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 Fueling that suspicion are recent discoveries of serious brain and
spinal cord infections - including encephalitis, meningitis and
myelitis - in people exposed to Zika.
Evidence that Zika's damage may be more varied and widespread than
initially believed adds pressure on affected countries to control
mosquitoes and prepare to provide intensive - and, in some cases,
lifelong - care to more patients. The newly suspected disorders can
cause paralysis and permanent disability - a clinical outlook that
adds urgency to vaccine development efforts.
Scientists are of two minds about why these new maladies have come
into view. The first is that, as the virus is spreading through such
large populations, it is revealing aspects of Zika that went
unnoticed in earlier outbreaks in remote and sparsely populated
areas. The second is that the newly detected disorders are more
evidence that the virus has evolved.
"What we're seeing are the consequences of this virus turning from
the African strain to a pandemic strain," said Dr. Peter Hotez, dean
of the National School of Tropical Medicine at Baylor College of
Medicine.
 The Zika outbreak was first detected in Brazil last year and is
spreading through the Americas. It has been linked to thousands of
suspected cases of microcephaly, a typically rare birth defect
marked by unusually small head size, signaling a problem with brain
development. Evidence linking Zika to microcephaly prompted the
World Health Organization to declare a global health emergency in
February.
The suspicion that Zika acts directly on nerve cells began with
autopsies on aborted and stillborn fetuses showing the virus
replicating in brain tissues. In addition to microcephaly,
researchers reported finding other abnormalities linked with Zika
including fetal deaths, placental insufficiency, fetal growth
retardation and injury to the central nervous system.
Doctors also are worried that Zika exposure in utero may have hidden
effects, such as behavioral problems or learning disabilities, that
are not apparent at birth.
"If you have a virus that is toxic enough to produce microcephaly in
someone, you could be sure that it will produce a whole series of
conditions that we haven't even begun to understand," said Dr.
Alberto de la Vega, an obstetrician at San Juan's University
Hospital in Puerto Rico.
First discovered in the Zika forest of Uganda in 1947, the virus
circulated quietly in Africa and Asia, causing rare infections and
producing mild symptoms. A 2013 outbreak in French Polynesia, the
largest at that time, led researchers to make the Guillain-Barre
link. Other neurological effects were noted but scientists made
little of them at the time.
A rare and poorly understood condition, Guillain-Barre can weaken
muscles and cause temporary paralysis, often requiring patients to
need respirators to breathe.
An estimated 32,000 people in the French Polynesia Zika outbreak
were infected, and 42 patients were confirmed to have
Guillain-Barre, a 20-fold increase in incidence over the previous
four years, the WHO reported. Another 32 patients had other
neurological disorders, including encephalitis, meningoencephalitis,
myelitis and facial paralysis.
 Guillain-Barre is an autoimmune disorder, in which the body attacks
itself in the aftermath of an infection. But the newly discovered
brain and spinal cord infections are known to be caused by a
different mechanism - a direct attack on nerve cells. That has
prompted scientists to consider whether the Zika virus also may
infect nerves directly in adults, as they already have suspected in
fetuses.
In medical journals published last month, doctors described
neurological syndromes in two patients that they attributed to Zika.
Doctors in Paris diagnosed meningoencephalitis, an infection of both
the brain and spinal cord, in an 81-year-old man who was
hospitalized after being exposed to Zika on a cruise.
Another French team reported acute myelitis, a paralyzing infection
of the spinal cord, in a 15-year-old girl who had been infected with
Zika on the French Caribbean island of Guadeloupe.
In its latest surveillance report, the WHO said the two cases
"highlight the need to better understand the range of neurological
disorders associated with Zika-virus infection."
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Other mosquito-borne viruses - including dengue, Japanese
encephalitis and West Nile - are known to directly infect nerve
cells in the brain and spinal cord. But such viruses are seldom
associated with Guillain-Barre, and never with microcephaly, said
Baylor's Hotez.
POSSIBLE EVOLUTION
In a recent paper, WHO researcher Mary Kay Kindhauser wrote that
Zika "appears to have changed in character," noting its transition
from a mild infection to one causing "large outbreaks linked with
neurological disorders."
Scientists studying Zika in Brazil now are reporting the same
neurological disorders seen in French Polynesia. From April through
July 2015, doctors in Brazil identified a spike in Guillain-Barre
cases.
In Salvador, there were roughly 50 reported cases of Guillain-Barre
in July alone, far more than would typically be expected, Dr. Albert
Ko, a tropical disease expert from Yale University who is studying
Zika in the coastal city of Salvador, recently told a research
symposium.
"Throughout Brazil, doctors have seen strange, atypical,
neurological manifestations," Ko said told the symposium.
Zika exposed patients have had other neurological problems as well,
including acute disseminated encephalomyelitis, which causes
inflammation of the myelin, the protective sheath covering nerve
fibers in the brain and spinal cord. Other patients experienced
tingling, prickling or burning sensations, which are often markers
of peripheral nerve damage.
In addition to Brazil and French Polynesia, at least 11 more
countries and territories have reported hundreds of cases of
Guillain-Barre syndrome linked to Zika. In Brazil, Guillain-Barre
cases jumped 19 percent to 1,708 last year.
El Salvador, a country that has an annual average of 196 cases of
Guillain-Barre, reported 118 cases in six weeks in December and
January.
Zika's arrival in Colombia in October 2015 was associated with
another increase in Guillain-Barre cases. The country typically
reports 242 cases of the syndrome a year, or about five a week. But
in the five weeks starting in mid-December, Colombia reported 86
cases of Guillain-Barre, or about 17 a week.
Dr. Carlos Pardo-Villamizar, a neurologist at Johns Hopkins
University School of Medicine, is studying Zika complications with
colleagues in five Colombian research centers. They have seen cases
of encephalitis, myelitis and facial paralysis associated with Zika
and want to understand what is triggering these complications.
They also want to study whether prior infection with dengue or
chikungunya - two related viruses - are contributing to neurological
disorders seen in patients with Zika.
Scientists are turning their attention next to Puerto Rico, where
Zika is expected to infect hundreds of thousands of residents by
year-end.
More cases hold the potential for "a better sense of the full
spectrum of disease that Zika is capable of causing," said Dr. Amesh
Adalja of the Center for Health Security at the University of
Pittsburgh Medical Center.
(Reporting by Julie Steenhuysen; additional reporting by Anthony
Boadle in Brasilia, Brazil; Editing by Michele Gershberg and Lisa
Girion)
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