How prepared are we for a widespread monkeypox outbreak?

By Pooja Toshniwal PahariaJul 25 2022Reviewed by Aimee Molineux

In a recent review published in Infectious Medicine, researchers summarized the epidemiology, etiology, clinical presentation, diagnosis and prevention and treatment strategies for monkeypox (MPX) caused by the monkeypox virus (MPXV).

An unexpected MPX outbreak in several non-endemic nations has raised global concerns. Most MPX cases of the ongoing 2022 outbreak were identified in gay, bisexual, or other men who have sex with men (GBMSM) with atypical clinical presentations. Prevention and control measures must be rapidly developed and adopted to prevent efficient human-to-human transmission of MPXV across the globe.

About the review

In the present review, researchers summarized the epidemiology, etiology, clinical presentation, diagnosis, and prevention and treatment strategies for MPX.

Epidemiology of MPX

MPXV was initially discovered in a Danish laboratory in 1958. The first human case of MPX was reported in 1970 in a nine-month-old male infant during smallpox eradication in the Democratic Republic of the Congo (DRC) and by 1980, MPX cases were nine times higher than the previous year in DRC. Between 1996 and 1997, an MPX outbreak occurred in the DRC with 511 MPX cases.

By 2009, 92 cases were reported in Africa and the count increased to 277 cases by 2019 in Africa. In September 2017, the largest MPX outbreak occurred in Nigeria, caused by a West African clade strain. From 2017 to 2019, 183 MPX cases were reported, increasing to 502 cases by October 2021. On 7 May 2022, the UK Health Security Agency (UKHSA) reported MPXV in an individual who had traveled to Nigeria. A week later, two MPX cases were reported with no travel history to Nigeria.  

After that, MPXV was detected in many non-endemic nations, and most non-endemic MPX cases reported a history of visits to North America and Europe. Between 1 January and 22 June 2022, 3413 MPX cases were reported across 50 nations/territories, 86% of which belonged to Europe, and MPXV was detected in China on 24 June 2022 and also in the United Kingdom (UK).

MPX etiology

MPXV is a linear, enveloped, double-stranded deoxyribonucleic acid (dsDNA) virus belonging to the Orthopoxvirus genus within the Poxviridae family with intracytoplasmic replication. The virus mainly comprises four components, namely, the outer envelope comprising lipoproteins, the lateral bodies, the outer membrane, and the inner core. The ends of the MPXV genome comprise the inverted terminal repeat (ITR) sequence and 190 open reading frames (ORFs) with more than >180 nucleotides.

MPXV sequences have been phylogenetically grouped into the West Africa clade and the Congo Basin or Central Africa clade with case fatality rates of 3.6% and 10.6%, respectively. MPXV detected in 2022 has been found to contain 50 single nucleotide polymorphisms (SNPs), exceeding the previous mutation rates for Orthopoxviruses, indicative of increased MPXV adaptability to human beings.

Transmission and clinical manifestations of MPX

MPX is primarily a zoonotically transmitted infection and MPXV has several animal reservoirs such as chimpanzees, monkeys of Kenya, elephants of Africa, wild boar, antelope, Gambian rats, dogs, anteaters and squirrels of West Africa. MPXV is transmitted on exposure of a human to an MPXV-infected animal/person/or MPXV-contaminated material via animal to person or from person to person via contact with infectious ulcers, body fluids, scabs, or materials contaminated by MPXV or through respiratory droplets, sex or intimate contact. Individuals not receiving smallpox vaccinations are at an increased risk of MPX infections.

MPX symptoms are similar but less severe than smallpox symptoms and MPXV incubates for one to two weeks; however, the severity of MPX symptoms may increase in children, immunocompromised individuals and pregnant females. In the initial invasion phase (five days), patients experience chills, fever, intense headaches, lymphadenopathy, asthenia, exhaustion, myalgia and back pain.

Within one to three days of fever onset, the skin eruption phase commences characterized by a rash beginning on the patient’s face followed by it rapidly spreading to the extremities, hand palms and feet soles, oral cavity, conjunctiva and the cornea in a centrifugal manner. Skin lesions begin as macules, papules, vesicles, and pustules that develop crusting and turn into scabs that eventually fall off in two to four weeks. Notably, MPX cases in the ongoing 2022 outbreak have presented atypical clinical presentations with initially a genital or perianal rash in MSM individuals.

Diagnosis, treatment and prevention of MPX

Specimens for MPXV testing include those obtained from the surface, exudate, roof or crust swabs from skin lesions, saliva and nasopharyngeal swabs.  MPX is primarily diagnosed based on viral isolation and real-time reverse transcription-polymerase chain reaction (RT-PCR). As secondary tests, acute and convalescent serum samples may be used to detect anti-MPXV immunoglobulin M (IgM) and IgG.

To date, no MPXV-specific treatment is available and antivirals such as brincidofovir, cidofovir and tecovirimat may provide supportive and symptomatic treatment by alleviation of symptoms by reducing disease sequelae, and by managing complications. MPX patients must remain isolated until the scabs fall off and use designated items such as towels, clothes, and utensils.

Conclusions

The authors stated three main reasons for the ongoing 2022 outbreak, which are as follows: (i) MPX has caused mild symptoms, and thus, MPXV transmission has not been controlled well in time; (ii) MPXV sequences mutated faster than expected during the current MPX outbreak and; (iii) Herd immunity declined with time ever since the discontinuity of vaccinations against smallpox in the 1970s.

MPX is an international health concern that warrants coordinated global efforts to enhance awareness, increase MPXV testing, develop effective antivirals, disinfect spaces and adopt preventive strategies to limit MPXV transmission. Strict quarantine measures must be undertaken, the import of African primates and rodents must be restricted and the JYNNEOS or ACAM2000 vaccinations must be administered, especially to individuals in close contact with MPX patients. In addition, smallpox vaccinations may be made available in cases of emergency.