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New test results from the Centers for Disease Control and Prevention provide the best evidence to date that a mosquito-borne virus is causing Brazil’s alarming rise in babies born with abnormally underdeveloped heads, a top official said Wednesday.

The results are not definitive proof that Zika virus infections during pregnancy are causing some women to give birth to babies with microcephaly, but they add to mounting evidence that the large wave of infections that began in Brazil last May is linked to the extraordinary increase in microcephaly cases.

“I wouldn’t use [the term] smoking gun, but what I would say is that these data provide the strongest evidence to date of a possible link between Zika virus and microcephaly and other congenital abnormalities,” Dr. Lyle Petersen, the director of the CDC’s division of vector-borne diseases, told STAT.

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Brazil said it has recorded at least 3,530 cases of microcephaly and 46 deaths since the increasing number of cases was recognized last October. The country saw fewer than 200 cases of microcephaly annually over the previous five years. 

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Zika virus is transmitted to people by two species of mosquitoes, Aedes aegypti and Aedes albopictus. (The latter is thought to play a more minor role in spread.) Both those species are found in parts of the southern United States.

To date the virus’s rapid spread through South and Central America has not led to discoveries of infected mosquitoes in continental United States. But in late December, the CDC reported an infection in a resident of Puerto Rico who had not traveled.

A few US travelers have been infected outside the country and have tested positive for infection after returning home. One such case was reported this week in Houston.

As the virus sweeps through countries to the south, Petersen said, more of these imported cases will occur.

“There could be very large numbers of people returning. And they would return to basically every state,” he said.

Scientists at the CDC examined the brains of two infants who died within 24 hours of being born with microcephaly, as well as placenta samples from two women who miscarried fetuses with the condition.

Researchers in Brazil — where a more than twentyfold increase in the rate of babies born with microcephaly has been seen in the past few months — had earlier found evidence of Zika virus in amniotic fluid drawn from two pregnant women who were carrying fetuses diagnosed in utero as having microcephaly.

Using two different types of tests — polymerase chain reaction, or PCR, and immunohistochemistry — the CDC scientists found evidence of Zika virus in the brains of the newborns who died. Petersen said this provides “very strong evidence of infection in the brains of these two infants.” The placenta samples also tested positive for the virus by PCR.

The accumulation of evidence pointing to Zika virus as the cause of the microcephaly cases has led Scott Weaver, an expert in arboviruses — viruses transmitted by mosquitoes, ticks, and fleas — to question why the CDC has not warned pregnant women or women of child-bearing years who might get pregnant to avoid travel to locations reporting Zika virus circulation.

Such a warning might have a significant impact on travel to Brazil in the lead-up to this year’s Summer Olympics in Rio de Janeiro.

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Still, Weaver, director of the Institute for Human Infections and Immunity at the University of Texas Medical Branch in Galveston, said he is surprised the CDC hasn’t issued such a warning.

Petersen said the agency is in the process of updating its advice for Americans who might be traveling to countries where they could become infected with Zika virus. It will address the issue of the risk to pregnant women, he said, but he would not give specifics. Petersen said the revised guidance will be issued “in the next day or two.”

Petersen said the CDC is also working with the Council of State and Territorial Epidemiologists to increase reporting of Zika infections in the US. States are currently not required to notify the CDC of Zika cases, but the CDC is hoping states and territories will voluntarily report infections that come to light.

Tracking the disease in the US may be tough, however. Zika infections are typically mild.  An infected person may experience a fever, flu-like fatigue and aches and may have a skin rash. Such symptoms might not prompt people to see their doctors ­ — while doctors may not think to test for Zika virus.

Other difficulties lie ahead as this virus continues to move, a New England Journal of Medicine article makes clear.

Developing a vaccine to prevent Zika infections will pose significant challenges, warned Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and Dr. David Morens, a medical historian at the institute.

Epidemics with mosquito-borne viruses like Zika, West Nile, and others are sporadic and unpredictable. “Preemptively vaccinating large populations in anticipation of outbreaks may be prohibitively expensive and not cost-effective, yet stockpiling followed by rapid deployment may be too slow to counter sudden explosive epidemics,” they said.

Fauci and Morens suggested broad-spectrum drugs capable of treating multiple viruses are urgently needed. That call comes the same day a report on learning from the lessons of West Africa’s Ebola outbreak called for the creation of a WHO committee charged with spurring development of drugs and vaccines needed to combat disease threats, to ensure the world does not again face a deadly disease without any vaccines or drugs to curb its spread.