HIV/AIDS Skepticism

Pointing to evidence that HIV is not the necessary and sufficient cause of AIDS

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

Posted by Henry Bauer on 2007/12/30

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.

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10 Responses to “ARE INTESTINAL WORMS GOOD FOR US? ARE THEY GOOD FOR AFRICANS? FOR AFRICAN CHILDREN?”

  1. Martin Kessler said

    Such a sad story. The unethical quacks and pseudo-scientists involved would never have gotten funding if they acted like real doctors and scientists. What gets me is obviously the people who did the studies were well educated in their related disciplines – logic alone would have guided ethical researchers to look at these poor populations objectively. This kind of thing makes me so angry – what can you do when rich countries are involved in iatrogenic genocide renamed as treatment for HIV? If Hitler had declared through “research” by his chief medical officer Dr. Mengele that the Jews were infected with a rare contagious virus and determined that the treatment would be with a potion made with Zyclon B as the solution, Hitler would have been looked on as a great humanitarian for saving the world from being infected by the Jewish Plague.

  2. Claus Jensen said

    Re the helminth post, I was struck by this from the review:

    “Together, the cumulative available evidence suggests a possible benefit of de-worming on plasma HIV-1 RNA levels but not CD4 counts or clinical status over a short period of follow-up.”

    So I had a look at the review study, and, as far as I can see, only one of the papers (the randomized schistosomiatis trial) attempted to evaluate clinical outcome:

    “This study also evaluated differences in CDC clinical staging between the treated and untreated group. At the 3-month visit, there were no differences with regard to the number of individuals in CDC stage A, B or C (43:20:1 for the treatment arm compared to 44:20:2 in the untreated arm) although the study was underpowered for this assessment” (first paragraph p. 5 of the review study).

    This demonstrates the usual lack of interest in clinical status compared to the viral load and CD4 surrogate markers. But just as importantly, it’s the CDC (not WHO or any other) staging system which is used to evaluate the clinical status. If the guidelines are followed rigidly, this classification system is next to useless because only progression from one “HIV disease” category to the next would register:

    “The CDC categorization of HIV/AIDS is based on the lowest documented CD4 cell count (Table 1) and on previously diagnosed HIV-related conditions (Tables 2 and 3). For example, if a patient had a condition that once met the criteria for Category B but now is asymptomatic, the patient would remain in Category B.” http://www.aidsetc.org/aidsetc?page=cm-105_disease

    So, if a helminth patient exhibited symptom X, first, the condition would have to register as “HIV related”. Second, even if the symptom were to disappear upon de-worming, the subject would remain in the severest category previously registered.

    This being the case, of course a 3 month follow-up in a single “underpowered” study would show no significant difference in “clinical progression” towards AIDS and death. However, it would remain optional for the researchers whether to report any symptomatic “relief” or other benefits gained from the helminth treatment.

    In other words, the ethical question concerning withholding obviously beneficial treatment is elegantly skirted by staying focused on “HIV
    disease” and its specific classifications.

  3. cytotalker said

    Not surprisingly, I have noticed scarce mainstream attention paid to research revealing immune impairment similar to that which is considered unique to HIV infection in populations that are HIV-negative and helminth infected. Chronic immune activation and its resulting immune derangements characterize but are not unique to HIV.

    Here is the corrected link to the above-mentioned study on immune derangement due to non-hiv helminthic infection: http://cmr.asm.org/cgi/content/abstract/17/4/1012

  4. hhbauer said

    Cytotalker: Many thanks indeed for that citation. Considering that a large proportion of Africans are helminth-infected, and that there’s supposed to be an HIV epidemic in Africa, this work couldn’t be more significant.

    UNAIDS data show no increase in “HIV” prevalence over the years, which would be extraordinary for a sexually contagious infection that first entered only two or three decades ago; but constant prevalence would be entirely consistent with an endemic infection that affects about 1/3 of the population.

    The work is so interesting that I copy the abstract here:

    “Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) infection. It is present also, with very similar characteristics, in very large human populations infested with helminthic infections. We have tried to review the studies addressing the changes in the immune profiles and responses of hosts infected with either one of these two chronic infections. Not surprisingly, several of the immune derangements and impairments seen in HIV infection, and considered by many to be the “specific” effects of HIV, can be found in helminth-infected but HIV-noninfected individuals and can thus be accounted for by the chronic immune activation itself. A less appreciated element in chronic immune activation is the immune suppression and anergy which it may generate. Both HIV and helminth infections represent this aspect in a very wide and illustrative way. Different degrees of anergy and immune hyporesponsiveness are present in these infections and probably have far-reaching effects on the ability of the host to cope with these and other infections. Furthermore, they may have important practical implications, especially with regard to protective vaccinations against AIDS, for populations chronically infected with helminths and therefore widely anergic. The current knowledge of the mechanisms responsible for the generation of anergy by chronic immune activation is thoroughly reviewed.”

    Clinical Microbiology Reviews, 17 (#4, October 2004) 1012-1030; Gadi Borkow and Zvi Bentwich, “Chronic Immune Activation Associated with Chronic Helminthic and Human Immunodeficiency Virus Infections: Role of Hyporesponsiveness and Anergy”

  5. cytotalker said

    Might I add that the “HIV” and the helminthic cases are by no means unique. T cell exhaustion occurs during many chronic infections commonly linked to “HIV” infection and also in cancers.

    http://www.sciencedaily.com/releases/2007/10/071018123550.htm

    It brings to mind Hans Selye’s three stages of reaction to stress, ignored and then forgotten by the medical establishment: shock, prolonged adaption, and, for the unlucky, exhaustion.

  6. Hi. In your in-depth analysis on Walson et al’s PLoS NTD article and current work–you neglected to mention that accompanied by his article was another article (disclosure: I am one of the co-authors) that commented on and pushed for programatic interventions involving treating helminthic infections in the population. To see this paper, http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000160

    Additionally, though you pose your question in a sarcastic tone implementing that these researchers do not know what they are doing or are performing experiments in an atmosphere of cohesion and indifference– it is clear that you do not have sufficient immunological background to understand the complicated implications of helminth treatment. Do you understand the implications of having a high Th2 profile? By eliminating the helminths, that population is no longer protected against allergy and asthma (Maizels, R.M. (2005) Infections and allergy – helminths, hygiene and host immune regulation. Curr Opin immunology 17: 656-661.)

    Do you not understand how clinical research works? Research now that can implicate via RCT gold standard epidemiological surveys public health policy has huge implications to in the immediate future treat people who need care. No large-scale RCT study has proven that by eliminating helminth infections, one can decrease viral load, increase CD4, restore the CD4/CD8 ratio and delay time to starting ARZs. If they can do this, it can have HUGE public health and on-the-ground medical implications. How can that be bad?

    I agree with you that I believe eliminating helminths in those co-infected with HIV is an important global health step that must be taken. I do not though think it is productive nor wise to criticize dedicated medical researchers who have committed their entire professional lives to working/living in the developing world in order to help improve the morbidity and mortality of whole communities.

  7. hhbauer said

    Carrie Lee Teicher:

    We agree on the important points:
    1. There should be “programatic interventions involving treating helminthic infections in the population.”
    2. “eliminating helminths in those co-infected with HIV is an important global health step”

    I had been aware of, and had even considered writing satirically about, the idea of infecting people with helminths because of the speculative guesswork that it might protect against allergies and asthma. On the other hand, it’s already known beyond speculation that helminth infection can cause anemia, exacerbate malnutrition, etc. etc. If one can de-worm people cheaply, as is indeed possible, that’s the first thing to do, in my view.

    I wrote this about clinical trials in 1992: “severe conflict is inherent in clinical research, between giving care and acquiring knowledge. For valid knowledge to come about, clinical trials must compare those receiving treatment with ‘controls’, similarly ill individuals who are not given the experimental treatment”; and so on (Scientific Literacy and the Myth of the Scientific Method, University of Illinois Press, 1992, still in print).

    As to “dedicated medical researchers who have committed their entire professional lives to working/living in the developing world in order to help improve the morbidity and mortality of whole communities”, let me recall the hoary wisdom that the path to hell is paved with good intentions.

    My objections to the Stolzfus research program include the use of African children as subjects in clinical trials that would not be approved in the United States. After all, there would be no difficulty in causing “first-time intestinal worm infections” in American children in order to see whether that “contribute[s] to severe anemia and malnutrition in children under two years of age”. In fact, I would invite Stolzfus and his co-workers to use their own children in such studies.

    The ethical guidelines for research on human subjects call for providing at minimum the prevailing “standard of care” to those enrolled. What makes work in Africa so appealing to researchers is that the typical standard of care there is little or none, which is one reason why trials there are approved by oversight boards here. I don’t like that.

    As to the information that might come about CD4 counts and the like, my views are of course informed by the mainstream, peer-reviewed publications that have found no correlation among CD4 counts, viral load, and clinical progression, as well as those that describe the “side”-effects of antiretrovirals, see the Treatment Guidelines or look at my blogs of 14 and 15 December.

    Unfortunately, “public health policy” about HIV/AIDS has never been informed by “RCT gold standard epidemiological surveys”. The published data from HIV tests in the United States show unequivocally that what is being detected in those tests is not an infectious agent—see The Origin, Persistence and Failings of HIV/AIDS Theory (McFarland 2007), http://failingsofhivaidstheory.homestead.com/

  8. Gene said

    Carrie Lee Teicher asks Professor Bauer: “Do you understand the implications of having a high Th2 profile?”

    It’s a shame, a real shame that this question was never asked before mass vaccination campaigns in Africa, all of which can impact negatively in the very terms that Dr Teicher has provided us: so-called viral load and inverted helper suppressor/cytotoxic T-cell ratios. And what about circulating immune complexes that were measured in the 1978-1984 US AIDS patients and theorized to have a negative impact on “cell-mediated immunity”? That is before “convenient HIV” showed up.

    Can the “dedicated medical researchers who have committed their entire professional lives to working/living in the developing world” possibly be mistaken that they are more important than providing a basic infrastructure “in order to help improve the morbidity and mortality of whole communities”? Is it possible, my God, that low T-cells could have something to do with malnutrition and the lack of energy for the required cell divisions?

    And even in many situations— *gasp* —doing more harm than good by injecting malnourished people with viral fragments — something that is no longer countenanced even by “immunology”?

  9. Russ Mitchell said

    It’s all a measure of one’s perspective I suppose, isn’t it? The treatment of helminth’s in a population that suffers most from lack of food is afterall quite similar to studying the effects of malnutrition in a group with and without helminths. The perspective that treating for helminths should be obvious to those studying HIV seems akin to saying that helminths should be treated in a population suffering from malnutrition. Afterall we could just treat for malnutrition by feeding them, or maybe that is too obvious. Isn’t there some evidence that in healthy populations, a helminth infestation has beneficial effects. Just pondering it all…

    • Henry Bauer said

      Russ Mitchell:
      Any research on human beings is supposed to offer the subjects some potential benefit, or greater potential benefit than the risk of harm. I see no excuse for not feeding malnourished people while using them as subjects in trials of things that cost far more than would be the cost of feeding them. I see it as like the Tuskegee experiment or the Nazi experiments on prisoners.

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