International study of 528 monkeypox (MPX) cases: results from the 2022 outbreak need to inform new management guidelines
The results include data from 16 countries and present an up-to-date understanding of the current crisis. This includes important differences to medical papers from endemic countries. A 56-page appendix includes an image library showing the diversity of the rashes and lesions in 24 cases, including progression over time. 
The review includes 528 PCR-confirmed cases from April to June 2022, managed at 43 hospitals (26 in Europe, 10 in Canada) and is published in the NEJM.
Nearly all cases (98%) were in gay, bisexual or other men who have sex with men, with 95% reporting the potential for sexual transmission. One person was trans/non-binary and no cases were in women. Median age was 38 (range: 18 to 68), 75% were white.
HIV coinfection was reported in 41% of cases (n=241) and median CD4 was 680 cells/mm3 (IQR: 516 to 861). At least 96% of HIV positive cases were on ART, 95% with undetectable viral load. PrEP was used by 57% of the people who were HIV negative. Three people were newly diagnosed with HIV as part of MPX management.
Importantly, there are no obvious differences in baseline demographics, clinical symptoms or recovery times between people living with or without HIV. 
In the overall cohort, people were sexually active and were engaging with care to ensure they have good sexual health. PrEP use was high and HIV positive people were on effective ART. Most people had risk factors associated with previous MPX reports. This included, for example, having a median of five partners over the previous three months (IQR: 3 to 15) with 32% attending saunas or other sex-on-premises venues, 20% attending large events such as Pride and 20% reporting chemsex.
Nearly all cases (95%) presented with a rash, but only 58% of these matched the so-called typical form that progressed to being vesicular and pustular. Overall, 64% of people had less than 10 lesions, 11% had more than 20 lesions and 73% had at least one anal or genital lesion.
It is also notable that roughly 10% of cases (n=54) only had a single genital lesion, highlighting the potential for misdiagnoses as syphilis or another STI. There was also considerable variation in how lesions developed during infection, shown in the chronological photographs included in the online appendix. 
In a small subgroup of 30 cases with the most comprehensive medical records:
- Median time from first symptoms to positive PCR was 5 days (range, 2 to 20).
- Median time from the first skin lesion to additional lesions was 5 days (range: 2 to 11).
- The latest time point at which a lesion remained positive was 21 days.
Of the 23/30 cases with a clear exposure risk, the median incubation period was 7 days (range, 3 to 20).
When tested, MPX DNA was detected in nasopharyngeal tissue (26%), urine (3%), blood (7%) and semen (90%, 29/32). However, in addition to needing further research on whether the detected virus is replicant competent, close contact during sex is likely to explain most transmissions rather than contact with semen.
Even though 13% of people (n=70) were hospitalised, only 5% received antiviral treatment. This included tecovirimat (in 2%), IV or topical cidofovir (in 2%, and also no longer recommended) and vaccinia immune globulin (<1%).
Most hospitalisations were for pain management, including severe anorectal pain (n=21). Other difficult complications included tissue infections (n=18); pharyngitis (n=5); eye lesions (n=2); acute kidney injury (m=2); myocarditis (n=2); and to control wider infections (n=13).
Two other types of serious complications were reported. One case of epiglottitis in an HIV positive person with a CD4 count <200 cells/mm3; and two cases of myocarditis (one was HIV positive with a high CD4 count).
It is significant that no deaths were reported from this large cohort.
As a caution, the paper notes that because cases were identified by self-referral, this could underestimate asymptomatic infections.
The authors also discuss the importance of training for health workers and the active involvement of community organisations in the responses to MPX.
This impressive observational study is the largest case series to report the 2022 MPX outbreak. It adds essential information that will impact on the management on MPX in all countries.
This data will also be submitted to expand the international case definitions to include genital and anal lesions.
The image library is just as essential for providing clear examples showing the diverse presentations of MPX.
With 2,137 cases in the UK and more than 15,500 cases in at least 58 previously non-endemic countries, MPX is now a crisis. 
The virus is now predicted to become endemic for many months, with outcomes largely dependent on rapid access to vaccines for populations at higher risk.
Activists and health professionals have urgently called for funding to manage infections and vaccination to minimise further spread. 
Vaccines are already becoming available in the UK and an announcement earlier this week that a further 100,000 doses are ordered and expected by September. [5, 6]
Many people believe this still underestimates both the numbers needed and the high interest from people wanting to access the vaccine. London clinics report that online appointments for vaccines become fully booked within ten minutes of being released. 
Similar overwhelming demand for vaccination has been reported from New York, also raising issues of equity of access. [8, 9]
The recommended vaccine (Imvanex, Jynneos) is currently produced by one supplier. Demand has been increasing over the last two months and this will continue. In addition to the early UK order for 20,000 doses, the EU just increased their 50,000 dose order for member states to 150,000 doses and the US had already stockpiled 1 million doses as a caution against bioterrorism.
The vaccine was approved based on strong efficacy and safety data, and vaccination will have a major role in the global response. This is based on receiving two doses, 28 days apart. 
Proposals to prioritise single-doses in vaccine progammes need to include estimates of likely efficacy in information given to people receiving the vaccine. This should include efficacy following single and double doses, the time needed for protection to develop, and whether responses are impacted by HIV status. 
- Thornhill JP et al for the SHARE-net clinical group. Monkeypox virus infection in humans across 16 countries — April–June 2022. NEJM, doi: DOI: 10.1056/NEJMoa2207323. (21 July 2022).
- Supplement to: Thornhill JP et al. Monkeypox virus infection in humans across 16 countries — April–June 2022. NEJM. DOI: 10.1056/NEJMoa2207323.
https://www.nejm.org/doi/suppl/10.1056/NEJMoa2207323/suppl_file/nejmoa2207323_appendix.pdf (PDF – 32 MB)
- i-Base and UK-CAB. Monkeypox Q&A factsheet. (Updated 21 July 2022).
- UK organisations call for £51 million to urgently tackle monkeypox crisis. HTB (12 July 2022).
- UKHSA. Monkeypox cases confirmed in England – latest updates. (Updated 19 July 2022).
- UKHSA. Monkeypox outbreak: epidemiological overview. (Updated 19 July 2022).
- Personal discussion with sexual health services.
- NYC Health Department. NYC Health Department on monkeypox vaccination strategy and prioritisation of first doses. (15 July 2022).
- CBS New York. 3 mass vaccination sites open in New York City in fight to stop monkeypox outbreak (17 July 2022).
- EU daily news. Health Union: HERA secures additional vaccine doses in response to the ongoing monkeypox outbreak (18 July 2022).
- Imvanex. Summary of product characteristics.
- UK Health Security Agency (UKHSA). Monkeypox: infected people who are isolating at home: Information for people who have been diagnosed with a monkeypox infection and who have been advised to self-isolate at home. (9 June 2022).
This report was first published on 21 July 2022.