Human monkeypox epidemiology: A potential threat?

Introduction

As the world recovers from the shock of the COVID-19 pandemic and reflects on the lessons learned from the failure of global public health systems to contain the global outbreak of SARS-CoV-2, new infectious disease threats caused by global migration remain omnipresent, despite repeated calls for more proactive action. This is exemplified by the unprecedented and unexpected outbreaks of human monkeypox cases and clusters across Europe, the Americas, and Australia since May 7, 2022, which have once again caught global public authorities off guard. The first monkeypox case reported by the UK Health Security Agency on May 7 in the ongoing outbreak had travel links to Nigeria. 4 On May 14, two more cases were discovered in the United Kingdom; both lived in the same household but had no history of travel to Africa and had no contact with the case reported on May 7. Additional monkeypox cases have been reported to WHO from twelve member countries spread across three WHO regions. As of May 21, 2022, WHO had received reports of ninety-two laboratory-confirmed cases and twenty-eight suspected monkeypox cases from the United Kingdom, the United States, Canada, France, Germany, Belgium, Spain, Portugal, Italy, Sweden, and Australia. More cases are expected to be discovered.

The Pathogen's History and Characteristics

Monkeypox belongs to the orthopoxviral family, the most well-known member of which is smallpox. The double-stranded DNA virus was discovered in monkeys in the 1950s and has a diverse host range, most notably rodents. Human cases were first identified during the smallpox eradication campaign. Monkeypox is transmitted via respiratory droplets, direct contact, or fomites. The Centers for Disease Control and Prevention (CDC) also recognizes the theoretical risk of airborne transmission and recommends airborne infection control protocols to avoid it whenever possible. When providing care or otherwise in close contact with an infected person, such protocols may include the use of N95 masks and other personal protective equipment. The incubation period can last anywhere between 5 and 21 days, and a person is not contagious until symptoms appear. Historically, animal contact has been the primary mode of transmission, though human-to-human transmission does occur and has resulted in small, contained human outbreaks in the past. Severe complications, such as central nervous system involvement and airway compromise from lymphadenitis, can occur. Mortality has been reported to range between 1% and 10%, but this may vary in settings where advanced medical care is available.

Diagnosis

Given the current outbreak, clinicians who see patients with new onset febrile illness and rash should suspect monkeypox, especially if lymphadenopathy is present. In a centrifugal pattern, the rash usually begins in the mouth, then moves to the face, then to the extremities (including the palms and soles). Polymerase chain reaction testing of skin lesions or fluid results in a definitive diagnosis. These tests can be obtained from state public health laboratories. There is no such thing as a commercially available test.

Treatment

Although there is no standard-of-care treatment for monkeypox, smallpox antivirals with poxvirus activity, such as cidofovir, Brin cidofovir, and tecovirimat, have activity against monkeypox. The latter two drugs have FDA approval for use in smallpox treatment. Such medications would most likely be reserved for the treatment of severe cases or in immunocompromised individuals and would be obtained through a public health department or the CDC.

Prevention

Smallpox vaccines are effective against monkeypox and as postexposure prophylaxis. JYNNEOS (Bavarian Nordic), a newer-generation smallpox vaccine, has an FDA indication for the prevention of monkeypox, and the older-generation ACAM2000 can be used off-label for the same purpose. Vaccination of close contacts has successfully limited transmission in previous outbreaks. Prophylactic vaccine administration as soon as possible after possible exposure can abort or significantly reduce infection. If the smallpox vaccine is not available, vaccinia immune globulin may be used as an alternative postexposure prophylaxis agent.

Uncertainties Regarding the Current Outbreak

Several dozen monkeypox cases have been reported in Europe, the United Kingdom, and North America as of this writing. What distinguishes these cases—all of which occur outside the virus's endemic region—is the presence of person-to-person transmission, with many cases appearing to be unrelated to travel from an endemic country and the appearance of multiple, as-yet unlinked clusters. This suggests that undetected transmission chains have been occurring. Another unusual feature is that many of the cases that have been identified are in men who have sex with men (MSM), and many of these cases are being diagnosed at sexually transmitted infection (STI) clinics. This suggests that the virus is taking advantage of specific social networks. The most pressing immediate challenge is determining the origins of this outbreak. What is causing this outbreak, which is much larger and more widespread than previous outbreaks of monkeypox outside of Africa? Initial genetic analysis has revealed no genetic changes that are thought to increase transmissibility. Is the virus spreading via social media? Was it possible that clustering at specific events aided transmission? Rapid case investigations and case–control studies, which are currently underway, are critical to understanding this. Meanwhile, containment efforts will focus on increased case detection, isolation, contact tracing, and postexposure vaccination. If monkeypox outbreaks continue, primary care physicians, urgent care physicians, emergency medicine physicians, dermatologists, and those working in STI clinics are the most likely to identify new cases.