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Expected Increase In Microcephaly Cases In Brazil Fails To Materialize
Good News For
Public Health Creates A New Epidemiologic Mystery
Despite the fact that the Zika epidemic has spread
throughout Brazil since first being detected in early 2015, almost 90%
of microcephaly cases have been clustered in a relatively small
portion of the northeastern corner of the country where the epidemic
first took off (see WHO map below). Health officials expected a
similar surge in microcephaly to follow in the rest of the country,
but so far that has yet to materialize.
For instance, adjacent to the areas experiencing the
highest levels of microcephaly is Brazil’s second-most populous state,
Minas Gerais, which has reported only 3 cases of microcephaly to
date. Similarly, the rest of Brazil has seen only modest increases in
microcephaly despite widespread Zika transmission, leading officials
to question if Zika alone is truly responsible for the large increase
in severe brain abnormalities.
The Mystery
Fatima Marinho,
the Brazilian Health Ministry’s director of information and health
analysis, recently told the Globe and Mail,
“We know here Zika caused neurological damage – we have
no doubt – but the question is how can we explain this situation in
the epicentre that was not reproduced in other areas – in Colombia,
and in other states in Brazil. A lot of pregnant women were infected
and there were few cases of microcephaly or congenital malformation –
it must be more than Zika itself.”
Mystery In Columbia
A lot of attention is being paid to neighboring
Colombia, where nearly 100,000 suspected cases of Zika have been
reported since August of 2015 and as of yet there have been only 18
cases linked to birth defects. A preliminary report on the status of
Zika virus in Colombia published in June in the New England Journal of
Medicine found no birth defects or brain abnormalities at all in a
cohort of over 600 Colombian babies whose mothers showed symptoms of
Zika virus infection during their third trimester1. At the
same time, the overall levels of microcephaly reported in Colombia
have yet to show a significant increase. However, data from Brazil
have shown that there is a far greater risk of birth defects from
infection during the first or second trimester and the majority of the
pregnant women with first and second trimester infections have not yet
delivered.
New Study
Sparked by the unusual
geographic distribution of microcephaly cases, the Brazilian Health
Ministry is launching an official probe
enlisting the help of Oliver Brady, an
epidemiologist from the London School of Hygiene and Tropical
Medicine, and Simon Hay, the director of geospatial science at
the Institute for Health Metrics and Evaluation in Seattle. The study
is aimed
at identifying cofactors that may be acting in concert with Zika virus
infection to produce severe birth defects.
Leading Hypotheses
The Health Ministry’s new probe will explore a number
of theories that may explain the high density and severity of
microcephaly cases in northeastern Brazil.
1) One of the more frequently discussed hypotheses is
that co-infection with another virus either before or simultaneous
with Zika may alter the way the viruses interact with the mother and
fetus. Both dengue and chikungunya are endemic to Brazil and some
parts of the highly-affected northeastern region even experienced
measles during this time period.
2) Similarly, researchers at the Federal University of
Rio de Janeiro recently reported preliminary findings in an online
preprint describing the discovery of bovine viral diarrhoea virus (BVDV)
proteins in the brains of three fetuses with microcephaly2.
BVDV has not been known to infect humans but causes birth defects in
cattle.
3) Others have raised the possibility that
socio-economic factors may play a role, as mothers of affected fetuses
are overwhelmingly black or mixed-race (77% compared to52% of the
total population). The majority of these women are also poor, in
contrast to infection patterns of dengue which affects socio-economic
classes more equally in Brazil despite being transmitted by the same
mosquitos as Zika.
4) Finally, a recently published paper examined whether
vaccination patterns could be a potential factor3. The
authors found that clusters of microcephaly cases in the northeast of
Brazil overlapped with areas of the lowest yellow-fever vaccination
coverage in the country. The authors suggest that prior vaccination
for yellow fever may convey some protection against Zika, as they are
related flaviviruses. In fact, prior studies have shown that
flavivirus infections can produce cross-reactive antibodies for other
members of the virus family.
The Data Problem
Experts question the reliability of Brazil’s data and
estimates of microcephaly rates prior to the epidemic are considered
inaccurate. Many believe there was overreporting of microcephaly cases
once the epidemic took off and very few of these had confirmed
positive lab tests for Zika. Ernesto Marques, a professor of
infectious disease and microbiology at the University of Pittsburgh,
summed up the situation to the Globe and Mail, “The current
epidemiological info is very fragile.” As part of investigating
potential cofactors, an essential part of the Ministry’s new probe
will be a thorough reexamination of the microcephaly data itself and
how it’s being collected across different regions of the country.
Delay In Getting An Answer
Unfortunately, it might require time and the collection
of more solid data as the epidemic spreads across South and Central
America before scientists and public health officials can truly
address the role of cofactors in Zika-related birth defects.
Microcephaly rates in Colombia and the rest of the region over the
next year should go a long way towards answering the question of
whether the pattern in Brazil is a true anomaly. In addition, the
Zika in Infants and Pregnancy Study is now underway in Puerto Rico
tracking 10,000 pregnant women and examining a number of potential
cofactors related to nutrition, environment and socio-economic
status.
1.
https://tinyurl.com/z7bz5lj
2.
https://tinyurl.com/zlcmhls
3.
https://tinyurl.com/hgo5tvh
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