Thread by @adamjkucharski

Every year, we run an MSc session on the dynamics of monkeypox transmission, and our team have worked a lot on contact tracing & transmission chain analysis for a range of infections. So a few thoughts on current MPX outbreak… 1/

When MPX was first reported in the 1970s, it spread against a background of cross-protective immunity from smallpox vaccination, so the reproduction number R was initially very small (pubmed.ncbi.nlm.nih.gov/6249508/ & pubmed.ncbi.nlm.nih.gov/2850277/)… 2/

But remember R = R0 x S, where R0 is transmissibility in fully susceptible population and S is proportion susceptible. So R has increased in the years since discontinuation of smallpox vaccination and hence increase in S (pnas.org/doi/10.1073/pn…). 3/

Even if R is below 1 in mostly susceptible population, can still see large 'stuttering' outbreaks occasionally. So important to disentangle effects of:

A) chance events
B) change in virus characteristics (e.g. via evolution)
C) change in population in which virus spreading.
4/

For both Ebola in 2014 and Zika in 2016 we saw viruses that had circulated for decades finding new niches and exhibiting novel features (e.g. larger urban outbreaks, new transmission routes). 5/

Estimation of transmissibility can be further hindered by potential for superspreading, which may skew early estimates, and fact that the group at risk of initial spillover is often not same as group most at risk of human-to-human transmission (e.g. journals.plos.org/ploscompbiol/a…). 6/

So what about potential for rapid outbreak control? It's useful to refer to this classic paper by @ChristoPhraser @SRileyIDD et al: pnas.org/doi/10.1073/pn…. Adapted version of key figure below - based on historical patterns we'd expect MPX to sit at 'easier to control' end. 7/

In particular, historical evidence of distinctive symptoms, long-ish serial interval (i.e. delay between symptoms appearing in case & people they infect), and transmission mostly after symptoms suggest isolation + contact tracing can be very effective for MPX. 8/

In which case, the main variable influencing control would be the % of contacts of cases that can be traced. And if targeted vaccination planned (e.g. in a ring strategy like smallpox eradication), effectiveness of this approach will also depend on % contacts traced... 9/

For Ebola, we found narrow window where ring vaccination would give large extra benefit - if contact tracing working well, vaccination would have limited extra impact; if not working, could get continued transmission among missed contacts. More: ncbi.nlm.nih.gov/pmc/articles/P… 10/

In discussions of vaccination as measure for MPX, it's also worth referring to this piece from 2003 by @bugwonk on smallpox planning (using earlier generation vaccines), and the importance of considering potential for containment via other means: pnas.org/doi/abs/10.107…. 11/

Also, despite a longer MPX incubation period being useful for contact tracing, can hinder symptom screening (e.g. at travel hubs), because cases less likely to be symptomatic at arrival. More in analysis with @KatieMG and others from a few years ago: elifesciences.org/articles/05564. 12/

Incoming data will soon help firm up estimates of current MPX incubation period, per-contact transmission risk and symptom profile relative to infectiousness - which will help distinguish reasons for unusual pattern of cases, and implications for containment. 13/13