Thread by @mugecevik

It has been 2 months since the first cases were reported in the MPX multi-country outbreak, & the # of cases has now crossed 14k globally. While accurate information is critical to staying ahead, there is so much misinformation. An update on the current status of #monkeypox.🧵

Epidemiology:
Overall, over 14k MPX cases have been detected in 70 countries. 7 African countries have reported ~1400 cases this year. Some “non-endemic” countries are seeing cases w/o travel links or exporting cases, indicating ongoing community transmission. (n/1)

• 99.5% of cases are among men (where data available) 
• The mean age is 37
• Evidence continues to suggest community transmission with a disproportionate incidence among gay, bisexual and other men who have sex with men (GBMSM) gov.uk/government/pub…  (n/2)

Interconnected & dense networks of highly mobile individuals align w/ what we’ve seen so far with MPX. Disproportionate onward transmission can explain the sustained growth rather than increased transmissibility, as also shown by @sbfnk et al. (n/3)
 medrxiv.org/content/10.110…

Despite widespread speculations to the contrary, MPX predominantly occurring among GBMSM isn’t driven by ascertainment or sampling bias. According to the data by @UKHSA, we can see that the positivity rate among men is considerably high compared to women & children. (n/4)

Although we will see infections beyond GBMSM, it will likely be self-limiting given the differences in network patterns. But, we may see concentrated epidemics if it’s introduced to high-risk heterosexual networks, which are impacted by racism, poverty & oppression. (n/5)

Transmission dynamics:
The incubation period matches historical data w/ a median of 9d. Epi evidence suggests that likelihood of transmission is stronger w/ prolonged close contact as opposed to via exposure to common surfaces like desks, chairs, or public toilets. (n/6)

Theoretically, MPX can be transmitted to anyone through contact with body fluids, monkeypox lesions, or shared items. But, as per epi data, MPX clearly doesn’t transmit as readily as through intimate close contact. Here are some thoughts about why this might be. (n/7)

Also, transmission risk is multidimensional. Prolonged close contact seems to be key in transmission, but different exposures are not equally effective. The combination of network & contact patterns, exposure route & biology result in MPX disproportionally affecting GBMSM. (n/8)

Virology:
We would never expect current sequences to be 100% identical to the past ones. Question is whether the changes observed are within the expected range or not. It is challenging b/c we don’t have a good understanding of the MPX mutation rate. (n/9)

https://twitter.com/DeNovo_Fatima/status/1528965895023955973

48 SNP changes were detected compared to the 2018 sequences; 27 of these mutations are silent in that they do not change any of the viral proteins. There’s also a good chance these mutations aren’t adaptive. (n/10)

https://twitter.com/richardneher/status/1530852758189916160

If we account for APOBEC signalling, 42 fit the APOBEC, 3 fit a non-canonical APOBEC, and 2 don’t fit APOBEC. So, we perhaps have 2-5 mutations in 4 years, which fits the DNA virus expectation for the # of mutations. (n/11)

https://twitter.com/marionkoopmans/status/1531390342691491841?s=21&t=PYxxCwAb8GGj9Rl7Kzi3sg

So, while the discussions are ongoing and more work is needed to understand the function of these mutations, ongoing data suggest that MPX has not *recently* become more transmissible. If something did occur, it would have occurred back in ~2017, rather than more recently. (n/12)

Interestingly, a case with a travel link to East Africa or the Middle East was identified with a distinct sequence in the US. If a non-endemic country exports a case, there is a big chance of ongoing community transmission. (n/13)

https://twitter.com/nextstrain/status/1533086692130836482

So, it is likely that African outbreak is much more widespread than we’ve recognised. MPX has been escalating for many years in Africa, but these warning signs were largely overlooked. (n/14)

https://twitter.com/haidernajmul/status/1530817585339670530

Clinical presentation:
During the current outbreak, many cases have been described as having ‘atypical’ presentations w/ localised or solitary genital lesions or even proctitis alone. There are several explanations for these observed differences in presentation. (n/15)

1- We had limited knowledge about MPX until now. Given the differences in access to care & health-seeking behaviour in LMICs, probably previously reported cases were on the severe spectrum. So, we may, in fact, be seeing the whole range of MPX disease now. (n/16)

2- According to the previous reports, the site of clinical presentation mostly depends on the inoculation site. Given that the current epidemic is spread mainly via intimate sexual contact, the lesions seen in the genital area are likely a result of direct inoculation. (n/17)

3- Clinical presentation may be associated w/ virus load & illness severity. In DRC, primary household cases had higher lesion # than secondary household cases. They’ve noted a relationship btw severity & lesion counts independent of body location. (n/18) doi.org/10.1101/2022.0…

In summary, the current clinical presentation may not be distinct compared to the historical MPX description, especially the Nigerian outbreak, if we factor in healthcare access, the influence of exposure site, host factors and severity of illness on clinical presentation. (n/19)

There are many opportunities but also many challenges in controlling this outbreak. Limited testing, and the lack of resources to support self-isolation & already overburdened sexual health services to care for the increasing MPX load continue to be the biggest obstacles. (n/20)

Especially when the time to diagnosis is prolonged, patients suffer. Mainstay of treatment is supportive care, but symptoms like pain, which can be debilitating, can be successfully managed in the hospital with pain management and antivirals. Patients deserve better. (n/21)

There are big knowledge gaps in clinical management. Our recent analysis highlights a lack of up-to-date & evidence-based clinical management guidelines, which has implications for patient management. (n/22) @isaric medrxiv.org/content/10.110…

In summary, current outbreak continues to be the biggest MPX outbreak outside of Africa. But, important to remember that MPX is not SARS-CoV-2, and it requires a very different public health response. (n/23)

https://twitter.com/mugecevik/status/1528029433050931201

So, we should continue to inform those most at risk of MPX & that the virus can be transmitted through intimate /household contact. While we will observe infections in the non-MSM population, the risk of significant transmission in the broader public continues to be low. (n/24)

In theory, anyone can get MPX, but the risk is not the same for every person/ exposure. The narrative that MPX can affect everyone equally diverts attention away from addressing unmet needs. It’s a good PH practice to focus resources where it’s needed the most. (n/25)

Appreciation to many people working tirelessly on the ground, from clinical management, epi, and contact tracing to research and policy response. Especially great thanks to the SH/GUM teams & @UKHSA @bhiva @bashh & community groups leading the response in the UK. (n/26)

Ultimately still a lot to learn about the full spectrum of MPX disease, the relationship btw viral dose & disease presentation, transmission routes, MPX evolution & management. In the meantime, all resources must be directed to stop the outbreak in the most at-risk groups (n/27)

Absolutely. Understanding the duration of protection after infection/vax is critical. The role of condom use in reducing (rather than preventing) tx is important as well - pls note there are reports of cases acquiring MPX via non-penetrative sex, but it may reduce the risk.

https://twitter.com/joel_mossong/status/1549867977377447940

A NEW analysis of 528 #monkeypox infections in 16 countries by @profchloeorkin: 98% were GBMSM, 95% thought to acquire it during sex, and importantly patients presented predominantly w/ mucosal lesions (mouth, genital, anal/perianal, throat). @NEJM nejm.org/doi/full/10.10…

Painful lesions in the mouth, rectum, & difficulty swallowing as primary presenting complaint likely represents the inoculation site & suggests sexual activity as the suspected transmission route. All HCPs need to be aware of this diverse symptom profile.

https://twitter.com/mugecevik/status/1549858745416663042?s=20&t=2j22zSTzPw2mE8cZF4ASFQ