Zika virus not yet proved guilty
The illness appears linked to the birth defect microcephaly, but there is still a reasonable doubt.
The Zika virus has been indicted for a mysterious increase in cases of microcephaly, a rare birth defect that can leave a baby with an unusually small head and underdeveloped brain. The circumstantial evidence coming out of Brazil is so compelling that Dr. Margaret Chan, head of the World Health Organization, called Zika a threat of “alarming proportions.”
But if this were a murder trial, prosecutors would still have a long way to go to prove Zika’s guilt.
“It’s entirely possible there’s something else going on in Brazil — something unique to the population or environment in which transmission takes place,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
Some babies born with microcephaly have no apparent link to Zika, and many women who believe they were infected during pregnancy have given birth to healthy babies.
There are good reasons to suspect Zika. The virus was found in the severely underdeveloped brain of a 29week- old aborted fetus, according to a report this month in the New England Journal of Medicine. A subsequent study in the medical journal Lancet identified Zika in the amniotic f luid of infected pregnant women car- rying microcephalic fetuses.
But the search for a def initive culprit has become more urgent with the rising number of infections in the U. S. and around the world. So far, there have been 107 cases in the U. S., although all were acquired overseas. The total includes one infant with microcephaly whose mother had traveled to Brazil.
Brazil — ground zero of the microcephaly outbreak — has tallied at least 5,640 suspected and confirmed cases.
“We’re pretty clear that Zika is causing this,” said Dr. Albert Ko, an infectious- disease physician and epidemiologist at Yale who is helping Brazilian health authorities investigate the outbreak. “But we need to f irm those suspicions up.”
The Zika virus was f irst identified in 1947 in a rhesus monkey in Uganda’s Zika Forest. Five years later, it turned up in people in Uganda and Tanzania.
Over the next three decades, the virus spread through equatorial Africa and into Pakistan, Indonesia, Malaysia and other parts of Asia. Even as its footprint grew, human infections remained mild and rare.
Typical symptoms included a rash, red eyes, muscle aches and fever. They appeared to affect a minority of those infected and did not last long.
The virus was carried from Africa in the blood of mosquitoes in the Aedes genus. The insects pick it up by feeding on the blood of infected animals. The virus multiplies in the mosquito’s gut and migrates to the salivary glands, then spreads to a fresh victim when the mosquito has another meal.
The f irst hint that Zika might pose a serious threat came in 2007, when the virus took hold in the Micronesian island nation of Yap, situated about halfway between the Philippines and Guam with a population on the main islands of about 7,500.
In a four- month period in 2007, epidemiologists conf irmed 49 active Zika infections and identified an additional 59 probable infections. Experts estimated that between 68% and 88% of Yap citizens older than 2 had been infected with the virus, according to a 2009 report in the New England Journal of Medicine.
By 2013, Zika had spread to French Polynesia, where doctors confirmed 383 hu- man cases. Researchers believe about 11% of the territory’s roughly 275,000 inhabitants were sickened by the virus during a sevenmonth period, according to the European Center for Disease Prevention and Control.
At the time of the outbreak, doctors identified 42 people who suffered Zika-like symptoms and went on to develop Guillain- Barre syndrome, a mysterious disease in which the immune system attacks the body’s peripheral nervous system. Patients feel tingling and weakness in the legs, arms and upper body; in extreme cases, it can lead to paralysis and become life- threatening. However, health authorities could not say whether the cases were caused by Zika — especially because dengue was circulating in the region at the same time.
Over the next year, officials turned up a dozen cases of fetuses and infants with cerebral malformations typical of microcephaly, which often results in neurological problems and cognitive deficits. Although none of the women who carried these pregnancies had outward signs of Zika infections, four who were tested had antibodies to a Zika-type virus in their blood.
Zika may have gained a foothold in Brazil as early as December 2014, when patients in the northeastern state of Pernambuco began reporting mild skin rashes. Similar patients appeared in nearby states in early 2015. By April, doctors reported nearly 7,000 cases.
In July, officials conf irmed 49 cases of Guillain-Barre in the area. Most of these patients had previously been infected with Zika, dengue or chikungunya.
In Salvador, Brazil’s third- largest city, Dr. Manoel Sarno was among the f irst to report a sudden in- crease in microcephaly cases. In the space of two weeks in July, the maternalfetal medicine specialist diagnosed 40 cases of microcephaly in developing fetuses or babies born to his patients. Normally, his practice would see five or six such babies in an entire year.
Although the number of miscarriages has not been recorded, Sarno said he has seen a dramatic increase in these as well.
The surge was shocking, Sarno said, and its link to Zika was persuasive: Fully 82% of these babies’ mothers recalled having had symptoms typical of Zika infection during their pregnancies, most during their first trimesters. Questionnaires aimed at detecting other possible factors — such as alcohol consumption, socioeconomic status and medicines taken — found no clear patterns, he said.
Of the 5,640 suspected and confirmed cases of microcephaly in Brazil, officials have linked only 41 to laboratory- confirmed Zika infection in the mother, but the Health Ministry said it presumes most of the mothers of microcephalic babies were infected with the virus.
In addition, 30 “child deaths” — either during pregnancy or after birth — have been attributed to microcephaly and other central nervous system defects associated with Zika, and 80 more remain under investigation.
There are no blood tests that can reliably confirm a past Zika infection. Even if there were, all it would pro- vide epidemiologists is an association with microcephaly, not an explanation for it.
Many mothers of affected newborns may have been infected with other viruses in addition to Zika. Viral co- infections can sometimes have synergistic effects.
Health officials are also considering the possibility that an environmental toxin bears some responsibility for the microcephaly cases.
The Brazilian state of Rio Grande do Sul recently suspended use of pyriproxyfen, a larvicide used to control mosquitoes that was introduced in 2014.
Another potential scenario is that Brazilian women are more likely to have a genetic variant that increases the risk of microcephaly when they contract Zika during pregnancy.
All of these could be the case, or none.
For now, epidemiologists have their hands full trying to nail down some basic facts.
To build a case, they need to know what the “background rate” of microcephaly in Brazilian babies was before the current increase, and how often those microcephaly cases were linked to infections that can cause birth defects, such as cytomegalovirus or rubella.
They also need to know how many pregnant women must be infected with Zika to produce one microcephalic child, as well as the point during pregnancy when infection has to occur.
Another key piece of evidence is the number of microcephalic babies that are born to women with no history of Zika infection.
Unlike many countries now contending with Zika, Brazil has a well- functioning public health system. But off icials there are still unsure how much of the increase in microcephaly is due to better reporting by doctors and how many cases ought to be ascribed to other infections known to cause fetal brain abnormalities.
Until more evidence is in hand, there will be uncertainty as to whether, how often, and in whom Zika infection causes microcephaly.
“There’s so much that we don’t know, and that we need to know,” said Ko, the infectious- disease physician.