Zika virus and microcephaly: a relationship that demands actions and caution

Aedes aegypti, cosmopolitan mosquito, vector of arboviral diseases, as yellow fever, dengue, zika and chikungunya

After the announcement by the Health Ministry confirming the relationship between the microcephaly outbreak in Brazils Northeast and infection by Zika virus, all federative entities – Union, states and cities – have gathered efforts against the vector mosquito, the Aedes aegypti. In Pernambuco State, the Army has engaged the fight against the mosquito. These are times of caution, especially because the current focus is on pregnant women and women in reproductive age who might become pregnant in the near future.

As disclosed by a research conducted by the Flavivirus Laboratory at the Oswaldo Cruz Foundation (IOC-Fiocruz), Zika virus is able to cross the placental barrier and reach the amniotic fluid, which involves the fetus during pregnancy. The official confirmation of this relation, presented at the end of last November by the Health Ministry, came after the Evandro Chagas Institute, in Para State, identified the virus in exams conducted on a stillborn from Ceara State who was born with microcephaly and other congenital diseases.

Despite the concerns brought by the theme, Dr. Dorcas Lamounier Costa affirms very little or nothing can be done to change the course of the fetuses affected by Zika virus. This happens because Zika is a neurotropic virus, which means it tends to strike the hosts nervous system and can lead to microcephaly still in the placental environment.

Other viruses can lead to microcephaly, evidenced by the smaller than normal brain and head, as enterovirus, poliovirus and rubella. Children born with the congenital rubella syndrome eliminate the virus for months, in a mechanism known as immune tolerance, where the organism is not able to eliminate the attacking antigen, said the physician – PhD in Infectious Diseases and Tropical Medicine at the Federal University of Minas Gerais (UFMG). We wonder whether it could happen with zika virus in the same way, she complemented.

Information for women

Doctor Dorcas says a womans decision to become pregnant is untouchable, but she must be aware of the precautions and uncertainties this outbreak has brought to light. We recommend caution for those who intend to become pregnant and immense precaution keeping protected from the mosquito for those who are already pregnant, she explains.

She also highlights the need to understand all recommended measures to reduce the chance of infection, as using appropriate insect repellents for pregnancy. She [the pregnant woman or who wishes to become pregnant] must know how to eliminate the mosquitos potential breeding grounds in their house and workplace, but also become aware that the Aedes, despite its little flying range, can migrate a few hundred meters during its lifespan, she alerts.

The Health Ministry has recommended all pregnant women to take all prenatal tests, besides reporting any changes they perceive during pregnancy to health professionals. Long sleeves clothes are also recommended during all pregnancy.

Researches and cases in the Country

Investigations around the theme will continue, especially in the Fiocruz laboratories, in order to clarify questions about the transmission, action in the human body, fetal infection and periods of greater vulnerability during pregnancy.

Researchers at Pernambuco States Fiocruz developed three fronts to study the relationship between the virus and microcephaly. The first will investigate newborns with the malformation comparing them to healthy newborns from the same time range, a case-control study, inquiring about relevant facts during pregnancy, with an emphasis on Zika infection during pregnancy in order to confirm causal link. The entity is also trying to develop vaccines and faster diagnostic methods to identify the virus – currently, the tests must be done in laboratory by PCR (Polymerase Chain Reaction).

Another research will take place with pregnant women who reported symptoms of viral diseases, as rashes, who will be monitored until labor. The goal, according to the researchers, is to observe the microcephaly rate among women who were infected by Zika virus and those who were not. If allowed, amniotic fluid will be collected and analyzed.

Children diagnosed with microcephaly will be carefully monitored for at least two years in order to evaluate the development impairment and definition of management strategies. Another research, known as cohort study, will be conducted with pregnant women who had symptoms of viral diseases as rashes, who will be monitored until labor. The goal, according to the researchers, is to observe the microcephaly rate among women who were infected by Zika virus and those who were not. If allowed, amniotic fluid will be collected and analyzed.

About microcephaly, Pernambuco leads in newborns with the disease in the Country, with 804 of the 1,761 suspicious cases, reported in 422 cities in 14 states. According to the Health Ministry, around 200 Brazilian cities are currently at risk of dengue, chikungunya and Zika outbreaks. Zika has been confirmed in 18 states.

The (almost) unknown Zika challenge

The little information about Zika virus is among the major difficulties scientists currently have when investigating the theme. This is due to the few cases ever reported before the recent outbreaks.

The virus was first isolated in 1947 from a rhesus monkey from Zika forest, in Uganda, Africa, and in humans, in 1968 for the first time, in Nigeria.

Zika is considered endemic in East and West Africa. Serological evidences in humans suggest the virus has spread to Asia in 1966. Outside these two continents, the first reported case was in a Micronesian island, in the Pacific Ocean in 2007. A recent outbreak took place in the French Polynesia in 2013, where over 10 thousand cases were diagnosed.

According to Dr. Pedro Fernando da Costa Vasconcelos, from the Evandro Chagas Institute, there are no scientific basis to define the pathophysiological mechanisms involved in the virus pathogenesis in the human body. We must perform experimental studies in mice and, if possible, in non-human primates to gather these data, he explains.

It is also uncertain the period pregnant women are most vulnerable to the virus. At first, we believe the risk is greater during the first three months of pregnancy. Besides this, we also do not know exactly how the Zika acts in the human body, besides the fetal infection.

The microcephaly outbreak and the disease

The chat between a mother and a daughter, both neuropediatric doctors, was the beginning of the discovery of the microcephaly outbreak in Pernambuco. Ana Van der Linden, who works at the Professor Fernando Figueira Integral Medicine Institute, told her daughter Vanessa Van Der Linden, from the Barão de Lucena Hospital, she had seen seven microcephalic babies in a single day. That same day Vanessa reported seeing five similarly affected babies. After consulting with other specialists, 40 cases of microcephaly had been identified in a few days. The beginning of the investigation was conducted by Doctor Carlos Brito, collaborator at Fiocruz-PE, gathering data from the babies and their mothers.

According to a German study involving 680 children, 65% of babies with microcephaly present delayed psychomotor development or cognitive delays. Among these children in school or preschool age, only 28% attended regular schools while 72% had some special education support.

Visual or hearing problems and lower perception of pain has been reported among people with microcephaly. It is important to stress the causes for microcephaly are various and include factors that directly damage the nervous system, as infections and low oxygen supply for the fetus, alcohol and drug intake during pregnancy, mother malnutrition, besides genetic disorders, as inbreeding, explains Dr. Guilherme de Sousa Ribeiro from Fiocruz-BA.

Despite the unavailability of specific treatment for the disease, actions put in practice since the first years of age can enhance the development and life quality among those affected, that can be diagnosed by the physician during antenatal care. The most traditional analysis is performed after birth, with the first physical routine examination in the nursery in until 24 hours after birth – main period to perform active search for possible inborn disorders. The Health Ministry has recommended health professionals to be cautious when evaluating brain circumference and gestational age, as well as reporting cases under suspicion of microcephaly in the Live Births Information System (SINASC).

The mosquito and control measures

The A. aegypti, mosquito that also transmits dengue and chikungunya besides zika, is original from Egypt and spread throughout tropical and subtropical regions since the 16th century, period of the Age of Discovery. It is thought that the mosquito entered the Americas during the colonial period though slave ships.

In Brazil, the first reports about diseases transmitted by this vector – dengue and yellow fever – date from the end of the 19th century. The transmitting mosquito has already been eradicated from the Country in 1955, but a relaxation in the control measures lead to its reintroduction in national territory at the end of the 1960s. Now, the infestation by the mosquito is recurrent in all states. Only between January and November,2015, over 1.5 million notifications de qual doença? Zika?were reported.

Since the infestation rate by the Aedes aegypti is out of control in Brazil, the federal government recently announced that fighting the Aedes is the focus of the boards activity between December 2015 and January 2016.

According to the Minister of Health, Marcelo Castro, the goal is to avoid the exponential increase in the number of vectors next summer, especially in February when rainfall is greater. Still according to him, the federal government – in a joint work involving seven Ministries and in partnership with states and municipalities – will perform investments to fight the mosquito and provide health treatment for those infected and babies with microcephaly.

The federal government has made available the Army and Civil Defense for the State of Pernambuco and municipalities to eliminate the Aedes aegypti breeding sites.

Despite the governments efforts towards an intense action against the mosquito, a recent study published at PLoS One by a group of researchers from the Butantan Institute, shows the Aedes has evolved. The species has acquired the ability to reproduce in increasingly smaller volumes of water, which does not have to be clean anymore, as in the past. Besides this, the insect has gained resistance to some insecticides and even changed their feeding habits: before they would only bite during the day, and now they have been attacking at night as well. According to the researchers, a single artificial light is enough to guide it towards the victim.…