monkeypox: clinical presentation and epidemiology

 A recent article reviewed the clinical presentations and epidemiology of monkeypox infections worldwide (see monkeypox clinical presentation NEJM2022 in dropbox, or DOI: 10.1056/NEJMoa2207323) 

 

 

Details: 

-- 528 infections (confirmed by PCR) diagnosed between April 27 and June 24, 2022 at 43 sites in 16 countries (90% from  Europe and 6% from North America, but also from Argentina and Israel) 

-- those infected: 98% gay or bisexual men, 75% white, median age 38, 41% had HIV infection (controlled: in 97% with HIV VL <200, CD4 680) 

-- concomitant sexually transmitted infection: 109/377 (29%): 33 with syphilis (9%), 32 gonorrhea (8%), chlamydia 20 (5%), others 1% each) 

-- positive hepatitis C antibody: 30 (6%) 

-- history of smallpox vaccination: 49 (9%) 

-- transmission: 95% through sexual activity 

    -- median number of sex partners in prior 3 months: 5 

-- clinical features: 95% had a rash (64% had 10 or fewer lesions): 73% had anogenital lesions; 55% trunk, arms or leg lesions; 25% face; 10% palms/soles

    -- 41% had mucosal lesions 

        --anorectal lesions (61 patients): associated with anorectal pain, proctitis, tenesmus and/or diarrhea 

        --oropharyngeal lesions (26 patients):pharyngitis, odynophagia, epiglottitis, and oral or tonsillar lesions 

        -- conjunctival lesions (3 patients) 

    -- 54 patients had a single genital lesion 

-- systemic features, which frequently preceded the rash: fever (60%), lethargy (41%), myalgia (31%), headache (27%) 

    -- though skin rash most commonly was first 

-- physical exam: lymphadenopathy (56%) 

-- 30 of the patients had a clearly defined exposure, having a median time of 7 days until development of symptoms 

-- the latest time that PCR was positive was 21 drays after symptom onset 

-- no difference if HIV positive or negative [though essentially all had well-controlled HIIV] 

-- semen was tested in 32 people and was PCR-positive in 29 [though not studied to see if the virus was viable] 

 

-- monkeypox treatment: 5% of 528 people: 

    -- IV or topical cidofovir: 2% 

    -- tecovirimat: 2% 

    -- vaccinia immune globulin (<1%) 

Results: 

-- hospitalization in 70 persons (13%), for the following reasons: 

    -- severe anorectal pain (21 persons) 

    -- soft-tissue superinfection (18 persons) 

    -- pharyngitis limiting oral intake (5 persons), eye lesions (2persons), acute kidney injury (2 persons), myocarditis (2 persons), and epiglottitis in 1 person with HIV and CD4<200 

    -- infection control purposes (13 persons) 

-- no deaths were reported 

 

Commentary:

-- monkeypox was first described in humans in 1970 in the Democratic Republic of Congo, with sporadic outbreaks in Africa typically from contact with rodents and other wildlife, with limited secondary spread to humans  

-- as of 26August, the CDC reports 47,652 cases internationally with almost all countries reporting cases (see https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html ); the World Health Organization declared monkeypox an "evolving threat of moderate public health concern” on June 23, 2022 

    -- there have been a total of 13 reported deaths in the recent outbreaks

-- there have been cases in the past of sporadic monkeypox infections of pregnant women and one fetal death: of 222 symptomatic people from 2009-2011, one of four pregnant women had a fetal death after delivering a macerated stillborn with diffuse cutaneous maculopapular skin lesions over their body (see https://pubmed.ncbi.nlm.nih.gov/29029147/ ) 

    -- for a review of the epidemiology, symptoms, diagnosis, and management of prior monkeypox infections, see https://www.gov.uk/guidance/monkeypox , which notes that typical human transmission appeared to be through large respiratory droplets, close or direct contact with skin lesions, and possibly through contaminated fomites. However this infection was a generally self-limited one with the fatality rate rearing between 1 to 10% dependent on the viral clade 

    -- the initial virus from the Congo Basin was clade 1, which was associated with more severe disease and a 10% mortality; the West African variants were clade IIa and IIb, with the current variant more closely resembling clade IIb. This latter clade was implicated in Nigerian outbreaks in 2017 and 2018, as well as cases found in the United Kingdom, Israel, and Singapore in 2018 and 2019. There have been further evolutionary changes in the virus since then (see N Engl J Med 2022; 387:749-750; DOI: 10.1056/NEJMe2210535) 

    -- it is unclear why the mortality rate for the current monkeypox surge is so much less than that. is it related to the rapid spread currently and it takes more time to see mortality events??

-- it is currently unclear how long this current variant has been around for. It may well be increasing in prevalence with relaxation of Covid prevention measures, increased international travel, increased 1-to-1 contact, and potential confusion with similar lesions from other sexually transmitted infections 

-- there were several findings supporting sexual transmission: the location of the lesions (largely genital, anal, oral), detection in semen (though unclear if the virus was viable, since it was not tested), and the cluster of cases in high sexual risk situations (sex parties, saunas) 

-- not enough people were in this study to comment on the effect of the treatments. 56% of the persons were >50yo, 9% overall (40 people) had prior smallpox vaccination, but not sufficient information to comment on the role of prior smallpox vaccination 

-- the UK guidelines noted above suggest use of condoms for 8 weeks after an infection.  The limited data on semen PCR positivity found a maximum interval of 21 days, but not enough information to make a clear recommendation (and, it seems that condom use would be important anyway. Especially since so many concomitant STIs and the possibility of HIV transmission….) 

 

Limitations: 

-- this was an observational study, so not able to determine causality 

-- PCR was used to confirm infections, and not sure what the sensitivity/specificity is for monkeypox, or the appropriate timing of when PCR becomes positive in those infected, or the translation from PCR positivity to viable/transmissible virus 

-- this study involved only symptomatic people who were tested on a nonrandomized basis.

    -- No data on asymptomatic people or any of the associated specific issues (eg, viral loads, transmissibility, clinical outcomes long-term).

    -- Many people may have had very mild symptoms: mild URI symptoms may have preceded a minor rash, likely not leading to testing for monkeypox very often

    -- and in this study 5% did not have a rash at all. my guess is that there may be lots of people with the viral symptoms noted above but without a rash who were not checked for monkeypox...

        -- and this was likely the case even if they sought medical care

    -- which all means that especially in the setting of the rapidly increasing spread of monkeypox, we should be doing systematic random screening of asymptomatic/mildly symptomatic people in areas of high monkeypox prevalence

So, there are several take-home messages from this article: 

-- there was wide variety in the number of lesions present, with a significant number of infected people having only a single lesion, and 5% had no skin lesions

-- systemic features often preceded the rash, most commonly fever, lethargy, myalgia, and headache; lymphadenopathy was also common. there should be a lower bar to testing for monkeypox

-- severe pain and superinfection were relatively common and need to be appropriately treated 

-- coinfection with other STIs was quite common, especially with syphilis (which might cloud the picture: is the genital lesion from monkeypox or syphilis?, though syphilis is painless…) But there could still be confusion: 54 people had a single genital lesion (often seen with primary syphilis), and 10% had lesions on palms/soles (as seen in secondary syphilis). And in this cohort, the most common STI combination was monkeypox with syphilis

    -- so, how many people who actually had syphilis were diagnosed with/treated for syphilis when they had monkeypox?? or perhaps had both together???

    -- which also means that patients with other STIs should still be considered to have possible monkeypox and be tested?? (after all, we do test for HIV etc when a person has chlamydia...)

    -- though circumstantial evidence does suggest sexual spread of monkeypox, this did not seem to have been the case in the UK study of past infection. Perhaps there are other important mechanisms of transmission that we should be concerned about?? it does seem that monkeypox infections have a very rapid doubling time, perhaps even weekly (see https://www.seattletimes.com/seattle-news/health/monkeypox-cases-doubling-nearly-every-week-in-wa-as-us-set-to-declare-public-health-emergency/ ), suggesting the potential for many modes of transmission

       -- and, of course, the initial predominance of monkeypox in MSM does not mean that monkeypox will not infect others in the population (witness HIV, which was initially called GRIDS for gay-related immunodeficiency syndrome) 

-- it is reassuring that there were so few monkeypox deaths so far, but as with many viral infections, the sheer presence of many people with monkeypox may well lead to the development of more variants, and (as we know) the variants can be more transmissible and potentially more serious clinically

 

This article also has lots of pictures of monkey pox lesions (see https://www.nejm.org/doi/full/10.1056/NEJMoa2207323 )

geoff

 

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