Changelog:

23 July 2022
- Public Health Emergency of International Concern declared.
25 June 2022.
- Global spread determined. Monkeypox has 10+ confirmed cases in non-endemic countries totaling over 15% of world population and GDP.
- Asymptomatic or low-symptomatic spread determined. Monkeypox sometimes leaves scabs that are small and hard to see, and may even transmit asymptomatically.
- These changes mean that monkeypox fits 5/15 criteria.
- Forecasts for individual criteria and rough long-term modeling included. Because monkeypox seems overwhelmingly likely not to cause a global pandemic and has attained what I expect is a point of long-term stability in terms of the number of checklist criteria it fulfills, I will no longer be regularly updating this checklist.
17 June 2022.
- Lower CFR determined: It has been nearly a month since 100 confirmed/suspected cases were announced, and 3 weeks since 200 confirmed/suspected cases were announced. Monkeypox symptoms lasts 2-4 weeks, and there have been ~~zero~~ one death so far. Based on this, it appears that in the non-African countries affected early in the outbreak, the CFR is < 1%. This may change if the virus takes hold in less affluent non-endemic countries. EDIT: there was one death reported to the WHO but not reflected in the source I was using to write this comment.
- Demographic restriction: "Most cases" (i.e. > 50%, and possibly as high as 97%) are among men who have sex with men (MSM). The MSM population is 0.03-6.5% of men among all studies. This indicates that the most heavily affected population is < 15% of the total population.
- Note: Cases continue to expand geographically, and we may very well see at least 10 confirmed/suspected cases in countries comprising 15% of world population (currently we're at 13.6%).
- Overall, the outbreak now meets 3/14 criteria, though that may increase back to 4/14 criteria with further geographic spread.
As of 14 June 2022, I am continuing to monitor the situation and will update this post if and when new checklist criteria are met.
27 May 2022. With 10 confirmed cases in the USA, monkeypox has now infected at least 10 people in countries comprising 40% of world GDP and 8% of world population - not enough to meet the criteria of 15% of world GDP and population in non-endemic countries.
25 May 2022. Absence of any inherent geographic restriction on transmissibility changed from "unclear" to "yes," and updated information about spread of the virus across populations and economies.

6/14 criteria met so far.

I can't give you a perfect answer, but given that this is a novel illness on the front page of a major newspaper, it looks like it's time to pull out the checklist. Monkeypox currently meets 6/14 criteria for being in the approach phase for a possible pandemic. Note that many of the unmet factors are just reflective of the fact that it has not reached pandemic or proto-pandemic-level spread.

For comparison, Sars-CoV2 met 13/14 criteria by Feb. 20, 2020, about 2 months after it was first reported and just before the stock market crashed.

Qualitatively, we have effective and approved vaccine technology. Probably most importantly, despite it being over a month since we had 100 cases, nearly 4 weeks since we had 200 cases, and with over 4,000 cases now, only one person has died.

The disease (as we have seen it in the past) ~~does not appear to~~ ~~may not~~ probably does sometimes spread asymptomatically or with hard-to-detect/interpret symptoms. There is no guarantee that our vaccines will be effective against any possible changes in this monkeypox.

My interpretation is that this is a disease almost exclusively spreading within a highly promiscuous sexual network of men who have sex with men. Because this community is small, this high-infection pathway for transmission is probably contained by demography and poses little risk of spread into other demographics. Fortunately, it does not appear to be particularly life-threatening with access to modern medical care. I think this is a disease that people inside of the community most affected should treat with caution, but that those not having sex with promiscuous men who have sex with promiscuous men can probably safely ignore from a practical perspective.

Forecast from 25 June 2022:

What is the chance of this disease attaining 13/14 criteria, comparable to COVID-19? I have made some forecasts for individiual criteria. The interdependencies are complex. total deaths is dependent on CFR and infection counts. Spread to new demographics and vaccine escape are probably dependent on sheer number of cases. Hospital overwhelm, quarantines, pharmaceutical company efforts, and newspaper coverage are probably dependent on number of cases at a given time. However, under a perhaps dubious simplifying assumption that the chance of each criteria is independent, my raw Monte Carlo-based forecast is as follows:

5/14: 9%
6/14: 39%
7/14: 35%
8/14: 15%
9/14: 2%
10/14+: 0%

We can try "seeding this with uncertainty" to address the many modeling shortcomings and remaining questions. One way we can do this is by assigning each remaining serious possibility (5/14-12/14) equal probabilities of 12.5%, then addressing the "complete uncertainty" model in which all criteria could change somehow with equal probabilities of 7%, and then weighting the Monte Carlo model vs. the equal probabilities model (say a 70%/27%/3% weighted split). This gives probabilities as follows:

0 to 4/14: 0.8%
5/14: 9.5%
6/14: 31%
7/14: 28%
8/14: 14%
9/14: 5.4%
10/14: 3.7%
11/14: 3.6%
12/14: 3.6%
13 to 14/14: 0.4%

It therefore seems vanishingly unlikely that monkeypox will become comparable to COVID-19 in terms of the number of deaths or economic devastation that will be attributable to it in the long run.

Transmissibility: efficiency, intra-community spread, inter-community spread, outside view

Is there an efficient transmission route, such as respiratory droplets, airborne transmission or via the bites of common jumping or flying insects? Yes.
- "It can also spread from person to person through respiratory droplets, typically in a close setting, according to the CDC."
Does it seem to spread rapidly within affected communities, going from a few cases to a major local emergency within a month? If R0 has been credibly estimated, is the mean of the range higher than 1? Yes.
- Spain nearly doubled its cases over 9 days, increasing from 584 on 15 June 2022 to 1006 confirmed cases on 24 June 2022. The USA also doubled its cases over 9 days, going from 99 confirmed cases to 201 over the same time period.
- - Our World In Data, Monkeypox: Daily confirmed cases, by date of confirmation, 7-day rolling average, 24 June 2022
- "The CDC says it is also tracking multiple clusters of monkeypox that have been reported within the past two weeks in several countries that don't normally report monkeypox, including Portugal, Spain, and the United Kingdom."
- "We do have a level of concern that this is very different than what we typically think of from monkeypox." - Jennifer McQuiston, CDC
Has it achieved community spread in non-endemic countries on at least 3 continents, and in a set of countries comprising 15% of the world population (excluding endemic countries) and a total of 15% of world GDP? Yes (data).
- CDC defines "community spread" as "people have been infected with the virus in an area, including some who are not sure how or where they became infected," but this is not a universal definition and hard to determine from the news. I will use "at least 10 confirmed or suspected cases" as the criterion.
- These countries comprised 16% of non-endemic world population and 52% of world GDP (excluding endemic countries) on 25 June 2022.
Is screening for the disease difficult due to test unavailability/unreliability/slowness, vector-based transmission, or transmissibility that is highest in early/asymptomatic stages? Yes.
- A report exists from 2020 that describes asymptomatic spread in Cameroon.
- "In fact, some patients have only one or two small lesions that can easily be confused with lesions caused by several sexually transmitted diseases, such as herpes and syphilis. "I think that's actually supercritical," Vinh says, "Because you can see how these patients can be missed. But they are still contagious and may propagate the disease."... So in the classic monkeypox, described in textbooks, you're supposed to have two phases," Vinh says. But in this current outbreak, many people's symptoms don't fit this profile at all, say Vinh and several doctors involved with these cases. For starters, the rash often isn't on the face or extremities at all. Instead, it typically begins on the genitals or the anus. And sometimes it doesn't spread to other parts of the body. "You don't have head-to-toe skin pox lesions," Vinh says. "Instead it's localized to just one region of the body, like the genital regions. And some people have just one or two pox. So it's not numerous." "Sometimes it's not even a pox," he says, "but rather an ulcer or a crater."' - NPR interview with Donald Vinh, infectious disease doctor at McGill University.
- "Infection with monkeypox virus begins with an incubation period. A person is not contagious during this period... Persons with monkeypox will develop an early set of symptoms (prodrome). A person may sometimes be contagious during this period." - CDC

Danger: case fatality rates, overwhelm, economic impacts, treatment

If a credible case fatality rate has been estimated, is it 1% or higher? Alternatively, is the number of deaths divided by the number of confirmed cases being reported at around 5% or higher in at least 3 countries with reliable data? No.
- 23 July 2022: Over 17,000 cases have occurred, and the 5 reported deaths have occurred exclusively in African countries. This strongly indicates that the CFR is far below 1% outside of Africa.
Is there a concern about hospital overwhelm or medical supply shortages in industrialized nations? No.
- This disease requires isolation of the infected person. I suspect a 10% chance of widespread overwhelm and shortages if it stays constrained to the MSM population (80%) or an 80% chance of a period of overwhelm and shortages should it escape (20%). Total probability: 24%.
Does the disease heavily affect career-age people (age 25-65), or frequently leave survivors with lasting disability? No.
- "The case fatality ratio of monkeypox has varied between 0 and 11 % in the general population, and has been higher among young children. In addition, persons younger than 40 or 50 years of age (depending on the country) may be more susceptible to monkeypox as a result of the termination of routine smallpox vaccination worldwide after the eradication of smallpox." - WHO
- "Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and nature of complications. Complications of monkeypox can include secondary infections, bronchopneumonia, sepsis, encephalitis, and infection of the cornea with ensuing loss of vision."
Is there no clearly effective treatment or vaccine? No.
- "Vaccination against smallpox with vaccinia vaccine was demonstrated through several observational studies to be about 85% effective in preventing monkeypox."
- "However at the present time, the original (first-generation) smallpox vaccines are no longer available to the general public. A newer vaccinia-based vaccine was approved for the prevention of smallpox and monkeypox in 2019 and is also not yet widely available in the public sector."
- "There is currently no specific treatment recommended for monkeypox."
- Will the vaccines lose their efficacy if the virus mutates? Given that it's not too infectious and the ring vaccination strategy, I don't think this is the primary factor the virus is being selected against. My prediction is that there's a 10% chance this happens, contingent on my 80% probability that the virus remains primarily constrained to the MSM population. If it escapes into the broader population, then I'd give an 80% chance this will happen. I'll predict a total probability of this happening at 24%.

Spread limitations: demographics, geography

If some non-age-related demographics are heavily affected and others are not, do the heavily affected demographics amount to 15% or more of the population? If almost the whole population is about equally affected, mark this criteria as met. No.
- "Most cases are in men who have sex with men" - CIDRAP
  - How many is "most?" I don't have a hard number for that, but > 340 in 350 cases were among men (but not necessarily MSM) as of 28 May 2022. - Bisanzio, D., & Reithinger, R. (2022).
- Men who have sex with men accounted for 0.03% to 6.5% of men among all studies and ranged from 3.8% to 6.4% in the US, 7,000 to 39,100 in Canada, 0.03% to 6.5% in European countries, and 127,947 to 182,624 in Australia. - Mauck, Daniel E., et al. (2019)
- It's important to ask whether this will change. Will monkeypox jump outside of the MSM population? My prediction: 20% chance this will happen.
Is the disease potentially transmissible across most of the world population (i.e. does not work via a vector that has a geographically limited range)? Yes.
- "Monkeypox virus is mostly transmitted to people from wild animals such as rodents and primates, but human-to-human transmission also occurs." - WHO
- The ability of the virus to spread across the world during this outbreak convinces me to mark this item "yes."

Social effects: communications, shutdown, research, deaths

Has the disease made front page news on at least 3 different days in the New York Times, and also received the WHO designation "public health emergency of international concern" or the equivalent? Yes.
- My prediction: 15% chance this will happen. [Note: this prediction was incorrect and very overconfident.]
Has there been a quarantine of a city with over 1 million inhabitants? In a country comprising at least 5% of world population or GDP, has there been a cancellation of major public events, or travel restrictions on passengers arriving from or via this country? No.
- My prediction: 3% chance this will happen.
Has the pharmaceutical industry begun a widespread research effort to produce a novel treatment or novel vaccine, and/or has industry begun a major emergency effort to build physical infrastructure or equipment (hospitals, ventilators, etc)? No.
- My prediction: 3% chance this will happen.
Have the death toll reached at least 2,000? No.
- "As of 15 June, a total of 2103 laboratory confirmed cases and one probable case, including one death, have been reported to WHO." - WHO
- My prediction: 75% chance this will happen - let's say by 2030.
  - Let's do a Fermi estimate by comparison with HIV, another disease spreading heavily through sexual contact via MSM. Cases of MSM with HIV total about 0.1% of the US population. If monkeypox attains community spread in countries totaling 25% of world population, and infects 0.1% of the population of these countries, that is about 2 million people potentially infected.
  - There is also still a chance that the social response will contain viral spread, perhaps constraining it by 1-2 OOMs. I actually assign a higher probability that it constrains monkeypox by 2 OOMs than 1 OOM due to the nature of exponential growth. Let's estimate a 25% chance of constraint to 20,000 cases, and a 75% chance of no constraint.
  - To have less than 2,000 deaths, a CFR of < 0.1% would be required if there are 2 million cases, but would need to be < 10% if there are 20,000 cases. It's clear that the CFR is much less than 10%. More than 1,000 cases of monkeypox were reported to WHO on 8 June 2022, 17 days ago, and 2,000 cases were reported as of 15 June 2022, 10 days ago. There has been one death so far. The challenge is knowing when that person was infected. Worst case scenario is probably a CFR of 1%, but it could also be closer to 0.1%. I suspect it's not much lower than 0.1%. This suggests a 75% chance that there are > 2,000 deaths, contingent on failure to constrain monkeypox to below 100,000 infections or so.

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