Zika In Colombia - Preliminary Report - NEJM

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Zika Virus Disease in Colombia — Preliminary Report

http://www.nejm.org/doi/full/10.1056/NEJMoa1604037?query=TOC#.V2HjYIlqNDA.twitter=&t=articleBackground

 

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Oscar Pacheco, M.D., Mauricio Beltrán, M.S., Christina A. Nelson, M.D., Diana Valencia, M.S., Natalia Tolosa, M.D., Sherry L. Farr, Ph.D., Ana V. Padilla, M.D., Van T. Tong, M.P.H., Esther L. Cuevas, M.S., Andrés Espinosa-Bode, M.D., Lissethe Pardo, B.S., Angélica Rico, B.S., Jennita Reefhuis, Ph.D., Maritza González, M.D., Marcela Mercado, M.S., Pablo Chaparro, M.D., Mancel Martínez Duran, M.D., Carol Y. Rao, Sc.D., María M. Muñoz, M.D., Ann M. Powers, Ph.D., Claudia Cuéllar, M.D., Rita Helfand, M.D., Claudia Huguett, M.S., Denise J. Jamieson, M.D., Margaret A. Honein, Ph.D., and Martha L. Ospina Martínez, M.D.

June 15, 2016DOI: 10.1056/NEJMoa1604037

 

SOURCE INFORMATION

From Instituto Nacional de Salud (O.P., M.B., N.T., A.V.P., E.L.C., L.P., A.R., M.G., M.M., P.C., M.M.D., C.H., M.L.O.M.) and Ministerio de Salud y Protección Social (M.M.M., C.C.) — both in Bogota, Colombia; and the Centers for Disease Control and Prevention, Atlanta (C.A.N., D.V., S.L.F., V.T.T., A.E.-B., J.R., C.Y.R., A.M.P., R.H., D.J.J., M.A.H.).

Address reprint requests to Dr. Honein at the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, GA 30333, or at [email protected].

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Zika virus is a flavivirus transmitted primarily by the bite of an infected aedes mosquito. In Colombia, a country with a population of 48 million, Aedes aegypti and Aedes albopictusmosquitoes are the species that are most commonly found at elevations below 2000 m above sea level. Transmission of Zika virus from mother to fetus and sexual transmission have both been reported.1-3 Zika virus infection during pregnancy can cause microcephaly and other severe brain defects in the fetus or infant and has been associated with other adverse pregnancy and birth outcomes.

The first outbreak of Zika virus disease (ZVD) in continental South America occurred in Brazil, where autochthonous transmission was confirmed in May 2015.4 Although preliminary monitoring began in Colombia after the recognition of the outbreak in Brazil, the Colombian Instituto Nacional de Salud (INS) began official surveillance for ZVD in August 2015. In early October 2015, a ZVD outbreak was declared after the first cluster of laboratory-confirmed cases was identified in nine patients from northern Colombia. After that report, the INS retrospectively identified Zika virus in an archived serum sample from July 2015.

To characterize the epidemiology of ZVD in Colombia, we describe the incidence of ZVD according to sex and age, the distribution of ZVD geographically, and the pregnancy and birth outcomes for a subgroup of women who contracted ZVD during pregnancy. Since limited data are available on the persistence of Zika virus RNA in serum obtained from pregnant women,5 we examined the distribution of the days from symptom onset to serum collection among pregnant women who tested positive for the Zika virus on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay. Finally, we summarized all case reports of microcephaly from January 2016 through April 2016 without regard to known Zika virus infection.

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METHODS

Public Health Surveillance System

In Colombia, the INS maintains a national public health surveillance system for notifiable conditions, including dengue, chikungunya, and Zika virus infections, acute flaccid paralysis (in children ≤15 years of age), and congenital defects, including microcephaly. Information that is collected by health care centers is compiled and transmitted to the national public health surveillance system, which aggregates and publishes the results weekly. The typical reporting time by health care centers to preliminary national reporting is approximately 1.5 weeks. For this report, the study period was August 9, 2015, to April 2, 20166; cases that were retrospectively identified before epidemiologic week 32 (beginning on August 9, 2015) are not included because ZVD was not consistently monitored by the nationwide surveillance system before then.

For this analysis, ZVD cases include all the patients who were reported to the INS with symptoms of ZVD, with and without laboratory confirmation. Laboratory-confirmed ZVD is defined as the presence of clinical symptoms of ZVD and a positive serum result for Zika virus RNA on RT-PCR assay.

Molecular Detection of Zika Virus

During the study period, molecular detection of Zika virus was performed with the use of the SuperScript III Platinum One-Step RT-PCR System (Invitrogen). We used oligonucleotides ZIKV 1087/ZIKV 1163 and the ZIKV 1108-FAM probe in a final volume of reaction of 25 μl, according to the Lanciotti protocol.7 The sensitivity for the test is 25 genomic copies per reaction. The thermal profile consisted of a step of reverse transcription at 50°C for 30 minutes, activation of the enzyme at 95°C for 15 minutes, and 45 cycles at 95°C for 15 seconds and 60°C for 1 minute for hybridization and extension with the use of ABI7500 equipment (ThermoFisher Scientific).

Reporting of ZVD Cases

Starting in October 2015, the INS mandated immediate reporting of all symptomatic ZVD cases.8The initial case definition for ZVD was fever and at least one of the following symptoms: nonpurulent conjunctivitis, headache, rash, pruritus, or arthralgia, with no known alternative cause. On December 24, 2015, the symptom criteria were revised to include fever and rash, plus at least one of the following symptoms: nonpurulent conjunctivitis, headache, pruritus, arthralgia, myalgia, or malaise. Health care providers documented whether a patient met the symptom criteria, but these data were not reported to the INS and are not included in this report. On the basis of an investigation of a Zika outbreak in the department (i.e., state) of Bolivar in October 2015, the distribution of symptoms that were reported were rash (in 93% of patients), fever (in 80%), pruritus (in 76%), myalgia (in 65%), arthralgia (in 64%), headache (in 62%), conjunctivitis (in 55%), and malaise (in 34%).

Testing in Subgroups of Symptomatic Patients

The INS arboviral reference laboratory conducted RT-PCR testing for Zika virus RNA on samples obtained from a subgroup of patients with symptomatic ZVD from four subpopulations of interest: infants (<12 months), pregnant women, adults 65 years of age or older, and persons with coexisting illnesses (e.g., chronic conditions, cancers, and autoimmune disorders).8 Samples with negative Zika RT-PCR results were tested for dengue and chikungunya virus RNA by means of RT-PCR assay. Patients with negative Zika RT-PCR results are included in the case count because a blood sample may have been collected when Zika RNA was not detectable because of low viremia or because of the mild nature of symptoms, a factor that complicates the accurate report of a date of symptom onset. To explore detection of Zika virus RNA in serum, we analyzed the available data on RT-PCR results in samples obtained from pregnant women according to the number of days from the reported onset of symptoms to sample collection. Serologic testing for Zika virus immunoglobulin M antibodies was not available in Colombia during this study period.

Geographic Distribution of Outbreak

Case reports of ZVD include basic demographic information, such as age, sex, and date of symptom onset. To assess the geographic distribution of the outbreak, we mapped the incidence of reported ZVD for both the total population and pregnant women, according to the reporting area (32 states and 5 districts). We used the number of ZVD cases and population estimates to calculate the cumulative incidence of ZVD in the total population, according to age and sex, per 100,000 population and in pregnant women per 100,000 women of childbearing age.9,10 The total population was included for each reporting area, regardless of elevation above sea level.

Pregnancy Outcomes and Microcephaly

We report pregnancy and birth outcomes through the cutoff date for follow-up (May 2, 2016) in a subgroup of 1850 women who had delivered and had complete information on the gestational week at the time of symptom onset. The INS is monitoring pregnant women with reported ZVD and investigating case reports of adverse fetal and infant outcomes that might be related to Zika virus infection, including all case reports of microcephaly, defined as 3 SD below the mean for gestational age and sex, with confirmation 24 hours after delivery. We summarize case investigations for microcephaly from January through April 2016 that were collected without respect to Zika symptoms or the results of laboratory studies.11

Statistical Analysis

We used Poisson regression to estimate incidence ratios comparing female patients with male patients, along with 95% confidence intervals, using Proc Genmod software (SAS). Analyses with laboratory-confirmed cases only were also conducted. The analyses summarize data from ongoing surveillance and were conducted as part of public health practice.

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RESULTS

Patients with ZVD

From August 9, 2015, through April 2, 2016, a total of 65,726 cases of ZVD were reported in Colombia, with 2485 (4%) that were positive on RT-PCR assay. During this period, 11,944 pregnant women with ZVD were reported in Colombia, with positive results on RT-PCR in 1484 cases (12%). There is currently complete information on gestational age at the time of symptom onset for a subgroup of 1850 pregnant women with ZVD.

Among the 65,726 patients who were reported to have ZVD, 2336 (4%) were hospitalized at the time that the case was reported, including 938 of the 11,944 pregnant women (8%). The number of reported ZVD cases steadily increased from October 2015 through January 2016, with the largest number of cases reported during the week of January 31 to February 6 (epidemiologic week 5) (Figure 1FIGURE 1Patients with Symptoms of Zika Virus Disease (ZVD), Including Laboratory-Confirmed Cases, in Colombia (August 9, 2015–April 2, 2016).). From February 7 to April 2 (weeks 6 to 13), the number of reported cases decreased overall, although a few areas were reporting an increased number of cases at week 13.

Extent of ZVD Outbreak

Zika virus has spread rapidly throughout Colombia since the first locally acquired case was confirmed. The ZVD cases are widely distributed across Colombia, with at least one laboratory-confirmed case in 35 of the 37 reporting areas. Seventeen reporting areas had more than 1000 cases; 59,585 cases (91%) were reported from these 17 areas (Figure 2FIGURE 2Cumulative Incidence of Zika Virus Disease with Clinical Symptoms in Colombia, According to Reporting Area (August 9, 2015–April 2, 2016).). The highest incidence of ZVD (1342 per 100,000 population) was reported on San Andres and Providencia, islands in the Caribbean Sea, which was followed by an incidence of 655 per 100,000 in Norte de Santander, a state in the northeast region of the country adjacent to the Venezuelan border, and an incidence of 517 per 100,000 in the state of Huila. For pregnant women, the highest incidence of ZVD was reported in Norte de Santander (621 per 100,000 women of childbearing age), the city of Barranquilla (342 per 100,000), and the state of Huila (333 per 100,000) (Figure 3FIGURE 3Cumulative Incidence of Zika Virus Disease with Clinical Symptoms among Pregnant Women in Colombia, According to Reporting Area (August 9, 2015–April 2, 2016).). Similar geographic patterns were seen for laboratory-confirmed cases.

Of the 3384 Zika RT-PCR assays that were performed in Colombia during this time period, 2037 (60%) were conducted on samples obtained from pregnant women; 73% of the samples obtained both from the total population and from pregnant women had positive results. Among a subgroup of 1850 pregnant women with complete data, 582 had serum samples tested on RT-PCR assay; of these samples, 326 (56%) were positive for Zika virus (Figure 4FIGURE 4Distribution of Days from the Onset of Symptoms of Zika Virus Disease to Sample Collection.). Among samples that tested positive on RT-PCR assay, the mean number of days from the reported onset of symptoms to sample collection was 2.6 (median, 2.0; range, 0 to 21). For samples that were RT-PCR–negative, the mean number of days from the reported onset of symptoms to sample collection was 4.0 (median, 2.0; range, 0 to 76). Among the RT-PCR–positive samples, 10 of 326 (3%) were collected more than 7 days after symptom onset; among RT-PCR–negative samples, 17 of 256 (7%) were collected more than 7 days after symptom onset. Among all 555 samples that were collected up to 7 days after reported symptom onset, 316 (57%) were positive on RT-PCR assay. Among the RT-PCR–negative samples, 8 had positive results for dengue and 23 had positive results for chikungunya.

Female-to-Male Incidence Ratio

Two thirds of the reported ZVD cases were diagnosed in female patients, although these results were probably affected by referral and testing bias because of the concern about ZVD during pregnancy. There was significant variation in estimated incidence according to sex and age (Table 1TABLE 1Incidence of Zika Virus Disease with Clinical Symptoms in Colombia, According to Age and Sex (August 9, 2015–April 2, 2016).). Although the incidence of ZVD was similar in girls and boys who were 4 years of age or younger, the incidence was significantly higher among female patients than among male patients in all other age groups. The incidence of ZVD was approximately three times as high among girls and women between the ages of 15 and 29 years as among boys and men in the same age group. The highest incidence ratio comparing female patients to male patients was 3.42 (95% confidence interval [CI], 3.25 to 3.59) among those between the ages of 20 and 24 years. The incidence ratios between female patients and male patients were larger when the analyses were limited to laboratory-confirmed cases.

Data on Trimester of Infection

At the time of this report, most pregnancies with ZVD were still ongoing, and key data, including the trimester in which ZVD was diagnosed, are still being collected. Among a subgroup of 1850 pregnant women with ZVD for whom complete data on the trimester of infection were available, 532 reportedly contracted the infection in the first trimester, 702 in the second trimester, and 616 in the third trimester. At the time of data cutoff, among the women in whom ZVD had been diagnosed, pregnancies were ongoing in 84% of those with a diagnosis in the first trimester and in 71% of those with a diagnosis in the second trimester. For the 616 women in whom ZVD was diagnosed in the third trimester, 82% of their infants were born at term with a normal birth weight, 2% were born at term with a low birth weight, 8% were preterm, and 1% died during the perinatal period; 7% are still being followed. No cases of microcephaly or brain abnormalities have been reported in this group to date.

National Surveillance for Microcephaly

From January 1, 2016, to April 28, 2016, a total of 50 infants with possible microcephaly were reported to the national surveillance system for birth defects. Of these cases, 26 are still under investigation, and 20 were deemed to have resulted from causes other than Zika virus infection, including STORCH (syphilis, toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes) infections, genetic causes, neural-tube defects, and other causes among infants with negative results on Zika RT-PCR whose mothers had no symptoms of ZVD during pregnancy. Four infants with microcephaly had laboratory evidence of congenital Zika virus infection on RT-PCR assay, a negative STORCH evaluation, and normal karyotypes. Of the 4 infants, who were born between 37 and 39 weeks of gestation, 1 had abnormal brain findings on ultrasonography and 3 had abnormal findings on hearing evaluations. Other clinical findings for the cases included decreased muscle tone, problems sucking or swallowing, and amyoplasia of the lower limbs. None of the four mothers had symptoms of ZVD during pregnancy and therefore were not reported as part of ZVD monitoring.

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DISCUSSION

The outbreak of ZVD has spread rapidly throughout Colombia since the first cluster of laboratory-confirmed cases was identified in October 2015, with 65,726 cases reported, including in 11,944 pregnant women as of April 2, 2016. However, these numbers underestimate the total effect of the ZVD outbreak, since they do not account for asymptomatic infection or unreported clinical illness. High ZVD incidence was reported among girls and women between the ages of 15 and 29 years, which was three times the incidence among male patients in the same age group. Notably, it is unclear to what extent reporting and testing biases may be inflating the number of women who have been identified with ZVD because of the concern about Zika infection during pregnancy. Projections that are based on the timing of the outbreak in Colombia would suggest that women with first-trimester exposures are likely to deliver at term beginning soon after the cutoff date for this report.12

Case reports of microcephaly are starting to emerge and be investigated.11 Laboratory evidence of congenital Zika virus infection has been found in four infants born with microcephaly so far, all among women with asymptomatic Zika virus infection. In our analysis of a subgroup of 1850 pregnant women, more than 90% who were reportedly infected during the third trimester have delivered with no cases of microcephaly.

The higher incidence of ZVD among girls and women between the ages of 15 and 29 years than among boys and men in the same age group might be the result of a true increase in risk, reporting or testing bias, or increased health care–seeking behavior among female patients. However, among persons between the ages of 45 and 64 years, the higher ZVD incidence among women than among men suggests that women may actually have an increased susceptibility to symptomatic Zika virus infection, since in this age group a reporting bias that was based on concern with respect to pregnancy would have a lesser role. It is unknown whether sexual transmission from men to women has also played a role in the increased incidence in women. During the Zika outbreak on Yap Island in 2007, the reported rate of infection among female patients (17.9 per 1000) was also higher than that among male patients (11.4 per 1000); however, seroprevalence was similar in both sexes.13 In the current Zika outbreak in Puerto Rico, 64% of patients are female.14 Because 73% of all births in Colombia occur among girls and women between the ages of 15 and 29 years,10 the high incidence of ZVD in this age group is a major concern and highlights the urgency of prevention efforts targeting this group, who might have intended or unintended pregnancies. In addition, the association between Zika virus infection during pregnancy and adverse pregnancy and birth outcomes emphasizes the need to closely monitor the large cohort of pregnant women with ZVD and their infants.15,16

The number of days from the reported date of the onset of symptoms to sample collection for pregnant women with positive results on Zika RT-PCR ranged from 0 to 21 days, a range indicating that viremia with ZVD may last longer than a week. However, the longer intervals reported (i.e., >15 days) should be interpreted with caution, since they may represent aberrations in symptom recognition and reporting rather than a true extension of the period of positivity. The mild presentation of many cases of ZVD might make it difficult to accurately pinpoint the date of symptom onset, a factor that contributes to inaccuracies in estimating the time from symptom onset to sample collection, which may in turn affect the interpretation of laboratory test results. In a published case report, Zika RNA was detected in the serum of a pregnant woman at 4 weeks and 10 weeks after the clinical onset of infection but not after delivery.5 Further research is needed to better understand the persistence of viremia in pregnant women with ZVD.

Additional challenges with ongoing population-based surveillance of ZVD include remote locations, porous borders with neighboring countries, and underreporting by health care providers, all of which limit the ability to ascertain all cases of ZVD. Cases might be underreported if they occur in areas that are not considered to be at risk for ZVD, such as those at elevations of more than 2000 m above sea level. Geographic variation in ZVD cases corresponds to areas in which A. aegyptimosquitoes are prevalent in Colombia. In addition, changes in ZVD case definitions during our study period may have affected reporting, and some patients with afebrile ZVD might be missed, since fever is a required symptom in the case definition but is not always present during symptomatic Zika virus infection.2,13 However, it is unclear whether reporting areas strictly adhered to mandated symptom criteria when reporting ZVD cases, since these data are not available for analysis. Differential reporting of clinically compatible cases might occur, since the symptoms that were included in the case definition overlap with other conditions. Although a small percentage of symptomatic ZVD cases, mainly from the four priority groups, were laboratory-confirmed on RT-PCR assay, stratified analyses of laboratory-confirmed cases were consistent with the main findings. Health care providers have been advised to consider dengue and chikungunya virus infections when evaluating patients, since both viruses remain endemic and patients can have similar symptoms.

Providers are in a unique position to educate patients about the importance of mosquito-bite prevention to reduce the risk of all mosquito-borne illnesses. This counseling is particularly important for women, especially those at risk for unintended pregnancy in the context of a ZVD outbreak. In 2010, a total of 52% of pregnancies were unintended in Colombia, 61% of women of reproductive age used contraception, and less than half of sexually active women between the ages of 15 and 24 years reported the use of a condom during the last episode of sexual intercourse.17 Since ZVD can be transmitted sexually,3,18 providers should counsel pregnant women whose male sexual partners are at risk for Zika virus infection about the importance of condom use or abstinence to prevent Zika virus transmission.

The ongoing outbreak of ZVD in the Americas poses a major public health threat, particularly for fetuses of infected pregnant women.19 Nationwide population-based surveillance in Colombia has been critical for monitoring the status of the outbreak by focusing prevention efforts and rapidly assessing adverse outcomes. The INS continues to update its ZVD case counts and has started reporting the number of cases of microcephaly and the Guillain–Barré syndrome; links between Zika virus infection and these outcomes are being investigated further.11 The INS is implementing intensified surveillance of pregnant women with ZVD in selected sites to better understand the spectrum of adverse pregnancy and infant outcomes associated with Zika virus infection and to identify the effect of factors such as the timing of infection during pregnancy.

 

 

Supported by the Colombian Instituto Nacional de Salud and the CDC.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).

This article was published on June 15, 2016, at NEJM.org.

We thank the following persons for their critical contributions to this project: May Bibiana Osorio, Willian León, Jennifer Isenburg, Kara Polen, Suzanne Gilboa, Amanda Cohn, Jeanne Bertolli, Sarah Tinker, Lyle Petersen, Daniela Salas Botero, the Sivigila group at the Instituto Nacional de Salud, and the Secretaries of Health from each of the departments, districts, and municipalities in Colombia.

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   Hills SL, Russell K, Hennessey M, et al. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission — continental United States, 2016. MMWR Morb Mortal Wkly Rep 2016;65:215-216
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   Driggers RW, Ho C-Y, Korhonen EM, et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 2016;374:2142-2151
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   Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 2008;14:1232-1239
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    Reefhuis J, Gilboa SM, Johansson MA, et al. Projecting month of birth for at-risk infants after Zika virus disease outbreaks. Emerg Infect Dis 2016;22:828-832
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Zika Infection Late In Pregnancy Carries Little Risk of Microcephaly

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June 15, 20166:54 PM ET

Heard on All Things Considered

MICHAELEEN DOUCLEFF

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Eight months pregnant, Mara Torres stands next to a mosquito net placed over her bed in Cali, Colombia. Health officials in Cali have delivered mosquito nets to pregnant women to help protect them from the bites of mosquitoes that can transmit dengue, chikungunya or Zika.

Luis Robayo /AFP/Getty Images

For months, scientists in Colombia have been working on a massive study.

They've been tracking the health of thousands of pregnant women to try to figure out key questions surrounding the Zika virus.

Now the team has published its first major findings, and they offer a glimmer of good news.

Zika infections during the third trimester don't seem to cause severe birth defects, such as microcephaly, the scientists and their international colleagues reportWednesday in The New England Journal of Medicine.

In what they're calling a "preliminary report" from their larger study, the researchers tracked the pregnancies of nearly 600 women who were reportedly infected with Zika during their third trimester, as suggested by the timing of their symptoms.

None of the these women gave birth to a baby with microcephaly or other brain abnormalities.

"I think it's somewhat reassuring that there were not major birth defects identified," says Dr. Margaret Honein, an epidemiologist with the Centers for Disease Control and Prevention, who helped lead the study. "But I want to make sure we understand there is still a lot that we need to know."

For example, it's still unclear whether Zika infections late in pregnancy raise the risk for other complications, such as miscarriages or stillbirths. A small study published in February suggested this might be the case.

In that study, two women caught Zika in the third trimester. In one case, the woman had a stillbirth and in the other, the fetus showed symptoms of growth restriction inside the uterus.

Researchers have also linked Zika to neurological problems, such as abnormalities in vision and hearing. So Honein and her colleagues are tracking the babies in the current study for at least a year, to see whether any problems develop.

Scientists studying other infections contracted during pregnancy have turned up associations with problems that develop later in life, says Dr. Catherine Spong, the acting director of the National Institute of Child Health and Human Development, who was not involved in the Colombia study.

"Even simply having influenza during pregnancy increases the risk of lifelong issues, such as a higher rate of schizophrenia later in life," Spong says.

So it could be years before we know the full impact Zika has on babies — even when an infection happens during the third trimester.

"We don't have the full picture for how Zika impacts pregnancy," Spong says, especially when it comes to asymptomatic infections.

"One of the difficulties of trying to truly understand Zika is that the majority of studies that we have are with symptomatic women," Spong says. But up to 80 percent of people who get infected with Zika don't even know it.

Until we have more information, both Spong and Honein agree, the recommendations for pregnant women are the same: Don't travel to places where Zika is circulating. And if you have to, do everything you can to not get bitten by mosquitoes.

"It is critically important to protect pregnant women from this infection throughout their pregnancy," Honein says.

http://www.npr.org/sections/goatsandsoda/2016/06/15/482206200/zika-infection-late-in-pregnancy-carries-little-risk-of-microcephaly

 

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No wave of Zika birth defects in Colombia—yet

By Gretchen VogelJun. 15, 2016 , 6:15 PM

Zika virus infections late in pregnancy may pose less risk to the fetus than widely feared. Researchers report today that they found no overt birth defects among 616 babies in Colombia whose mothers showed symptoms of Zika virus disease in their third trimester of pregnancy.

The data, published in The New England Journal of Medicine, are preliminary, cautions Margaret Honein, an epidemiologist at the U.S. Centers for Disease Control and Prevention in Atlanta, one of the authors of the report. Data from other countries have suggested that the virus is most dangerous to a fetus early in pregnancy, so Colombia may still face a wave of birth defects in the coming months. “It’s somewhat reassuring” that few severe problems have appeared in the babies born so far, Honein says, “but this is by no means final.”

Zika virus, which emerged in Brazil last year and has been spreading quickly across Latin America, usually causes mild symptoms, if any. However, a spike in Brazil in cases of a birth defect called microcephaly, in which a baby’s head is smaller than it should be, raised  alarm that the virus might be dangerous for pregnant women and their fetuses. So far Brazil has reported more than 1500 cases of microcephaly associated with Zika infection. Animal, laboratory, and clinical data have confirmed that the virus easily infects and kills developing brain cells. In Brazil and elsewhere, doctors report that babies infected with Zika in utero display a range of problems at birth including brain, eye, hearing, and limb defects. One study of women in Rio de Janiero, Brazil, reported that nearly a third of women infected with Zika during pregnancy had some sort of adverse outcome. That study found problems even among women infected in the third trimester: Among five women with confirmed infections, there were two stillbirths and one case of fetal distress.

After Brazil, Colombia has the most cases of suspected Zika virus infection. Since August 2015, health officials there have logged more than 65,000 suspected cases. Researchers are following thousands of women who have had symptoms consistent with Zika virus disease during pregnancy to try to better understand the risk the virus poses. But so far the country has officially reported only seven cases of microcephaly related to Zika infection. That may be temporary. The data so far reflect outcomes only after a pregnancy is completed, Honein says. Suspected Zika cases peaked in January, and many of the women who have been infected are still pregnant. Although the number of cases of birth defects appears lower in Colombia so far, “it is premature to conclude there is a difference” in the rates of affected babies, she says.

The new Colombia data are interesting, but should be treated with caution, says Nikolaos Vasilakis, a virologist at the University of Texas Medical Branch in Galveston. Accurately detecting and diagnosing Zika virus disease is still a huge challenge, he notes, because Zika’s symptoms can be confused with those of other common diseases in the region, including dengue and chikungunya.

Honein says longer-term studies of pregnant women and their babies are needed. “We know that it [Zika] has caused devastating damage” in many infected fetuses, she says. “It’s really, really important to follow up those infants,” even those without obvious problems at birth.

http://www.sciencemag.org/news/2016/06/no-wave-zika-birth-defects-colombia-yet

 

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Nearly 12,000 Pregnant Women in Colombia Have Zika

• Alexandra Sifferlin @acsifferlin
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June 15, 2016

    

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The number is likely underestimated

 

 

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An early report on Zika spread in Colombia reveals that close to 12,000 pregnant women have the virus.

In the report released Wednesday in The New England Journal of Medicine, Colombian researchers and scientists at the U.S. Centers for Disease Control and Prevention (CDC) said that as of April, there were 65,726 cases of Zika reported in Colombia, with double the number of infections in women compared to men (this could be due to the fact that more women may be tested due to the risks to pregnancy).

The report also shows that 11,944 pregnant women have been reported to have Zika, with about 1,484 of those women confirmed with specialized laboratory testing.

 

 

The researchers looked at a group of close to 2,000 of those pregnant women and report that over 90% were infected during their third trimester, and no infants with birth defects have been identified so far in this group. One of the things scientists are hoping to learn from studies like this is why some women with Zika will give birth to babies with microcephaly and others will not. It’s suspected that the time of infection during pregnancy has a role, and the fact that the women who were infected later in pregnancy had healthy babies could be telling.

 

 

Among cases of microcephaly reported in Colombia so far this year, four babies had laboratory evidence of a Zika virus infection. All of these babies were born to mothers who did not have symptoms and were not under surveillance. Most people with Zika do not have symptoms, which is why U.S. health officials have recommended all pregnant women who have traveled to affected countries—or who have partners who have traveled to affected countries—get tested for the virus.

Nearly 12,000 reported Zika cases among pregnant women and 65,726 cases reported overall is substantial, but the researchers say this is likely an underestimate since the numbers don’t account for people who don’t have symptoms and are not tested.

The study authors note that in 2010, over half of all pregnancies in Colombia were unintended and less than half of sexually active women reported using a condom the last time they had sex, though 61% said they used contraception in general. “Since [Zika] can be transmitted sexually, providers should counsel pregnant women whose male sexual partners are at risk for Zika virus infection about the importance of condom use or abstinence to prevent Zika virus transmission,” the researchers write.

The study authors say the ongoing Zika outbreak is “a major public health threat.” Medical groups and experts are still pushing for Congress to provide adequate funding to respond to the outbreak.

http://time.com/4370775/zika-virus-colombia-pregnant-women/

 

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Zika infection can damage fetuses even if pregnant women show no symptoms

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By HELEN BRANSWELL @HelenBranswell

JUNE 15, 2016

The Zika virus can harm developing fetuses even if a pregnant woman’s infection is so mild she shows no symptoms, scientists from Colombia and the Centers for Disease Control and Prevention reportedWednesday.

Four women from Colombia who had asymptomatic Zika infections during pregnancy gave birth to babies who had microcephaly — an abnormally small head. The newborns were confirmed to have the Zika virus in their systems, the researchers reported in an article published in the New England Journal of Medicine.

“We do think the majority of Zika virus infections are asymptomatic. And this does provide some evidence that asymptomatic infections during pregnancy do pose a risk to the fetus,” said Margaret Honein, an epidemiologist and a senior author of the paper.

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“I think our level of concern for pregnant women is very high, for both symptomatic and asymptomatic infections with Zika virus,” Honein said.

It is estimated that 4 out of 5 people infected with the Zika virus are asymptomatic.

The same article reported that Zika infection late in pregnancy may not be as dangerous for the fetus as an infection early on. No cases of microcephaly or other obvious birth defects were seen among the babies born to a group of 616 Colombian women who contracted the Zika virus in their third trimester, the researchers reported.

Most of the women, however, were diagnosed by symptoms only, not blood tests — a limitation of the study, said Dr. Karin Nielsen-Saines, a professor of pediatric infectious diseases at the David Geffen UCLA School of Medicine.

Nielsen-Saines has been studying Zika infection in pregnancy in Brazil. She and colleagues reported in early March that as many as 29 percent of women who contract Zika during pregnancy may have a baby with birth defects, of which microcephaly is only the tip of the iceberg. 

Though the women in this study who were infected in the third trimester didn’t have babies with visible birth defects, that can’t been taken as an assurance these infants are all completely healthy. In fact, 2 percent were born with a low birth weight and 1 percent of the women miscarried late in their pregnancies.

As well, the authors didn’t report on brain scans of the infants. It’s known that some infants who were infected with Zika in the womb have tissue scarring in their brains. They may also have underdeveloped brains even though their heads are normal sized.

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Dr. Rita Driggers, director of maternal fetal medicine at Sibley Memorial Hospital in Washington, D.C., said the children in the study will have to be followed and tested to see if they experience developmental problems.

Driggers reported in March on a case in which a woman who was infected during her first trimester chose to terminate her pregnancy in week 21. Her ultrasounds hadn’t shown that the fetus was microcephalic, but an MRI showed brain abnormalities.

Honein said more research needs to be done on the babies born to the women infected in their final trimester of pregnancy.

“There hasn’t been a full evaluation done,” she said. “So I think it’s going to be important to follow up to really understand: Are there any eye abnormalities or vision problems? Are there any hearing-related problems? And are there any other developmental issues that might not become apparent immediately.”

The Colombian authors of the study were with the Instituto Nacional de Salud in Bogata and Colombia’s ministry of health and social protection.

Helen Branswell can be reached at [email protected] 
Follow Helen on Twitter @HelenBranswell 

https://www.statnews.com/2016/06/15/zika-infection-asymptomatic-pregnancy/