Mounting
Evidence Implicates Zika Virus In Microcephaly And Guillian-Barre
Cases
Firm Proof Awaits
Results From Case-Control And Cohort Studies
The lack of understanding about Zika virus, and
especially the lack of certainty about the cause of the reported
increases in microcephaly and Guillian-Barre Syndrome cases in Brazil
and other parts of the Americas, have prompted the World Health
Organization to declare a global public health emergency.
According to WHO’s Bruce Aylward quoted in the Washington Post,
“This is classic ‘building your boat while you sail it’. People said
that about Ebola and that was trying to get a bigger sail on the boat.
Here we’re still stitching the sail, and we’re not quite sure what
kind of sails you really need.”
Also quoted was David Heymann, London School of Tropical
Medicine and Hygiene epidemiologist, who contrasted Zika with Ebola
saying the Ebola epidemic was an emergency because of what was known
about the disease, whereas Zika is an emergency because of what is
unknown.
Burden of Disease
Zika Virus Infections:
The Brazilian Ministry of Health (MOH) has estimated
that as few as half a million or as many as 1.5 million infections
have occurred in that country. Columbia has reported more than 31,000
suspected cases and Cape Verde more than 7,000. Overall, some experts
estimate 3-4 million cases will occur over the next year.
According to WHO, the geographic range of the virus has
increased significantly in 2015-16 especially in the Americas with 28
countries or territories now affected.
Cases of Microcephaly:
Brazil has reported approximately 5,280 cases of
microcephaly or central nervous system abnormalities as of February,
including 108 deaths.
Cases of
Guillain-Barre syndrome:
Five countries in the Americas have reported increases
in Guillain–Barre syndrome in association with the Zika virus
outbreak. These cases in adults have been reported in much lower
numbers than the microcephaly cases. The largest number is from
Venezuela with 252 cases.
Proving Causality
While it is established that Zika virus is transmitted
by the aedes species of mosquito, and that prevention of Zika
is theoretically possible with effective mosquito control
and/or
effective protection against mosquito bites, the cause of the
microcephaly and GBS cases is less firmly established.
To truly pin down the role of Zika virus in microcephaly, a
collaborative case-control study between CDC, Brazil, and possibly
other scientists will be carried “to look in more depth at different
factors that the mothers were exposed to, and to look at laboratory
tests from the mothers and babies, and really get a better idea of
what proportion, if any, of these birth defects can be specifically
linked with the Zika virus,” according to CDC’s Anne Schuchat.
Smoking Gun
A critical ingredient will be hammering out a good case
definition of microcephaly since right now there are reports of
over-reporting and misdiagnosis among the approximately 5,000
officially reported cases. The study has begun as of mid-February
despite the strong conviction among Brazilian health authorities that
Zika is the cause of the microcephaly cases. The circumstantial
evidence or “smoking gun” is very strong and the Minister of Health
has been quoted saying “We have no doubt that the epidemic of
microcephaly that we are seeing in Brazil is caused by the Zika virus
outbreak.”
Favoring Causality
Arguments in favor of a causal link between Zika and
microcephaly are:
1.
There appears to be a significant increase in microcephaly cases since
2015 in association with an increase in Zika cases in Brazil. Initial
estimates are that the country averaged only about 163 microcephaly
cases per year prior to 2015 but has reported approximately 5,000 in
the last few months. In the northeastern state of Pernambuco,
microcephaly cases surged last year when only 9 cases are found in a
typical year.
2. Zika was actually detected in 41 babies among 462
confirmed cases of microcephaly in Brazil. A total of at least 508
microcephaly cases have been confirmed to date.
3. A review of birth data from the Zika outbreak in
French Polynesia in 2013-
14 indicated that the number of congenital abnormalities was increased
there as well from 0-2 annually to 18 in 2014-15, including 9
microcephaly cases. Four of the mothers later tested showed evidence
of having had Zika.
4. A baby born in Hawaii in December had a
serologically confirmed Zika infection. The mother had experienced
symptoms compatible with Zika in the second trimester.
5. The fetus of a baby in Slovenia had the virus
isolated after pregnancy termination.
Favoring Other
Etiologies
Arguments against a causal link:
1. Other viruses besides Zika such as dengue and chikungunya are
circulating. Also, other known non-viral causes of microcephaly have
not been ruled out.
2. Cases of microcephaly outside of
Brazil have not
been reported.
Reasons given to
explain this unexpected finding if Zika is a true cause include the
possibility that other affected populations have not been large enough
to produce the explosive spread possible in a large non-immune
population such as Brazil. This assumes the incidence rate among
pregnant women is low, and that previous outbreaks could not create a
detectable or highly visible “cluster” of microcephaly cases. Or there
may be other co-factors unique to Brazil that have helped make the
outbreak of neurological outcomes possible and apparent.
Expected Future Wave
of Cases
Another reason given by CDC Director Tom Frieden
is that “we’re not surprised not to see cases of microcephaly
in other countries because of the time frame between infection and
delivery.” This assumes Brazil was one of the earliest affected areas
and that a wave of cases will occur as time passes in other parts of
the Americas.
There is a suspicion that these numbers may include
over-reporting and misdiagnosis so that the correct number is still in
doubt. Another recent report on the WHO data portal suggests there has
been significant under-reporting of cases prior to 2015. Their best
estimate of the background rate is some 10 times higher than official
estimates or 2,725 cases annually with a minimum incidence of 92 per
100,000. This would make the current outbreak less extraordinary than
initially believed.
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