ARE INTESTINAL WORMS GOOD FOR US? ARE THEY GOOD FOR AFRICANS? FOR AFRICAN CHILDREN?

In FIRST: DO NO HARM! (19 December), I wrote: “In the determination to get rid of HIV, it is sometimes forgotten that the whole point is to make people better (WHAT HIV DRUGS DO, 15 December 2007).” At the time, I wondered whether I was overstating the case. But then Google Alerts brought news of a research program designed to find out whether starving people could benefit from antiretroviral drugs (DRUGS OR FOOD?, 25 December)—in other words, investigating whether HIV can be killed even in starving people. Now comes yet further confirmation that in the fight against HIV, people’s health and well-being takes second place, if that, to fighting that evil HIV:

“Does treating worms in HIV patients slow AIDS progression?” (Ivanhoe Newswire, 28 December)
“As many as half of the 25 million HIV-infected patients in Africa are also thought to have worms (helminths). There is evidence these worms may cause HIV to progress more rapidly into AIDS, so does de-worming slow down the progression?
Researchers from the University of Washington, Seattle wanted to find out. They did an extensive review of five studies that examined the link between being infected with worms and the progression of HIV to AIDS.”

What do worm infections do to people, whether or not they are HIV-positive?

“Parasitic worms or helminths . . . live inside their host . . . receiving nourishment and protection while disrupting their hosts’ nutrient absorption, causing weakness and disease.”

“Parasitic infections contribute to a range of health problems including malnutrition, anemia, and slow cognitive development. . . . 300 million people, 50% of them school-aged children, are severely ill due to worms. Intestinal worms account for an estimated 11-12% of the total disease burden for school-aged children (5 to 14 years) in low-income countries. Regular de-worming allows people to avoid the worst effects of chronic worm infections, even without an improvement in sanitation. . . . Regular use of inexpensive [emphasis added] albendazole or mebendazole tablets has been shown to improve the health of individuals suffering from worm infestations, with reduction of transmission in school-aged children having positive externalities for reduction of the disease burden in the entire population. . . . Efficacy of albendazole was demonstrated by a World Health Organization (WHO) assessment of de-worming among pre-school children in Nepal. . . . [resulting in] 76% reduction in anemia prevalence . . . after only two rounds of de-worming. Treatment is safe, even when given to uninfected children. A WHO taskforce recommended that pregnant women should be treated” (http://www.psi.org/our_programs/products/deworming.html).

So there’s no doubt at all that intestinal worms are bad for one’s health. But apparently some people think it’s more important to find out how worm infections interact with HIV than it is to de-worm infected people.

At least, that’s what the Google Alert from Ivanhoe Newswire alleged. I was rather reluctant to believe that; after all, the Tuskegee syphilis experiments on human beings have long been acknowledged as beyond the pale, and the name of Josef Mengele remains a fairly well remembered and useful caution, at least to people of my generation. So, reluctant to believe and recalling my friend’s admonition not to believe everything I read, perhaps especially on the Internet, I checked and found the source: “Treatment of helminth co-infection in individuals with HIV-1: A systematic review of the literature”, by Judd L. Walson & Grace John-Stewart, PLoS Neglected Tropical Diseases (www.plosntds.org) 1(3): e102. doi:10.1371/journal.pntd.0000102:

From the Abstract: “Some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate existing evidence on whether treatment of helminth infection impacts HIV-1 progression. . . . There are insufficient data available to determine the potential benefit of helminth eradication in HIV-1 and helminth co-infected adults. Data from a single RCT and multiple observational studies suggest possible benefit in reducing plasma viral load. The impact of de-worming on markers of HIV-1 progression should be addressed in larger randomized studies evaluating species-specific effects and with a sufficient duration of follow-up to document potential differences on clinical outcomes and CD4 decline.”

In case you suspect that I’ve ripped this out of context, here is the complete Author Summary:

“Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections. Parasitic infections with helminths (intestinal worms) are common in Africa and affect over half of the population in some areas. There are plausible biological reasons why treating helminth infections in people with HIV may slow down the progression of HIV to AIDS. Thus, treating people with HIV for helminths in areas with a high prevalence of both HIV and helminth infections may be a feasible strategy to help people with HIV delay progression of their disease or initiation of antiretroviral therapy. After a comprehensive review of the available literature, we conclude that there is not enough evidence to determine whether treating helminth infections in people with HIV is beneficial.”

This was not a direct study of people, of course, just a review of others’ work. Still, I thought that some discussion of the ethics of such studies might have been appropriate, so I scanned the article for “ethic”. I did find one occurrence:

“The ideal study design to determine anti-helminth treatment effect on HIV-1 progression is a randomized clinical trial. Thus, randomization to immediate versus deferred treatment was used in the single RCT of schistosomiasis eradication. However, the short period of follow-up ethically feasible for treatment deferral limits ability to determine longer term effects of anti-helminthics on HIV-1 progression.”

In other words, it’s unethical to keep “HIV-infected” people for too long off antiretroviral treatment, but it’s perfectly OK to leave them worm-infested indefinitely.

The authors of this study are in the Department of Medicine, University of Washington, Seattle. The study was funded by the University’s Center for AIDS Research (CFAR) and by the National Institutes of Health (NIH) (grant D43-TW00007 NIH/NIAID, AI27757 NIH Fogarty International Center). I was moderately curious about the grant from NIH, and looked a bit further. I found mention of an already completed NIH-funded study, “Treatment of helminth co-infection: short-term effects on HIV-1 progression markers and immune activation”: “Identifying methods to slow disease progression in patients with HIV-1 infection remains a top priority in many regions of the world. . . . Many of the individuals living in these countries are also co-infected with a variety of other diseases such as tuberculosis, malaria and soil-transmitted helminths. There are data to suggest that infection with these agents may activate the immune system in HIV-1 co-infected individuals and may lead to more rapid HIV disease progression. This study will evaluate the potential impact of treating helminths in HIV-1 seropositive individuals. Markers of disease progression and immune activation will be assessed. We will also measure the amount of virus in genital secretions to determine if treatment of co-infection can reduce the infectiousness of HIV in these individuals.”

I tried to access the provided link to the University of Washington Institutional Review Board , but didn’t have the required password.

Here once more is the single-minded obsession to deal with “HIV infection” that apparently leads some medical researchers and some bureaucrats in funding agencies and foundations to overlook the fact that starving people need food, that babies should not have their mitochondria damaged, and that worm-infested people are likely to have a poorer prognosis than others no matter what else they are infected with. Malnutrition does its damage NOW, worms cause malnutrition NOW, whereas untreated “HIV infection” is supposed on average to bring symptoms of illness in about 10 years. Yet some people seem determined to find out what happens to “HIV” in people who are malnourished and worm-infected.

Such studies continue to be funded, including by NIH. “Empiric therapy of helminth co-infection to reduce HIV-1 disease progression” is another clinical trial, “not yet open for participant recruitment”, whose “Sponsors and collaborators” are the University of Washington, the Kenya Medical Research Institute, and the Centers for Disease Control and Prevention. The principal investigator is Judd L. Walson, whose meta-analysis revealed the need for further studies. There was no link to the “Informed Consent” statement that will no doubt be used after approval by the committees that monitor research on human subjects.

But it’s not only the effect of worm infestation on HIV that we want to know more about. Admittedly, we know that worms are bad for people, but how exactly? Do they contribute to iron deficiency? To anemia? To stunted growth of children? To loss of appetite? How do hookworm infestation and malaria relate to iron status and anemia in 0-to-5-year-olds, and how do these relations change with age? We couldn’t learn all those interesting things if we just de-wormed people. Have a look on PubMed under “Stoltzfus helminth” and you’ll find a dozen studies of these and similar matters published in the late 1990s by Dr R J Stoltzfus (School of Hygiene and Public Health, Johns Hopkins University) and various collaborators. (For people of my generation, that “Sponsors and collaborators” strikes a not-so-funny bone. “Collaborator” had quite a special meaning for us in the old days.)

There’s always more to be studied, so the Wellcome Trust approved an award in 2000 to help Stoltzfus and collaborators to find out more about “Effects of intestinal helminth infection in early childhood on immune response, inflammation, anemia and malnutrition”:

“Using a cohort of 2000 rural Zanzibari children, this programme will explore whether first-time intestinal worm infections contribute to severe anemia and malnutrition in children under two years of age, and whether treatment of the infections can prevent those adverse effects. This will test the hypothesis that first time intestinal worm infections in young children cause an immune response that suppresses children’s appetite, causes them to break down muscle protein and blocks the formation of red blood cells. In subsamples of children, specific mechanisms relevant to the hypothesis will be assessed, including specific aspects of the immune response that might be deleterious (e.g. intestinal blood loss, defects in blood production and breakdown of muscle protein).

Malnutrition, measured as low weight-for-age, is one of the strongest known risk factors for child mortality in developing countries. Severe anemia may also contribute to mortality in children, especially when it coexists with respiratory illness. Both malnutrition and anemia are also associated with behavioural alterations and delays in child development. This programme will seek to achieve a clearer understanding of the role of intestinal worm infections in these conditions that affect so many children in developing countries.”

No doubt you’ll be as pleased as I was to discover that the Wellcome Trust also funds research on ethics in biomedical research.