The Zika virus landscape has got a little more complicated. Zika virus infections cannot be accurately diagnosed solely on the basis of microcephaly screening, reveals a study published today (June 30) in the journal The Lancet. “Substantial proportion” of newborns with definite or probable Zika virus infection had normal head circumference.

According to the study, one in five (20 per cent) newborns with confirmed or probably Zika virus infection had head circumference in the normal range and one third (33 per cent) of the newborns with confirmed or probably Zika virus infection were not born to mothers who had rash during pregnancy.

The researchers reviewed all 1,501 newborns that were already investigated by Brazil’s health authorities between November 2015 and February 2016. While 899 cases were found to be normal, the remaining 602 newborns either had definite or probable Zika virus infection (76 had definite Zika virus infection and 526 were probable cases).

The study warns that focusing on microcephaly (small head) alone will lead to an underestimation of true magnitude of Zika epidemic. Besides head circumference, signs and symptoms of brain abnormalities should also be included in screening criteria to detect all newborns affected by Zika virus, the study suggests.

Following the Zika outbreak in northeast Brazil, a surveillance system for microcephaly was set up and suspected cases were selected solely on the basis of small head circumferences.

Head circumference is misleading

While Zika virus infection during the first trimester of pregnancy is more likely to cause microcephaly, infection during the third trimester is associated with brain damage despite having normal-sized heads. While there are less chances of under-reporting of microcephaly during an epidemic, babies affected late during pregnancy will be missed as they have normal head circumference, the researchers warn.

Cranial growth takes place only up to 30 weeks, so newborns infected late in pregnancy will not have microcephaly but can still present with important brain damage. In addition, some children may present neuropsychomotor development alterations possibly related to Zika virus infection regardless of presenting microcephaly at birth, which may also be related to Zika infection in the third trimester.

“We cannot say that all these babies with normal head circumference but with brain damage were born to mothers who had contracted Zika infection in the third trimester of pregnancy,” highlights Giovanny V.A Franca, the first author from the Ministry of Health, Brazil in an email sent to me.

Revision of protocol

“Our study shows that 40 per cent of originally suspected cases ended up being normal newborn babies with small heads and 42 originally discarded cases were considered as definite or probable cases, which means that focusing on microcephaly alone will underestimate the true magnitude of this major epidemic. The Brazilian Ministry of Health is revising the current protocols in light of the findings from the study and the current literature,” says Dr. Franca.

Is there a way to know when the mothers were infected? “Currently, the only way to know exactly when the mothers were infected is through laboratory techniques during acute infections. However, according to the current literature, an estimated 80 per cent of persons infected with Zika virus are asymptomatic,” Dr. Franca says.

Monitoring all children

So will Brazil be reinvestigating even babies with normal head circumference for brain damage? “The Brazilian Ministry of Health has established a system for registration and follow-up of all children with neuropsychomotor development alterations, regardless of suspected exposure to Zika virus infection during pregnancy. The system will allow monitoring all children who need specialized medical assistance, as well as investigating the aetiology of the brain damage,” he said.

The presence of rash can positively predict Zika virus infection in only 71 per cent of the suspected cases. “Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies,” the authors write. It is important to keep in mind that an estimated 80 per cent of persons infected with Zika virus are asymptomatic, which means that most mothers are expected not to report rash during pregnancy, Dr. Franca says.

Feasibility

“For incorporating new information besides microcephaly and rash during pregnancy to detect all affected cases, neurological signs and symptoms could be eligible, but might be difficult to obtain in most settings because of insufficient specialised personnel,” Dr Jörg Heukelbach from the Federal University of Ceará, Brazil, and Dr Guilherme Loureiro Werneck from the State University of Rio de Janeiro, Brazil, write in a linked Comment piece.

The focus should, therefore, be on developing accurate serologic test that could be incorporated in to routine pre-natal care.

As of June 15, 1,581 cases of confirmed microcephaly and other nervous system disorders cases have been reported in Brazil. According to the authors, the first wave of microcephaly epidemic is “almost over”, which is due to infections spread by mosquito bites taking place in the first six months of the year. Whether there will be a second wave of microcephaly cases due to infection during the first half of 2016 remains to be seen.

Published in The Hindu on June 30, 2016