Monkeypox: Is it worth worrying about?

Linchuan Zhang asked and paid me to write this up.

Summary

Basically no. The disease remains highly confined to the gay community. The chances of it becoming a seriously threatening pandemic like Covid-19 are low.

If you are a sexually active gay man , it is likely wise to limit your number of sexual partners as you are at a large risk.

The largest and hardest to quantify threat is a mutation. Additional concern here due to APOBEC3.

Has Monkeypox growth gone linear?

We are just shy of 3 months since tracking of Monkeypox began. As of Aug 5th, there are ~800 cases per day worldwide. At this point in Covid, there were ~82000 per day worldwide. In the US, there are ~300 cases per day. For covid, there was ~30000 per day. Covid was ~100x further along. Now, this doesn’t prove that Monkeypox isn’t undergoing exponential growth but it does suggest that it isn’t as fast. Furthermore, some look into the charts at Our World in Data seems to show that growth isn’t accelerating fast worldwide.

According to this article on the 29th, monkeypox was growing “exponentially” at 5000 cumulative cases in the US, and predicted that that number would grow every week to 10000 (by August 5th). The current number is ~7000. Worldwide, the 7-day average has remained between 800-900 for around 10 days. Due to the number of unreported cases, it of course could be growing exponentially but the data doesn’t seem to suggest this.

It is still too early to call but it’s likely that this strain is no longer growing exponentially.

Real vs Confirmed Cases

A big lesson from Covid was not to treat confirmed cases as the only cases. Due to the fact that monkeypox looks different on everyone and the typical case doesn’t look like pictures on the internet (monkeypox usually presents simply as some discoloration in the area of infection, often near a genital area), my 90% confidence interval is that there is an additional 100-800% of cases currently unreported. This number is particularly high due to the usual symptoms being unlike pictures on the internet and due to the fact that in Africa, where I suspect there may be many unreported cases due to infrastructure and a higher stigma surrounding homosexuality.

Gay Community

Depending on where you look 95%+ of cases seem to be transmitted sexually between gay/​bisexual men. This study reports 98% of cases being gay/​bisexual men. Nearly all cases are contracted through sexual activity among men having sex with men. I would guess that due to some stigma surrounding gay sex in certain countries, it’s possible that all but a few cases have been spread through sexual activity between men. As an aside, if you are someone who has sex with other men, it would probably be a good personal decision to limit your number of partners. While Monkeypox spread is rather limited to the gay community thus far, it is certainly not saturated in the gay community, particularly among those who are sexually active. As a quick BOTEC, New York has the most cases in the US. There are about 20M people in New York, 50% are men and about 5% are gay/​bi which is 500,000 men. Maybe 40% are sexually active so we are looking at 200,000 gay men in New York state. About 2000 men in New York have a confirmed case of Monkeypox.

Probability of Escaping the MSM Community

If the disease spreads far, at some point the disease would escape the gay community since it is technically spread through skin-to-skin contact, not an STI. Many other skin-to-skin activities exist (martial arts, etc.) and it is likely possible to spread through surfaces (towels, sheets, etc.). At 10,000 cases in the US, it is likely to stay within the gay community. At 100,000 cases, I expect an over 50% chance that it escapes the gay community.

Mutation Rate

I’ll preface this section by stating I have little background in genetics/​biology at the necessary level.

It seems that the current strain is linked to a high number of ~50 mutations from cases isolated in 2018/​2019. This is a large number of mutations, much larger than expected for Orthopoxyviruses (where 1-2 mutations per year are expected). This is about an order of magnitude more than one would expect for this virus. For example, there are 46 single nucleotide polymorphisms (SNPs) that separate the current strain from a 2018 strain. Among these 46 SNPs, what is concerning is that there is a strong mutational bias with 26 being GA>AA and 15 being TC>TT. This and some further evidence suggests that apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) enzymes have a role in MPXV (monkeypox virus) evolution. Further evidence of APOBEC3 is seen by the fact that MPXV is A: T rich.

This is the most worrying aspect of Monkeypox, that APOBEC3 enzymes are present and causing non-random mutations. To get a better idea of how scary this is, I’d want a better idea of how common these mutation-accelerating enzymes are. Preliminary research suggests they are uncommon but not rare. Current MPXV doesn’t seem that serious and spread is slow, and mortality is slow but there could be a significant mutation risk. See this Nature article to read more about where I got a lot of this information.

Virulence

Monkeypox is typically not very virulent. Mainly flu-like symptoms and a rash. I can’t find any QALY estimate but using the one for symptomatic HIV of ~0.82 seems reasonable. There have only been 9 deaths among those with confirmed cases out of ~30000 infections which is a death rate of 0.03%. For comparison, Covid has a death rate of ~1% of confirmed cases

Cost-effective Intervention?

Very rough calculation.

Assuming that mutation risk gives a 5% chance that monkeypox could spread as far as covid, to ~1B cases, given the death rate of 0.03%, monkeypox could kill around 300,000 people. Given a 5% chance of it getting this far on its own, we are looking at a worst-case scenario of averting the deaths of around 15,000 people. For an intervention to be cost-effective, it would need to cost on the order of $50M to eliminate the chance of spreading as far as Covid. At this rate, simple solutions like paying gay men to abstain from sex becomes impractical.

Conclusion

Monkeypox is concerning and should be monitored but EAs shouldn’t yet spend significant time worrying about it or diverting their attention from typical cause areas.