The first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis has confirmed causality, it is revealed today.
The preliminary findings are found in the analysis of 32 cases that have been studied, but the full extent of the effect will only be available when all 200 cases and 400 controls are analysed, say researchers from the UK and Brazil.
The teams examined the link between microcephaly and in utero Zika virus infection on request of the Brazilian Ministry of Health, which declared the microcephaly epidemic a Public Health Emergency of International Concern in 2016.
The preliminary findings, published in The Lancet Infectious Diseases, examined infants born with microcephaly delivered in eight public hospitals in Pernambuco State in North Eastern Brazil between 15 January and 2 May, 2016.
For each case, two controls – the first two infants born the following morning without microcephaly in one of the eight hospitals – were selected.
Researchers collected blood samples from cases and controls and samples of cerebrospinal fluid were collected from cases with microcephaly. All were tested for Zika virus and Zika virus antibodies. Blood samples were also collected from mothers and analysed for Zika and dengue virus. Infants with microcephaly had their head circumference measured and most underwent brain imaging.
They found that 24 out of 30 (80%) mothers of infants with microcephaly had Zika virus infection, compared with 39 of 61 (64%) mothers of controls.
A total of 13 of 32 cases (41%) tested positive for Zika virus infection in blood or cerebrospinal fluid samples, while none of the 62 controls tested positive for Zika virus infection in blood samples. A high proportion of mothers also tested positive for dengue and other infections such as cytomegalovirus, rubella, and toxoplasma.
However, there was no significant difference between mothers of cases and controls. Seven of the 27 cases with microcephaly who had a brain scan had brain abnormalities, which suggests that congenital Zika virus syndrome can be present in neonates with microcephaly and no brain abnormalities.
Study author Dr Thália Velho Barreto de Araújo, Federal University of Pernambuco, Recife, Brazil, said: “A high proportion of mothers of new-borns with and without microcephaly had been infected with Zika virus, reflecting the rapid spread of Zika infection in this region.
“However, when we compared laboratory confirmed Zika virus infection in new-borns with and without microcephaly, we found that about half of the cases with microcephaly had laboratory confirmed Zika virus infection, compared to none of the healthy controls.
“The presence of Zika virus antibodies in the cerebrospinal fluid indicates infection in the neural system of the neonate, but interestingly not all cases of microcephaly had brain abnormalities.”
The authors says that detecting Zika virus or antibodies in blood and cerebrospinal fluid is the only current method of testing for Zika virus in new-borns but it is not known how reliable this method is. Such limitations might explain in part why 19 (59%) of microcephaly cases were not confirmed as positive for Zika virus.
“This is the first case-control study to examine the association between Zika virus and microcephaly using molecular and serological analysis to identify Zika virus in cases and controls at the time of birth,” said Dr Velho Barreto de Araújo.
“Our findings suggests that Zika virus should be officially added to the list of congenital infections alongside toxoplasmosis, syphilis, varicella-zoster, parvovirus B19, rubella, cytomegalovirus, and herpes. However, many questions still remain to be answered including the role of previous dengue infection.”
Velho Barreto de Araújo T, Cunha Rodrigues L, Arraes de Alencar Ximenes R et al. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. Lancet Infect Dis 16 September 2016. [abstract]
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