CSF Zika IgM In 30 Microcephaly Cases In Brazil - Lancet

[niman]

Correspondence

 

Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30253-7/fulltext

 

Edited April 19, 2016 by niman

[niman]

Marli Tenorio Cordeiro

,

 Lindomar J Pena

,

 Carlos A Brito

,

 Laura H Gil

,

 Ernesto T Marques

Published Online: 18 April 2016

DOI: http://dx.doi.org/10.1016/S0140-6736(16)30253-7

 

 

 

[niman]

The epidemic of microcephaly in Brazil has been declared a Public Health Emergency of International Concern by WHO.1 The declaration states that a causal relationship between Zika virus infection during pregnancy and microcephaly is strongly suspected, although not yet scientifically proven.1 The hesitancy to accept causation in the presence of much epidemiological circumstantial evidence is due to the paucity of laboratory confirmation of Zika virus in affected neonates. Here, we report the serological confirmation of Zika virus infection in the CNS of 30 neonates with microcephaly.

[niman]

The epidemic of microcephaly in Brazil has been declared a Public Health Emergency of International Concern by WHO.1 The declaration states that a causal relationship between Zika virus infection during pregnancy and microcephaly is strongly suspected, although not yet scientifically proven.1 The hesitancy to accept causation in the presence of much epidemiological circumstantial evidence is due to the paucity of laboratory confirmation of Zika virus in affected neonates. Here, we report the serological confirmation of Zika virus infection in the CNS of 30 neonates with microcephaly.

From Oct 21 to Oct 30, 2015, we collected blood and cerebrospinal fluid (CSF) samples from 31 neonates with microcephaly in the state of Pernambuco, Brazil, most of whom were born between Sept 12 and Oct 27, 2015, in public maternity hospitals. The samples were collected on average 9 days after birth (range 1–40 days; 20 of 31 neonates in the first week after birth). The neonates were kept in hospital while results from brain imaging and laboratory tests were awaited. Serum and CSF samples were tested by RT-PCR or real-time RT-PCR, or both, for Zika, dengue, and chikungunya genomes. Viral RNA was not detected, probably because infections in the mother occurred at least 6 months before giving birth. The 31 samples of CSF and serum were tested for IgM specific for Zika virus using capture ELISA based on the US Centers for Disease Control and Prevention (CDC) Emergency Use Authorization protocol with reagents from Robert Lanciotti (CDC Fort Collins, CO, USA). Simultaneous tests were done for dengue virus to investigate cross-reaction between these two flaviviruses. The ratio of patient optical density to negative control value (P/N) was calculated (table).2

[niman]

Table 

IgM against Zika virus and dengue virus in the serum and CSF of neonates with microcephaly, Pernambuco State, Brazil, 2015, by age (days) at testing

ELISA values are patient optical densities divided by negative control densities (P/N); values less than 2 were considered negative, 2–3 equivocal, and more than 3 positive. CSF=cerebrospinal fluid.

[niman]

Zika-specific IgM was detected in 30 (97%) of 31 CSF samples and in 28 (90%) of 31 serum samples. One CSF sample tested negative. Monotypic response to Zika virus in the CSF was confirmed by plaque reduction neutralisation test. Since IgM does not cross either the placenta barrier or the blood–brain barrier, the presence of IgM in the CSF indicates that the neonate had the infection in the CNS.3, 4 The finding of Zika-specific IgM in the CSF of those 30 of 31 neonates with brain abnormalities indicates that they had a congenital infection with Zika virus. We believe that this is very strong evidence that the microcephaly was a consequence of Zika virus infection.

We declare no competing interests. We thank Laura C Rodrigues and the Microcephaly Epidemic Research Group for their support.

[niman]

References

1. WHO. WHO Director-General summarizes the outcome of the Emergency Committee regarding clusters of microcephaly and Guillain-Barré syndrome.http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/; Feb 1, 2016. ((accessed Feb 12, 2016).)
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2. Lanciotti, RS, Kosoy, OL, Janeen, J et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008; 14: 1232
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     • Tunkel, AR, Glaser, CA, Bloch, KC et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008; 47: 303–327
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