Worst case: HIV + TB

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(This article is part of a series of articles on tuberculosis that I wrote for the Summer 2008 issue of NYU Physician.)

When HIV joins forces with TB, the results can be horrific. The neck bulges with lumps as big as an orange, filled with pus-like fluid teeming with the germs that cause TB. Occasionally, these bacteria travel through the blood and lymph vessels, forming lesions in the liver, spleen, and beyond. In chest X-rays, it looks as if the lung were studded with small nodules the size of millet seeds.

This gruesome scenario is rarely seen when TB is the sole affliction. But as HIV ravages the immune system, TB quickly and effortlessly spreads through the body. HIV’s compounding effect on TB has long been known, but recently scientists have discovered that this pernicious partnership works both ways. TB, in turn, eases the path of HIV, dismantling the system that keeps the virus under control in the lungs, allowing it to mutate and multiply.

“If you have HIV and TB, then TB 
will kill you much more rapidly,” notes Michael Weiden, M.D., associate professor of medicine and environmental medicine. In fact, TB is the leading cause of death among people who are HIV-positive, accounting for one-third of AIDS deaths worldwide.

Male circumcision: A new defense against HIV

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(This article was #15 in Discover Magazine’s top 100 stories of 2007.)

Male circumcision cuts the risk of HIV transmission in men by about 60 percent and should be scaled up in countries hardest hit by the epidemic, the World Health Organization (WHO) announced in March, citing compelling evidence from three large trials in Kenya, Uganda, and South Africa.

Since the 1980s, dozens of smaller studies have suggested that countries with high rates of circumcision, like the Muslim nations of western Africa, have lower rates of AIDS, whereas southern* Africa, where circumcision is rare, has been ravaged by the epidemic. There, a 2006 study suggests, circumcision could prevent about 6 million HIV infections and 3 million deaths over 20 years. Still, the WHO held back its recommendation until 2007, citing the need for randomized clinical trials.

“Circumcision was ignored for ages,” says Daniel Halperin, an AIDS researcher at the Harvard School of Public Health, who laid out the case for circumcision in The Lancet as far back as 1999. “What I mainly criticize the WHO for is that, even with dozens and dozens of powerful studies, they refused to even talk about it.”

Circumcision is thought to prevent infection because the underside of the foreskin is rich in immune cells that are particularly vulnerable to HIV. Small tears in the foreskin during intercourse can also allow the virus to slip into the body.

Circumcision could reduce the odds of an infected man’s transmitting the virus to a female partner by 30 percent or more. For all its benefits, though, the WHO cautions that it should not replace standard methods of prevention like the use of condoms.

Polio’s return traced to lapses in India

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(This article was #60 in Discover Magazine’s top 100 stories of 2006.)

In May a 39-year-old man in Namibia tested positive for poliovirus, marking the country’s first case in 10 years. Since then, the outbreak there has reached 20 confirmed cases.

This year 10 other formerly polio-free countries are once again battling the disease. Genetic sequencing has traced cases in five of the countries, including Namibia, to a polio strain in India, where the virus remains endemic. As of October 2006, a total of 358 cases have occurred in the poor, densely populated north Indian state of Uttar Pradesh alone, up from 29 in 2005.

The World Health Organization has taken India to task, saying its outbreak is endangering efforts worldwide to keep the disease at bay. To protect a high-risk community from polio, at least 95 percent of the children must be vaccinated; but in late 2005 and early 2006 the vaccination rates in Uttar Pradesh dipped to between 85 and 90 percent.

The Indian government, vowing to eliminate polio by 2007, has discussed a pilot project using an injectable vaccine in addition to oral drops. The injectable vaccine is thought to offer better protection against polio infection in children with diarrhea, which is common in the area.

Finally: hints of HIV turnaround in South Africa

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(This Opinion column ran on Nature’s news site on November 3, 2006. You can see the original post here.)

It’s about time that this country hard-hit by AIDS promised help for the afflicted, says Apoorva Mandavilli.

aids-in-southafrica-grafitiHIV causes AIDS. That’s not news to you or me, but shockingly it has taken years for the government in South Africa — where about 1,000 people die of AIDS every day — to acknowledge that fact and pledge to provide medicines.

In the past few weeks, the country’s deputy president Phumzile Mlambo-Ngcuka has publicly promised to expand access to AIDS tests, antiretroviral drugs and prevention programmes to those who most need them.

That sounds sensible — if a rather obvious thing for a politician to say — but it’s a far cry from what South Africans had heard until recently.

Health minister Manto Tshabalala-Msimang has extolled the virtues of beetroot, lemon juice and garlic in fighting AIDS. At the international AIDS conference in Toronto this August, her booth prominently featured those items. Six years earlier, at the same conference in Durban, President Thabo Mbeki said he didn’t know anyone with AIDS and questioned its link to HIV.

It’s about time the government changed its tune. As the richest country in Africa, South Africa is in a much better position to combat AIDS than its poorer neighbours. But thanks to the government’s appalling neglect, it hasn’t seen any decline in the rate of new infections.

Health agency backs use of DDT against malaria

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(Nature asked me to write this article after the editor saw my feature in Nature Medicine on DDT’s return. The feature came two months ahead of the announcement that the WHO would back DDT. This article appeared the week after the announcement, in the 21 September 2006 issue.)

After decades of being shunned 
as an environmentally damaging chemical, the pesticide DDT is once again being touted as the most effective way to fight malaria.

The World Health Organization (WHO) announced on
15 September that it will support the indoor spraying of pesticides generally, and DDT specifically, to control mosquitoes in countries with high rates of malaria. The US Agency for International Development signalled a similar shift in policy back in May.

Although these agencies never formally opposed DDT, they did not fund countries to purchase it, and instead actively promoted the use of insecticide-treated bednets. Malaria rates have continued to rise in the meantime, claiming more than a million lives a year, mostly in sub-Saharan Africa. The agencies now advocate combining the two approaches.

“I have to pinch myself a little to believe that they’ve done this, but I’m really, really happy they have,” says Amir Attaran, professor of law and medicine at the University of Ottawa, Canada, who has long criticized the agencies for their malaria policies.

In sharp contrast to its previous stance, the WHO also admitted for the first time that it stopped supporting DDT despite evidence of its effectiveness. “There are 
lots of data there, but people are 
so emotional about the issues,” says Arata Kochi, director of the WHO’s Global Malaria Programme. “Science comes first and we must take a position based on the science and the data.”

DDT, or dichlorodiphenyl-trichloroethane, is an organochlorine that is more effective, cheaper and longer-lasting than the alternatives. Fears about its use date back to the 1960s when Rachel Carson’s book, Silent Spring, famously chronicled its devastating effects on the environment. In the years that followed, the United States and many European countries banned DDT.

These countries once used thousands of tonnes of the pesticide for agricultural purposes. But the use of DDT for malaria control is very different: small quantities are sprayed once or twice a year on the inside walls and ceilings of houses.

Following widely publicized success with DDT in some countries such as India and South Africa, others began clamouring for the pesticide. “A lot of countries, especially in southern Africa, have become bullish about the use of DDT,” says Richard Tren of the non-profit group Africa Fighting Malaria.

PDF: Health agency backs use of DDT against malaria

Make anything, anywhere

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(I wrote this article for Nature in August 2006. I spent a day at the FabLab outside Johannesburg, South Africa, amazed in particular at the unusual projects that housewives dreamed up. I was also convinced I would never make it out of Johannesburg alive, but that’s a story for another day. You can download a pdf of this article.)

Can everyone use technology creatively? Engineers at the Massachusetts Institute of Technology think so and have launched ‘Fab Labs’ around the world to prove it.

Valentina Kwofie, electronics pioneer

Neil Gershenfeld has been teaching a class called “How to make (almost) anything” to some of the brightest young adults in the United States for years. But it took an eight-year-old girl in a small village in Ghana to show that anyone, any- where, really can make just about anything.

One evening in June 2004 — the day after Gershenfeld had left Ghana having taught a week-long version of his class in the village — little Valentina Kwofie began cobbling together a circuit board.

Hours passed. Several times Kwofie’s par- ents stopped by the lab Gershenfeld had set up, imploring, “Valentina, let’s go home, let’s have dinner, let’s go to bed.” It was the first time any- one in the village, Takoradi, had made a circuit board: people crowded around, watching her nimble fingers manoeuvre parts half the size of a grain of rice. Finally, long past her bedtime, she crafted a board that worked.

Gershenfeld, director of the Center for Bits and Atoms at the Massachusetts Institute of Technology (MIT), hadn’t known what to expect when he put the fabrication laboratory, or ‘Fab Lab’, technology that he worked with at MIT into the context of rural Africa. What he got was inspiration. “This eight-year-old girl in Ghana was making microcontroller circuit boards for the love of it, for the joy of discovery,” he recalls. “That ordinary people can do it and want to do it was very surprising.”

The Fab Lab in which Kwofie made her circuit has been followed by others around the world, each equipped with the same key machines. Today, there are ten Fab Labs — above the Arctic Circle in Norway, in Costa Rica, India and South Africa — and within the next year, fifteen others are planned, of which five will be in Africa.

Together, these labs are showing that giving people the ability to make things for themselves can be the fastest way to solve their problems, particularly in communities with little access to education or technology.

DDT returns

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I wrote this article for Nature Medicine in July 2006. This was a big scoop. The news flew mostly under the radar, with the big announcement due that September. But I had heard rumblings of it at conferences, and was able to get fantastic access to (and quotes from) Arata Kochi, then head of the WHO’s malaria program. You can download a pdf of this article.)

The most infamous pesticide in history is also the most effective weapon against malaria. Ready or not, DDT is on its way back to Africa. Apoorva Mandavilli reports.

It’s possibly the most reviled chemical on the planet. Every adult anywhere in the world could list its supposed evils. And it’s been the subject of a long and bitter battle that defies traditional divisions of liberal and conservative.

But here it is, poised for a comeback.

After decades of being marginalized as a dangerous pesticide, DDT—short for dichloro-diphenyl-trichloro ethane—is set to be reintroduced into countries that have tried, and failed, to win the fight against malaria.

Big impact: Small amounts of DDT sprayed on walls can help control malaria.
Afp photo Alexander Joe
Natalia Soto / LN

On 2 May, the United States Agency for International Development (USAID), arguably the most powerful donor agency in the world, endorsed the indoor spraying of DDT for malaria control. The World Health Organization (WHO) is set to follow. In its new guidelines, a final version of which is expected to be released later this summer, the WHO is unequivocal in its recommendation of DDT for indoor residual spraying.

For the many African countries riddled with malaria, this is welcome news. “We in southern Africa feel extremely happy,” says John Govere, integrated vector control officer for the WHO’s Southern Africa Malaria Control Programme.

Malaria kills as many as 1 million people each year, about 90% of them in Africa. Someone dies of malaria every 30 seconds—and most of those are pregnant women and children under the age of five. Even the millions who survive can be reinfected, leaving them bedridden and decimating economies.

Little surprise then, that just days after USAID’s announcement, Tanzania said that it would lift its DDT ban. Others soon followed.

For these impoverished countries, the choice may seem clear: DDT is cheap and lasts longer than other pesticides, so it has to be sprayed less often. Most pesticides work by killing mosquitoes on contact, but DDT also repels them.

“DDT is the most effective chemical, the most effective insecticide in terms of malaria,” says Arata Kochi, director of the WHO’s Global Malaria Programme.

Silent spring
If DDT is that effective, why has it been so vilified? “You’ve heard of Rachel Carson? Well that’s your answer,” says Maureen Coetzee, chief of vector control research at South Africa’s National Institute for Communicable Diseases. “DDT was so abused in the ’50s and ’60s that it is still suffering from that abuse.”

In the 1940s, DDT was considered a miracle chemical. Airplanes sprayed thousands of tons of the pesticide, coating acres of crops, villages and cities with abandon.

By 1949, the US was malaria free. Between 1955 and 1969, the Global Malaria Eradication Campaign also relied heavily on DDT. In Europe, India, South America, Africa, wherever it was used widely, DDT cut malaria rates dramatically and saved millions of lives.

Then came Carson’s Silent Spring— credited with launching the environmental movement—which famously described DDT’s horrific effects on the food chain, and the stark silence left behind by dying birds. The book was so effective that to this day, any mention of DDT instantly evokes images of bald eagles and thinning eggshells.

DDT soon became a symbol of Western governments’ rash embrace of science. In the US and in Europe, environmental groups waged a successful campaign against the pesticide. Based largely on its effect on the environment—and on public opinion—the US Environmental Protection Agency in 1972 banned DDT. Norway and Sweden had begun the trend in 1970, and the UK signed on in 1986.

Environmental groups that still oppose DDT see its use in developing countries as a double standard. On the other hand, note champions of DDT, most of those groups are based in countries where malaria is only a distant memory.

“I think the whole push of the environmentalists like Rachel Carson and many others to eliminate all uses of DDT are, quite honestly, responsible for millions and millions and millions of human deaths,” says Don Roberts, professor of tropical public health at the Uniformed Services University of the Health Sciences in Maryland.

Money talks
In theory, any country is free to use DDT. The Stockholm Convention of 2001 sought a global ban on DDT, but many countries and scientists argued against the ban, citing its value in malaria control. The final treaty made an exemption for DDT’s use in public health, but called for countries to gradually phase out the pesticide.

Still, in places where malaria was still endemic, the treaty spelled disaster.

Most African nations are heavily dependent on foreign aid and can ill afford to cross a line drawn by donor agencies.

USAID never banned DDT outright, for instance, but nor did it fund DDT’s purchase—which amounts to the same thing. For that reason, the May announcement is widely seen as a change in policy even though the agency doesn’t position it as such.

The World Bank went one step further, making the ban of DDT a condition for loans. The WHO supported the use of bednets dipped in insecticide over indoor spraying, even though malaria rates continued to increase. DDT was “further ignored and intentionally or unintentionally suppressed,” by these agencies, says Kochi.

“People are very emotional about DDT, even within the WHO,” Kochi says, adding that much of the reaction to DDT was a response to political pressure. Since his arrival at the agency in late 2005, he has pushed for the return of indoor spraying not just to Africa, but wherever malaria continues to be a problem.

The WHO plans to field test its new guidelines for indoor residual spraying in Yemen, Sudan and two countries in south eastern Asia. “Quite often in this field, politics comes first and science second,” Kochi says. “We must take a position based on the science and the data.”

Disputed dangers

Watch out: In the 1940s, DDT was sprayed aerially for agriculture.
Associated Press

The WHO recommends 12 insecticides including DDT—which is an organochlorine—six pyrethroids, three organophosphates and two carbamates. In terms of toxicity to humans, DDT is considered safer than many of the others.

Because only small quantities are sprayed on the walls for malaria control, “unless you go and lick the wall, you’re not likely to ingest the insecticide,” notes Coetzee.

Over the years, however, based primarily on data from agricultural use, DDT has been linked to various illnesses—but those studies are rarely convincing and never consistent.

DDT was thought to cause liver and breast cancer and disrupt hormonal balance, for example, but the claims have since been debunked (Lancet356, 267–268; 2000; Nat. Med. 6, 729–731; 2000). Studies have found that in areas where DDT is sprayed for malaria control, mothers show traces of DDT in their blood and breast milk (Bull. World Health Organ. 68, 761–768; 1990). Some scientists say those levels might trigger premature births and a shorter time for breast-feeding (Lancet 366, 763–773; 2005), but the results are much disputed.

Most recently, researchers in California reported in July that babies of mothers exposed to DDT fare worse on mental tests and motor skills tests (Pediatrics 118, 233–241). But critics note that the study followed only 360 women and that because the mothers were born in Mexico—where DDT was used for agriculture till 1995—the researchers cannot link the exposure to malaria control.

But even critics of DDT agree that in countries ravaged by malaria, the benefits far outweigh the risks. “I’d rather have a child with three IQ points less than have a dead child,” says Brenda Eskenazi, lead researcher of the Mexico study.

Although DDT might be a short-term solution for malaria control, however, more research is needed before it can be regarded as entirely safe, Eskenazi and others caution.

For instance, when assessing DDT’s effect on malaria, global agencies should measure rates of total infant mortality, and not just malaria-related deaths, says Walter Rogan, an epidemiologist at the US National Institute on Environmental Health Sciences. That would help catch any adverse affects DDT may have on infant health, he says.

“I think that DDT is not entirely a benign compound,” Rogan says. “If you’re going to use it, you should consider the idea that it might do harm.”

Within walls
DDT’s use in malaria is far different from its application in agriculture. In contrast to indiscriminate aerial spraying several times a year, individuals spray a small amount—about two grams per square meter, a fraction of that used in agriculture—on the inside walls and eaves of houses, where mosquitoes rest.

Because DDT is not sprayed outdoors, there is little chance of it getting into the environment, notes Simon Kunene, chair of the malaria subcommittee for the Southern African Development Community (SADC).

But with thousands of tons of the cheap pesticide available, some of it will inevitably be diverted for agricultural use, experts warn.

“What concerns me a lot is that it’s going to be misused and end up in the environment,” says Mark Rowland, a malaria control expert at the London School of Hygiene and Tropical Medicine.

The WHO is considering a method that South Africa has developed over the years. Precise amounts of DDT are shipped from a central location to the area where they are needed, minimizing middlemen en route, and once spraying is complete, the containers are returned for checking.

But South Africa, with its relatively well-developed infrastructure, may be an exception, argues Rowland. From 1991 to 1998, Rowland led a malaria control program for Afghan refugees in Pakistan. That program employed a similar method, using packets of DDT that were closely supervised. Still, some packets were misused, Rowland says. “It’s very difficult to monitor every kilogram that gets distributed.”

Fine print
The best long-term prospect may be to develop safe and effective alternatives, several of which are being developed by public-private partnerships.

Meanwhile, the use of DDT, and of indoor spraying generally, is expected to rise sharply.

“People are now beginning to appreciate how effective indoor residual spraying can be,” says Richard Greene, director of the Office of Health, Infectious Disease and Nutrition in USAID’s Bureau for Global Health.

Unless done well, however, using DDT may be dangerous—and powerless against malaria.

For spraying to be effective, at least 80% of the affected area must be covered. Global agencies must first map the distribution and behavior of different kinds of mosquitoes and, most important, patterns of resistance to insecticides. “The last thing you want to do is select for resistance,” says Coetzee.

Convincing the local community to let people into their homes and spray their walls is another formidable challenge. At the height of the epidemic, people are generally terrified enough to do whatever it takes. But once the mosquitoes—and, as a bonus, the cockroaches—disappear, so does people’s tolerance.

Because DDT lasts longer than other pesticides—up to a year compared to six months with pyrethroids—it needs to be sprayed less often, making its use less challenging for governments.

“What can I say? It has worked for us,” says Kunene. “They’ll see the results. Give me one year or two years. There’ll be a big difference.”

Published online: 27 July 2006.

The coming epidemic

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(Reporting on this article was one of the most emotional experiences of my career. I met many, many sex workers, drug addicts, activists, truck drivers and housewives who had never heard the word AIDS before they were told they were dying from it. As someone born and raised in India, I found the many individual stories heartbreaking, and the denial of the officials deeply sad and scary. This article appeared in Nature in July 2005 as part of a special package on Indian science called Nature Outlook: India. A couple of years after the article appeared, the Indian government revised its numbers drastically downward. I’m deeply skeptical of its estimates, but haven’t yet been able to dig into the truth. You can download a pdf of this article.)

A staggering 5.1 million people are estimated to be HIV positive in India. Apoorva Mandavilli finds a country on the brink of a crisis.

Our son was born in June 1998. He was healthy but after eight months, he had diarrhoea and fever all the time. He was in the hospital many times. The sixth time, they diagnosed him with AIDS. That was when we found out that my wife and I have HIV. Our son died 12 July 2002. I also started to get sick. I didn’t take my medicines regularly; they didn’t tell me not to do that. Now my health has become worse. I haven’t worked in six months.We’ll be paupers. I don’t know what we’re going to do.

— Suresh, air-conditioning technician

Suresh is sitting in a small, dark room at an AIDS clinic in the southern Indian city of Chennai. This city is where the first cases of HIV in India were discovered in 1986 after a police sweep of sex workers. Nearly 20 years later, there are an estimated 5.1 million cases in India, a number second only to that in South Africa. The difference is that in India the epidemic has not yet peaked. According to the CIA, the number of cases in India could top 20 million by 2010.

Struggling to make an impact

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(I wrote this article for Nature as part of a special report on malaria. It was published 9 August, 2004.)

Hampered by bureaucracy, politics and ineffectual policies, critics claim that the international Roll Back Malaria (RBM) partnership is failing, and is a long way off its goal of halving malaria deaths by 2010. Few of the 44 African countries that signed up to its main goals, including providing immediate access to treatment for 60% of patients by 2005, have followed up with increased resources.

Allan Schapira, RBM coordinator at the World Health Organization (WHO), disputes that the programme is off-course, arguing that it will take years for the impact of current initiatives to become apparent. “There’s no basis for the contention that deaths from malaria have gone up,” he says, adding that tracking trends in malaria-specific deaths over short periods is difficult. What is clear, however, is that no data show substantial drops in deaths in sub-Saharan Africa, where most cases occur.

RBM was launched in 1998 by the WHO, the World Bank, the United Nations Development Programme and UNICEF, and is now supported by 90 countries. It has raised the disease’s international profile, says Roger Bate of the American Enterprise Institute for Public Policy Research, a Washington-based think-tank. “Unfortunately, I think that’s kind of where the good news ends,” he says. “If RBM were a government, it would be voted out of office.”

In 2002, an external evaluation panel concluded that RBM was failing at regional and national levels, and was too isolated from local health policies (see Nature 419, 422; 2002). It also found the World Bank’s commitment to be ambivalent. “We are committed to doing a lot more, to doing much better,” says Olusoji Adeyi, communicable-diseases coordinator at the bank.

RBM has since been reorganized to make it more accountable to malarial countries,
and to have a tighter focus on fewer countries. Mark Young, UNICEF’s senior health adviser for RBM, points to ‘basket funding’, where money is pooled nationally and health ministries make spending decisions. But critics also complain about the programme’s inertia in replacing obsolete drugs with more effective, but costlier, artemisinin-based drugs (see Nature 429, 588; 2004). In addition, they question its focus on mosquito nets soaked in insecticides to the exclusion of indoor spraying with DDT and other insecticides.

RBM claims that it promotes DDT wherever appropriate, but argues that nets are safer and more effective. Spraying is difficult to push through politically, says Schapira, with pressure from government and other donors. “We have had very, very strong lobbying over DDT,” he says. “We have had to give up.”

The biggest issue, says Schapira, is money. Most new funding for African countries is coming from the Global Fund to Fight AIDS, Tuberculosis and Malaria, although it is far short of the billions needed. “We have the tools and the strategies, but without more money it will be a disaster.”

PDF: Struggling to make an impact

AIDS care ignores children

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(This article was published on Nature’s news site on 13 July, 2004. I reported this from the XV International AIDS Conference in Bangkok.)

Companies fail to design drugs for kids.

Around 700,000 children were infected with HIV in
2003.

Bangkok – The global fight against AIDS is not addressing children, the very group that is hit hardest by the pandemic, says the medical charity Médecins Sans Frontières (MSF).

In recent years, there has been considerable progress in developing diagnostic tests and anti-AIDS drugs for adults. But doctors lack the simple tools needed to diagnose and treat children infected with the virus.

“Children are a discriminated minority, they are a marginalized community,” David Wilson, medical coordinator of MSF in Thailand told the XV International AIDS Conference in Bangkok.

In 2003, an estimated 700,000 children under the age of 15 were newly infected with HIV. Most of these live in sub-Saharan Africa.