Zika and microcephaly: Meet the people who helped identify the emergency

In early 2015, a mysterious illness began affecting the population of Camaçari in Bahia. The symptoms, which included eruptions on the skin, caused the population to blame the sudden “allergy” on water quality.

When infectious disease specialist Antonio Bandeira, who had seen various patients with the symptoms at the Hospital Santa Helena in Camaçari, described the situation to virologist Gubio Soares Campos of the Universidade Federal da Bahia (UFBA), the researcher decided to investigate blood samples from patients in an effort to identify what both already suspected was a virus.

Bandeira took 25 samples to the Virology Laboratory of the UFBA’s Instituto de Ciências da Saúde [Institute of Health Sciences] where they were subject to analysis by Campos and Silvia Inês Sardi.

“We began testing for various viruses — dengue, chikungunya, measles, West Nile virus — everything turned out negative,” Campos recalls. He had already read articles on the zika virus and had seen photos of patients in the acute stages of the illness. Since they had biological molecular material to allow them to work with zika, they also decided to test the samples for that virus which had yet to be identified in Brazil.

“Much to our surprise, we began finding positive samples. We utilized two molecular biology techniques and all tested positive.” The virologist reported the situation to the Ministry of Health to which he sent the patient samples. Having confirmed the results in a reference laboratory, in early May the Ministry issued a public announcement that the virus had reached Brazil.

In October Bandeira, Campos and Silvia authored an article describing the unprecedented discovery in the journal Emerging Infectious Diseases.

Emblematic case of twins

A few months later in early August a case drew the attention of pediatric neurologist Vanessa Van Der Linden, a physician at the Hospital Barão de Lucena and the Associação de Assistência à Criança Deficiente [Disabled Child Healthcare Association — AACD] of Recife. She had seen twins born at the end of July of whom one had microcephaly and the other not.

“I checked everything for this little boy — toxoplasmosis, cytomegalovirus, parvovirus — every agent that could possibly lead to a congenital infection. Everything turned out normal. I was already investigating genetic diseases when numerous cases of microcephaly began appearing at the Hospital Barão de Lucena on around September 15.” Over the course of two weeks Vanessa examined five patients. Under ordinary circumstances it would be unusual to see more than one case a month.

“All showed the same characteristics on the ultrasound, which resembled microcephaly due to cytomegalovirus. I began to think this was something unusual, that it was being caused by some new infectious agent,” she says. The fact that she already had the case of the twins in the back of her mind further increased her suspicions.

Vanessa began to send patients to a reference center for infectious diseases in Recife, the Department of Pediatric Infectious Diseases at the Hospital Universitário Oswaldo Cruz of the Universidade de Pernambuco (Huoc-UPE), which was also receiving babies with microcephaly from other institutions.

“There aren’t many pediatric neurologists in Recife and we have excellent relations. We began contacting other centers and discovered that they too were receiving cases of microcephaly. Communication between doctors was excellent,” she says.

Babies arrive at the reference center

Meanwhile, Dr. Maria Ângela Rocha, head of the Department of Pediatric Infectious Diseases at Huoc-UPE, had begun receiving babies with the condition in early September. “Some pediatric neurologists working here in Recife said they would be sending in some cases of microcephaly because they were noticing an increase in the number of these and wanted us to investigate a possible cause,” she says.

“It was a totally unexpected number because such pathologies don’t come in bursts,” says Maria Ângela. The tomographies suggested the microcephaly was probably associated with a process of infection, but tests for agents that could be related to the symptoms came up negative.

The physicians began asking themselves what difference in the scenario could be causing this phenomenon. “People knew there had been a major outbreak of dengue in March 2015 because everything had been classified as dengue. But zika and chikungunya were already circulating in the area and that’s why we began to consider that possibility.”

Physicians contact the Secretariat of Health

When she began investigating mothers of babies with microcephaly, Vanessa Van Der Linden noticed that nearly 70% of them had a history of cutaneous rash (blotches on the skin) at the start of pregnancy, a condition that has occasionally been regarded as a symptom of dengue.

In October, she approached the Secretariat of Health of the State of Pernambuco to discuss the increase in cases and scheduled a meeting with the epidemiology oversight team. “Armed with tomographies indicating that the cases were related to congenital infections and with a history of cutaneous rash in the mothers, we had discussions with epidemiological staff who were already investigating an outbreak of zika,” Vanessa explains.

This is how the suspicion arose that those cases that at the beginning of the pregnancy of those mothers giving birth in August or September were still being identified as dengue could in fact be linked to the zika virus.

Thanks to the warning from the physicians, the Secretariat of Health of the State of Pernambuco drafted a protocol requiring all cases of microcephaly in the state to be reported, in addition to informing the Ministry of Health of the situation. On November 11, the government declared a national public health state of emergency due to the cases of microcephaly.

Submission of samples to Fiocruz

Meanwhile, cases of microcephaly started coming to notice in Paraíba. Dr. Adriana Melo of the maternity unit of the Instituto Elpídio de Almeida (Isea) in Campina Grande began suspecting a link between the zika virus and microcephaly following discussions with professionals in Pernambuco. On her own initiative she took the step of collecting amniotic fluid from two pregnant mothers whose babies had been diagnosed with microcephaly in ultrasound tests.

The samples, which were sent to the Flavivirus Laboratory of the Instituto Oswaldo Cruz (IOC/Fiocruz), led to the discovery that the virus was capable of being transmitted through the placenta, a fact hitherto unknown to science that reinforced evidence of a link between zika and microcephaly.

Family panic

“It was an unprecedented case. We had never seen so many cases of microcephaly in international medical literature. Here in Pernambuco we were dumbfounded,” Maria Ângela explains. “It was an avalanche. There were babies with an extremely small head circumference, with significant lesions revealed on the tomography. This left everyone all the more concerned not only with respect to the gravity of the situation but also for what it represented to public health.”

Nearly 340 babies with microcephaly are being treated at the Huoc-UPE, which together with the Instituto de Medicina Integral Professor Fernando Figueira [Professor Fernando Figueira Integrative Medicine Institute] (IMIP) is one of the major centers of reference for this deformity in Pernambuco.

“I feel for those mothers who, aside from having a special needs baby, find themselves in the position of having someone discuss the matter in the newspapers and on TV every day. They are extremely vulnerable,” says Vanessa. She describes how the situation has spread panic among families who are now afraid of conceiving. At AACD alone, where she works as a pediatric neurologist, nearly 80 babies with microcephaly are being treated.

Original article published in Portuguese in G1.