Monkeypox – passed as prologue

In this issue of Log, Thornhill et al. report of 528 people with monkeypox in a cohort spanning 16 countries on five continents.1 The authors provide important demographic, epidemiological, and clinical details about the largest cohort of patients reported in the latest outbreak of emerging infectious diseases of global significance. Diagnosis was based on polymerase chain reaction (PCR) testing of swab samples taken from lesions, mostly in the skin, anogenital area, nose or throat. The authors note a diverse set of dermatological and oropharyngeal clinical manifestations that in many cases could be confused with a variety of other diseases, including several sexually transmitted infections. Most patients had 10 or fewer lesions, with 10% having only one genital lesion, results consistent with other previous reports. The lesions ranged in appearance from maculopapular to vesiculopustular to crusty, with the anogenital region being the most common site. The additional appendix to the article (available with the full text of the article on NEJM.org) contains an excellent range of images of lesions to aid in case recognition. Although there were no deaths in the cohort, 13% of those infected were hospitalized for pain management or secondary infections.

Monkeypox has been recognized as an endemic disease in West and Central Africa since 1970, when it was diagnosed in a 9-month-old child in the Democratic Republic of Congo who had not been vaccinated against smallpox.2 Since then, cases have been reported in Central and West Africa and can be classified on the basis of molecular characteristics into two large groups, often referred to as the Congo Basin (clade I) and West Africa (clades IIa and IIb [formerly clades 2 and 3]) groups.3.4 West African clades cause disease most resembling the emerging epidemic in countries where the disease is not endemic, while the Congo Basin clade causes more severe disease, with associated mortality by 10%. Early genomic analyzes suggest the current global outbreak is caused by clade IIb viruses similar to those that caused a Nigerian outbreak in 2017 and 2018, which included cases that were exported to the UK, Israel and Singapore in 2018 and 2019; viruses in the current outbreak are characterized by a pattern of evolutionary changes potentially mediated by apolipoprotein B catalytic polypeptide-like 3 (APOBEC3) enzymes.5 It should be noted that there appears to have been a recent change in the epidemiological characteristics of monkeypox in Africa, where cases are now occurring in new geographic areas, possibly facilitated by climate change and deforestation leading to changes in the environmental interface between humans and animals. reservoir (or reservoirs).6

The emerging epidemiological pattern of these cases bears a striking resemblance to the first cases of HIV/AIDS. In the current study, men who identified as gay or bisexual accounted for 98% of cases. The classic mode of transmission of monkeypox virus infection is thought to be direct contact between the lesion and the skin. So far, there has been very little evidence of household spread of any form of monkeypox other than among caregivers, suggesting that this infection is not spread by casual contact and likely requires prolonged or repeated exposure to virus-shedding lesions. In the present study, the finding of PCR positivity in 29 of 32 semen samples, the presence of isolated oropharyngeal lesions in 23% of infected individuals, and the observation that 73% of individuals in the cohort had anogenital lesions suggest that sexual transmission may also play a role. Given the little we know about the epidemiological characteristics of the current epidemic, it is prudent to consider an observation made during the first year of the HIV/AIDS pandemic: “…any assumption that it will remain limited to a particular segment of our society is really an assumption without scientific basis.seven Thus, additional detailed epidemiological and observational cohort studies, serological surveys and continued surveillance of new cases are of crucial importance.

If we compare the situations at the start of AIDS, Covid-19 and the current global epidemics of monkeypox, some interesting similarities and differences emerge. In the case of AIDS, the etiological agent was unknown and no effective specific countermeasures were available. Today, we know the cause and have effective therapies; however, it has taken years to get to this point, and we are still short of a vaccine. In the case of Covid-19, the etiological agent was quickly identified; however, we lacked effective countermeasures. Today, we have effective diagnostics, vaccines and therapies, after about a year of intense research and development. In contrast, in the case of monkeypox, the etiologic agent has been known for decades. A licensed monkeypox vaccine—Ankara’s non-replicative modified vaccine (Jynneos [called Imvamune in Canada and Imvanex in Europe]Bavarian Nordic) – and a monkeypox vaccine available under the FDA Expanded Access Investigational New Drug mechanism (live vaccinia virus [ACAM2000, Emergent BioSolutions]) are in the national strategic stock. In addition, two drugs (tecovirimat and brincidofovir) had already been licensed through the “animal rule” for the closely related variola virus (which causes smallpox). Studies on the disease and its animal reservoirs are underway in Africa,8 and a randomized, placebo-controlled lead of tecovirimat was about to start in the Democratic Republic of Congo.9 Thus, the challenge for the public health and research communities in this time of emergency response is to ensure the effective and equitable availability and distribution of existing countermeasures to those in need while carrying out the rigorous studies needed to define what clinical effectiveness may be, understand any potential safety issues, and guide appropriate use.

The current monkeypox epidemic presents a new set of challenges for patients as well as the medical and biomedical research communities. By the time the article by Thornhill et al. was published online, approximately 14,000 cases have been reported worldwide; at the time of writing this editorial (about 2 weeks later) that number had doubled.ten Lessons learned during the responses to AIDS and Covid-19 should help us organize a more effective and efficient response to monkeypox, and the response to monkeypox should, in turn, help inform our response to the next inevitable infectious disease. emerging or re-emerging pandemic potential.