Tuesday, December 12, 2017

Lancet: Case-Control Study Confirms Association Between Zika and Microcephaly


Despite an abundance of anecdotal data and the results of preliminary case-control studies linking maternal Zika infection to the sharp increase in microcephalic births in Brazil in 2015-2016, there have been competing theories that vaccines, the release of GM mosquitoes  or the use of larvicides in drinking water, may have been responsible (see WHO: Dispelling Rumors Surrounding The Zika Virus & Microcephaly).
In August of 2016, the Lancet published Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study by Thalia Velho Barreto de Araújo, PhD et al. which found that the `data suggest that the microcephaly epidemic is a result of congenital Zika virus infection.'
As cases of microcephaly began to be reported following Zika outbreaks outside of Brazil, concerns over the role of GM mosquitoes and exposure to the larvacide pyriproxyfen have lessened somewhat.

Yesterday The Lancet published a follow-up final report on the case control study mentioned above, which presents evidence of an `absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines', and confirms maternal Zika virus infection as the cause of increased microcephaly in Brazil.
Association between microcephaly, Zika virus infection, and other risk factors in Brazil: final report of a case-control study

Thalia Velho Barreto de Araújo, PhD, Prof Ricardo Arraes de Alencar Ximenes, PhD, Demócrito de Barros Miranda-Filho, PhD, Wayner Vieira Souza, PhD, Ulisses Ramos Montarroyos, PhD, Ana Paula Lopes de Melo, MSc, Sandra Valongueiro, PhD, Maria de Fátima Pessoa Militão de Albuquerque, PhD, Cynthia Braga, PhD, Sinval Pinto Brandão Filho, PhD, Marli Tenório Cordeiro, PhD, Enrique Vazquez, PhD, Danielle di Cavalcanti Souza Cruz, MD, Claudio Maierovitch Pessanha Henriques, MSc, Luciana Caroline Albuquerque Bezerra, MSc, Priscila Mayrelle da Silva Castanha, PhD, Rafael Dhalia, PhD, Ernesto Torres Azevedo Marques-Júnior, PhD, Prof Celina Maria Turchi Martelli, PhD
, Prof Laura Cunha Rodrigues, PhD 

Published: 11 December 2017

DOI: http://dx.doi.org/10.1016/S1473-3099(17)30727-2 |



A Zika virus epidemic emerged in northeast Brazil in 2015 and was followed by a striking increase in congenital microcephaly cases, triggering a declaration of an international public health emergency. This is the final report of the first case-control study evaluating the potential causes of microcephaly: congenital Zika virus infection, vaccines, and larvicides. The published preliminary report suggested a strong association between microcephaly and congenital Zika virus infection.


We did a case-control study in eight public maternity hospitals in Recife, Brazil. Cases were neonates born with microcephaly, defined as a head circumference of 2 SD below the mean. Two controls without microcephaly were matched to each case by expected date of delivery and area of residence. We tested the serum of cases and controls and the CSF of cases for detection of Zika virus genomes with quantitative RT-PCR and for detection of IgM antibodies with capture-IgM ELISA. We also tested maternal serum with plaque reduction neutralisation assays for Zika and dengue viruses. We estimated matched crude and adjusted odds ratios with exact conditional logistic regression to determine the association between microcephaly and Zika virus infection.


We screened neonates born between Jan 15 and Nov 30, 2016, and prospectively recruited 91 cases and 173 controls. In 32 (35%) cases, congenital Zika virus infection was confirmed by laboratory tests and no controls had confirmed Zika virus infections. 69 (83%) of 83 cases with known birthweight were small for gestational age, compared with eight (5%) of 173 controls. The overall matched odds ratio was 73·1 (95% CI 13·0–∞) for microcephaly and Zika virus infection after adjustments. Neither vaccination during pregnancy or use of the larvicide pyriproxyfen was associated with microcephaly. Results of laboratory tests for Zika virus and brain imaging results were available for 79 (87%) cases; within these cases, ten were positive for Zika virus and had cerebral abnormalities, 13 were positive for Zika infection but had no cerebral abnormalities, and 11 were negative for Zika virus but had cerebral abnormalities.


The association between microcephaly and congenital Zika virus infection was confirmed. We provide evidence of the absence of an effect of other potential factors, such as exposure to pyriproxyfen or vaccines (tetanus, diphtheria, and acellular pertussis, measles and rubella, or measles, mumps, and rubella) during pregnancy, confirming the findings of an ecological study of pyriproxyfen in Pernambuco and previous studies on the safety of Tdap vaccine administration during pregnancy.


Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations.

Some earlier studies also linking Zika infection to microcephaly and other neurological and developmental disorders includes:

MMWR: Review Of 13 Infants Born with Congenital Zika Virus Infection But Without Microcephaly
MMWR: Hearing Loss In Infants With Zika Related Microcephaly

BMJ: Congenital Zika Syndrome with Arthrogryposis

The Lancet: Two Congenital Zika Virus Studies

NEJM: Zika Virus And The Risk Of Microcephaly 
Brazil: Expanded Spectrum of Congenital Ocular Findings in Microcephaly

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