Monkey study reveals Zika damage in developing brain

Pig-tailed macaque
Pig-tailed macaque

muuraa / iStock

Showing the closest link yet between Zika virus and fetal brain injury in an animal model that closely resembles humans, researchers today described brain abnormalities in the fetus of a macaque experimentally infected during the late stage of her pregnancy.

In other developments, Thailand reported several more Zika cases, many of them linked to a cluster in Bangkok, as the number of infections in Singapore grew steadily. In Florida, health officials denied a newspaper report charging problems with Zika reporting, and Broward County began aerial spraying withan organic pesticide as a prevention step.

Brain damage patterns similar to human findings

Researchers based at the University of Washington Health Sciences inoculated a 9-year-old pregnant pigtail macaque at five locations on the forearm with a Zika dose designed to approximate that of a probing and biting mosquito. The mother was inoculated at 119 days of gestation, which corresponds to about 28 weeks of a human pregnancy.

The group reported its findings today in Nature Medicine.

The researchers noted that primates are a useful animal model for studying Zika virus, because gestations—including the structure of the placenta—and timing of nerve and brain development are similar.

They used a 2010 Zika strain from Cambodia, which is nearly identical to the one that fueled Brazil's outbreak. The mother didn't show any symptoms, such as fever, rash, or conjunctivitis. However, it didn't take long for the scientists to see changes on the images they used to monitor the fetal brain.

Lakshmi Rajagopal, PhD, project leader and associate professor of pediatrics at University of Washington Medical Center, said in a press release from the center, "We were shocked when we saw the first MRI [magnetic resonance image] of the fetal brain 10 days after viral inoculation. We had not predicted that such a large area of the fetal brain would be damaged so quickly." The researchers saw periventricular lesions in the occipital-parietal lobes.

Weekly ultrasounds had also shown a growth lag in the fetal biparietal diameter. White matter stopped growing about 3 weeks after inoculation at a rate that would have resulted in microcephaly, according to the report.

Rajagopal added that the speed of the damage hints that the strategy to prevent fetal brain injury may need to be a vaccine or a preventive medicine taken at the time of the mosquito bite. "By the time a pregnant woman develops symptoms, the fetal brain may already be affected."

Researchers conducted a cesarean section at 162 days gestation, near the mother's due date, corresponding to about week 38 of a human pregnancy. Autopsy revealed Zika virus in the fetal brain at levels higher than in the mother, as well as evidence of the virus in the eye, liver, and kidney.

Krista Adams Waldorf, MD, the study's lead author and professor of obstetrics and gynecology at the University of Washington, said in the press release, "Our results remove any lingering doubt that the Zika virus is incredibly dangerous to the developing fetus and provides details as to how the brain injury develops."

Patterns seen in the infected pregnant macaque and her fetus seem to parallel congenital Zika infections in humans, and the investigators note that the white matter injury would likely lead to visual problems and neurodevelopmental delay.

The team wrote that more studies are needed to investigate the fetal injury mechanisms, adding that the pigtail macaque, which is known to be susceptible to multiple flaviviruses, may be very useful for testing vaccines that drugs developed to curb Zika-related birth defects.

Cases climb in Thailand, Singapore

Against the backdrop of a sudden rise in Zika cases in Singapore, Thailand yesterday announced 22 new cases, including that of a pregnant woman who reportedly gave birth with no complications, Reuters reported today. The cases are all from an area in Bangkok's central business district.

According to the report, Thailand has confirmed more than 100 Zika infections since January and is monitoring 30 pregnant women, including 6 that have given birth with no apparent complications, Reuters said, citing the country's health ministry.

Health and local officials are downplaying the Zika risks, due to concerns about the tourism industry and because of perceptions that dengue, which is more widespread in the country, is a more serious threat, Reuters reported.

Meanwhile, over the weekend and through today Singapore reported 29 more cases, putting its total since the end of August at 329. Its health ministry noted yesterday that it is monitoring eight pregnant women with Zika infections. An overview on Zika clusters from Singapore's National Environment Agency indicates that 4 of those cases were reported today.

Elsewhere in Asia, Japanese health officials today confirmed a Zika infection in a Vietnamese woman who sought care at a Tokyo hospital, Japan Times reported today. The women was infected in Vietnam, a Japanese health ministry official said. Her illness was the first confirmed in Tokyo, though the country has reported 11 cases since 2013, all of them imported.

Both Vietnam and Thailand are on the World Health Organization's (WHO's) list of countries with possible endemic transmission or evidence of local mosquito-borne Zika infections in 2016.

Florida developments

The Florida Department of Health (Florida Health) today issued a statement on a Sep 10 Miami Herald report that said health officials are underplaying the scope of Zika spread, possibly because of concerns about the impact on tourism.

The Herald story said the state wasn't reporting infections in tourists exposed to the virus in Florida and was scaling back the level of detail about its investigations.

Florida Health said the story is misleading and that the claims in it are "inaccurate." It said its staff provides updated information on its Zika response daily, but noted that confirming or ruling out a local case can take a week or two.

Herald reporters pointed out that the health department doesn't specify how many local cases involved pregnant women. In its response, Florida Health said it is working to strike a balance between protecting patient privacy and providing information critical to protecting public health. The agency added that knowing the pregnancy status of people infected locally is not necessary information to protect public health.

Meanwhile, Broward County began aerial spraying early this morning, targeting six areas with Bti (Bacillus thuringiensis israelensis), an organic larvicide. In a Sep 9 statement, the county said the areas were chosen based on requests from Florida Health, population density, and the number of women of childbearing age.

Florida Health's Broward County Director Paula Thaqi, MD, MPH, said there's no active Zika transmission in Broward County and no active investigations. She said one case from the county was confirmed, but the case was closed and officials determined no one else was infected.

See also:

Sep 12 Nature Med abstract

Sep 12 University of Washington press release

Sep 12 Reuters story

Sep 11 Singapore health ministry statement

Singapore NEA Zika cluster Web site

Sep 12 Japan Times story

Sep 8 WHO weekly Zika situation report

Sep 12 Florida Health statement

Sep 10 Miami Herald story

Sep 9 Broward County press release

This week's top reads