OTIMATI, South Africa —
While around the world a vast majority of AIDS victims are men, Africa has long been the glaring exception: Nearly 60 percent are women. And while there are many theories, no one has been able to prove one.
In a modest public health clinic behind a gas station here in South Africa’s rural KwaZulu/Natal province, a team of Norwegian gynecologists thinks it may have found a new explanation.
It is far too soon to say whether the Norwegian team is right. But even skeptics say the explanation is biologically plausible. And if it is proved correct, a low-cost solution has the potential to prevent thousands of infections every year.
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The team believes that African women are more vulnerable to HIV because of a chronic, undiagnosed parasitic disease: genital schistosomiasis (pronounced shis-to-so-MY-a-sis), often nicknamed “schisto.”
The disease, also known as bilharzia and snail fever, is caused by parasitic worms picked up in infested river water. It is marked by fragile sores in the far reaches of the vaginal canal that may serve as entry points for HIV, the virus that causes AIDS. Eyrun F. Kjetland, who leads the Otimati team, says that it is more common than syphilis or herpes, which can also open the way for HIV.
Also, the foreign bodies in the sores — the worms and eggs — attract CD4 cells, the immune system’s sentinels, and those are the very cells that HIV attacks.
The worms can be killed by a drug that costs as little as 8 cents a pill. Kjetland’s team is trying to determine whether that will heal the sores in young women.
Some prominent AIDS experts doubt the schistosomiasis theory, pointing out, for example, that urban women raised far from infested water also die of AIDS. But proponents of the theory say that two decades ago, many experts were just as skeptical of the idea that circumcision protected men against HIV. It was not until 2006 that three clinical trials proved it correct.
Schistosomiasis “is arguably the most important cofactor in Africa’s AIDS epidemic,” said Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine. “And it’s a huge women’s health issue: Everyone has heard of genital mutilation and obstetric fistulas. But mention this, and the headlights just go dim.”
The idea is slowly gaining ground. The Bill & Melinda Gates Foundation, the United Nations, the National Institutes of Health, and the Danish and Norwegian governments have given grant support. But leaders of the two agencies that pay for the fight against global AIDS want more evidence before diverting funds from their campaigns for condoms, drugs and circumcision.
“We need to track all these things down and see what’s a cause and what’s just another disease you have at the same time, like cervical cancer,” said Mark R. Dybul, executive director of one of the agencies, the Global Fund to Fight AIDS, Tuberculosis and Malaria.
Eric Goosby, who recently finished a five-year stint as coordinator of the other agency, the President’s Emergency Plan for AIDS Relief, or PEPFAR, agreed that vaginal sores could help the virus enter. “But it’s complicated,” he added. “A lot of women who have HIV don’t have schisto, and vice versa.”
From her small clinic just off the highway here, Kjetland makes visits to high schools where she has government permission to work because their communities have the highest rates of schistosomiasis. On the dirt roads of the Valley of a Thousand Hills, it can take her hours to reach each one.
Through school nurses, she gives deworming drugs to all students, male and female. (To her frustration, although the drug is sold by generic makers for as little as 8 cents a pill, South African patent laws permit only the Bayer version, which costs $4.)
Then she meets with groups of girls ages 16 and up to ask the sexually active ones to come to Otimati for gynecological exams and blood tests.
“I am as gentle as I can be, much more gentle than sex is for them,” she said, “but even the slightest touch and they bleed.”
Gentleness is part of Kjetland’s nature. A 49-year-old stepmother of five, she watches like a mother over the girls in her study. She ordered that extra rooms be built where they can cry if they test positive for HIV. She tries to make sure the boys in their schools never realize she chooses only sexually active girls. And she has KFC delivered, since it is a treat for girls who often have only cornmeal mush to eat for days on end.
Though trained in Norway, she has spent most of her life in Africa, growing up in Tanzania as the eldest of a missionary couple’s six children, attending prep school in South Africa, and, after college and medical school in Norway, doing graduate work in Malawi and Zimbabwe.
An estimated 200 million Africans have had schistosomiasis. Although rarely fatal, the bleeding it causes in children can lead to anemia, stunted growth and learning problems. It is caused by tiny worms that live in freshwater snails and emerge with pointed heads that can penetrate the skin of people collecting water or washing clothes.
Once inside, the worms mate, with the female living in a cleft in the male’s body “like a hot dog in a bun,” Kjetland said. Most nest in the urinary tract — bloody urine is a symptom — but a portion end up in the vagina, creating “sandy patches” of damaged tissue and calcified eggs.
Studies by Kjetland in Zimbabwe and South Africa and by Jennifer A. Downs of Weill Cornell Medical College in Tanzania have shown that women with the patches are about three times as likely as their neighbors to be infected with HIV. A gold standard study to prove the connection would be both impractical and unethical: Researchers would have to divide hundreds of infant girls into two groups, give half deworming drugs and half placebos, wait until they were perhaps 20 years old, and see how many had HIV. No ethics board would approve placebos under those conditions.
So Kjetland studies teenagers, hoping to heal their sores and see if their HIV infection rates are lower than the norm. (In grown women, the sores persist even after the worms die.)
For years, theories have abounded as to why African women become infected with HIV: for example, that they are more likely to have overlapping sexual partners — not always by choice — while women elsewhere have boyfriends or husbands in series. That rape, incest and domestic violence are rife in southern Africa, where the AIDS epidemic is worst. That syphilis and herpes are rampant. That impoverished, fatherless young women are forced to pay with sex for food, clothes, grades and even car rides.
The schisto hypothesis can now be added to that list, but to some prominent experts it remains unlikely. One is Daniel Halperin, an epidemiologist at the Ponce School of Medicine and Health Sciences in Puerto Rico. He knows how it feels to be doubted: In the 1990s, he was the chief proponent of the theory that circumcision protected men against HIV.
He argues that tropical West Africa, where schisto is common, has little HIV, while countries with little schisto, like arid Botswana and mountainous Swaziland, have sky-high HIV rates.
Salim Abdool Karim, a renowned South African AIDS researcher who admires Kjetland’s work, is also skeptical. His team follows more than 1,000 women in an area only 40 miles from Otimati with equally high HIV rates.
“We’ve studied genital tracts in detail for 20 years, photographing them sequentially,” he said, “and we see no sandy patches.”
Upon hearing that, Kjetland reached for the mounted magnifying scope she uses to examine girls. “They’re not looking in the right places,” she said.
Most gynecologists, she explained, are trained to look for cancer, which usually starts near the center of the cervix, while sandy patches are tucked away in crevices that can be seen only by swinging the scope to extreme angles, she said. It takes her weeks to train doctors to find them consistently, she said.
Fighting schisto across Africa would take extensive pill distribution, but Hotez, the Baylor dean, argues that it is worth it.
Seventy million African children could be dewormed twice a year for 10 years at a cost of $112 million, he said in an essay titled “Africa’s 32 Cents Solution for HIV/AIDS” (32 cents being the cost of two generic deworming pills twice a year). That is cheap compared with the $38 billion PEPFAR is expected to spend on AIDS in that period, he said.
A vaccine would be even better, and several are in development, including one at the Sabin Vaccine Institute, which Hotez also heads. But even if one works, “it will be at least five to 10 years before the testing is finished,” he said. “We shouldn’t wait for that.”