The curious case of larvicides causing microcephaly

microcephaly comparison - CDC, National Center on Birth Defects and Developmental Disabilities
Microcephaly comparison. – Image: CDC, Natioanl Center on Birth Defects and Developmental Disabilties

In the beginning, a rather ludicrous rumour made the rounds — genetically modified mosquitoes released in Brazil, by a British biotech company Oxitec to control Aedes aegypti mosquitoes that cause dengue, was responsible for the Zika virus disease outbreak. The conspiracy theory was started by one Redditor who proposed the link.

The genetically modified mosquitoes are unlikely to have caused the outbreak as the male mosquitoes carrying a dominant lethal gene that cause the mosquito larvae to die before adulthood. Even the location of release of the GM mosquitoes and the Zika outbreak were separated by around 400 miles.

Next, anti-vaccine groups claimed that the TDAP vaccine given to pregnant women to protect against diphtheria, pertussis and tetanus was causing microcephaly (babies born with a small head or the head stops growing after birth). But the propaganda lost steam as the group could not prove how the vaccine given to pregnant women well after the head has fully developed could cause microcephaly.

Now, an Argentine doctors’ organisation, the University Network of Environment and Health has claimed that the pyriproxyfen larvicide added to drinking water and not Zika virus may be the responsible for the elevated number of suspected microcephaly cases reported from North-east Brazil.

“Malformations detected in thousands of children from pregnant women living in areas where the Brazilian state added pyriproxyfen to drinking water is not a coincidence, even though the Ministry of Health places a direct blame on Zika virus for this damage,” the report says.

Despite the Zika virus being found in the placenta, amniotic fluid of mothers and in the brains of foetuses and newborns, researchers and the WHO have only suggested a strong association between the virus and microcephaly; the causal link between the virus and microcephaly is yet to be established. “The latest evidence suggests that Zika virus infection during pregnancy may be linked to microcephaly in newborn babies. No scientific evidence to date confirms a link between Zika virus and microcephaly,” a February 12 WHO Zika situation report notes.

However, in the case of the larvicide, leave alone finding the causal link between the chemical and microcephaly, even a strong association between pyriproxyfen and microcephaly has not been scientifically proven. The larvicide has been used for the last 18 months.

“Pyriproxyfen is a growth inhibitor of mosquito larvae, which alters the development process from larva to pupa to adult, thus generating malformations in developing mosquitoes and killing or disabling them. It acts as an insect juvenile hormone or juvenoid, and has the effect of inhibiting the development of adult insect characteristics (for example, wings and mature external genitalia) and reproductive development,” the report notes.

No basis

According to an article published in the Wall Street Journal, Medardo Ávila Vazquez, a pediatrician and neonatal development specialist at the Universidad de Córdoba who belongs to the group, has “acknowledged that the group hasn’t done any lab studies or epidemiological research to support its assertions, but it argues that using larvicides may cause human deformities.”

Even in its report, the doctors from the Brazilian Association for Collective Health (ABRASCO) have demanded that “urgent epidemiological studies” be undertaken to find the causal link.

Meanwhile, during the weekend, health officials in Rio Grande do Sul took cognisance of the report and suspended the use of the larvicide Pyriproxyfen to destroy mosquito eggs and larvae in the state’s drinking water supplies as a “preventive measure.”

The ban was imposed despite the Brazilian government and U.S. health authorities asserting that there was no scientific basis linking use of the chemical to the birth defect.

Higher incidence

A paper published in “Zika Open,” a collection maintained by the World Health Organisation to post papers within 24 hours while undergoing peer review, reveals that contrary to the general notion, every year the number of babies born with microcephaly may be higher in Brazil.

In Paraíba, one of the nine States within the epicentre of the epidemic, has a database that has information about 100,000 neonates born since 2012.  The researchers were able to cull the head circumference data of 16,208 neonates.  Surprisingly, at 2-8 per cent (depending on the classification criteria used) the incidence of microcephaly was “much higher than expected.”

What comes out clearly from this study is that the number of cases of microcephaly has been higher even before the Zika outbreak and the start of larvicide use.

Need for caution

According to a February 5 paper in The Lancet, the number of microcephaly cases reported must be interpreted with caution. Before 2015, the number of reported cases annually in Brazil was below 200. But it shot up between mid-2015 and January 30, 2016 to 4,783 suspected cases. Of these cases, clinical, laboratory, and imaging examinations have been completed only in 1,103 cases, and “404 (36.2 per cent)” children have been confirmed as having microcephaly. “Among the confirmed cases, brain abnormalities were detected by imaging in 387 babies and Zika virus was detected in 17 babies, including in two foetal losses.”

One of the reasons for elevated numbers could be the higher cutoff used for classifying microcephaly. Till December 8, 2015, Brazil used head circumference of less than or equal to 33 cm as cutoff for term newborn babies (both sexes and all gestational ages); it was reduced to 32 cm since then.

Also, the use of fixed cutoff head circumference measurements for all term infants may be inappropriate, the journal states. The reason: “about 68 per cent of term newborn babies in Brazil are below 40 weeks’ gestational age.” Brazil has the “highest caesarean section rate in the world.”

According to the WHO, there are “many potential causes of microcephaly, but often the cause remains unknown. The most common causes include: infections in the womb: toxoplasmosis (caused by a parasite found in undercooked meat), rubella, herpes, syphilis, cytomegalovirus and HIV; exposure to toxic chemicals: maternal exposure to heavy metals like arsenic and mercury, alcohol, radiation, and smoking; genetic abnormalities such as Down syndrome; and severe malnutrition during foetal life.”

Published in The Hindu February 16, 2016

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