Evidence of Zika Virus Infection in Brain and Placental Tissues In Brazil - MMWR

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Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses — Brazil, 2015

Early Release / February 10, 2016 / 65(06);1–2

http://www.cdc.gov/mmwr/volumes/65/wr/mm6506e1er.htm?s_cid=mm6506e1er_e

 

Edited February 10, 2016 by niman

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Roosecelis Brasil Martines, MD, PhD1; Julu Bhatnagar, PhD1; M. Kelly Keating, DVM1; Luciana Silva-Flannery, PhD1; Atis Muehlenbachs, MD, PhD1; Joy Gary, DVM, PhD1; Cynthia Goldsmith, MS1; Gillian Hale, MD1; Jana Ritter, DVM1; Dominique Rollin, MD1; Wun-Ju Shieh, MD, PhD1; Kleber G. Luz, MD, PhD2; Ana Maria de Oliveira Ramos, MD, PhD3; Helaine Pompeia Freire Davi, MD, PhD4; Wanderson Kleber de Oliveria, MD5; Robert Lanciotti, PhD6; Amy Lambert, PhD6; Sherif Zaki, MD, PhD1 (View author affiliations)

 

Corresponding author: Roosecelis Brasil Martines, [email protected], 404-639-3886.

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1Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), CDC;2Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 3Department of Pathology, Federal University of Rio Grande do Norte, Natal, Brazil;4Service for Ascertaining Death in the State of Rio Grande do Norte (SVO/RN), Natal/RN, Brazil; 5Ministry of Health, Brazil; 6Arboviral Diseases Branch, Division of Vector-Borne Diseases, NCEZID, CDC.

 

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Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).

Since November 2015, CDC has been developing assays for Zika virus testing in formalin-fixed, paraffin-embedded (FFPE) tissue samples. In December 2015, FFPE tissues samples from two newborns (born at 36 and 38 weeks gestation) with microcephaly who died within 20 hours of birth and two miscarriages (fetal losses at 11 and 13 weeks) were submitted to CDC, from the state of Rio Grande do Norte in Brazil, for histopathologic evaluation and laboratory testing for suspected Zika virus infection. All four mothers had clinical signs of Zika virus infection, including fever and rash, during the first trimester of pregnancy, but did not have clinical signs of active infection at the time of delivery or miscarriage. The mothers were not tested for antibodies to Zika virus. Samples included brain and other autopsy tissues from the two newborns, a placenta from one of the newborns, and products of conception from the two miscarriages.

FFPE tissues were tested by Zika virus reverse transcription-polymerase chain reaction (RT-PCR) targeting the nonstructural protein 5 and envelope genes using general methods for RT-PCR (4), and by immunohistochemistry using a mouse polyclonal anti-Zika virus antibody, using methods previously described (5). Specific specimens from all four cases were positive by RT-PCR, and sequence analysis provided further evidence of Zika virus infection, revealing highest identities with Zika virus strains isolated from Brazil during 2015. In the newborns, only brain tissue was positive by RT-PCR assays. Specimens from two of the four cases were positive by immunohistochemistry: viral antigen was noted in mononuclear cells (presumed to be glial cells and neurons within the brain) of one newborn, and within the chorionic villi from one of the miscarriages. Testing for dengue virus was negative by RT-PCR in specimens from all cases.

For both newborns, significant histopathologic changes were limited to the brain, and included parenchymal calcification, microglial nodules, gliosis, and cell degeneration and necrosis. Other autopsy tissues and placenta had no significant findings. Tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV were negative in the two mothers who experienced miscarriages. Placental tissue from one miscarriage showed heterogeneous chorionic villi with calcification, fibrosis, perivillous fibrin deposition, and patchy intervillositis and focal villitis, while tissue from the other miscarriage had sparsely sampled normal-appearing chorionic villi.

This report describes evidence of a link between Zika virus infection and microcephaly and fetal demise through detection of viral RNA and antigens in brain tissues from infants with microcephaly and placental tissues from early miscarriages. Histopathologic findings indicate the presence of Zika virus in fetal tissues. These findings also suggest brain and early gestational placental tissue might be the preferred tissues for postmortem viral diagnosis. Nonfrozen, formalin-fixed specimens or FFPE blocks are the preferred sample type for histopathologic evaluation and immunohistochemistry, and RT-PCR can be performed on either fresh frozen or formalin-fixed specimens. To better understand the pathogenesis of Zika virus infection and associated congenital anomalies and fetal death, it is necessary to evaluate autopsy and placental tissues from additional cases, and to determine the effect of gestational age during maternal illness on fetal outcomes.

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References

1. Zanluca C, de Melo VC, Mosimann ALP, Dos Santos GI, Dos Santos CN, Luz K. First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz 2015;110:569–72.  CrossRef PubMed
2. Victoria CG, Schuler-Faccini L, Matijasevich A, Ribeiro E, Pessoa A, Barros FC. Microcephaly in Brazil: how to interpret reported numbers? Lancet 2016. Epub February 5, 2016.  CrossRef
3. Schuler-Faccini L, Ribeiro EM, Feitosa IML, et al. ; Brazilian Medical Genetics Society–Zika Embryopathy Task Force. Possible association between Zika virus infection and microcephaly—Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:59–62.  CrossRef PubMed
4. Bhatnagar J, Blau DM, Shieh WJ, et al. Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications. Am J Trop Med Hyg 2012;86:335–40.  CrossRef PubMed
5. Shieh WJ, Blau DM, Denison AM, et al. 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol 2010;177:166–75.  CrossRefPubMed

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* Updated information about local transmission of Zika virus is available online (http://www.cdc.gov/zika/geo/index.html).

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Zika virus: 'Strongest evidence yet' of effect on babies

• 22 minutes ago
•  
• From the sectionLatin America & Caribbean

Image copyrightAFP

Image captionAuthorities in some countries affected by the virus have advised women to delay pregnancy

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One of the US's most senior public health officials has revealed the "strongest evidence to date" of the effect on babies of the Zika virus.

Dr Tom Frieden, head of the Center for Disease Control (CDC), was testifying before politicians in Washington.

He said that data from the cases of two infants in Brazil who died soon after birth indicated the virus had passed from mother to child.

However, he said the suspected link was still not definite.

There are thought to have been more than 4,000 cases in Brazil alone of babies born with microcephaly - abnormally small brains - and where the transmission of Zika virus from mother to child is suspected of being the cause.

Dr Frieden said intensive research was under way to find out much more about the mosquito-borne virus and to develop a vaccine for it, although he warned that that could still be years away.

"We will likely see significant numbers of [Zika] cases in Puerto Rico and other US territories," Dr Frieden warned.

He said the CDC would issue grants to US states at risk of Zika to better control mosquitoes.

Also on Wednesday, the World Health Organization (WHO), which has called the outbreak a "global public health emergency", issued guidance for women on how to protect themselves.

It said that until more is known on whether sexual contact can transmit Zika, "all men and women living in or returning from an area where Zika is present - especially pregnant women and their partners - should be counselled on the potential risks of sexual transmission and ensure safe sexual practices".

"These include the correct and consistent use of condoms, one of the most effective methods of protection against all sexually transmitted infections," the WHO said.

The use of contraception is a controversial issue in the region because of the Catholic Church's stance against it.

However, the Church has rejected calls from liberal Catholics for a softening of its position on the issue in light of the outbreak.

"Microcephaly has been occurring in Brazil for years. They are taking advantage of this moment to reintroduce the abortion topic," Bishop Leonardo Ulrich Steiner, secretary general of the Brazilian Bishops' Conference, told the Estado de Sao Paulo newspaper.

The WHO said it was not advocating travel restrictions to the area but advised pregnant women, or those trying to become pregnant, to seek medical advice before travelling to areas where Zika is present.

http://www.bbc.com/news/world-latin-america-35543371