The Zika virus has been the primary suspect in the large increase in incidence of microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some of the cases is strong, its role as the primary cause of the large number of cases in Brazil has not been confirmed. Recently, the disparity between the incidences in different geographic locations has led to questions about the virus’s role. Here we consider the alternative possibility that the use of the insecticide pyriproxyfen for control of mosquito populations in Brazilian drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog which has been shown to correspond in mammals to a number of fat soluble regulatory molecules including retinoic acid, a metabolite of vitamin A, with which it has cross-reactivity and whose application during development has been shown to cause microcephaly. Methoprene, another juvenile hormone analog that was approved as an insecticide based upon tests performed in the 1970s, has metabolites that bind to the mammalian retinoid X receptor, and has been shown to cause developmental disorders in mammals. Isotretinoin is another example of a retinoid causing microcephaly in human babies via maternal exposure and activation of the retinoid X receptor in developing fetuses. Moreover, tests of pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence for developmental toxicity, actually found some evidence for such an effect, including low brain mass and arhinencephaly—incomplete formation of the anterior cerebral hemispheres—in exposed rat pups. Finally, the pyriproxyfen use in Brazil is unprecedented—it has never before been applied to a water supply on such a scale. Claims that it is not being used in Recife, the epicenter of microcephaly cases, do not distinguish the metropolitan area of Recife, where it is widely used, and the municipality, and have not been adequately confirmed. Given this combination of information about molecular mechanisms and toxicological evidence, we strongly recommend that the use of pyriproxyfen in Brazil be suspended until the potential causal link to microcephaly is investigated further.
Introduction: The 2014 Ebola outbreak in West Africa raised many questions about the control of infectious disease in an increasingly connected global society. Limited availability of contact information made contact tracing diffcult or impractical in combating the outbreak.
Methods: We consider the development of multi-scale public health strategies that act on individual and community levels. We simulate policies for community-level response aimed at early screening all members of a community, as well as travel restrictions to prevent inter-community transmission.
Results: Our analysis shows the policies to be effective even at a relatively low level of compliance and for a variety of local and long range contact transmission networks. In our simulations, 40% of individuals conforming to these policies is enough to stop the outbreak. Simulations with a 50% compliance rate are consistent with the case counts in Liberia during the period of rapid decline after mid September, 2014. We also find the travel restriction to be effective at reducing the risks associated with compliance substantially below the 40% level, shortening the outbreak and enabling efforts to be focused on affected areas.
Discussion: Our results suggest that the multi-scale approach can be used to further evolve public health strategy for defeating emerging epidemics.