In this issue of The Lancet Infectious Diseases, we report two independent cases of potential mpox (formerly know as monkeypox) reinfection. Two men had PCR-confirmed mpox with typical signs and symptoms. Following resolution, both men had negative PCR tests. After a symptom free interval of 1 and 4 months and condomless sex, one developed proctitis and the other a typical lesion with genital involvement. On further investigation, they tested positive for monkeypox virus again. Unfortunately, it was impossible sequence virus from the second episodes to determine whether the virus was identical (indicating relapse) or different (indicating reinfection) from the first episode. Potentially, PCR could also have picked up lingering virus from the sexual exposure that had not caused infection, although several swabs were positive, making this less likely. Uncertainty remains whether these cases represent true reinfection, relapse or viral remnants.
This conundrum illustrates the challenge of evidence gathering and reporting during outbreaks. On the one hand, evidence often is incomplete, uncertain and/or anecdotal; on the other hand, there is an urgent need for data to inform care, outbreak investigations, and public health interventions. We have seen this repeatedly, for example, with mpox, COVID-19, and avian influenza. It is unlikely that we can fundamentally overcome the challenge between uncertain initial data and the need for evidence to guide outbreak responses. Hence, we must carefully consider the uncertainty of the data we have and communicate the data, limitations and unanswered questions in an understandable and timely manner. Furthermore, we should have the humility and openness to say ‘we don't know yet’. and if contradictory data comes to light admit to being wrong. In fact, uncertainty and revising our conclusions based on emerging evidence is part of the scientific process and expected.
As an aside, we often are asked whether we lower the publication bar for outbreak submissions to the journal. Simply looking at the number of patients, methods, and amount of data, one could easily think that there is a lower bar for outbreak papers published in many journals and, while this might be true on such technical grounds, the ‘bar’ for information is the same across papers. A large part of the decision to publish a paper in our journal relies on how it informs either clinical practice or policy, and single cases are often very informative during early outbreaks.
Nuanced communication of early evidence is particularly important in today's world where outbreaks are often news, both in traditional news media and on social media. Case data are immediately discussed, not only by researchers, but also by journalists and the public, and this can result in misinformation or misinterpretation. In this context, medical professionals, researchers and journals have a key role in providing clear and relevant information (no or delayed information allows misinformation to fill this gap). Furthermore, ‘prebunking’, ie explicitly stating what the evidence shows and does not show, is essential. In our case, the report of of potential mpox reinfection does not mean that everyone who has recovered from mpox will get reinfected. We don't know yet whether these cases were true reinfection and if they were, how high the risk of reinfection would be.
Nevertheless, these two cases (and another case reported elsewhere) suggest that patients, healthcare providers and researchers need to be vigilant and continue testing recovered people who present with signs and symptoms suggestive of mpox. Furthermore, we urge collecting samples for virus isolation and sequencing, so that reinfection can be distinguished from relapse. Finally, any suspected or confirmed reinfection should be notified to public health bodies and feed into vaccination policies.
This is emerging evidence and we do not quite know what to make of it. Should everyone who has recovered from mpox be scared? No, please don't panic but stay alert. These are isolated cases, where the second episode of PCR positivity presented with milder and shorter disease. So far, the ultimate proof of reinfection through sequencing is missing and PCR values indicate that there was less viral DNA present in these second episodes than during the first infection. In this situation, vigilance is prudent and if the evidence changes, we should be ready to act.
For the other case of potential reinfection see Sex Transm Infect 2023; published online Jan 27. https://sti.bmj.com/content/early/2023/01/26/sextrans-2022-055736
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