Via NEJM, a remarkable letter: Zika Virus Infection and Associated Neurologic Disorders in Brazil. Excerpt and then a comment:
The spread of ZIKV in Brazil has been associated with an increase in the incidence of neurologic disorders, most visibly in cases reported as GBS[Guillain-Barré syndrome] and microcephaly. Weekly reports of cases from hospitals reveal that the incidence of GBS was markedly higher in the northeast region in 2015 and 2016 and in other areas of Brazil in 2016 than in the years before the ZIKV epidemic (2010 to 2014) (Figure 1B, and Section 3 in the Supplementary Appendix).
The rise and fall of suspected cases of ZIKV infection and GBS were approximately synchronous in 2015, although a comparison of the two case series suggests that the incidence of ZIKV infection was underreported in the northeast region early in 2015 (Figure 1B). In Pernambuco state, some of the cases of ZIKV infection were probably misclassified (mainly as dengue) in clinics in 2015, and such misclassification could have been widespread.
The incidence of microcephaly peaked in late November 2015 (week 47), an average of 23 weeks after the start of the epidemics of ZIKV infection and GBS (Figure 1B). If there was a delay of 3 weeks between the exposure of patients to ZIKV and the development of GBS (i.e., an incubation period plus a typical reporting delay), infections leading to microcephaly would have occurred on average 12 weeks after conception (i.e., with about half the cases occurring during the first trimester and half later in pregnancy) (Section 4 in the Supplementary Appendix).
In view of the apparent resurgence of ZIKV infection and GBS early in 2016, we anticipated a further increase in cases of microcephaly later in the year. But such a resurgence did not happen (Figure 1B), for at least three possible reasons.
The first possibility is that in 2016, infections that were attributed to ZIKV and that were linked to an increase in the incidence of GBS were caused by another arbovirus that is also transmitted by Aedes aegypti mosquitoes, since by then there was herd immunity against ZIKV infection after widespread infection in 2015.
Dengue virus has been identified throughout the Americas (Section 5 in the Supplementary Appendix) but does not appear to be a major cause of GBS. Chikungunya virus was introduced into Brazil in 2014 and caused successively larger epidemics in the northeast region in 2015 and 2016. Chikungunya is a cause of GBS as well, and some chikungunya infections were evidently misclassified as ZIKV infection in Pernambuco in 2016 (Brito C: personal communication). Chikungunya has not been identified as a cause of microcephaly.
A second possibility is that ZIKV infection during pregnancy is a necessary but not a sufficient condition for the development of microcephaly in newborn infants — in other words, the presence of some other unknown cofactor that is not essential for GBS is required.
A third possibility is that fear of the adverse consequences of ZIKV infection led to fewer conceptions or a greater number of pregnancy terminations in 2016. Routinely collected data are not yet complete enough to determine whether birth rates fell or abortion rates increased in 2016 (Section 6 in the Supplementary Appendix). However, since any changes in the number of live births would be small, this hypothesis cannot be the principal reason why few cases of microcephaly were reported in the northeast region in 2016.
For an excellent discussion of this study, see Helen Branswell's new article in STAT.