by Alex Perkins
I’m writing to highlight some work that lab postdoc Amir Siraj just published in a paper in BMJ Global Health about the potential risk of Zika virus (ZIKV) infection in Asia. In this paper, Amir applied methods to 15 countries in Asia that we originally developed in another paper to assess the population at risk of ZIKV infection in the Americas early in the epidemic there.
Some of the key findings from this new work include the following.
There are a lot of people in Asia, and a lot of them would be at risk of Zika virus infection IF they were all susceptible and a widespread epidemic occurred there. Ever since we first made our projections for the Americas, we have been interested in making similar projections for Asia. Both regions are inhabited by lots of people and are hotbeds of transmission for dengue virus, which is similar in many ways to ZIKV. For the Americas, our projections indicated that as many as 93 million people could become infected before the epidemic would burn out through the buildup of herd immunity. For Asia, Amir’s projections indicate that as many as 785 million would become infected, approximately eight times the equivalent figure for the Americas! On the one hand, the fact that this number is larger for Asia than the Americas is not surprising given how much larger the population is in the Asian countries we considered. On the other hand, it turns out that this projection is also quite a bit higher in Asia on a per capita basis than it is in the Americas. This suggests that, were ZIKV or some other ZIKV-like arbovirus to ever cause a widespread epidemic in Asia, it could be larger in scale than what we recently saw with ZIKV in the Americas.
Pre-existing immunity is clearly a dominant mitigating factor in the risk that Zika virus poses to Asia, but the interaction between pre-existing immunity and other factors is complicated. Although aggregate projections of millions of people at a regional scale are simplest to think about, we have always felt that the real value in our approach is in the projections it makes at a local level. After all, our methods do not account for spatial processes and are actually projections of epidemic size conditional on there being an epidemic in the first place. This is important to keep in mind because, while a continent-wide Zika epidemic is very unlikely to ever happen in Asia due to substantial pre-existing immunity (reviewed in this paper), local epidemics have happened in Asia and will continue to happen there over time. The situation we imagine in Asia is that, at some point in the past, many areas probably experienced a Zika epidemic that attained something along the lines of the size we projected, but since then the proportion immune to ZIKV infection has been declining as people alive during previous epidemics have died and others have been born. In Amir’s new paper, he applies some theoretical ideas to argue that a given level of pre-existing immunity should have a disproportionately large influence on reducing epidemic size in populations with relatively low transmission potential. Unfortunately, that means that populations with the highest transmission potential could still be relatively vulnerable to future epidemics, despite the presence of pre-existing immunity.
Now that there are a few empirical estimates of epidemic size from the Americas, we can tell that it looks like our original projections are holding up fairly well. There is still relatively little information about how many people have been infected by ZIKV in the epidemic in the Americas, but four local estimates have been published that can be compared with our projections. One appears spot on, two are within the range of uncertainty, another was quite a bit higher than our projection, and on average our projections tended to be a little lower than empirical estimates. We will be very interested to compare our projections to additional empirical estimates as they are reported, but for the time being we feel that this result reinforces the value of our projections for the Americas in the absence of more comprehensive data.
In addition to summarizing the key results, there are a couple of other important things to note.
While these results do help advance understanding of the population at risk of ZIKV infection in Asia to some degree, they should not be viewed as predictions of what we think will actually happen. For one thing, the Zika epidemic in the Americas and elsewhere has slowed down considerably over the last year. In fact, the bigger challenge at this stage is figuring out which areas will have any ZIKV infections so that vaccine trials can take place. In other work recently posted as a preprint on bioRxiv, we are trying to figure that out. In addition, the World Health Organization declared an end to the Zika Public Health Emergency of International Concern several months ago. Our feeling is that they were right to do so given how the immediacy of the situation has diminished but the long-term concern has solidified, especially given how little we know about what actually happened over the last few years in the Americas (more in this paper on that).
If this new paper does not reflect what we think will actually happen, then what good is it? Just because we do not think that these projections indicate what will actually happen does not mean that they cannot be useful. One way that these projections can be applied is to facilitate more realistic projections for a specific location following a serological survey. Another is to identify areas with the highest risk of a large epidemic, which could then be prioritized as targets for surveillance efforts or serological studies. Yet another is to provide early projections for this region in the event of a newly emerging disease with characteristics similar to Zika. This study alone will not answer all of the many questions about Zika in Asia, but nor will most other studies if considered in isolation. In the spirit of facilitating these and other applications that we cannot foresee, the code underlying this work and the detailed projections themselves are freely downloadable at http://github.com/asiraj-nd/zika-asia.