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[FONT="] [h=1]Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study[/h] Dr Thalia Velho Barreto de Ara?jo, PhD
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, Prof Laura Cunha Rodrigues, PhD
, Prof Ricardo Arraes de Alencar Ximenes, PhD
, Dem?crito de Barros Miranda-Filho, PhD
, Ulisses Ramos Montarroyos, PhD
, Ana Paula Lopes de Melo, MSc
, Sandra Valongueiro, PhD
, Maria de F?tima Pessoa Milit?o de Albuquerque, PhD
, Wayner Vieira Souza, PhD
, Cynthia Braga, PhD
, Sinval Pinto Brand?o Filho, PhD
, Marli Ten?rio Cordeiro, PhD
, Enrique Vazquez, PhD
, Danielle Di Cavalcanti Souza Cruz, MD
, Cl?udio Maierovitch Pessanha Henriques, MSc
, Luciana Caroline Albuquerque Bezerra, MSc
, Priscila Mayrelle da Silva Castanha, PhD
, Rafael Dhalia, PhD
, Ernesto Torres Azevedo Marques-J?nior, PhD
, Prof Celina Maria Turchi Martelli, PhD
on behalf of investigators from the Microcephaly Epidemic Research Group the Brazilian Ministry of Health the Pan American Health Organization Instituto de Medicina Integral Professor Fernando Figueirathe State Health Department of Pernambuco? ?Investigators contributing on behalf of these organisations are listed at the end of the report
Open Access
DOI: http://dx.doi.org/10.1016/S1473-3099(16)30318-8 |
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Article Info[/h]
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[h=2]Summary[/h] Jump to SectionIntroductionMethodsResultsDiscussionSupplementary MaterialReferences
[h=3]Background[/h] The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.
[h=3]Methods[/h] We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities.
[h=3]Findings[/h] Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0?12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55?5 (95% CI 8?6?∞); OR 113?3 (95% CI 14?5?∞) for seven cases with brain abnormalities; and OR 24?7 (95% CI 2?9?∞) for four cases without brain abnormalities.
...
Surprisingly, in our study, only seven of 27 cases who had CT scan investigation had brain abnormalities. This finding contrasts with results of the few published series of children with microcephaly, in which neonates with the disorder had brain abnormalities detected by imaging.19,20, 33, 35 Whether neonates with microcephaly and normal brain imaging were excluded is not clear.20,33 Our results showed that the association between laboratory-confirmed Zika virus infection and microcephaly was present in cases who had normal findings on brain imaging, suggesting that congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities. In view of these findings, patients with microcephaly and normal brain imaging findings should not be excluded from surveillance and diagnosis of congenital Zika virus infection.
[FONT="]Our results suggest that the detection of Zika virus-specific IgM (CDC protocol) in neonates with microcephaly is an adequate method for the diagnosis of congenital Zika virus infection (although not for its exclusion). The question of flavivirus cross-reactivity, particularly for dengue,24, 33 might not be relevant in neonates, because intrauterine infection with dengue is unlikely, and maternal IgM does not cross the placenta. A recent report of Zika virus and dengue virus-specific IgM in neonates with microcephaly showed the usefulness of testing for Zika virus-specific IgM.36 We suggest that detection of Zika virus-specific IgM in serum is a useful alternative when cerebrospinal fluid collection is a challenge.
...
If the causal link between Zika virus infection during pregnancy and microcephaly is true, Zika virus is the cause of the Public Health Emergency of International Concern, and we should prepare for the epidemic of microcephaly to expand to all countries with current autochthonous Zika virus transmission and to those countries where transmission of the virus is likely to spread.38, 39[/FONT]
[FONT="]We conclude that the microcephaly epidemic is a result of congenital Zika virus infection. We recommend that the list of congenital infections normally referred to as TORCH (toxoplasmosis, others [syphilis, varicella-zoster, parvovirus B1], rubella, cytomegalovirus, and herpes) is renamed as TORCHZ, and that we prepare for a global epidemic of microcephaly and other manifestations of congenital Zika syndrome.
...
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30318-8/fulltext[/FONT]
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Press enter key to Email the author, Prof Laura Cunha Rodrigues, PhD
, Prof Ricardo Arraes de Alencar Ximenes, PhD
, Dem?crito de Barros Miranda-Filho, PhD
, Ulisses Ramos Montarroyos, PhD
, Ana Paula Lopes de Melo, MSc
, Sandra Valongueiro, PhD
, Maria de F?tima Pessoa Milit?o de Albuquerque, PhD
, Wayner Vieira Souza, PhD
, Cynthia Braga, PhD
, Sinval Pinto Brand?o Filho, PhD
, Marli Ten?rio Cordeiro, PhD
, Enrique Vazquez, PhD
, Danielle Di Cavalcanti Souza Cruz, MD
, Cl?udio Maierovitch Pessanha Henriques, MSc
, Luciana Caroline Albuquerque Bezerra, MSc
, Priscila Mayrelle da Silva Castanha, PhD
, Rafael Dhalia, PhD
, Ernesto Torres Azevedo Marques-J?nior, PhD
, Prof Celina Maria Turchi Martelli, PhD
on behalf of investigators from the Microcephaly Epidemic Research Group the Brazilian Ministry of Health the Pan American Health Organization Instituto de Medicina Integral Professor Fernando Figueirathe State Health Department of Pernambuco? ?Investigators contributing on behalf of these organisations are listed at the end of the report
Open Access
DOI: http://dx.doi.org/10.1016/S1473-3099(16)30318-8 |
[h=2]
Article Info[/h] [/FONT]
[FONT="]
[/FONT]
[FONT="]
[h=2]Summary[/h] Jump to SectionIntroductionMethodsResultsDiscussionSupplementary MaterialReferences
[h=3]Background[/h] The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy.
[h=3]Methods[/h] We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities.
[h=3]Findings[/h] Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0?12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55?5 (95% CI 8?6?∞); OR 113?3 (95% CI 14?5?∞) for seven cases with brain abnormalities; and OR 24?7 (95% CI 2?9?∞) for four cases without brain abnormalities.
...
Surprisingly, in our study, only seven of 27 cases who had CT scan investigation had brain abnormalities. This finding contrasts with results of the few published series of children with microcephaly, in which neonates with the disorder had brain abnormalities detected by imaging.19,20, 33, 35 Whether neonates with microcephaly and normal brain imaging were excluded is not clear.20,33 Our results showed that the association between laboratory-confirmed Zika virus infection and microcephaly was present in cases who had normal findings on brain imaging, suggesting that congenital Zika virus syndrome can be present in neonates with microcephaly and no radiological brain abnormalities. In view of these findings, patients with microcephaly and normal brain imaging findings should not be excluded from surveillance and diagnosis of congenital Zika virus infection.
[FONT="]Our results suggest that the detection of Zika virus-specific IgM (CDC protocol) in neonates with microcephaly is an adequate method for the diagnosis of congenital Zika virus infection (although not for its exclusion). The question of flavivirus cross-reactivity, particularly for dengue,24, 33 might not be relevant in neonates, because intrauterine infection with dengue is unlikely, and maternal IgM does not cross the placenta. A recent report of Zika virus and dengue virus-specific IgM in neonates with microcephaly showed the usefulness of testing for Zika virus-specific IgM.36 We suggest that detection of Zika virus-specific IgM in serum is a useful alternative when cerebrospinal fluid collection is a challenge.
...
If the causal link between Zika virus infection during pregnancy and microcephaly is true, Zika virus is the cause of the Public Health Emergency of International Concern, and we should prepare for the epidemic of microcephaly to expand to all countries with current autochthonous Zika virus transmission and to those countries where transmission of the virus is likely to spread.38, 39[/FONT]
[FONT="]We conclude that the microcephaly epidemic is a result of congenital Zika virus infection. We recommend that the list of congenital infections normally referred to as TORCH (toxoplasmosis, others [syphilis, varicella-zoster, parvovirus B1], rubella, cytomegalovirus, and herpes) is renamed as TORCHZ, and that we prepare for a global epidemic of microcephaly and other manifestations of congenital Zika syndrome.
...
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30318-8/fulltext[/FONT]
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