised status. Complications are also more frequent in immune-compromised people than in healthy adults.

Complications may occur in the lungs, brain, and cornea in the form of bronchopneumonia, sepsis, encephalitis, Keratitis, and secondary bacterial infection. There can be a loss of vision. The case fatality rate is extremely low in monkeypox. Children may be more severely affected and show a high rate of death which has been noted in Africa.

The presence of unique sequences of viral DNA may be detected in the samples taken from the skin lesion by utilizing the polymerase chain reaction (PCR) test. In India, the test can be undertaken on the clinical specimens sent through the integrated disease surveillance program (IDSP) network to the National Institute of Virology (NIV) laboratory in Pune. Monkeypox virus nucleic acid detection test (fluorescence PCR method) is a key diagnostic test. Tianglong’s kit uses a 3-in-1 single tube design that can detect the specific sequences of the viral DNA for the early and rapid diagnosis of monkeypox.

Monkeypox has to be differentiated from chickenpox, herpes simplex, secondary syphilis, and smallpox.

Monkeypox is usually a self-limited disease with symptoms lasting two to four weeks. It is not life-threatening, but is disruptive and painful. The people who are infected should be isolated and managed. It will facilitate the prevention of the spread of the infection. There is no proven specific therapy to treat the disease. Tecovirimat, Cidofovir, or Brincidofovir, antiviral agents have shown to be active against orthopox viruses and are repurposed to treat monkeypox infection. These agents might shorten the duration of symptoms and reduce the contagiousness of the disease. Tecovirimat is administered at a dose of 600 mg twice a day for 14 days. Brincidofovir is the least studied drug and it is given in a dose of 200 mg once a week for 3 weeks. Bed rest, a nourishing diet, hydration with fluids, and antipyretics are advised to the patient. The secondary bacterial infection needs the use of antibiotics.

Contacts are to be monitored daily for the appearance of clinical features for 21 days from the last contact with a patient or fomite during the infectious period. People visiting the home of an individual with monkeypox should protect themselves by wearing a well-fitting mask, avoiding touching contaminated surfaces, maintaining proper hand hygiene, avoiding sharing eating utensils, clothing, bedding, or towels, and following home disinfection guidelines. Though the monkeypox virus can linger on many common household objects (couches, light switches, computer mouse, blankets), it is unlikely to be alive and the chances of the spread of infection are low.

A vigil has to be kept on suspected cases exhibiting vesicles on the face, palm, or soles and cervical lymphadenopathy. Awareness has to be raised about the risk factors and people are to be educated about the steps to be taken to reduce exposure to the virus and to adopt preventive strategies for monkey pox.¹⁰

The smallpox vaccine is likely to offer protection against monkeypox infection as both etiological agents are closely related. However, it is difficult to prove as the administration of smallpox vaccination has been discontinued since 1980 following the eradication of smallpox from the World. However, it appears that the smallpox vaccine can give protection against monkeypox in 85% of individuals. Since the immunity offered by the vaccine given before 1980 has waned, there is a likelihood of a resurgence of infection. A newer vaccine based on a modified, live attenuated vaccinia virus—Jyenneos vaccine (Imvmune or Imvanex) and live vaccinia virus— ACAM2000 vaccine has shown to be effective in the prevention of both smallpox and monkeypox. Jyenneos vaccine is administered in a two-dose series. ACAM2000 is administered as a single dose, but requires multiple skin punctures. These vaccines can be administered as post-exposure prophylaxis. Though preparations against the pandemic have been made, there is no need for mass vaccination.

Every country has to step up surveillance, spread awareness, and ensure that the risk groups are not stigmatized.