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Deworming: not all it’s cracked up to be?
Summarising reliable research using scientific methods is a bit of a no-brainer for most of us in research synthesis and health policy nowadays. And it can make a difference – since 1994 the Cochrane Infectious Diseases Group have been preparing systematic reviews in malaria, tuberculosis, diarrhoea and tropical diseases-and a few have really made a difference. In the 1990swe synthesised 40 trials, many published in French, that helped show an abandoned drug for treating malaria, amodiaquine, was quite a bit better than the drug everyone was using at the time. In 1998, the Cochrane review of insecticide treated bednets for malaria clearly showed deaths were reduced in children. In 2001, we summarised trials of oral rehydration salt solution that helped show that the solution everyone was using in the little silver sachets from UNICEF had too much salt in it. It’s always good to pull research together that helps us do the right things in policy and makes us feel good.
And sell is what is going on: deworming looks like a wonder cure for poverty. The World Health Organization (WHO) say these deworming drugs (usually albendazole or mebendazole) mean that school age children can “earn their way out of poverty” through substantial impacts on intellectual development and cognition. WHO also argue that deworming drugs contribute to child survival, help promote gender equality and empower women, although WHO confuse their argument by conflating the evidence between different helminth infections. Nevertheless, a policy of deworming the intestinal helminths has some very influential supporters from all over the world backing it, includingNobel Laureates.
Empty bottles of albendazole. Image Credit: US Navy
The Cochrane review on community programmes to deworm children of intestinal helminths has just been updated. We want people to read it, particularly those with an influence on policy, because it is important to understand the evidence, but the message is pretty clear. For the community studies where you treat all school children (which is what WHO advocates) there were some older studies which show an effect on weight gain after a single dose of deworming medicine; but for the most part, the effects on weight, haemoglobin, cognition, school attendance, and school performance are either absent, small, or not statistically significant. We also found some surprises: atrial published in the British Medical Journal reported that deworming led to better weight gain in a trial of more than 27,000 children, but in fact the statistical test was wrong and in reality the trial did not detect a difference. We found a trial that examined school performance in 2659 children in Vietnam that did not demonstrate a difference on cognition or weight that has never been published even though it was completed in 2006. We also note that a trial of 1 million children from India, which measured mortality and data collection completed in 2004, has never been published. This challenges the principles of scientific integrity. However, I heard within the last week that the authors do intend to get the results into the public domain-which is where it belongs.
We want to see powerful interventions that help people out of poverty, but they need to work, otherwise we are wasting everyone’s time and money. Deworming schoolchildren to rid them of intestinal helminths seems a good idea in theory, but the evidence for it just doesn’t stack up. We want policy makers to look at the evidence and the message and consider if deworming is as good as it is cracked up to be.
Paul Garner is Professor at the Liverpool School of Tropical Medicine, founder and coordinating editor of the Cochrane Infectious Diseases Group. He is Director of a Consortium dedicated to ensuring decisions in the health sector in middle and low income countries are informed by independent synthesis of all relevant, reliable research, funded by the UK’s Department for International Development.
Deworming should remain an essential cornerstone for NTD control
Peter J. Hotez, Neeraj Mistry and Alan Fenwick
Since 2005, we have strongly advocated for the expansion of global deworming efforts when used in an integrated package of up to four drugs in order to simultaneously target seven or more neglected tropical diseases (NTDs), including up to three intestinal helminth infections, i.e., ascariasis, hookworm infection, and trichuriasis, together with lymphatic filariasis, onchocerciasis, schistosomiasis, and trachoma. Many of these infections geographically overlap and are often co-endemic. With regards to the deworming component for the intestinal worms, a new July 2012 Cochrane review by Taylor-Robinson et al.just concluded that deworming has little or no effect (or at best an inconsistent effect) on improving childhood anemia, cognition, school attendance and performance, so that it is “probably misleading” as they put it to “justify contemporary deworming programmes.”
Jars of Ascaris lumbricoides(2269 worms from 114 people). Image Credit: Andrew Hall
For us, such conclusions are disappointing based on our analysis from the existing evidence that deworming for intestinal worms is an essential cornerstone of the integrated approach to NTD control. Having said that, we read the Cochrane review and feel that the authors worked hard to assemble most of the major deworming studies, conducted a sound systematic review, and went to some lengths to stay measured in their conclusions that deworming children “appears promising, but the evidence base is small.” Our initial assessment of the Taylor-Robinson et al work is that they conducted a sound study.
Nonetheless, we do feel that their work may have been conducted in ways that could potentially “stack the deck” against seeing more dramatic and consistent beneficial effects of deworming. Below are some thoughts on ways that Taylor-Robinson et al might want to proceed if they were to undertake a version 2.0 of the analysis.
1) All intestinal worms are not the same.
While it is tempting to lump all soil-transmitted intestinal helminths as a single group (sometimes referred to as “STHs”) the truth is that the five major STHs are each quite different in the type of disease and pathology they produce. Below is a listing of the five major STHs and an approximate estimate of the number of people they infect:
Ascaris lumbricoides: 800 million
Necator americanus: 500-600 million
Trichuris trichiura: 500-600 million
Ancylostoma duodenale: 100 million
Strongyloides stercoralis: 30-100 million
Each of these STHs will produce very different nutritional effects on their human hosts. For instance only the hookworms, Necator americanus andAncylostoma duodenale, because of their ability to feed on host blood, will typically produce significant iron-deficiency anemia. Therefore, we would not expect to see any effects of deworming on improving child hemoglobin unless the studies were done in areas where there was a high level of hookworm transmission (and therefore high prevalence and intensity) of either N. americanus or A. duodenale infections. Indeed a systematic review by Smith and Brooker concluded that moderate- and heavy-intensity hookworm infections were associated with lower hemoglobin in school-aged children, while all levels of infection intensity were associated with lower hemoglobin in adults. Moreover, they were able to show a positive impact of roughly 2g/l of hemoglobin depending on the anthelminthic medicine used.
An adult Ascaris lumbricoides worm. Image Credit: CDC Division of Parasitic Diseases
2) Not all intestinal worms respond to the same deworming medication.
Each of the STHs also differs in their response to anthelminthic chemotherapy. For instance in a 2008 systematic review Keiser and Utzingerfound that single dose mebendazole produces only a 15% cure rate against hookworm infection, and indeed the Smith and Brooker analysis confirmed that mebendazole does not improve anemia whereas albendazole does. However, albendazole treatment failures for hookwormhave also been reported. Such concerns have prompted our efforts to develop a hookworm vaccine (as well as other NTD vaccines) as an alternative intervention(s). Other differential effects to albendazole and mebendazole to the major STHs have also been described. Therefore any analysis needs to look at the specific types of worms present and the medication used for deworming.
3) Only moderate and heavy intestinal helminth infections typicallycause measurable disease.
Generally speaking in an area where STHs areendemic approximately 10-30% of the pediatric population will suffer from moderate or heavy infections. Uninfected children or even many lightly infected children would typically not develop sequelae from malnutrition. Therefore, effects of deworming would only be expected in areas of high STH transmission, and even then only in a percentage of the infected population. This means that conducting a trial with randomization will mean a dilution of the benefits because only a percentage of those included will show a measurable improvement.
Rapid STH re-infection often occurs following treatment, which is the basis for recommending annual deworming or even two or three treatments annually in areas of high STH transmission. Therefore, it is important to evaluate the nutritional effects within a modest time frame following deworming.
5) Underlying host and environmental factors.
The ability to detect a health improvement from deworming may also depend on whether children in the area under study simultaneously suffer from low nutritional intake or if they are co-infected with other pathogens.
Without due consideration of the factors listed above, we worry that using the current approach described by Taylor-Robinson might possibly be too blunt of an instrument to detect nutritional and other improvements as a result of pediatric deworming. There is no doubt that if a child in the UK or USA was shown to have worms, they would be dewormed immediately and without question. We recommend considering a version 2.0 analysis that effectively incorporates the issues and factors described above. In the meantime we hope that global deworming with essential medicines will continue for children living the world’s low- and middle-income countries.
Peter Hotez, MD PhD, is President of the Sabin Vaccine Institute and Director of the Texas Children’s Hospital Center for Vaccine Development. In this role Prof. Hotez leads an international effort to develop vaccines for neglected Tropical Diseases. He is also the Texas Children’s Hospital Endowed Chair in Tropical Pediatrics, and Professor of Pediatrics and Molecular Virology and Microbiology and Dean of the National School of Tropical Medicine at Baylor College of Medicine. Prof. Hotez is a member of the Institute of Medicine of the National Academies and is the author of over 250 papers in scientific journals, as well as the recently published, Forgotten People, Forgotten Diseases (ASM Press). Prof. Hotez is Co-Editor-in-Chief of PLoS Neglected Tropical Diseases.
Professor Alan Fenwick, OBE, is Director of the Schistosomiasis Control project at Imperial College London, an organisation which has delivered over 100 million treatments against schistosomiasis and intestinal helminths to children in Africa since 2003. He is also Professor of Tropical Parasitology at Imperial College and a global advocate for control of Neglected Tropical Diseases.
Dr. Neeraj Mistry is the Managing Director at Global Network. He was a founding member and former vice president of the Global Business Coalition on HIV/AIDS, Tuberculosis and Malaria (GBC) where he led the work on co-investment and public-private partnerships with the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund. Dr. Mistry received his medical degree from Witwatersrand Medical School in Johannesburg, South Africa, and holds a Master’s degree in health policy and economics from the London School of Economics and Political Science.
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