A new mosquito-borne threat to pregnant women in Brazil [Zika]

Monday, 8th of February 2016

A new mosquito-borne threat to pregnant women in Brazil

Marcia Triunfol

Published Online: 23 December 2015

Also at http://dx.doi.org/10.1016/S1473-3099(15)00548-4

An apparent connection between the emergence of Zika virus and an unusual rise in microcephaly has alarmed Brazilian authorities. Marcia Triunfol reports.

In April, 2015, a few cases of Zika virus infection were reported in Bahia, a state to the northeast of Brazil. Patients developed a rash, conjunctivitis, arthralgia, and mild fever. Initially, it seemed that the newcomer would be just one more virus causing a dengue-like illness in a population that has been struggling against dengue for too long.

However, in October that year, doctors and health authorities in Brazil noticed an increasing number of newborn babies with microcephaly in Pernambuco, another state in the northeast region, while new cases of microcephaly continued to appear in other states. On Dec 15, the Ministry of Health confirmed 134 cases of microcephaly believed to be associated with Zika virus infection—a further 2165 cases in 549 counties in 20 states are under investigation. All confirmed cases are limited to four states in the northeast region of Brazil. Rio Grande do Norte, the state with the highest incidence of congenital microcephaly, jumped from one case in 2014 to 35 cases in 2015. From 2010 to the beginning of 2015, the incidence of microcephaly in the country had been around 180 cases per year.

Interestingly, Bahia, which was one of the first states where Zika virus was isolated, does not have any confirmed cases of microcephaly yet reported. Amilcar Tanuri, a virologist at the Federal University of Rio de Janeiro, is yet to be convinced about the direct association between Zika and congenital microcephaly. “The contrasting outcome of Zika infection in mothers and their babies is intriguing”, he says. Although the mother develops an almost imperceptible rash and mild cold-like symptoms, the baby can develop microcephaly and even die, yet Tanuri feels other elements, and possibly other viruses, are contributing to the high incidence of microcephaly.

Ana Bispo, a virologist and head of the Flavivirus Laboratory at Instituto Oswaldo Cruz in Rio de Janeiro and the first researcher to partly sequence the virus from the amniotic fluid of two mothers whose babies were affected by microcephaly, believes that the finding is a “strong indication of the correlation between Zika virus and the increasing number of microcephaly cases observed in Brazil”.

Zika is an arbovirus mainly transmitted by the Aedes aegypti mosquito. The virus is closely related to other flaviviruses, including dengue and chikungunya. Two types of Zika virus, the African and the Asian, have been identified. Phylogenetic analysis has showed that the virus circulating in Brazil is of the Asian type, and is similar to the one associated with an outbreak in French Polynesia in 2013.

Although there are no reports in the scientific literature of an association between Zika virus and congenital microcephaly, a Rapid Risk Assessment alert from the European Centre for Disease Prevention and Control states that health authorities in French Polynesia have recently reported increasing numbers of cases of CNS malformations and polymalformative syndrome during 2014–15. Didier Musso, director of the Emerging Infectious Diseases Unit at Institut Louis Malardé in Papeete, French Polynesia, feels it is possible that co-circulation of Zika virus and other viruses are involved. This possibility could explain not only the potential association between Zika and microcephaly but also the high incidence first noted in French Polynesia and now in Brazil of Guillain–Barré syndrome—an autoimmune disorder that is also being associated with Zika infection.

According to a recent study uploaded to bioRxiv, a biological research preprint server, researchers at the University of São Paulo and Institut Pasteur de Dakar suggest that the Zika virus has gone through important changes that might aid its recent urban expansion. According to Caio Cesar de Melo Freire, “the virus has adapted to use the same cellular machinery used by its host, increasing its replication and titers. For instance, it uses the same codons used by the host’s housekeeping genes”.

Zika outbreaks are also being reported in other countries in South and Central America. According to WHO and the Pan American Health Organization, autochthonous cases of Zika have been detected in Colombia, El Salvador, Guatemala, Mexico, Paraguay, Suriname, and Venezuela. Yet, among all countries where Zika has been detected, Brazil is currently the only one where the outbreak seems to be strongly associated with a very high incidence of microcephaly.

However, the high incidence of microcephaly is not the only peculiarity associated with Zika virus in Brazil. An initial study done in the state of Bahia shows that most individuals (six of seven) infected at the beginning of the outbreak were women aged around 30 years. Later, data analysis of 40 women presented by Alexander Vargas, at the Ministry of Health, showed that all mothers whose newborn babies had microcephaly, between August and October, 2015, in Pernambuco, belong to low-income families. More data is needed to establish if Zika has any preference for particular hosts.

For now, the Ministry of Health has recommended that pregnant women use repellents at all times. Cláudio Maierovitch, the director of the communicable disease surveillance department at the Ministry of Health has stated that now is not a good time to get pregnant in high-risk areas in Brazil.

It is not clear how exactly the virus arrived in Brazil. Although some suspect that the Football World Cup in 2014 might have brought to Brazil an even greater disgrace than the 7-1 loss against Germany, researchers in French Polynesia highlight that none of the Pacific countries with circulating Zika participated in the games and suggest that the Va’a World Sprint Championship canoe race is a more likely factor. The canoe race took place in Rio de Janeiro in August, 2014, and athletes from French Polynesia, New Caledonia, the Cook Islands, and Easter Island—all countries with high incidence of Zika at the time—participated in the event.

More recently, cases of chikungunya infection, which is also transmitted by A aegypti, are increasing in the country. The strategy adopted by health authorities to combat all three viruses at once, is to educate the population on how to tackle mosquito proliferation. On the scientific front, studies are underway on the dissemination of mosquitoes infected with wolbachia, a bacterium that infects arthropod species including A aegypti. Pedro Lagerblad de Oliveira of the Molecular Entomology Unit of the National Institute of Science and Technology says studies have shown that virus infection and transmission to human beings is impaired in mosquitoes infected with wolbachi because the bacterium does not coexist with other pathogens. Also, the offspring of an infected female mosquito, of either sex, carry the wolbachi infection, and the offspring of a non-infected female with an infected male are sterile. In time, wolbachia-infected mosquitoes are expected to become predominant. The strategy seems effective against dengue, chikungunya, and malaria; whether it will also work against Zika virus remains to be seen.