An opportunity seized: rapid clinical research provides insights into monkeypox virus dynamics and durations of infectiousness

Monkeypox is not a new disease; it was first detected in humans in the Democratic Republic of the Congo in 1970. Clinicians and scientists in countries in west and central Africa have previously reported the course of disease and virological findings from a number of clade I and clade II monkeypox virus outbreaks.1, 2, 3 However, the unprecedented international outbreaks in 2022, caused by clade IIb monkeypox virus, and driven by human-to-human transmission, have provided additional opportunities to describe clinical manifestations and investigate viral dynamics in individuals with monkeypox.

In The Lancet Infectious Diseases, Clara Suñer and colleagues⁴ report their study of 74 outpatients with monkeypox during Spain's 2022 clade IIb monkeypox virus outbreak that mostly affected gay, bisexual, and other men who have sex with men. Participants provided a variety of sample types at six time points up to 2 months from enrolment. The study showed that the greatest amount of monkeypox virus DNA is found in skin lesion swabs, followed by rectal swabs, whole blood, oropharyngeal swabs, and semen samples. The median durations of detectable monkeypox virus DNA varied across the compartments sampled, from just 5 days for blood to 25 days for skin lesions.

Although DNA detected by PCR can be useful in studying viral shedding, the authors also did virus isolation on selected samples, which is a better proxy for infectious virus. Virus could not be isolated from any sample type collected beyond day 15 of illness and only one (2%) of 43 semen samples had monkeypox virus DNA loads in the range in which virus isolation would probably be successful. Although exposure to virus in semen is a potential route of transmission, direct contact with skin or mucosal monkeypox lesions is a more likely route of transmission during sex.⁵

Some public health agencies recommend a period of self-isolation or the avoidance of prolonged close contact to reduce onward transmission and the use of condoms during and following illness. Average viral shedding data such as those presented by Suñer and colleagues will help inform such guidance. However, the results from this study are from specific populations infected with clade IIb monkeypox virus and, therefore, might not be generalisable to all outbreaks or all populations affected by monkeypox. Severely immunosuppressed patients are one example population in whom infection and infectiousness could be prolonged,⁶ and such patients were rare in this study. Evidence of resolution of monkeypox signs and symptoms, combined with a minimum period from onset (eg, 15 days), might be an appropriate, practical indicator for ending isolation or resuming contact with others, at least for typical community patients with non-severe clade IIb monkeypox.

Suñer and colleagues did their study during a window of opportunity, recruiting sufficient participants before the number of new cases thankfully decreased in the second half of 2022, which epitomises a good outbreak research response and suggests the scientific community is applying lessons learned after delayed responses to previous emerging infection outbreaks.⁷

The greatest burden of monkeypox, both historically and in the future, is probably borne by African countries with zoonotic reservoirs; several of these countries also show substantial human-to-human transmission during monkeypox outbreaks.2, 8 The greatest number of reported monkeypox cases in 2022 have occurred in non-African countries, but it is probable that many cases of monkeypox go undetected in parts of west and central Africa, for multiple reasons.⁹ Therefore, besides providing equitable and fair access to vaccines, treatments, and diagnostics for monkeypox in Africa, there should be equal opportunities for people living in African countries to participate in, and benefit from, monkeypox research.

The 2022 clade IIb outbreaks show that monkeypox virus can spread globally via international travel, and that it can exploit a transmission niche—such as a socio-sexual network—when it finds one. Meanwhile, outbreaks of clade I and clade II infections continue in Africa. Although different monkeypox outbreaks might be connected, the groups affected, the patterns of disease, the modes of transmission, and the effect on health and wellbeing often vary between countries. This variation means that research questions might differ between countries, outbreaks, and affected populations, and this needs to be reflected in study designs and research priorities.¹⁰

Future morbidity and mortality from monkeypox is difficult to predict, but as the virus infects an increasing number of people and enters new populations, future outbreaks of monkeypox might look different from the outbreaks we see today. Despite the challenges involved and the many competing priorities, it is vital that research efforts continue and intensify, particularly in African countries with recurring outbreaks. A failure of the global community to enable a truly global response to monkeypox, including research efforts in all affected regions, could prove to be self-defeating.

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JD is an investigator and medical monitor on clinical studies of antiviral therapies for monkeypox, sponsored by the University of Oxford. He has no financial conflicts of interest to declare. JD is supported by grants made to the University of Oxford the National Institute of Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, the UK Public Health Rapid Support Team, and the Moh Family Foundation. JD is an Honorary Consultant at UKHSA; views expressed do not necessarily represent those of the UK Department of Health and Social Care or the UK Health Security Agency. CO is employed by the Nigeria Centre for Disease Control and Prevention (NCDC). Views expressed here do not necessarily represent those of NCDC or the Federal Government of Nigeria. CO has no financial conflicts of interest to declare. Both authors contributed equally to conceptualisation, writing, reviewing, and editing.