Proof Positive


BITOKE BISALILE, UGANDA—It had to be witchcraft. For more than a year, Matia Katongole just kept getting thinner. His stepmother remembers his feet: As the bones showed through ever more sharply, they seemed to elongate.

Matia’s family decided, with rising terror, that the hex had come from Tan-zania. Matia was a trader in beans, rope, pots, and anything else he thought might turn a profit, and he conducted much of his business with Tanzanians across the nearby border. Matia had once bought some goods on credit but failed to fully pay back the loan. Now, he was too weak to make amends and lift the curse, so his father sent one of Matia’s busi-ness partners back across the border with a goat, copious quantities of local banana wine, and 80,000 shillings—far more than the original goods had been worth.

It didn’t work. Less than a month later, Matia’s father was holding his son, trying to give him a little tea. “Matia vomited,” his father recalls, “and died in my lap.”

That was 1980, before villagers here in Uganda’s Rakai District had seen enough patients like Matia to coin their own term for the new disease, Slim, and before enough trickled into clinics for medical authorities to suspect that they had an epidemic on their hands. Not until five years after Matia’s death was Slim proven to be AIDS. This week, after an estimated 14 million Africans have followed Matia’s fate, the first World AIDS Conference ever held on African soil opens, bringing about 10,000 doctors, researchers, and activists to Durban, South Africa.

Past World AIDS Conferences have often slighted the contributions of African science. At the last one, held two years ago in Geneva, the editor of the British medical journal The Lancet noted that whenever third-world speakers rose to present their findings, “seats emptied and the hall began to bleed delegates.” But this conference, chaired by South African doctors, offers a chance to showcase research conducted on the continent where HIV almost certainly originated and where the epidemic is far worse than anywhere else.

But earlier this year, African science got snubbed by a most unlikely source: South African president Thabo Mbeki. Apparently after surfing the Web, Mbeki resurrected the notions of a small group of self-styled “AIDS dissidents,” the most prominent of whom is University of California virologist Peter Duesberg. These AIDS deniers—who have conducted almost no original scientific AIDS research, let alone on the African continent—argue that HIV does not cause AIDS and that the disease does not exist at all in Africa. The estimated 12 million African children orphaned by AIDS have simply lost their parents to the old, endemic diseases of poverty and inadequate sanitation. The full quarter of the adult population thought to be infected with HIV in some African countries carry only a harmless “passenger virus.”

Mbeki recently convened a scientific panel split almost evenly between mainstream researchers and people who espouse such fringe views, catapulting their notions to center stage. Mainstream scientists—at first reluctant to believe that anyone could fall for a theory with hardly more scientific support than Matia’s ideas of witchcraft—are now circulating a sign-on statement declaring that HIV causes AIDS. The prestigious journal Nature plans to publish it.

Mbeki—who along with Nelson Mandela is scheduled to speak at the World AIDS Conference—has seemingly backpedaled. Yet there is no doubt that he seriously entertained the denialist ideas. His office solicited the advice of Duesberg colleague David Rasnick, who responded with a letter coauthored by Charles Geshekter, a professor of African history at California State University, Chico, who often takes the lead in arguing that AIDS in Africa doesn’t exist. After their surreal letter to Mbeki was made public, inciting a storm of criticism, the South African president penned his own letter to Bill Clinton, comparing the AIDS deniers to antiapartheid activists and medieval heretics burnt at the stake. U.S. diplomats were reportedly so shocked they checked to make sure the letter wasn’t a hoax.

What makes this all so extraordinary is that Mbeki—who constantly speaks of leading an “African renaissance” in economics, culture, and science, and who says he consulted the dissidents to help avert a “superimposition of Western experience on African reality”—apparently chose to slight African science in his search for an African solution. Instead, he gave disproportionate credence to a group of mostly Western theorists who seem especially ignorant—indeed, almost contemptuous—of science conducted in Africa and the clinical experience of African physicians.

Yet African research has provided crucial information to the world’s understanding of AIDS, proving, for example, that HIV is not spread by mosquitoes. And now, as the astronomical cost of medication is finally becoming a headline issue, African science is showing that the drugs work every bit as well in African patients as they do in Westerners.

In Uganda, many of the scientists who helped discover the epidemic are still studying it. Their story epitomizes the research of a continent.

David Serwadda’s first inkling was the four patients with Kaposi’s sarcoma. That cancer, called KS, is endemic in Uganda, but largely confined to older men who usually get easily treatable lesions on their arms and legs. From late 1983 through ’84, when Serwadda was doing his residency in Kampala’s Mulago Hospital, four patients—all younger than 45, all from Uganda’s rural Rakai District—presented with an unusual form of the cancer that raged throughout the body. One 26-year-old woman originally came in with the lesions on her head and torso, which was unusual enough. But an autopsy revealed that the cancer had invaded her tonsils, stomach, liver, spleen, heart, and lungs.

In Zambia, a no-nonsense cancer surgeon named Anne Bayley had also seen this new type of KS—13 patients in 1983, eight of whom were dead by the end of that year. She was virtually certain it was related to the new disease that was killing American gay men, many of whom had aggressive KS, so she started alerting colleagues. Serwadda, too, had read about the new disease among homosexuals, and he wrote Bayley about the KS patients he was seeing. But Serwadda wasn’t convinced they had AIDS: “I was thinking, ‘The disease is here already? Even in black heterosexual women?’ ”

The chance to find out came in 1984, when the antibody test was developed for HIV, then called HTLV-III. For best results, blood samples had to be fresh, so Serwadda got up before dawn, drew blood and biopsies, and sent them off to London with a passenger who took them as carry-on. But because of a postal error, Serwadda wouldn’t learn the results for several months.

In the meantime, he was transferred to the medical ward, where he encountered patients wasting away with intractable diarrhea. Many of these patients had a distinctive skin rash or oral thrush, a rare fungal infection that signals immune suppression. “You would ask these patients where they were from,” he recalls, “and it was always Rakai, Rakai, Rakai District. That was very strange.”

What ultimately distinguished the new cases is that they wouldn’t heal. Desperate, the doctors tried treating their patients for TB, or typhoid, or malaria, but patients with Slim would not get better, or would only improve for a short time before succumbing to relentless new infections.

In their letter to Mbeki, Rasnick and Geshekter wrote, “It is nearly impossible to distinguish the common symptoms attributable to HIV disease or AIDS from those of malaria, tuberculosis, or malnutrition.” The speck of truth in this statement is that HIV does not itself cause the illnesses that ultimately kill AIDS patients. Instead, HIV slowly destroys the immune system, leaving the patient vulnerable to whatever microbes circulate in the environment. In the early stages of AIDS, when the immune system is only partly weakened, it can be hard to differentiate an ordinary patient from one infected with HIV. The rare diseases, such as aggressive KS, don’t usually attack until later in the illness. That’s why Roy Mugerwa, who began practicing medicine long before AIDS, never had a eureka moment. Instead, he recalls, “You observed over time patients coming in with symptoms you can’t explain. You are stuck, and that strikes you as queer.”

TB, for example, is almost always confined to the upper lungs. But in HIV patients, it frequently spreads elsewhere in the body. Who got TB also changed. Mary Mbaziira, a veteran nurse at Masaka Hospital just north of Rakai, remembers that before the advent of AIDS, TB was largely confined to “very poor people or those herding cattle,” who contract the germ from raw milk. As AIDS spread, who came down with TB? “People around,” she says, gesturing expansively.

Geshekter concedes that there may have been an increase in the illnesses associated with AIDS, but claims that any such rise was caused not by HIV but by the economic damage wreaked on Uganda by the dictatorships of Idi Amin and Milton Obote, the wars for liberation, and the imposition of financial “reform” by Western organizations such as the International Monetary Fund. He points to the work of Cambridge University history professor John Iliffe, who documents how public-health spending in Uganda plummeted during the 1970s and early ’80s by as much as 85 percent as per capita GDP shriveled.

Apart from the fact that Iliffe is “appalled” by Geshekter’s interpretation of his work, the poverty theory doesn’t fit the facts. In interviews with doctors, Slim patients almost never mentioned food shortages, and Rakai, where the disease originated in Uganda, is very fertile. What’s more, war refugees suffered symptoms that were markedly different, recalls Nelson Sewankambo, now dean of Uganda’s Makerere University Medical School: “I had never seen the constellation of symptoms and signs that we began to see with Slim.”

So when Serwadda finally received the test results from those four KS patients, he rushed to show them to Sewankambo. Every one of them had tested positive for HIV. All but one of the control patients with ordinary KS had tested negative. “That’s when it dawned on us,” says Serwadda. AIDS was in Uganda.

Almost immediately, Serwadda started spending his weekends at the medical library, leafing through case notes made by Sir Albert Cook, a missionary doctor who established Uganda’s first hospital more than 100 years ago. Cook’s renowned case notes, containing his hand-drawn anatomical sketches, “are very detailed and meticulous,” says Serwadda.

As a doctor treating Slim patients, Serwadda knew what he was looking for—not just the words diarrhea or wasting, but clinical descriptions that matched what he was seeing. He kept going back for months, carefully turning the yellowed, brittle pages. But, he says, “I didn’t see it.”

In the wards, however, he and other doctors were seeing more and more of it. In Zambia, Anne Bayley plotted her aggressive KS cases on a graph and realized that while the total numbers were still small, the increase was exponential—an exploding epidemic. In Uganda, the newspapers started reporting on the strange new Slim epidemic in Rakai, prompting a team from the Ministry of Health to investigate. They didn’t test the blood for HIV, but they did allow a brash surgeon named Wilson Carswell to send it, at his own expense, for testing.

When almost all of the samples came back HIV-positive, Carswell organized an expedition to Rakai, consisting of himself, Serwadda, Bayley, Sewankambo, Mugerwa, and a taciturn virologist named Robert Downing. At Masaka Hospital and homes in Rakai villages, the team examined more than 100 patients. They diagnosed 29 people as having Slim and sent their blood to England for HIV testing.

Every one of those 29 patients tested positive.

“I was scared for my country,” recalls Serwadda. To learn the true scope of the epidemic and how to control it, Serwadda, Sewankambo, and Mugerwa drafted a research proposal. “These were Ugandans who wrote the proposal, not foreigners who said, ‘Do A, B, and C,’ ” recalls Sewankambo. “I’m proud of that.”

Maria Wawer, a public-health researcher from Columbia University, later agreed to collaborate with the Ugandans and help secure American funding. The result was the well-known Rakai Project, which is still producing important research. Separately, the Uganda Virus Research Institute and the British Medical Research Council launched another research project in Masaka, which has produced almost 100 scientific articles.

In their letter to Mbeki, Geshekter and Rasnick asked, “What evidence is there that people with antibodies to HIV live shorter, poorer lives than people in the same community who do not have antibodies to HIV? We know of no such evidence.” In fact, each of these Ugandan research projects has conducted exactly the acid test Geshekter and Rasnick asked for, by looking at HIV-positive people living side by side with those who are HIV-negative. If poverty were the real cause of AIDS, then there should be little difference between the fates of the infected and the uninfected.

But the studies found that HIV-infected people died at a rate more than nine times higher than uninfected people. And the Masaka study found that infected people died a full two decades younger, at a mean age of just 34.

Even more compelling evidence that HIV is lethal emerged out of a tragic lapse in Kinshasa, capital of the Democratic Republic of the Congo, then called Zaire.

When the HIV antibody test became available, Kinshasa’s sprawling and impoverished main hospital lacked stores of screened blood and staff to run the tests 24 hours a day. During this window period, children came to the hospital in critical need of a blood transfusion, usually because of malaria. With the child facing death, doctors would transfuse unscreened blood, saving samples from the child and the donor for later testing.

In this way, the famous research team Project SIDA, named for the French acronym for AIDS, identified 90 originally uninfected children who were given HIV-infected blood. Among children who survived the illness for which they were given the transfusion, those who received HIV-infected blood suffered a death rate 16 times higher than controls.

“Let me take you back,” says Sewankambo. In the beginning, the high proportion of Ugandans with HIV puzzled him. “My thinking was very much affected by the North: This is a gay disease. But if there wasn’t that much homosexuality in our community, and we knew there wasn’t any, really, then what was the mode of transmission? I was expecting mosquitoes.”

The mosquito hypothesis was easy to test. Sewankambo and others examined households in which at least one person had AIDS, testing everyone, including children and grandparents. If AIDS was spread by mosquitoes, the virus should be present almost randomly, and certainly it should be in many children, who are the most susceptible to malaria.

Nothing of the sort was found. Of the sexual partners of the AIDS patients, a striking 71 percent were infected. Yet of the other people living in the household, with whom the patients were not having sex, only two out of 100 of were infected—a woman who was sexually active and her two-year-old son. “It did certainly suggest strongly that it was sexually transmitted,” says Sewankambo.

Yet in their letter to Mbeki, Geshekter and Rasnick insisted that the sexual spread of HIV is “merely a very popular assumption,” and pointed to a study conducted among couples in California showing that the odds of a man transmitting HIV to a woman during a single act of intercourse are slightly less than one in a thousand. From such first-world studies, they concluded that HIV is not frequently transmitted among heterosexuals anywhere.

“Outrageous,” says the lead author of that study, Nancy Padian, who is also conducting research in Zimbabwe. “It’s more likely that the epidemiology of a disease would differ in different locations than be the same—just look at cancer and heart disease.”

As for African research, it leaves no doubt that HIV is spread heterosexually. The sex and age distribution of HIV on the continent mirror patterns seen with other STDs. Risk factors for having HIV include more sexual partners, being a prostitute, having had sex with a prostitute, and a history of STDs. In Uganda, two studies stand out. In one, wives were more than 100 times more likely to contract HIV if their husband had the virus than if he didn’t. The other study, coauthored by Serwadda and Sewankambo, looked at couples in which one partner had HIV and the other didn’t. What they found was shockingly simple: The higher the level of HIV in the infected partner, the greater the chance of transmitting it. This study suggests that if a vaccine could merely reduce the amount of HIV in the bodies of infected people, the epidemic could be curtailed. Clearly, this has tremendous implications for the whole world—and it came from research in Africa.

On the wall of Jane’s apartment, just above a gilt legend that reads, “Thinking of you,” is a photograph of her youngest son. Daniel had always been a sickly child, but only when he lay in a hospital bed with both kidneys failing was he tested for HIV. That’s when doctors tested Jane, but the fact that she was also infected barely registered. “All my heart was on my boy,” she recalls.

But after Daniel died, Jane’s medical records show that she suffered from Kaposi’s sarcoma, tuberculosis of the lymph nodes, and painful fungal infections that failed to respond to treatment. One bacterial infection caused an abscess in her thigh, and another infected her blood. Jane felt so tired that she couldn’t climb the three flights of stairs to her apartment without stopping to rest several times.

“I called in her brothers,” says her doctor, Peter Mugyenyi, “and I told them, ‘Look, your sister is going to die unless you mobilize money’ ” to pay for anti-HIV drugs. They did, and she began taking a cocktail of three drugs on September 3, 1999. “By two weeks,” says Jane, “I was able to walk up the stairs without stopping.” Now, even her KS lesions have vanished and she is worried about gaining weight, not losing it.

The AIDS dissidents claim that HIV drugs actually cause AIDS diseases—an absurd notion for Africa, where only a tiny sliver of patients can muster the money to pay for the drugs. Still, Geshekter and Rasnick wrote to Mbeki, “The only blessing of poverty is that it may protect poor Africans from the highly toxic anti-HIV drugs that have already killed thousands, perhaps tens of thousands of Americans.” In line with such thinking, Mbeki has questioned whether AZT is too toxic to administer.

What’s more, his spokesperson, Parks Mankahlana, declared that whether HIV causes AIDS remains an open question “because there’s no doctor that injects a human being that has got HIV/AIDS and that person gets healthy in two or three days’ time.” That’s true, but medical science has come closer to curing AIDS than any other viral disease. The drugs do not eradicate HIV from the body; they only suppress it. But once they became available, clinics all over the developed world recorded sharp reductions in disease and death among people with HIV.

If AIDS in Africa were merely misdiagnosed old diseases, then the anti-HIV drugs should have no effect or, as the deniers claim, a harmful one. But Jane’s recovery is typical of African AIDS patients lucky enough to afford the expensive therapies.

Mugyenyi, Jane’s doctor, runs the Joint Clinical Research Centre, the main site for a special program that offers the HIV drugs at a discount. Still, they remain so costly that most of Mugyenyi’s patients wait until they are very sick before starting therapy.

By carefully tracking his patients, Mugyenyi has demonstrated that those like Jane who can afford the recommended three drugs do better than those who can pay for only two. And, says Mugyenyi, the contrast with those who cannot afford any drugs—or who exhaust their resources and must stop the medication—is sharp: Those off therapy almost always sicken and die, while those on the drugs usually get better.

But Mugyenyi is going further. He is in the process of measuring how effectively the drugs suppress the amount of HIV in a patient’s blood and then “correlating that with clinical improvement.” In other words, he is gathering the evidence to show that the better the drugs suppress HIV, the better the patient does. “We are demonstrating that here,” he says, “in Africa.”

Research interns: Carl Bialik and Elinore Longobardi

Testing the Test

Sixteen nations, all in sub-Saharan Africa, have at least a tenth of their adults infected with HIV, according to United Nations figures announced last week. But according to AIDS dissidents, those figures are “meaningless” and no cause for alarm because the HIV antibody test is unreliable.

They point out that other microbes and conditions such as pregnancy can create false positive results. And they note that in some African countries, national surveillance is conducted with just one type of test.

What they fail to mention are the quality-control measures African countries have put in place. In South Africa, for example, the testers get tested with blood sent by a central lab, and in Uganda, the national surveillance team confirms every positive result with a different type of test. Using these and other measures, both countries have found that the antibody tests are accurate more than 98 percent of the time.

These days, there are many kinds of tests, some of which look for material from the virus itself rather than antibodies. For more than 12 years, Ugandan researcher Benon Biryahwaho has helped analyze the tests to make sure they are accurate in his country. “By combining different methods and processes,” he explains, “we narrow the window for error.” —M.S.


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