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 The hospital is one of three in this city on Brazil’s eastern coast
where investigators are studying the most urgent question of the
Zika outbreak: Is the virus causing a spike in birth defects, and,
if so, how great is the risk?
The answer will help shape the response to the rapid spread of Zika
throughout the Americas. Concerns over the potential link to
microcephaly have prompted a U.S. alert advising pregnant women
against travel to 31 countries and territories with outbreaks.
Officials in El Salvador, Colombia, Ecuador and Jamaica have urged
women to delay pregnancies. The many unknowns about Zika's effects
and transmission have cast a shadow over plans for the Olympic Games
in Rio, set to begin in early August.
The evidence so far is compelling enough that the World Health
Organization declared an international health emergency Feb. 1. But
it is mostly circumstantial: Suspected cases of microcephaly - a
rare birth defect characterized by small head size and an
underdeveloped brain - spiked 30-fold in late 2015, months after
Zika's arrival in Brazil.
There is harder evidence as well. Brazilian researchers have
isolated the virus in brain tissue and amniotic fluid of 17 babies
and stillborn fetuses with microcephaly whose mothers had symptoms
of Zika infection during pregnancy.
The finding provides scientific plausibility that Zika could cause
microcephaly, a condition that can result in developmental delays as
well as seizures, hearing loss, vision problems and trouble
swallowing. They can range from mild to severe.
"We know the virus can cross the placenta," said Dr. Albert Ko, a
tropical disease specialist at Yale University and the Oswaldo Cruz
Foundation, a government research institute in Salvador. "It can
infect the baby, and it's likely the reason why these fetuses were
stillborn or had congenital malformations. That is what we know up
to this point."
The study in the Salvador hospitals is one of several aimed at
proving or debunking the suspicion that Zika causes microcephaly.
In the northeastern city of Recife, Dr. Ernesto Marques, a
researcher from the University of Pittsburgh and Fiocruz Pernambuco,
the state arm of the Oswaldo Cruz Foundation, is finalizing plans
for a similar study in 12 hospitals.
Separately, the U.S. Centers for Disease Control and Prevention is
planning a retrospective study looking at microcephaly cases already
reported and comparing them to healthy births.
ACHIEVING CONSENSUS
The virus was discovered in 1947 in Uganda's Zika Forest. For
decades, Zika had been associated only with mild symptoms, making it
less of a concern than similar mosquito-transmitted viruses, such as
dengue and yellow fever.
Brazil is investigating more than 4,000 suspected cases of
microcephaly reported since October and, so far, has confirmed more
than 400. That is a significant increase from about 150 cases in a
typical year.
Experts believe it will take six to nine months to begin to
understand whether Zika can cause microcephaly. But it may take
longer to reach scientific consensus.
To establish proof that a microbe causes a disease, researchers
often follow Koch's postulates, a method developed in the 19th
century and used to show the HIV virus was responsible for AIDS in
1984, three years after the first cases emerged in the U.S.
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The method requires researchers to establish that the suspected
pathogen is strongly associated with disease and that it can be
passed from one infected host to an uninfected host and cause
disease. The pathogen also must be isolated and grown outside the
host, a step that Marques said had been accomplished with Zika.
The epidemiological studies are case-controlled - following and
comparing pregnancies that result in healthy babies to those that
result in cases of microcephaly. They are looking for evidence that
the Zika virus is passed from infected mothers onto fetuses who
develop microcephaly.
THE STUDIES
The study in Salvador hospitals is funded by Brazil's Ministry of
Health and the U.S. National Institutes of Health. It aims to rule
out Zika as a suspect in cases where other causes of microcephaly -
including genetic disorders, cytomegalovirus and rubella infections,
or exposure to drugs or alcohol during pregnancy - are found.
In apparently normal babies, Ko and his colleagues will look for
problems other than microcephaly that could be related to fetal Zika
infection, such as vision and hearing impairment, intellectual
disability, bone and growth problems, and liver and spleen damage.
Such problems can also occur with exposure to other viruses, such as
rubella, that cause microcephaly.
"One possibility is that those microcephaly babies are just the
severest cases and that they are only a small proportion of all the
babies who were infected," Ko said.
Along with full clinical and imaging tests, Ko's team is testing
babies and mothers for active Zika infections or antibodies.
Pregnant women are asked about any fever, rash, itching or red eyes
to determine possible exposure, said Almeida, hospital director at
Roberto Santos General. They receive fetal ultrasounds to look for
signs of microcephaly, such as brain calcifications.
The study now includes more than 80 babies with microcephaly, and
hundreds of normal births. Within the microcephaly group, some of
the babies have unusual lesions in the eyes and ears. Preliminary
results could be shared with the scientific community within the
next month, Almeida said.
In a recent case, Zika virus was found in the brain, bone marrow and
spinal fluid of a stillborn baby who had severe brain lesions, he
said. Head measurements suggest the baby also had microcephaly. The
mother had no Zika symptoms during pregnancy, suggesting that the
virus may cause microcephaly even in asymptomatic women.
"We see the patients, and we are very, very scared," Almeida said.
"You can't imagine the suffering of the pregnant women in Brazil."
In Recife, Marques is gearing up a similar study that aims to enroll
200 babies with microcephaly and 400 healthy babies by June or July
in 12 hospitals. Marques hopes to have some answers by August.
No one wants answers more than Dr. Manoel Sarno, a fetal medicine
specialist on Ko's team. In July, Sarno began to notice a spike in
microcephaly cases among patients who recalled having Zika symptoms.
Since then, he has identified 80 cases of microcephaly and has wept
with many of the mothers.
"I know all the world has a lot of questions," he said. "We do
also."
(Reporting by Julie Steenhuysen; Editing by Michele Gershberg and
Lisa Girion)
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