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 Genetic tests and clinical symptoms have enabled scientists to
partially track Zika, and Brazil guesses up to 1.5 million people
have been infected in the country.
The World Health Organization says as many as 4 million people could
become infected across the Americas and that Zika has already been
locally transmitted in at least 30 countries.
But a true measure of the outbreak and its implications is
impossible until doctors can quickly and reliably identify Zika
through serology, a common test of blood contents that measures
antibodies triggered in the immune system by a given infection.
Laboratories in Brazil, the United States and elsewhere are rushing
to develop serology tests that can accurately identify Zika
antibodies while ignoring those triggered by other related viruses
with similar structures. For years, the similarities have confused
serology research.
Brazil's government, desperate for tests to deploy at clinics and
hospitals across the continent-sized country, hopes such a test
could be developed in months.
 Many researchers are skeptical.
"The likelihood of this happening soon is close to zero," says
Robert Lanciotti, chief of the U.S. Centers for Disease Control and
Prevention's diagnostics laboratory in Fort Collins, Colorado. "It
is a long-standing problem that many people have been unable to
solve even with cutting-edge molecular biology."
At stake is knowing just who may have carried an infection that does
not even show symptoms in four out of five people who get it. Even
for those that do get the aches, mild fever and rash most associated
with Zika, the symptoms can easily be confused with those of other
tropical maladies.
Sure diagnoses would also enable scientists to better understand
suspected links to microcephaly, a condition marked by abnormally
small head size that can result in development problems.
Brazilian officials believe Zika may be associated with more than
4,000 suspected cases of microcephaly since October. Researchers
have identified evidence of Zika infection in 17 cases, either in
the baby or in the mother, but have not confirmed that Zika can
cause microcephaly
The lack of clear diagnoses is part of the reason that the number of
confirmed links between Zika and microcephaly lags so far behind the
number of those suspected.
"The testing available now is very limiting because we need to know
far more about who actually had this infection to be able to
research the virus and its complications," says Claudia Nunes dos
Santos, a researcher on Zika serology and the director of molecular
virology at a lab operated by the Oswaldo Cruz Foundation, a
prominent government health institute, in Curitiba, in southern
Brazil.
VIRAL RESEMBLANCE
So far, confirmed cases of Zika have been proven by so-called PCR
tests, which identify genetic material from the virus but are
available only at major laboratories and can only be used during the
few days when the virus is causing symptoms in patients.
Serology, on the other hand, is used widely at most hospitals and
for many viruses can detect antibodies for months or years after an
infection.
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With Zika and the related family of flaviviruses, which cause yellow
fever, West Nile, dengue and several other tropical illnesses,
serology stumbles because of resemblance among a protein they share.
The resemblance causes so-called "cross reactions" when searching
for antibodies, meaning that past infection by any one of the
viruses can make it seem as if a patient had one of the others.
In a country where dengue is prevalent, and many people have taken
yellow fever vaccines, the problem to date has been intractable. The
most advanced methods so far, which use a technique called
neutralization to measure specific antibodies, still fail when used
on samples from people with previous flavivirus infections.
"There is a test, but it's not a good test," says Mauricio Lacerda
Nogueira, head of the virology lab at the São Jose do Rio Preto
medical school in the state of São Paulo. "It's not going to work
with someone who has been exposed to related viruses."
Still, some researchers are optimistic, arguing that the urgency of
the Zika outbreak is leading to more concentrated research by a
greater number of scientists.
Some small private laboratories say they have already developed more
accurate serology for Zika, even though none has gone through the
rigorous process of validation by the scientific community and
regulators.
Such validation is essential not just to determine the reliability
of a test's claims, but also to measure them using geographic,
genetic and other variables.
And while partial progress may be welcome for epidemiological
purposes, such as calculating the number of cases and determining
the rate of contagion, doctors and patients need certainty to make
clinical decisions.
That is a particularly difficult issue when it comes to an illness
that may make some pregnant women, after testing positive, want to
consider abortions – especially in Brazil and many other countries
in Latin America where terminating pregnancies is illegal.
"You have to be careful of what the implications are," says Michael
Diamond, a physician who researches flaviviruses at Washington
University School of Medicine in St. Louis. "The threshold for
clinical decisions must be high."
(Additional reporting by Brad Brooks and Anthony Boadle; Editing by
Kieran Murray)
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