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 tomay 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.
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.
“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.
“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.
I note that this particular checklist results in an alarm bell which basically cannot go off until a pandemic is already well under way. Like, the “3 continents” item or the “medical supply shortages” or “quarantine of a city” or “front page news” are essentially hindsight indicators; by that point the pandemic has already reached significant scale. In hindsight, February 20 2020 was very late to start paying attention to covid.
My starting point was based on the efficient markets hypothesis. I figured that it would be hard to come to correctly calibrated confidence about the economic consequences of a pandemic faster than the market. So I tried to integrate the most relevant-seeming information we had just prior to the market crash of 2020, and see if it was possible to do a little bit better. Predicting the outcome with correctly calibrated confidence in early February, mid-January, or early January would have been progressively more impressive, but I wanted to set myself an easier task.
Hopefully, this checklist retains utility as a tool for earlier warning, as it can serve as a sort of dashboard for monitoring a developing outbreak. For example, as an increasing number of checklist items move from “no” to “yes,” or as they become closer to “yes,” we become increasingly concerned. There’s tons of room for improvement in this checklist!
As a side note, this checklist would have beaten the FDA to declaring Sars-CoV2 a pandemic by 3 weeks. The WHO declared Sars-CoV2 a pandemic on March 11, whereas Sars-CoV2 would have met 13 of these 14 criteria no later than Feb 20, 2020.
Note also that Wuhan was locked down on Jan. 23 2020, after the Chinese government first identified a cluster of sick people in mid-December. So there was a 1-month time lapse between first detection and major city lockdown, which occurred a month prior to Feb. 20.
This points out the dilemma. A major city lockdown seems like a hindsight indicator, but what about 18 deaths?
The New York Times had at least two articles by Jan. 8 on the “mystery flu,” though they were on page A13. Only the Jan. 23 articles made page A1. So perhaps the “front page” criteria should be relaxed.
Prospectively, you can just look at the first handful of patients, and simply infer epidemiological parameters in a rough way, and make an adequate mechanistic projection of what will happen (at least… in the absence of functional human responses).
This points out the dilemma. A major city lockdown seems like a hindsight indicator, but what about 18 deaths?
If you have 18 deaths, and every patient’s social network has been contact traced and tested and all the rest are negative, then even if the mortality is 90%, if the infection sequence looks like this...
...then the R0 is very low and also the epidemic is over! <3
On the other hand: Suppose your patient zero is the first death, then what if the other 17 deaths had direct exposures to patient zero, and especially what if some of those 17 dead people’s second order contacts are fleeing from quarantine doctors...
...then the R0 > 17 most likely, and I really really hope Madagascar closes the ports, so that at least some human society survives the biohorror that is about to unfold.
(Logically, all of the second order contacts of those 18 dead should be racing towards the quarantine doctors, because in a coherently sane system they would obviously have a PERSONAL INCENTIVE to seek out the amazing expert care and paid vacation that are properly owed to the first thousand or so patients in any potential epidemic… because the doctors reasoning about how to head-off the expansion of the new disease would understand incentives and have the budget to bribe patients into cooperating with what is best for the health of the herd… but people are not logical, in general, so… yeah… Madagascar closing its ports would be a much more realistic thing to actually hope for AFTER most of the biohorror is inevitably baked in and AFTER the madness starts to occur in a way that is legible to people who cannot reason but can “get a vibe” from other people.)
The R0 is the main exponential parameter for a disease, within the field of epidemiology.
As the saying goes “never turn your back on an exponentially growing process”.
Once you know the likely near future R_t of a disease, you know how exponential it will be, and therefore you know whether the disease will exist in the future.
If the R_t goes down to 0.5 and stays there for long enough, then the disease will go extinct and the R_t will become undefined <3
The rest of the parameters in epidemiology (like attack rate and mortality and so on) are useful for figuring out, conditional on the disease existing in the wild, how bad things will be in terms of health impacts...
....but since the health impacts of a non-existent disease are negligible, a low R0 absolves nearly every other sin that a disease might otherwise be exhibiting.
Using the lock-down of the city in China as a proxy for “when to worry”, you are OUTSOURCING “your ability to mechanistically reason” to competent reasoners in the (authoritarian and unelected) government of China.
They wouldn’t be able to use your instrument to make the decision that your instrument takes as an input. That would be circular! ;-)
But your instrument can piggy back on them simply directly reasoning about reality directly.
Suppose they get a convenience sample of medical data to estimate the R0, and made two mechanistic predictions using exponential growth: 1) “what the country looks like (with this R0) if we don’t lock down our city” and 2) “what the country looks like (with this R0) if we successfully lock down our city” and
then choosing the policy that causes fewer deaths in the wider country.
That produces a signal. That signal can go into your instrument.
But if you can just directly get the patient data yourself, you can predict what they predict BEFORE they make their announcements.
Also, suppose that those government officials just thought it would be funny for everyone else to get the disease too. Then they wouldn’t lock down their city and you wouldn’t get the signal.
Or suppose they thought that “overpopulation exists and is bad” and were pro-actively in favor of death for practically everyone? Murder monkeys like this exist! They’re not even ashamed of it, and newspapers like that are not even protested for espousing pro-genocide ideologies.
Another way to break the signal might be if hypothetical city-lockdown-deciders specifically authorize people to travel around the world on purpose if they were sufficiently morally monstrous (or sufficiently aware that almost everyone high enough on the food chain of OTHER countries is ALSO basically psychopaths, and then they consciously spread disease to other places according to a “pre-emptively defensive” logic based on realistic doctrines that insist that if they have a new weakness then everyone else should also have that weakness for their own relative safety).
All such morally monstrous calculations or behavioral changes could BREAK the “city lockdown” signal, for your instrument.
It is cleaner and less noisy and cheaper and less entangled with extraneous signals to just LOOK AT MECHANISTIC REALITY instead of having to compute who is evil and what their incentives are before you try to think about whether to copy them for reasons you don’t yet mechanistically understand.
(at least… in the absence of functional human responses).
This is the limiting factor of our ability to infer R0 from reported cases at this early stage in practice. This monkeypox outbreak in Europe provoked an immediate and intense social response, both to identify cases and to prevent further spread.
The number of cases reported is a function of both the actual extent of disease spread and the increased amount of testing and public awareness, which relates in a complicated way to disease spread and to earlier public awareness efforts.
Clearly, we can experience such a huge spike of viral spread that increased testing can’t possibly account for it, as we saw in Omicron.
In the first few days of the monkeypox outbreak, increased case reports were probably a function of disease spread. Now, though, I am very uncertain about whether to attribute increased cases to better testing and social awareness for a disease that was already there, or to actual viral spread.
If we see about 1,000 cases or more in the next couple weeks, though, or see it achieving community spread outside Europe, I’ll definitely start to think this is getting out of hand. By then, we’ll also have more information about its genetics, how it spreads, and the CFR among the European population.
Why would a country share of global GDP have anything to do with a disease being on trace to become pandemic ?
Do you think 10 000 000 cases in India are intrinsically less worrying than 1 000 000 in China ? Or 200 000 in the USA ?
That’s a great question! First, this checklist is very much a pilot effort, and I welcome this sort of interrogation and feedback.
My rationale is that GDP is what allows us to make the products to fight the virus. In addition, an infection that hammers high-GDP countries is more likely to disrupt global supply chains, compounding the virus’s effects. We tend to label as “pandemics” diseases that affect industrialized nations. Part of my motivation for the original checklist was to anticipate not only the disease burden, but also the intensity of social response (stock market, government).The total GDP of affected countries seems much more clearly linked to that social response, and worth including for this reason.
To be fair I think the GDP is a significant criterion for a highly contagious disease because the richest people tend to travel more both inside and outside their country, and hence spread the disease faster. Just the way you wrote it sounds weird.
Speaking of a HIV pandemy seems justified. Malaria is very different in fact it’s definitely endemic rather than pandemic—some places have malaria, some don’t.
“Does the disease heavily affect career-age people (age 25-65), or frequently leave survivors with lasting disability?”
This is rightly ticked off as “No”, but I think it morally counts as “Yes” if there is more danger to young children. That’s scarier in itself, and from COVID it seems people are also more likely to accept very extreme NPIs to protect children, meaning there might well be a large economic impact.
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
zeroone 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 tomay notprobably 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.
“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.
Great info, thanks!
I note that this particular checklist results in an alarm bell which basically cannot go off until a pandemic is already well under way. Like, the “3 continents” item or the “medical supply shortages” or “quarantine of a city” or “front page news” are essentially hindsight indicators; by that point the pandemic has already reached significant scale. In hindsight, February 20 2020 was very late to start paying attention to covid.
For sure!
My starting point was based on the efficient markets hypothesis. I figured that it would be hard to come to correctly calibrated confidence about the economic consequences of a pandemic faster than the market. So I tried to integrate the most relevant-seeming information we had just prior to the market crash of 2020, and see if it was possible to do a little bit better. Predicting the outcome with correctly calibrated confidence in early February, mid-January, or early January would have been progressively more impressive, but I wanted to set myself an easier task.
Hopefully, this checklist retains utility as a tool for earlier warning, as it can serve as a sort of dashboard for monitoring a developing outbreak. For example, as an increasing number of checklist items move from “no” to “yes,” or as they become closer to “yes,” we become increasingly concerned. There’s tons of room for improvement in this checklist!
As a side note, this checklist would have beaten the FDA to declaring Sars-CoV2 a pandemic by 3 weeks. The WHO declared Sars-CoV2 a pandemic on March 11, whereas Sars-CoV2 would have met 13 of these 14 criteria no later than Feb 20, 2020.
Note also that Wuhan was locked down on Jan. 23 2020, after the Chinese government first identified a cluster of sick people in mid-December. So there was a 1-month time lapse between first detection and major city lockdown, which occurred a month prior to Feb. 20.
Jan. 23 is also the first day for which Our World In Data begins tracking worldwide COVID-19 deaths. There were 18 deaths by that day.
This points out the dilemma. A major city lockdown seems like a hindsight indicator, but what about 18 deaths?
The New York Times had at least two articles by Jan. 8 on the “mystery flu,” though they were on page A13. Only the Jan. 23 articles made page A1. So perhaps the “front page” criteria should be relaxed.
Prospectively, you can just look at the first handful of patients, and simply infer epidemiological parameters in a rough way, and make an adequate mechanistic projection of what will happen (at least… in the absence of functional human responses).
If you have 18 deaths, and every patient’s social network has been contact traced and tested and all the rest are negative, then even if the mortality is 90%, if the infection sequence looks like this...
Patient0--patient1--p2--p3--p4--p6--p8--pA--pB--pC--pD--pF--pG (end)\--p5--p7--p9 (end) \--pE--pH--pI (quarantined)...then the R0 is very low and also the epidemic is over! <3
On the other hand: Suppose your patient zero is the first death, then what if the other 17 deaths had direct exposures to patient zero, and especially what if some of those 17 dead people’s second order contacts are fleeing from quarantine doctors...
...then the R0 > 17 most likely, and I really really hope Madagascar closes the ports, so that at least some human society survives the biohorror that is about to unfold.
(Logically, all of the second order contacts of those 18 dead should be racing towards the quarantine doctors, because in a coherently sane system they would obviously have a PERSONAL INCENTIVE to seek out the amazing expert care and paid vacation that are properly owed to the first thousand or so patients in any potential epidemic… because the doctors reasoning about how to head-off the expansion of the new disease would understand incentives and have the budget to bribe patients into cooperating with what is best for the health of the herd… but people are not logical, in general, so… yeah… Madagascar closing its ports would be a much more realistic thing to actually hope for AFTER most of the biohorror is inevitably baked in and AFTER the madness starts to occur in a way that is legible to people who cannot reason but can “get a vibe” from other people.)
The R0 is the main exponential parameter for a disease, within the field of epidemiology.
As the saying goes “never turn your back on an exponentially growing process”.
This maxim applies to diseases no less than it applies to CPU speeds, or the endowments of perpetual trusts, or oxytocin feedback loops.
Once you know the likely near future R_t of a disease, you know how exponential it will be, and therefore you know whether the disease will exist in the future.
If the R_t goes down to 0.5 and stays there for long enough, then the disease will go extinct and the R_t will become undefined <3
The rest of the parameters in epidemiology (like attack rate and mortality and so on) are useful for figuring out, conditional on the disease existing in the wild, how bad things will be in terms of health impacts...
....but since the health impacts of a non-existent disease are negligible, a low R0 absolves nearly every other sin that a disease might otherwise be exhibiting.
Using the lock-down of the city in China as a proxy for “when to worry”, you are OUTSOURCING “your ability to mechanistically reason” to competent reasoners in the (authoritarian and unelected) government of China.
They wouldn’t be able to use your instrument to make the decision that your instrument takes as an input. That would be circular! ;-)
But your instrument can piggy back on them simply directly reasoning about reality directly.
Suppose they get a convenience sample of medical data to estimate the R0, and made two mechanistic predictions using exponential growth:
1) “what the country looks like (with this R0) if we don’t lock down our city” and
2) “what the country looks like (with this R0) if we successfully lock down our city” and
then choosing the policy that causes fewer deaths in the wider country.
That produces a signal. That signal can go into your instrument.
But if you can just directly get the patient data yourself, you can predict what they predict BEFORE they make their announcements.
Also, suppose that those government officials just thought it would be funny for everyone else to get the disease too. Then they wouldn’t lock down their city and you wouldn’t get the signal.
Or suppose they thought that “overpopulation exists and is bad” and were pro-actively in favor of death for practically everyone? Murder monkeys like this exist! They’re not even ashamed of it, and newspapers like that are not even protested for espousing pro-genocide ideologies.
Another way to break the signal might be if hypothetical city-lockdown-deciders specifically authorize people to travel around the world on purpose if they were sufficiently morally monstrous (or sufficiently aware that almost everyone high enough on the food chain of OTHER countries is ALSO basically psychopaths, and then they consciously spread disease to other places according to a “pre-emptively defensive” logic based on realistic doctrines that insist that if they have a new weakness then everyone else should also have that weakness for their own relative safety).
All such morally monstrous calculations or behavioral changes could BREAK the “city lockdown” signal, for your instrument.
It is cleaner and less noisy and cheaper and less entangled with extraneous signals to just LOOK AT MECHANISTIC REALITY instead of having to compute who is evil and what their incentives are before you try to think about whether to copy them for reasons you don’t yet mechanistically understand.
This is the limiting factor of our ability to infer R0 from reported cases at this early stage in practice. This monkeypox outbreak in Europe provoked an immediate and intense social response, both to identify cases and to prevent further spread.
The number of cases reported is a function of both the actual extent of disease spread and the increased amount of testing and public awareness, which relates in a complicated way to disease spread and to earlier public awareness efforts.
Clearly, we can experience such a huge spike of viral spread that increased testing can’t possibly account for it, as we saw in Omicron.
In the first few days of the monkeypox outbreak, increased case reports were probably a function of disease spread. Now, though, I am very uncertain about whether to attribute increased cases to better testing and social awareness for a disease that was already there, or to actual viral spread.
If we see about 1,000 cases or more in the next couple weeks, though, or see it achieving community spread outside Europe, I’ll definitely start to think this is getting out of hand. By then, we’ll also have more information about its genetics, how it spreads, and the CFR among the European population.
Why would a country share of global GDP have anything to do with a disease being on trace to become pandemic ? Do you think 10 000 000 cases in India are intrinsically less worrying than 1 000 000 in China ? Or 200 000 in the USA ?
That’s a great question! First, this checklist is very much a pilot effort, and I welcome this sort of interrogation and feedback.
My rationale is that GDP is what allows us to make the products to fight the virus. In addition, an infection that hammers high-GDP countries is more likely to disrupt global supply chains, compounding the virus’s effects. We tend to label as “pandemics” diseases that affect industrialized nations. Part of my motivation for the original checklist was to anticipate not only the disease burden, but also the intensity of social response (stock market, government).The total GDP of affected countries seems much more clearly linked to that social response, and worth including for this reason.
That said, this has been critiqued (https://www.statnews.com/2021/07/06/why-arent-diseases-like-hiv-and-malaria-which-still-kill-millions-of-people-a-year-called-pandemics/), and that critique is strong and one I’m very sympathetic to.
To be fair I think the GDP is a significant criterion for a highly contagious disease because the richest people tend to travel more both inside and outside their country, and hence spread the disease faster. Just the way you wrote it sounds weird.
Speaking of a HIV pandemy seems justified. Malaria is very different in fact it’s definitely endemic rather than pandemic—some places have malaria, some don’t.
You love to see it.
I was gonna comment somewhere on this page “Too long, didn’t read, what options should I buy?”, but now we have a checklist for that. Thanks!
“Does the disease heavily affect career-age people (age 25-65), or frequently leave survivors with lasting disability?”
This is rightly ticked off as “No”, but I think it morally counts as “Yes” if there is more danger to young children. That’s scarier in itself, and from COVID it seems people are also more likely to accept very extreme NPIs to protect children, meaning there might well be a large economic impact.