Zika-infected Pregnant Women Have More to Fear

According to a recent study, screening for microcephaly can no longer adequately determine whether or not a baby has suffered abnormalities due to a congenital Zika infection.

To recruit study participants, the researchers used an outbreak surveillance system implemented by the Ministry of Health (MOH) of Brazil on November 19, 2015. The study included cases identified since the start of the program until February 27, 2015. Approximately 6,000 cases had been reported within that window and 5,554 of these were cases in which the infants were not stillborn.

Of these cases, the researchers studied only the ones which had been previously investigated at the state level. The data collected from the MOH included information regarding sex, gestational age, imaging results, maternal history of rash, first week mortality rates, weight at birth, and head circumference based on InterGrowth measuring standards. These cases, 1501 live-born infants in Brazil, were categorized based on probability of infection with the Zika virus, based on neuroimaging and laboratory results. This was the largest case study on suspected congenital Zika infection to date.

The five categories were as follows:

• Definite cases: Showed laboratory evidence of infection with Zika virus
• Highly probable cases: Infants presented with specific neuroimaging findings, but negative laboratory results for other congenital infections
• Moderately probable cases: Infants presented with specific neuroimaging findings, however researchers could not rule out other congenital infections
• Somewhat probable cases: Infants presented with nonspecific neuroimaging findings
• Discarded cases Those that did not present with any findings

The researchers concluded that maternal rash during pregnancy (602 definite and probable cases in comparison to 899 discarded cases) was associated with a smaller head circumference, and death in the first week after birth. However, because fetal cranium development occurs by week 30, maternal rash late in the pregnancy can still indicate neurological abnormalities, despite normal head circumference. Furthermore, lead author, Cesar G. Victora, MD, PhD, Universidade Federal de Pelotas, Brazil, clarified that there was no history of maternal rash in one-third of definite or probable cases.

The authors state that these conclusions may suggest that infection with Zika in newborns may result in brain damage. Findings also suggested that among those congenitally infected with Zika, some infants may not be affected at all.

Of significance was that more than 100 definite or probable cases presented with normal head circumference. In a press release, Victora was reported as saying, “Although we believe that the underreporting of microcephaly cases is rare during the epidemic, newborns infected with the virus late in pregnancy may go unreported due to their head size being within normal range… A surveillance system aimed at detecting all affected newborns should not just focus on microcephaly and rash during pregnancy and should be revised, and examination of all newborns during epidemic waves should be considered.”

Because it is inevitable for routine surveillance systems to miss reporting important data, the authors suggest taking these findings with caution. The researchers have yet to determine an ideal head circumference cut-off point, since Zika virus congenital syndrome is rapidly and continuously changing.

Although there has been a recent drop in the number of microcephaly cases reported in Brazil, Victora warns, “Because a new wave of Zika virus infection took place in Southeastern Brazil in early 2016, there could be a second wave of microcephaly at the end of the year.”

Scientists are continuously discovering new implications of Zika virus congenital syndrome. Therefore, it is imperative that women of childbearing age, and their male sexual partners (who can transmit the virus through semen), follow infection preventive measures, such as clearing standing water containers from the vicinity of their homes, avoiding mosquito bites and travel to areas with active Zika transmission, and finally, receiving a vaccine or antiviral drug when either becomes available.

Recently, Sanofi Pasteur announced that they have partnered up with doctors from the Reed Army Institute of Research in the development of a vaccine to prevent Zika infections. A press release issued by the US Army confirms that the vaccine successfully prevented infections in mice. Currently the vaccine is being tested on monkeys. Human testing will commence later in the year.

Interestingly, the findings of a study that is still in peer-review suggest that the hepatitis C drug sofosbuvir inhibits the replication of the Brazilian Zika virus strain by targeting the virus’ RNA polymerase activity. More information on this study will be forthcoming.