HEALTH:

Researchers link infant brain infection to central African rainfall

A grotesque and devastating brain condition that stalks infants in sub-Saharan Africa waxes and wanes with rainfall, opening a new door for how health officials can manage it, according to recent findings.

Researchers studying hydrocephalus in Uganda found that the infections leading to the condition surge around the edges of the region's rainy seasons. The results reveal a previously unknown link between climate and this neurological condition. The scientists published their findings late last year in the Journal of Neurosurgery: Pediatrics.

Hydrocephalus, according to the National Institutes of Health, arises when cerebrospinal fluid builds up in pockets in the brain. This happens when birth defects and certain infections inflame brain tissues, closing off the passages that let these fluids circulate, thereby increasing pressure inside the skull. This debilitating illness can damage cognition and swell the heads of infants whose skulls are not fully fused.

The condition is the most common reason for neurosurgery in children around the world. Scientists estimate there are 100,000 cases of hydrocephalus stemming from infection in sub-Saharan Africa annually. Of the infants who survive, within five years one-third are dead, one-third are severely impaired and one-third remain healthy.

"Once a sick infant comes in with a substantial infection, you've lost part of the game already," said Steven Schiff, director of the Center for Neural Engineering at Pennsylvania State University and a co-author. "The scale of these problems is far, far out of proportion with the priority that the global health community has given it."

Searching for clues

In addition, tracking down the culprits behind hydrocephalus poses a tremendous challenge, let alone treating and preventing it. Many hydrocephalus cases emerge in the developing world, areas with few diagnostic and treatment options. By the time most mothers bring their babies with swollen heads and bulging eyes to a clinic, the infection itself is gone, so doctors have a hard time figuring out which specific pathogens are causing the disease.

Treatment typically involves placing a shunt, a tube that drains excess fluids from the brain to another part of the body. However, infections plague shunts in poverty-stricken areas, and when blocked, shunts create life-threatening complications.

But researchers found some leads in fighting hydrocephalus. Benjamin Warf, director of neonatal and congenital anomaly neurosurgery at Boston Children's Hospital and another co-author, said the issue piqued his interest in 2000, when he opened the CURE Children's Hospital of Uganda in Mbale.

"From the day we opened our gates there, after 2000, there was a steady stream of mothers coming in with babies with severe hydrocephalus," Warf said. "That turned out to be the single biggest issue we had to deal with."

Warf and his team responded by taking more rigorous data, conducting ultrasound and computer tomography scans, and tracking patient histories and infection timings. "The thing that became obvious was that 60 percent of our young children clearly had the hydrocephalus secondary to infection, and almost always it was a neonatal infection, an infection in the first month of life," he said.

The infection usually came in the form of neonatal sepsis, a blood infection. However, doctors could not culture a pathogen from afflicted babies because the organisms would burn themselves out, though not before doing significant damage. Health officials also had a hard time anticipating when these conditions would emerge. "There were times we would see a deluge of patients," Warf said. "I could never make any sense of the pattern."

Finding them in rainfall data

After visiting Warf in Uganda, Schiff took some samples from patients to see whether he could find traces of an infectious agent, conducting a genomic analysis to see what organisms he could piece together and how they changed in different environments and circumstances. He also collected soil samples and residues from the homes of infected children.

On top of this, Schiff and his team used National Oceanic and Atmospheric Administration rainfall data and climate models to develop a high-resolution precipitation map of Uganda, studying patterns at the district level. Piecing this information together, Schiff found four infection peaks per year, straddling the apexes of Uganda's two wet seasons.

"It was very obvious in the raw data," he said. "These children were getting brain infections in intermediate [rainfall] levels."

The researchers theorized some mechanisms behind this phenomenon. "Newborn infants in central Africa are born in an environment where there is a tremendous amount of exposure to environmental materials," Schiff said. He noted that in rural areas, infants contend with livestock regularly, especially animal dung, which people use as a building material and as a fuel.

In dry conditions, the bacteria from animals or soil that cause hydrocephalus may be dormant or die off. Under heavy rains, the water may dilute the bacteria too much to cause many infections. But when the climate conditions are just right, the environment in rural communities forms a deadly festering brew. Another possibility is that an insect like a mosquito that thrives in these rainfall conditions spreads the disease.

Gains in a $1B puzzle of pain and poverty

By tracking these infection sweet spots, the researchers hope to create disease forecasts that can help families and health officials take precautions. The scientists also want to trace which pathogen is most likely causing hydrocephalus during a given time of year, because different bacteria peak at different times and in different locations. This way, doctors can begin treatment earlier for the likely pathogen instead of burning through precious time waiting for test results to give a precise answer or using a scattershot course of antibiotics.

"The ultimate goal is to try to identify the common organisms and how they change with region and climate," Warf said. With a better handle on these variables, medical personnel can also anticipate how these patterns will change with greater urbanization, changes in land use and a shifting climate.

Hydrocephalus infection forecasts can also help guide development efforts. In a previous study, Warf found that the economic benefit of treating hydrocephalus in sub-Saharan Africa exceeds $1 billion. With a regional model of infection risk, health officials can better allocate resources and focus on the most effective strategies for a given area, whether it's improving housing or enhancing water quality or mosquito control measures. In turn, prevention and treatment can help people in rural areas break the cycle of poverty and build better lives for themselves and their children.

Doctors are also pursuing other treatment options. "We push the envelope a bit on treating hydrocephalus without putting in a shunt," Warf said. One alternative technique some doctors favor, called endoscopic third ventriculostomy, uses an endoscope to create an opening inside the brain, allowing cerebrospinal fluid to circulate and avoiding a shunt.

Both Schiff and Warf are in Africa this week to continue their efforts. Schiff said his next project is to assess how the land plays a role in these infections, seeing where and how topography influences infection patterns. Another important aspect, according to Warf, is to construct health policies that address the root causes of these infections, especially the social elements like education and living standards.