November 2, 2022

expert reaction to study looking at monkeypox transmission before symptoms appear

A contact tracing study published in the BMJ looks at transmission dynamics of monkeypox in the United Kingdom.

Dr Jake Dunning, Senior Research Fellow in Emerging and High Consequence Infectious Diseases, Pandemic Sciences Institute, University of Oxford, said:

“The shorter serial intervals identified in this study are intriguing and the analysis is robust.  It suggests, but does not provide definitive evidence of, asymptomatic or pre-symptomatic transmission of monkeypox.  It’s an important piece of the transmission jigsaw, but personally I want to see it joined up with other pieces from other types of studies before we say asymptomatic or pre-symptomatic transmission is known to account for a substantial proportion of transmission in the clade IIb outbreak affecting mostly gay, bisexual and men who have sex with men (GBMSM) in the UK.  For example, it would be great if we could have studies of close contacts of confirmed cases – particularly sexual contacts – where they volunteer to complete symptom diaries daily and provide daily or alternate-day swab samples (for monkeypox, it could be skin, throat, genital and rectal swabs) for a few weeks following exposure, plus have blood taken at recruitment and weekly for a few weeks, to look more accurately at rates of asymptomatic, pre-symptomatic, pauci-symptomatic and symptomatic infection following exposure.  My research group did something similar for COVID-19 contacts; that was challenging enough, but it’s even harder for monkeypox, and especially where most monkeypox transmission – in the clade IIb outbreaks affecting GBMSM – appears to be occurring via close contact during sex.  Furthermore, many countries experiencing clade IIb infections are seeing a significant decrease in new cases; this is great news, but makes it much harder to launch studies of contacts of cases at this point.  Animal models can also help provide clues, but less so when it comes to looking at asymptomatic/pre-symptomatic transmission in humans that involves close physical contact – of which there are multiple types – during sex.

“It’s also really important to note that while close contact with an infected person is important for human to human transmission in all outbreaks of monkeypox, it would be wrong to assume that asymptomatic or pre-symptomatic transmission – if it does occur – accounts for similar proportions of human to human transmission across different outbreaks in different settings; e.g., outbreaks in rural parts of the Democratic Republic of the Congo versus outbreaks affecting GBMSM in London.  Echoing the important points made in the accompanying editorial, and also at the ASTMH conference in Seattle this week, monkeypox is a global health problem requiring concerted efforts to understand this re-emerging and expanding infectious disease.  Global equity applies to designing and conducting relevant, context-specific research studies, in addition to global, fair access to medical care, vaccines and treatments.”

Dr Boghuma Kabisen Titanji, Assistant Professor of Medicine, Emory University (Atlanta), said:

“I think the authors perform a robust analysis with adequate adjustments to reduce bias.  The sample size is large and the estimates of incubation period likely more accurate than those reported by much smaller studies.  The point the authors make about asymptomatic transmission based on the serial interval being shorter than the incubation period is interested and convincing based on the analysis performed and also confirms observations made from clinical studies¹ were monkeypox has been detected in samples collected for routine STI screening from asymptomatic individuals.  This needs confirmation by more studies but has implications for vaccination-based disease elimination strategies which should be seriously considered.  What proportion of cases are asymptomatic and how much do these cases contribute to seeding new transmission chains?  These are urgent questions that need answers.”

1 https://www.acpjournals.org/doi/10.7326/M22-2183

‘Transmission dynamics of monkeypox in the United Kingdom: contact tracing study’ by Thomas Ward et al. was published in the BMJ at 22:30 UK time on Wednesday 2 November 2022.

DOI: 10.1136/bmj-2022-073153

Declared interests

Dr Jake Dunning: “I am an Honorary Consultant and a member of the Technical Advisory Group on monkeypox at UKHSA, where some of the study authors work, but I was not involved in the study nor the published paper. Views expressed are my own and do not necessarily represent those of UKHSA, NIHR, the NHS or the Department of Health and Social Care.

I am involved in scientific studies of treatments and vaccines for monkeypox, but I have no financial links, direct or indirect, with manufacturers of treatments and vaccines for monkeypox. 

I am a Member of the WHO’s Emergency Committee for monkeypox, but I am not commenting on behalf of WHO or the Committee.”

Dr Boghuma Kabisen Titanji: “I have no conflicts of interest.”