Giving What We Can no longer conducts our own research into charities and cause areas. Instead, we're relying on the work of organisations including J-PAL, GiveWell, and the Open Philanthropy Project, which are in a better position to provide more comprehensive research coverage.
These research reports represent our thinking as of late 2016, and much of the information will be relevant for making decisions about how to donate as effectively as possible. However we are not updating them and the information may therefore be out of date.
Donating to an organisation which focuses on treating children with parasitic worms through mass drug administration (MDA) represents an excellent giving opportunity for a donor focused on having a high impact on both health and economic empowerment. As the drugs used to treat parasitic worms have only mild side effects, they can be administered without the need for individual diagnosis (which is both expensive and requires medical expertise). In addition, the drugs used to treat parasitic worms are cheap to manufacture and often donated by pharmaceutical corporations. This means that children can be dewormed effectively at very low cost.
We focus here on MDA of praziquantel (used to treat schistosomiasis) and albendazole (used to treat soil-transmitted helminth infections) as these treat two diseases both with very high prevalence, and strong evidence of treatment efficacy. There is some limited evidence that suggests that children in high prevalence areas who are dewormed with these drugs have substantially higher lifetime incomes. There is also limited evidence that they may also complete more years of schooling, and have higher levels of general health. The evidence supporting the efficacy of deworming is complicated by the many different types of infection, and long timescales involved. Although there is still disagreement over the precise extent of the flow-through effects of deworming, the extremely low cost of treatment still implies that it can be expected to be a highly effective intervention - impacts on long-term productivity and wider health benefits simply add further to the case for MDA as an effective intervention.
This report focuses on schistosomiasis and soil-transmitted helminth infections, which are both parasitic worms infections. Both these diseases are classed as Neglected Tropical Disease (NTDs), a group of diseases which primarily affect those living in poor countries.
Schistosomiasis is caused by parasites that are transmitted through freshwater snails. The parasite emerges from the snail, contaminating the water, and is transferred to humans through contact with the skin. When the parasite is inside the human host, it lays eggs. Schistosomiasis infections can be cleared cheaply with the drug praziquantel, even though in areas with high worm prevalence, reinfection can be rapid (within a year) if mass drug administration is not sustained.
Soil-transmitted helminths (STH) are parasitic worms which infect humans through contact with soil infected with feces. STH infections are often asymptomatic and so are difficult to detect but may contribute to weight loss. There are three kinds of soil-transmitted helminth: ascaris (which causes ascariasis), whipworm (trichuriasis) and hookworm (hookworm infections). All three types of infection are treated with albendazole or mebendazole.
Parasitic worms affect almost a third of the world’s population. As infections are often asymptomatic, and current diagnostic methods are inexact, prevalence is difficult to measure accurately. The WHO estimate that approximately 2 billion people are infected with STH worldwide (many people have multiple infections). Table 1 shows approximate splits between the different infections.
|Infection||Number of infections6|
|Ascaris||800m - 1.2bn|
|Hookworm||576m - 740m|
Table 1: Number of infections for different parasitic worm infections. Source: CDC
Estimates of individual disease burden vary widely. Although the base infections have relatively low disability weightings on average (most cases have subtle impacts on health), schistosomiasis (0.005) and STH (0 - 0.006) may significantly impair development and lead to lower quality of life and income particularly among the more heavily infected (see Development effects). Schistosomiasis can also cause more severe symptoms and death if untreated. NTDs account for 1.2% of the DALY burden in developing countries.
Schistosomiasis and soil transmitted helminths primarily affect people in poor countries. Schistosomiasis disease burden is highest in Sub Saharan Africa, while STH disease burden affects South Asia and South America about equally . The burden of disease by country income group in 1990, 2010 and 2020 (projected) varies.
There are three main ways in which these diseases impact people:
There is some evidence suggesting that combination deworming has a large impact on future life prospects.
Recently, a Cochrane review called into question the evidence for the impact of STH deworming on schooling.
A recent Cochrane review of randomised controlled trials (RCTs) examined the effectiveness of treating STH with albendazole (and other drugs). The main conclusion of the review was that, while deworming pre-screened children (who have been confirmed to be infected) for STH may significantly increase weight gain, deworming all children through MDA had no statistically significant effect on weight gain, haemoglobin levels, or educational indicators. We have written an extensive blog post on the topic and still believe that deworming is probably a very cost-effective intervention. It is important to note that this review applies only to STH, and not to schistosomiasis. In addition, the review has a number of limitations:
This highlights a limitation of systematic reviews of RCTs for policy decision as a series of well identified studies were excluded from the review and no cost-effectiveness analysis was conducted. In particular, the Baird and Croke studies were excluded on the basis that the control group eventually received deworming treatment. However, given that this would reduce the scale of the positive results, we do not believe this is a good reason for exclusion. While we appreciate the need for rigid exclusion criteria in meta-analyses, all available evidence should guide health policy decisions. We note, however, that we have talked to the authors of the Cochrane review and they are currently preparing a manuscript that criticizes the natural experiments above.
Overall, we believe that, on balance, it is likely that combination deworming has a substantial impact on future income, but that there is also some contradictory evidence. However, given that mass deworming is very cheap, the potential long term developmental benefits are large, and there are a number of important papers excluded from the recent Cochrane study, we believe that mass deworming remains one of the best interventions a donor could donate to.
The scientific literature on general health effects of parasitic worms is complex and difficult to appraise. This is not only because there are different worm infections (schistosomiasis and several types of soil transmitted infections) and differences in prevalence and intensity of worm infections, but also because there is substantial amount of disagreement in the scientific literature.
The authors of the most recent Cochrane systematic review and meta analysis on deworming for soil-transmitted intestinal worms in children (mentioned above) conclude that:
“Treating children known to have worm infection may have some nutritional benefits for the individual. However, in mass treatment of all children in endemic areas, there is now substantial evidence that this does not improve average nutritional status, haemoglobin, cognition, school performance, or survival.”
It is important to note that this review applies only to STH, and not to schistosomiasis. We have written an extensive blog post on the topic and still believe that deworming is probably a very cost-effective intervention.
However, the conclusions of the review on health outcomes do not relate to schistosomiasis. Schistosomiasis is associated with more severe ill-health than STH. Consequently, the disease burden is higher, and treating it might be more cost-effective than treating STH. Even the Cochrane review agrees that there is benefit of treating populations with schistosomiasis:
“The evidence for the benefit of treating populations with schistosomiasis is fairly clear, as the infection has a very substantive effect on health." (Danso-Appiah 2008 as cited in the Cochrane Review by Taylor-Robinson et al. 2015 1)
Some parasitic worms are associated with anemia, a condition which results from a lack of haemoglobin in the blood. The extent of this effect is difficult to measure and depends on the particular infection, however there is evidence that individuals affected by schistosoma mansoni were 2.86 times as likely to have anemia and those with hookworm were 1.65 times as likely. Combination deworming (where drugs are administered for a number of different types of infection) is associated with a +2.37 g/L increase in haemoglobin levels. It is not clear whether STH-only treatment has a significant impact on haemoglobin levels. Overall, though, GiveWell suggests that the impact of parasitic worms on general health is likely to be small. However, given the very low cost of treatment, MDA could still be a cost-effective intervention, in expectation, purely on the grounds of reducing anemia and potentially improving general health.
While death due to schistosomiasis is rare, it can cause a range of symptoms and manifestations including painful urination, blood in the urine, blood in the stool, anemia, kidney failure, bladder cancer, genital inflammatory lesions in both men and women, sterility (in urogenital schistosomiasis), stomach pain, liver damage, ascites, acute gastrointestinal bleeding, nutritional deficiencies, and urinary tract infections. Urogenital schistosomiasis is also considered to be a risk factor for HIV infection, especially in women.
One primary cause of death from schistosomiasis is liver failure (with kidney failure, bladder cancer, and portal liver fibrosis also contributing greatly). Liver failure can occur ten years after initial infection and can have a number of other causes, as can kidney failure and so on, meaning that estimating the disease burden of schistosomiasis is difficult. One systematic review estimated that 280,000 people die from schistosomiasis each year but GiveWell has criticised the methodology used. The Global Burden of Disease project estimated that about 5,500 people died of schistosomiasis in 2013 and 4,500 people died from Ascariasis (the only STH infection which is confirmed to cause mortality). Overall, the death toll of both schistosomiasis and STH infection is likely to be relatively small in comparison to other conditions - malaria, for instance, causes between 438,000 and 1 millions deaths each year. A large RCT on the health effects of STH deworming in North India found no significant reductions in mortality.
Deworming for schistosomiasis may reduce HIV and malaria prevalence, but deworming for Ascariasis (one of the STHs) may increase malaria prevalence.
A series of papers have suggested that mass drug administration to reduce schistosomiasis and STH infections may have positive side effects.Schistosomiasis incidence has been found to be associated with malaria and HIV infections due to the immunodeficiency it causes and, particularly, the manifestation of genital schistosomiasis symptoms (both male and female). For HIV infections in particular, RCTs with rhesus monkeys have shown that this relationship is likely to be causal. MDA may therefore have the side effect of reducing both malaria and HIV prevalence, with different analyses suggesting that averting one HIV case through treating schistosomiasis costs as little as US$52–260.
On the other hand, one recent review concludes that that some worms, notably Ascaris, are associated with protection from severe complications of malaria and that others, notably hookworm, lead to increased malaria incidence or prevalence. Other factors might include the worm infection intensity, as well as age on the outcome of co-infections. The authors conclude that:
“Although it is tempting to rush to the conclusion that deworming patients would reduce malaria [due to Hookworm and schistosomiasis], it still seems wise to be attentive to the potential scenario of an increase of severe malaria [due to protective effects of Ascaris]. Monitoring the incidence of malaria and severe malaria before and after vertical de-worming campaigns seems a minimum test to make sure there is a better understanding of what is going on at a population level”.
It should also be noted that a very recent randomized controlled trial did not find that repeated anthelmintic treatment had any impact on malaria infection prevalence, parasite density and frequency of malaria attacks. Overall the link between, on one side, schistosomiasis and STH and, on the other, malaria and HIV is a relatively new area of enquiry and we would welcome more research on this topic.
It has also been found that schistosomiasis infection is linked with multiple forms of cancer, and that MDA treatments may reduce cancer incidence. Links between schistosomiasis and bladder (squamous cell carcinoma) and bile duct (cholangiocarcinoma) cancer have been found, and there is some limited evidence that schistosomiasis might be associated with prostate cancer too. Liver fluke infection is also recognised as a cause of liver cancer and can be effectively treated with Praziquantel. It has also been suggested that schistosomiasis might interact with Tuberculosis, Hepatitis, and Appendicitis, but we have not investigated these links in more detail.
The interventions used to combat schistosomiasis and STH can be broadly split into three categories: treatment, vector control, and improvements in water, sanitation and hygiene (WASH).
Treatment can be implemented either on a case-by-case basis, or through mass drug administration (MDA). As individual diagnosis (at least $6.89 per patient) is generally more expensive than the cost of administration, we have identified MDA as a high impact area for donors.
Vector control involves reducing the population of parasites by reducing their animal reservoir, for example using chemicals to reduce snail populations in infected areas. Controlling the population of snails (mulluscicide) has been shown to be reasonably effective in reducing infection rates. Another option which has recently been suggested is to manipulate the genetics of snails to reduce transmission. Unfortunately, however, we have not found any charities which carry out snail control with high cost-effectiveness and genetic manipulation of snails is still in the early stages of research so it is unclear how effective and how costly this might be.
Improvements in sanitation are another important way to reduce the transmission of parasitic worms which spread through water contaminated with fecal matter. Elimination of parasitic worms may require an integrated approach of both sanitation and deworming treatments, but we focus here on MDA due to its higher cost-effectiveness, scalability, and the greater number of effective charities working in this area.
It is also worth noting that, while there is currently no vaccine for human schistosomiasis, several candidates are in different stages of preclinical and clinical development. The major targets are urogenital and intestinal schistosomiasis, which account for 99% of the world's 252 million cases, with 90% of these cases in Africa. These products often focus on vaccinating children, in some cases following mass treatment with praziquantel.
A human hookworm vaccine is also being tested in several countries. A recent model of the economic and epidemiologic impact of the vaccine suggests that both vaccine and MDA are highly cost-effective and that, from the societal perspective, vaccination was less costly and more effective in almost all scenarios. The article concludes that a human hookworm vaccine could become a key technology in effecting control and elimination efforts for hookworm globally.
Mass deworming is primarily carried out in areas with relatively high prevalence of schistosomiasis and/or STH infections. Albendazole is used to treat STH. Praziquantel is used to treat schistosomiasis. Combination deworming involves administering treatments for both types of parasitic worm. As the side-effects of the drugs are relatively minor, they can be administered to the whole population without the need for individual diagnosis, keeping costs low and reducing the need for skilled health professionals. MDAs can target everyone in a particular area or can specifically target at-risk groups such as children. Schools are often used as a distribution platform and teachers can be trained to distribute the drugs safely. As the treatment only requires drug distribution, MDA can be undertaken in relatively short timescales. The WHO recommends that MDA is carried out twice yearly in endemic areas.
Mass drug administration is very cheap. As praziquantel and albendazole have few significant side effects, they can be safely administered to large parts of the population without the need for individual diagnosis, which is both expensive and requires trained medical practitioners. GiveWell estimates that Deworm the World initiative (one of our promising top charities) can deworm a person for approximately $0.80 and the Schistosomiasis Control Initiative (one of our established top charities) can deworm a person for approximately $1.26 (this includes the estimated cost of teacher time and donated drugs). A recent study modelled the cost of treatment in Uganda for different distribution sizes and found broadly similar figures, and concluding that there were significant economies of scale to mass drug administration, with the average cost of STH deworming falling below $0.50 for the largest distributions (see Figure 7). It should be noted that this study was conducted by a researcher affiliated with SCI. It has also been found that the cost-effectiveness of deworming may be considerably higher than is typically estimated - this is because, due to the binary disability weighting used, incremental improvements in health are generally not included in the recorded effects and the total effects are hence underestimated.
There is strong evidence that mass deworming results in lower rate of worms infections. Two Cochrane meta-studies have concluded that deworming for schistosomiasis has a substantial impact on schistosomiasis infections, with 60% of those treated with praziquantel cleared of infection after one to two months of treatment. Moreover, the number of schistosome eggs found in the urine was reduced by 95%, helping to interrupt transmission. Another meta-study, published in 2000, found that administration of albendazole was very effective in reducing levels of hookworm and ascariasis, although the median cure rate for whipworm infection was relatively low at 38%.
As we explained above, lower rates of worm infection might impact human lives through three routes: long term impact on child development affecting schooling and income; general health effects from reducing anemia; avoidance of severe symptoms and death from worm infections.
However, it is not easy to quantify the benefits of deworming. A recent review of the cost and cost-effectiveness of soil transmitted helminth treatment programmes found that estimates of the cost-effectiveness of combination deworming for school aged children varied from $5 to $80 per DALY. Specifically, the Miguel and Kremer paper mentioned above found that combination deworming costed $5 per DALY averted. The 1993 Disease Control Priorities Project estimated the cost was between $6 and $33 per DALY. The 2006 Disease Control Priorities Project estimated the cost was between $8 and 19$ per DALY, though GiveWell found substantial mistakes in the evaluation. GiveWell estimates that the cost-effectiveness of the intervention is roughly $28.19-$70.48 per DALY averted for schistosomiasis treatment and $82.54 per DALY for STH treatment. However, it should be stressed that the review concluded that the absence of cost data and inconsistencies in the collection and analysis methods constitutes a major research gap for deworming. Moreover, GiveWell does not employ these estimates in its assessment of the analysis of deworming, since it believes attempts to estimate the cost-effectiveness of deworming within the disability-adjusted life-year (DALY) framework have been problematic, in part dues to the fact that the estimates are extremely sensitive to many assumptions.
A recent paper in Lancet estimated the incremental cost-effectiveness (ICER) of expanding treatment to all adults as well as children. It found an approximate ICER of $127 per DALY averted. The incremental cost-effectiveness ratio of community-wide MDA is relative to targeting at children.
Note that the cost-effectiveness of MDA might be improved by its effect on HIV and malaria. Depending on the efficacy of MDA, the analysis mentioned above suggests that averting one HIV case through treating schistosomiasis costs as little as US$51.68–259.31. If we assume that 20 DALYs are lost per infected adult, this translates to US$2.58-12.97 per DALY averted (our calculation). It should be stressed however, that these estimates are not supported by a sufficiently large body of evidence for us to be confident of their accuracy.
Researchers continue to be worried about the development of drug resistance to praziquantel, as it is the only drug currently recommended by the World Health Organization for the treatment and control of human schistosomiasis. Some signs of resistance of schistosomes against praziquantel have been observed in the laboratory, but in the field only isolated cases of tolerance to praziquantel have been observed so far, while true resistance has not been recorded. The Schistosomiasis Control Initiative (SCI) claims that parasites are unlikely to develop resistance to praziquantel due to its unique mode of action.The National Institutes of Health has recently awarded a $3.5 million grant over five years to understand the genetic changes in the schistosomiasis parasite that lead to drug resistance.
A recent report argues that climate change will make temperatures more suitable for schistosomiasis transmission over the next 20 years, not only in terms of spread to other currently non-endemic countries, but also in terms of increasing the intensities of the disease in countries currently affected. The authors suggest that this increase in infection and reinfection intensity may reduce the impact of control and elimination programmes. On the other hand, with the resulting increase in need and thus scalability of these programs, this might also mean an increase in their effectiveness.
A study of an integrated NTD control program in Mali found both positive and negative impacts on the wider health system. Positive impacts included increased funding for medical professionals. Negative impacts included distraction of staff from core activities and fragmentation of the monitoring and evaluation system. These effects were heterogeneous between different districts. Districts with more robust health systems tended to have more positive spillover effects. Limitations of the study include: it was qualitative research specific to Mali so may not be generalisable to other settings; it was an integrated NTD program, which might use a higher proportion of healthcare professional time (mass drug administration is largely staffed by community volunteers); and it was one of the first integrated NTD programs (evidence suggests that vertical health interventions become better integrated with health systems over time). Finally, this analysis did not account for fewer NTD related complication burdening the healthcare system after MDA.
While MDA lowers infection rates, these treatments must be provided indefinitely when there are no major improvements in water quality and sanitation. Yet, we lack high quality evidence on the precise effects of WASH interventions on schistosomiasis and STH. Recent reviews have shown that WASH access and practices are generally associated with reduced odds of STH infection that there are good reasons to believe that improvements in WASH should, in general, reduce the force of schistosomiasis transmission. However, both reviews note that further research is warranted to determine the magnitude of benefit of WASH interventions. Moreover, significant improvements in WASH practices typically take time and happen over multiple decades.
A recently published study argues that historically, schistosomiasis control programmes which have focussed on vector control (mainly by controlling the snail population, as snails are an intermediate host of worms) have produced greater reductions of the prevalence of schistosomiasis than programmes that just deliver mass drug administration. However, the authors do not make any claims about the cost-effectiveness of snail control relative to MDA. They simply show that the average snail control programme has reduced schistosomiasis prevalence more than the average MDA programme, but if snail control programmes are more expensive we could still prefer to fund MDA as it reduces schistosomiasis more cost-effectively.
There is a high treatment gap for schistosomiasis deworming. Scale up of treatment remains slow in the 10 highest burden countries in Africa (see Table 2). The WHO estimate that only 34% of children who required deworming treatment globally received it in 2013. Access is limited by both economic and logistical constraints: even for households which can afford to pay for treatment, drugs such as praziquantel are sometimes not accessible in sub-Saharan Africa.
|Country||Number of people requiring deworming (millions)||Number of people treated (millions)||Coverage (%)|
Table 2: Treatment gap for schistosomiasis deworming in countries with highest prevalence (2012)
The number of people who are targeted to receive deworming is rising (see Figure 8) and a recent report by the World Health organisation estimates that the overall costs for all kinds of preventive chemotherapy in the coming year are in the hundreds of millions (see Figure 9; see Figure 10 for a split between the costs of Schistosomiasis and STH). While countries such as Brazil and India completely covered the cost of distributing the donated medicines using their own resources, poorer countries such as the DRC, Senegal and Niger are not in a position to execute these programs by themselves. Bigger aid donors such USAID do not completely fund such programs. Thus, it is very much conceivable that charities working on MDA for schistosomiasis and STH might play a substantial part implementing such future deworming programs and thus require substantially more funds. This could become subject to change in case bigger agencies such as USAID recognize the cost effectiveness of interventions targeting NTDs.
We therefore conclude that additional funding of treatment for parasitic worms could be spent productively.
This conclusion is based, in part, on the number of people targeted for coverage with integrated preventive chemotherapy for selected NTDs and the overall projected costs of all preventive mass drug administration against NTDs including schistosomiasis and soil transmitted helminths in the coming years. We also considered the projected costs of preventive mass drug administration against schistosomiasis and soil transmitted helminths in the coming years. [^fn-1039]: Croke, K. "Does Mass Deworming Affect Child Nutrition? Meta-analysis, Cost ..." 2016. http://emiguel.econ.berkeley.edu/assets/miguel_research/77/worms_v93.pdf