Answer by Tirumalai Kamala:
- Zika was historically rarely associated with human disease outbreaks, with only one reported cluster of 7 human cases in Indonesia in 1981 (1).
- Human Zika virus was sporadically isolated in East and West Africa in the absence of epidemics (2, 3,).
- Association between Zika and congenital microcephaly was first observed only in Brazil in October 2015, shortly after the country first confirmed Zika virus cases in May 2015.
- Subsequently,also reported a similar link ( ).
- Right now, there's a spatio-temporal, not causation, link between Zika and microcephaly cases in Brazil (see figures below from) and in French Polynesia.According to a(PAHO) Epidemiological Alert issued on 1 Dec, 2015 ( ), 'As of 30 November 2015, 1,248 cases (99.7/100,000 live births) of microcephaly, including 7 deaths, have been reported in 14 states of Brazil, which are under investigation (3). In 2000, the prevalence of microcephaly in newborns in Brazil was 5.5 cases/ 100,000 live births and in 2010 it was 5.7 cases / 100,000 live births. This data demonstrates a twentyfold increase in comparison to the rate observed in previous years. The data was obtained from the Live Births Information System (Sinac, per its acronym in Portuguese) which captures epidemiological data related to pregnancy, births and congenital malformation, in addition to the socio-demography of the mothers.' (According to PAHO, Sinac is a universal system, which captures information on births in the entire national territory of Brazil. Available at: ).Zika virus outbreaks first began to be reported in Polynesia in 2007.
- After that original 1981 report (1),in the Federated States of (estimated population ~11000) experienced a Zika virus outbreak in 2007 ( , ), where for the first time using an originally designed PCR to detect it, Zika virus RNA was found in acute phase disease serum samples. A much smaller population, this outbreak reported no spike with congenital microcephaly, an easily identifiable condition. Why? Was it missed or was it absent? Or is it linked to frequency, i.e., more infected people, higher the chances of congenital microcephaly? Not yet known.
- Compared to the 2007 Micronesian outbreak, a much higher number of people were infected with Zika virus during a 2013 outbreak in, where by week 51, there were a total of 5895 suspected Zika virus cases ( ).
- Recently, French Polynesia also reported a spatio-temporal link between Zika and congenital microcephaly, 'On 24 November 2015, the health authorities of French Polynesia reported an unusual increase of at least 17 cases of central nervous system malformations in foetuses and infants during 2014–2015, coinciding with the Zika outbreaks on the French Polynesian islands. These malformations consisted of 12 foetal cerebral malformations or polymalformative syndromes, including brain lesions, and five infants reported with brainstem dysfunction and absence of swallowing. None of the pregnant women described clinical signs of ZIKV infection, but the four tested were found positive by IgG serology assays for flavivirus, suggesting a possible asymptomatic ZIKV infection. Further serological investigations are ongoing. Based on the temporal correlation of these cases with the Zika epidemic, the health authorities of French Polynesia hypothesise that ZIKV infection may be associated with these abnormalities if mothers are infected during the first or second trimester of pregnancy' (). Why in 2015 but not in 2013? What's different? Are 2015 Brazilian and French Polynesian Zika virus isolates different from the 2007 Yap State outbreak, different as in greater trans-placental transfer? Not yet known.Prior to the Brazilian Ministry of Health announcement (), there's no report in the scientific literature suggesting such a link, only serologic evidence and sporadic virus isolation from humans and mosquitoes in Africa and Asia (see figure below from ) while the 2007 Micronesian Yap State Zika virus outbreak was the first time it was detected outside Africa and Asia.In order to conclude that Zika and only Zika caused these cases of congenital microcephaly, investigations need to carefully rule out
- Other infections, particularly
- Genetic risk factors
- Maternal exposure to toxins/chemicals
- Maternal consumption of potentially teratogenic drugsthough the last three are unlikely to explain the sudden spike in 2015.The Brazilian Ministry of Health reported the presence of Zika virus RNA in amniotic fluid samples of two pregnant women with fetal microcephaly in Paraiba state in 2015 (). This suggests trans-placental Zika virus transfer, bringing us closer to a causal link.Meantime, as of Dec 2015, Colombia reported averaging >1000 Zika virus cases per week for over a month (). This may unfortunately mean that 2016 births in Colombia will show if Zika and congenital microcephaly link is generalizable ( ). A causal link would be scary since this is a mosquito-borne disease, unlike most vertically transmitted infections, i.e., chances of getting infected are not in the pregnant mother's full control.Bibliography1. Olson, J. G., and T. G. Ksiazek. "Zika virus, a cause of fever in Central Java, Indonesia." Transactions of the Royal Society of Tropical Medicine and Hygiene 75.3 (1981): 389-393.2. Simpson, D. I. H. "Zika virus infection in man." Transactions of the Royal Society of Tropical Medicine and Hygiene 58.4 (1964): 339-348.3. Moore, D. áL, et al. "Arthropod-borne viral infections of man in Nigeria, 1964-1970." Annals of tropical medicine and parasitology 69.1 (1975): 49-64.4. Fagbami, A. H. "Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State." Journal of Hygiene 83.02 (1979): 213-219.5. Microcephaly in Brazil potentially linked to the Zika virus epidemic. European Centre For Disease Prevention And Control, 24 Nov, 2015.6. PAHO Epidemiological Alert, 1 Dec, 2015.7. Lanciotti, Robert S., et al. "Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007." Emerging infectious diseases 14.8 (2008): 1232.8. Duffy, Mark R., et al. "Zika virus outbreak on Yap Island, federated states of Micronesia." New England Journal of Medicine 360.24 (2009): 2536-2543.9. Cao-Lormeau, Van-Mai, et al. "Zika virus, French polynesia, South pacific, 2013." Emerging infectious diseases 20.6 (2014): 1085.10. PAHO Epidemiological Alert, 17 Nov, 2015.11. Hayes, Edward B. "Zika virus outside Africa." Emerging infectious diseases 15.9 (2009): 1347.12. Ministério da Saúde (Brazil). Microcefalia – Ministério da Saúde divulga boletim epidemiológico [Internet]. Brasília: Ministério da Saúde; 2015 [updated 2015 Nov 17; cited 2015 Nov 17]. Available from:13. Oubreak News Today, Robert Herriman, Dec 19, 2015.14. Oubreak News Today, Robert Herriman, Dec 20, 2015.Thanks for the A2A, Christian Dechery.