Parasitic Worms

Electron micrograph of an adult male Schistosoma worm. The bar (bottom left) represents a magnification of 500 μm. (David Williams / commons.wikimedia.org)

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Notice about research

Giving What We Can no longer conducts its own research into charities and cause areas. Instead, we're relying on the work of organizations 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 However we are not updating them and the information may therefore be out of date.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.

1.Importance

1.1.What are Parasitic worms?

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[1][2]. 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.


1.2.How do they affect people?

Parasitic worms affect almost a third of the world’s population. As infections are often asymptomatic, and current diagnostic methods are inexact[3], prevalence is difficult to measure accurately. The WHO estimate that approximately 2 billion people are infected with STH worldwide[4][5] (many people have multiple infections). Table 1 shows approximate splits between the different infections.

InfectionNumber of infections[6]
Schistosomiasis200-600m
Ascaris800m - 1.2bn
Whipworm604-795m
Hookworm576m - 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),[7] schistosomiasis (0.005[8]) 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.[9]

Figure 1: NTDs account for 1.2% of the DALY burden in developing countries.[10]

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 (see Figure 2). Figure 3 and 4 show the burden of disease by country income group in 1990, 2010 and 2020.

Figure 2: Geographical concentration of intestinal parasitic worms and schistosomiasis.[11]
Figure 3: Burden of disease by country income group for nine NTDs, in 1990, 2010 and projected for 2020.[12]
Figure 4: Burden of disease by country income group for nine NTDs, in 1990, 2010 and projected for 2020.[13]

There are three main ways in which these diseases impact people:

  • General health - parasitic worms may be associated with anemia, a condition which results from a lack of haemoglobin in the blood. Anemia can be particularly severe for pregnant women as a major risk factor during childbirth.[14][15]
  • Severe symptoms - Schistosomiasis can cause death and serious morbidity such as female genital schistosomiasis.
  • Developmental effects - parasitic worms may have substantial effects on schooling and future earning potential.[16][17][18]

1.2.1.Developmental effects

There is some evidence suggesting that combination deworming has a large impact on future life prospects.

  • One paper by Bleakley examined the impact of hookworm eradication in the American South and found that childhood infection with hookworm was associated with reduced levels of school enrollment, school attendance, and literacy. A long-term follow-up found that childhood infection with hookworm reduced occupational income by approximately 23%.[19] These results provide suggestive evidence that hookworm eradication is associated with substantial increases in future earnings. On the other hand, we are careful not to draw strong conclusions from this paper as it was a retrospective study (raising the possibility of publication bias) with limited external validity for MDA in Sub-Saharan Africa due to differences in schooling infrastructure and the variety of eradication tools used.

  • Another important study by Baird et al. examined experimental variation in school-based combination deworming (for schistosomiasis and STH) in Kenya.[20] Treatment was assigned between three groups of school. The treatment groups were assigned, on average, 2.4 more years of deworming than the control group. After ten years, boys in the treatment group were found to work 17% more hours each week and were more likely to hold desirable manufacturing jobs. Girls in the treatment group were 25% more likely to have attended secondary school and tended to spend more time on cash crops than traditional agriculture. These are substantial results, but may not be completely generalizable as the baseline infection rates were very high (90%).[21]

  • Another study in 2014 by Croke looked at the long term educational impact of a cluster-randomised Uganda deworming programme on test scores.[22] It found that children in treated villages have significantly higher test scores than children in control villages. This is important as it provides evidence of a mechanism by which deworming may affect future income.

  • The above finding is consistent with another study by Ozier in 2014 which found that, ten years after deworming, average test scores for children under the age of 2 (who were not dewormed themselves) increased in villages which had been dewormed (the author suggests this is because of interruptions in transmission).[23]

  • A 2015 study provided additional support for these results, finding an association between STH infection and worse cognitive ability, worse nutritional status, and worse school performance.[24]

  • Numerous other studies have found strong negative correlations between STH and schistosomiasis infections and productivity (workdays lost, average bonus earnings, productive capacity and overall earnings).[25][26][27][28][29][30][31] It is hence plausible that treating STH infections will result in improved cognitive ability, improved nutritional status, improved school performance, improved earnings, improved productivity,  and also improved long-term economic 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:

  1. None of the studies above were included in the review for a number of reasons:
  • Bleakley - a retrospective analysis rather than an RCT
  • Ozier - treatment group had not been dewormed as the study was trying to identify positive spillovers
  • Croke and Baird - children in the control group may have eventually received deworming treatment

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.

  1. MDA is a more cost-effective way of treating STH than selective deworming of pre-screened children. This is because the cost of screening is 4-10 times the cost of treatment.[32] The children who would have been treated in a pre-screened treatment will also be treated by MDA and so realise any health benefits which they would have gained from just treating pre-screened children. It is therefore possible that analyses of MDA have diluted the impact of deworming (by including uninfected children) to the extent that they are no longer statistically significant, but that infected children still benefit from MDA. The WHO have upheld their advice to undertake MDA in areas where prevalence is above 20% as they believe it remains “the most cost-effective strategy to reach infected children and improve their health and well-being.”[33]

  2. A number of the papers included in the study which find no evidence of an impact on schooling levels are randomised at the individual level.[34][35][36] If deworming has positive spillover effects (which seems likely for a communicable disease), this would lead these studies to underestimate the benefits of deworming. The exception was one cluster RCT in Vietnam which showed no significant impact on mathematics or Vietnamese test scores.[37] We have not reviewed this study in detail but believe that it may represent some contradictory evidence to the efficacy of deworming on schooling.

  3. A recent paper argues that the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it adds that is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. It goes on to argue that urgent investment in studies powered to detect direct morbidity effects due to STH is required.[38]

  4. Another meta-analysis disputes the findings of the Cochrane review.[39] The classification of deworming studies by the most recent review has changed with regards to the number of doses of deworming treatment and the prevalence of worms. They rerun the meta-analysis using previous Cochrane review classification criteria and find statistically significant effects of deworming on child weight. Furthermore, this updated meta-analysis argues that the Cochrane review does not include all relevant studies and as a result, the Cochrane analysis is underpowered and does not have a large enough sample size to detect effects that are large enough to make deworming cost-effective. Due to limited sample size, the Cochrane review would conclude that MDA has no effect, even if the effect size was large enough to make MDA cost-effective. The updated meta-analysis has 22 estimates from 20 papers, which as twice as many as the Cochrane review, and this includes papers which were not yet published at the time of Cochrane review. Using this updated sample they reject the hypothesis of deworming having no effect with p < 0.001.

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.

1.2.2.General health effects

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[40] (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. [41][42][43] Consequently, the disease burden is higher, and treating it might be more cost-effective than treating STH.[44] 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)[45]

1.2.2.1.Anemia

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.[46][47] 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.[48] It is not clear whether STH-only treatment has a significant impact on haemoglobin levels.[49] Overall, though, GiveWell suggests that the impact of parasitic worms on general health is likely to be small.[50] 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.

1.2.3.Severe symptoms and mortality

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.[51] 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).[52] 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[53] but GiveWell has criticised the methodology used.[54] 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).[55] 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.[56] A large RCT on the health effects of STH deworming in North India found no significant reductions in mortality.[57]

1.2.4.Impact of deworming on HIV and malaria prevalence

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[58] and HIV[59][60][61] infections due to the immunodeficiency it causes and, particularly, the manifestation of genital schistosomiasis symptoms (both male[62] and female[63]). For HIV infections in particular, RCTs with rhesus monkeys have shown that this relationship is likely to be causal.[64] 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.[65]

On the other hand, one recent review[66] 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.[67] 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”.[68]

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.[69] 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.[70][71] Liver fluke infection is also recognised as a cause of liver cancer and can be effectively treated with Praziquantel.[72][73][74] It has also been suggested that schistosomiasis might interact with Tuberculosis[75], Hepatitis[76], and Appendicitis[77], but we have not investigated these links in more detail.

2.Tractability

2.1.How can the problem be addressed?

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)[78] is generally more expensive than the cost of administration[79], 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.[80] Controlling the population of snails (mulluscicide) has been shown to be reasonably effective in reducing infection rates.[81] Another option which has recently been suggested is to manipulate the genetics of snails to reduce transmission.[82] 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.[83]

Improvements in sanitation are another important way to reduce the transmission of parasitic worms which spread through water contaminated with fecal matter.[84][85] Elimination of parasitic worms may require an integrated approach of both sanitation and deworming treatments,[86][87] 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.[88]

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.[89][90] The article concludes that a human hookworm vaccine could become a key technology in effecting control and elimination efforts for hookworm globally.

2.2.Mass drug administration

2.2.1.How does it work?

Figure 6: A child is given a deworming tablet at a deworming day in India (Image: Evidence Action / evidenceaction.org).

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.[91] 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.[92]

2.2.2.Cost-effectiveness

Mass drug administration is very cheap. As praziquantel and albendazole have few significant side effects,[93][94] 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[95] (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).[96] 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.[97]

Figure 7: Average cost per STH treatment by district size[98]
Figure adapted from [99]. “Effectiveness and cost-effectiveness of school-based mass drug administration; (A–C) Effectiveness and (D–F) cost-effectiveness of school-based mass drug administration as a function of the number of at-risk SAC treated within the district are shown according to effectiveness measure (appendix). The number treated was calculated by varying the treatment coverage of SAC at risk of infection within the district, with treatment coverage defined as the proportion of the targeted population (ie, SAC) receiving treatment. In (D–F) the smaller the cost-effectiveness ratio, the more cost effective mass drug administration is deemed to be. Results assume a 50-year time horizon, a period of implementation of 10 years (ie, ten annual treatment rounds), a 3% discount rate, and a total population size of 200 000 individuals, 32% of whom were SAC. SAC=school-age children.”

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.[100][101] 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%.[102]

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.[103] Specifically, the Miguel and Kremer paper mentioned above found that combination deworming costed $5 per DALY averted.[104] The 1993 Disease Control Priorities Project estimated the cost was between $6 and $33 per DALY.[105] The 2006 Disease Control Priorities Project estimated the cost was between $8 and 19$ per DALY,[106] though GiveWell found substantial mistakes in the evaluation.[107] 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.[108] 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.[109]

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 (see Figure 5).[110]

Figure 5: Incremental cost-effectiveness ratio of community-wide MDA relative to targeting at children[111]

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.[112][113] If we assume that 20 DALYs are lost per infected adult,[114] this translates to US$2.58-12.97 per DALY[115] 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.

2.2.3.Possible offsetting/negative impacts

2.2.3.1.Are parasites developing resistance to praziquantel?

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.[116] 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.[117][118] The Schistosomiasis Control Initiative (SCI) claims that parasites are unlikely to develop resistance to praziquantel due to its unique mode of action.[119]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.[120]

2.2.3.2.Are reinfection rates increasing?

A recent report[121] 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.

2.2.3.3.Is there a negative impact on the wider health system?

A study of an integrated NTD control program in Mali found both positive and negative impacts on the wider health system.[122] 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[123]). Finally, this analysis did not account for fewer NTD related complication burdening the healthcare system after MDA.

2.2.3.4.Is deworming effective without also improving sanitation?

While MDA lowers infection rates, these treatments must be provided indefinitely when there are no major improvements in water quality and sanitation.[124] 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[125] that there are good reasons to believe that improvements in WASH should, in general, reduce the force of schistosomiasis transmission.[126] 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.

2.2.3.5.Is vector control more cost-effective?

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.

3.Neglectedness

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.[127] 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.[128]

CountryNumber of people requiring deworming (millions)Number of people treated (millions)Coverage (%)
Nigeria60.63.25%
Ethiopia22.1--
DRC18.0--
Mozambique13.51.310%
Kenya11.8--
Tanzania10.13.131%
Cameroon9.92.122%
Uganda8.61.619%
Malawi6.83.243%
Ghana6.62.030%
Total168.116.6-

Table 2: Treatment gap for schistosomiasis deworming in countries with highest prevalence (2012)[129]

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.

Figure 8: Number of people targeted for coverage with integrated preventive chemotherapy, selected NTDs [130][131]
Figure 9: Overall projected costs of all preventive mass drug administration against NTDs including schistosomiasis and soil transmitted helminths in the coming years[132].
Figure 10: Projected costs of preventive mass drug administration against schistosomiasis (upper panel) and soil transmitted helminths (lower panel) in the coming years.[133]

4.Footnotes

  1. Bethony, Jeffrey et al. "Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm." The Lancet 367.9521 (2006): 1521-1532.

  2. Taylor-Robinson, David C et al. "Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance." Cochrane Database Syst Rev 7 (2015).

  3. King, Charles H. "Parasites and poverty: the case of schistosomiasis." Acta tropica 113.2 (2010): 95-104.

  4. Hotez, Peter J et al. "Combating tropical infectious diseases: report of the Disease Control Priorities in Developing Countries Project." Clinical infectious diseases 38.6 (2004): 871-878.

  5. "WHO | Soil-transmitted helminth infections." 2012. 26 Feb. 2016 <http://www.who.int/mediacentre/factsheets/fs366/en/>

  6. "CDC - Soil-transmitted Helminths." 2011. 26 Feb. 2016 <http://www.cdc.gov/parasites/sth/>

  7. Murray, Christopher J, and Alan D Lopez. Global burden of disease. Cambridge, MA: Harvard University Press, 1996.

  8. A disability weight of 0.005 means that two hundred years of life with schistosomiasis is valued the same as 0.995 years of completely healthy life.

  9. "Global Burden of Disease (GBD) | Institute for Health Metrics …" 2014. 4 Mar. 2016 <http://www.healthdata.org/gbd>

  10. "Global Burden of Disease (GBD) | Institute for Health Metrics …" 2014. 29 Feb. 2016 <http://www.healthdata.org/gbd>

  11. "Global Burden of Disease (GBD) | Institute for Health Metrics …" 2014. 29 Feb. 2016 <http://www.healthdata.org/gbd>

  12. Adapted from Stolk, Wilma A., et al. "Between-country inequalities in the neglected tropical disease burden in 1990 and 2010, with projections for 2020." PLoS Negl Trop Dis 10.5 (2016): e0004560.

  13. Adapted from Stolk, Wilma A., et al. "Between-country inequalities in the neglected tropical disease burden in 1990 and 2010, with projections for 2020." PLoS Negl Trop Dis 10.5 (2016): e0004560.

  14. Butler, Sara E et al. "Mechanism of Anemia in Schistosoma mansoni–Infected School Children in Western Kenya." The American journal of tropical medicine and hygiene 87.5 (2012): 862-867.

  15. Danso-Appiah, Anthony et al. "Drugs for treating urinary schistosomiasis." Cochrane Database Syst Rev 3 (2008).

  16. Baird, Sarah et al. "Worms at work: long-run impacts of child health gains." Berkeley: University of California at Berkeley (2011).

  17. Croke, Kevin. "The long run effects of early childhood deworming on literacy and numeracy: Evidence from Uganda." Unpublished Manuscript (2014).

  18. Bleakley, Hoyt. "Economic effects of childhood exposure to tropical disease." The American economic review 99.2 (2009): 218.

  19. Bleakley, Hoyt. "Disease and development: evidence from hookworm eradication in the American South." The Quarterly Journal of Economics 122.1 (2007): 73.

  20. Baird, Sarah et al. "Worms at work: long-run impacts of child health gains." Berkeley: University of California at Berkeley (2011).

  21. Baird, Sarah. "What are the economic be nefits of mass deworming of children?." (2015).

  22. Croke, Kevin. "The long run effects of early childhood deworming on literacy and numeracy: Evidence from Uganda." Unpublished Manuscript (2014).

  23. Ozier, Owen W. "Exploiting externalities to estimate the long-term effects of early childhood deworming." World Bank policy research working paper 7052 (2014).

  24. Liu, Chengfang et al. "Soil-transmitted helminths in southwestern China: a cross-sectional study of links to cognitive ability, nutrition, and school performance among children." PLoS Negl Trop Dis 9.6 (2015): e0003877.

  25. Lenk, Edeltraud J et al. "Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review." PLoS Negl Trop Dis 10.2 (2016): e0004397.

  26. Audibert, Martine, and Jean-Franζois Etard. "Impact of schistosomiasis on rice output and farm inputs in Mali." Journal of African Economies 7.2 (1998): 185-207.

  27. Barbosa, FS, and DP Pereira Da Costa. "Incapacitating effects of schistosomiasis mansoni on the productivity of sugar-cane cutters in northeastern Brazil." American Journal of Epidemiology 114.1 (1981): 102-111.

  28. Kamel, MI et al. "Impact of schistosomiasis on quality of life and productivity of workers." East Mediterr Health J 8.2/3 (2002): 354-362.

  29. Leshem, Eyal et al. "Acute schistosomiasis outbreak: clinical features and economic impact." Clinical infectious diseases 47.12 (2008): 1499-1506.

  30. Umeh, JC, O Amali, and EU Umeh. "The socio-economic effects of tropical diseases in Nigeria." Economics & Human Biology 2.2 (2004): 245-263.

  31. Wu, Xiao-Hua et al. "Studies of impact on physical fitness and working capacity of patients with advanced Schistosomiasis japonica in Susong County, Anhui Province." Acta tropica 82.2 (2002): 247-252.

  32. Taylor-Robinson, David C et al. "Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance." Cochrane Database Syst Rev 7 (2015).

  33. "WHO | WHO advisory body upholds continued deworming of …" 2015. 29 Feb. 2016 <http://www.who.int/neglected_diseases/news/update-deworming-children/en/>

  34. Simeon, Donald T, Sally M Grantham-McGregor, and Michael S Wong. "Trichuris trichiura infection and cognition in children: results of a randomized clinical trial." Parasitology 110.04 (1995): 457-464.

  35. Kruger, M et al. "Effects of iron fortification in a school feeding scheme and anthelmintic therapy on the iron status and growth of six-to eight-year-old schoolchildren." FOOD AND NUTRITION BULLETIN-UNITED NATIONS UNIVERSITY- 17 (1996): 11-21.

  36. Watkins, William E, José R Cruz, and Ernesto Pollitt. "The effects of deworming on indicators of school performance in Guatemala." Transactions of the Royal Society of Tropical Medicine and Hygiene 90.2 (1996): 156-161.

  37. Hall, Andrew et al. "A review and meta‐analysis of the impact of intestinal worms on child growth and nutrition." Maternal & child nutrition 4.s1 (2008): 118-236.

  38. Campbell, Suzy J., et al. "Complexities and Perplexities: A Critical Appraisal of the Evidence for Soil-Transmitted Helminth Infection-Related Morbidity."PLoS Negl Trop Dis 10.5 (2016): e0004566.

  39. Croke, K. "Does Mass Deworming Affect Child Nutrition? Meta-analysis, Cost …" 2016. http://emiguel.econ.berkeley.edu/assets/miguel_research/77/worms_v93.pdf

  40. Taylor‐Robinson, David C et al. "Deworming drugs for soil‐transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance." The Cochrane Library (2015).

  41. Colley, DG. "Human schistosomiasis - The Lancet." 2014. <http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61949-2/abstract>

  42. "PLOS Neglected Tropical Diseases: The Global Burden of …" 2015. 25 Jul. 2015 <http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002865>

  43. Kjetland, Eyrun F, Peter DC Leutscher, and Patricia D Ndhlovu. "A review of female genital schistosomiasis." Trends in parasitology 28.2 (2012): 58-65.

  44. "Cost-Effectiveness in $/DALY for Deworming … - GiveWell." 2011. 26 Jul. 2015 <http://www.givewell.org/international/technical/programs/deworming/cost-effectiveness>

  45. Note that the cited paper does not say much about the health benefits of deworming for schistosomiasis, and is more to illustrate that even the authors of the Cochrane review agree that Schistosomiasis population deworming is indicated

  46. Chami, Goylette F et al. "Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages." PLoS Negl Trop Dis 9.10 (2015): e0004193.

  47. Butler, SE. "Mechanism of Anemia in Schistosoma mansoni–Infected … - NCBI." 2012. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516261/>

  48. Smith, Jennifer L, and Simon Brooker. "Impact of hookworm infection and deworming on anaemia in non‐pregnant populations: a systematic review." Tropical medicine & international health 15.7 (2010): 776-795.

  49. "Combination deworming (mass drug … - GiveWell." 2010. 9 Feb. 2016 <http://www.givewell.org/international/technical/programs/deworming>

  50. "Combination deworming (mass drug … - GiveWell." 2010. 9 Feb. 2016 <http://www.givewell.org/international/technical/programs/deworming>

  51. "CDC - Schistosomiasis - General Information - Centers for …" 2010. 26 Feb. 2016 <http://www.cdc.gov/parasites/schistosomiasis/gen_info/faqs.html>

  52. Strickland, G Thomas. "Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors." Hepatology 43.5 (2006): 915-922.

  53. van der Werf, Marieke J et al. "Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa." Acta tropica 86.2 (2003): 125-139.

  54. "Combination deworming (mass drug … - GiveWell." 2010. 9 Feb. 2016 <http://www.givewell.org/international/technical/programs/deworming>

  55. "Global Burden of Disease (GBD) | Institute for Health Metrics …" 2014. 9 Feb. 2016 <http://www.healthdata.org/gbd>

  56. "WHO | Malaria." 2004. 9 Feb. 2016 <http://www.who.int/mediacentre/factsheets/fs094/en/>

  57. Awasthi, Shally et al. "Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial." The Lancet 381.9876 (2013): 1478-1486.

  58. Mbah, Martial L Ndeffo et al. "Impact of Schistosoma mansoni on malaria transmission in Sub-Saharan Africa." PLoS Negl Trop Dis 8.10 (2014): e3234.

  59. Mbah, Martial L Ndeffo et al. "Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa." Proceedings of the National Academy of Sciences 110.19 (2013): 7952-7957.

  60. Mbah, Martial L Ndeffo et al. "Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa." Proceedings of the National Academy of Sciences 110.19 (2013): 7952-7957.

  61. Walson, Judd L, Bradley R Herrin, and Grace John‐Stewart. "Deworming helminth co‐infected individuals for delaying HIV disease progression." The Cochrane Library (2009).

  62. Stecher, CW. "PubMed - NCBI." 2015. <http://www.ncbi.nlm.nih.gov/pubmed/26298443>

  63. Walson, Judd L, Bradley R Herrin, and Grace John‐Stewart. "Deworming helminth co‐infected individuals for delaying HIV disease progression." The Cochrane Library (2009).

  64. Chenine, Agnès-Laurence et al. "Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure." PLoS Negl Trop Dis 2.7 (2008): e265.

  65. Mbah, Martial L Ndeffo et al. "Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa." Proceedings of the National Academy of Sciences 110.19 (2013): 7952-7957.

  66. Nacher, Mathieu. "Interactions between worms and malaria: good worms or bad worms." Malar J 10.259 (2011): 1-6.

  67. Salazar-Castañon, Víctor H, Martha Legorreta-Herrera, and Miriam Rodriguez-Sosa. "Helminth Parasites Alter Protection against Plasmodium Infection." BioMed research international 2014 (2014).

  68. Nacher, Mathieu. "Interactions between worms and malaria: good worms or bad worms." Malar J 10.259 (2011): 1-6.

  69. Kinung’hi, Safari M et al. "The impact of anthelmintic treatment intervention on malaria infection and anaemia in school and preschool children in Magu district, Tanzania: an open label randomised intervention trial." BMC infectious diseases 15.1 (2015): 1.

  70. Figueiredo, Jacinta Chaves et al. "Prostate adenocarcinoma associated with prostatic infection due to Schistosoma haematobium. Case report and systematic review." Parasitology research 114.2 (2015): 351-358.

  71. Brindley, Paul J, José M Correia da Costa, and Banchob Sripa. "Why does infection with some helminths cause cancer?." Trends in cancer 1.3 (2015): 174-182.

  72. "Cancer (Part 2 of 2) - Giving What We Can." 2016. 22 Jun. 2016 <https://www.givingwhatwecan.org/report/cancer-2#53-hepatitis-b-vaccination-treatment-of-parasites-liver-cancer-bladder-cancer>

  73. Sripa, Banchob et al. "Liver fluke induces cholangiocarcinoma." PLoS Med 4.7 (2007): e201.

  74. Sripa, Banchob et al. "The tumorigenic liver fluke Opisthorchis viverrini–multiple pathways to cancer." Trends in parasitology 28.10 (2012): 395-407.

  75. Li, Xin-Xu, and Xiao-Nong Zhou. "Co-infection of tuberculosis and parasitic diseases in humans: a systematic review." Parasit Vectors 6.1 (2013): 79.

  76. Gasim, Gasim I, Abdelhaleem Bella, and Ishag Adam. "Schistosomiasis, hepatitis B and hepatitis C co-infection." Virology Journal 12.1 (2015): 19.

  77. Botes, SN et al. "Schistosoma Prevalence in Appendicitis." World Journal of Surgery (2015): 1-4.

  78. Worrell, Caitlin M et al. "Cost analysis of tests for the detection of Schistosoma mansoni infection in children in western Kenya." The American journal of tropical medicine and hygiene 92.6 (2015): 1233-1239.

  79. Taylor-Robinson, David C et al. "Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance." Cochrane Database Syst Rev 7 (2015).

  80. King, Charles H, and David Bertsch. "Historical perspective: snail control to prevent schistosomiasis." PLoS Negl Trop Dis 9.4 (2015): e0003657.

  81. King, Charles H, Laura J Sutherland, and David Bertsch. "Systematic Review and Meta-analysis of the Impact of Chemical-Based Mollusciciding for Control of Schistosoma mansoni and S. haematobium Transmission." PLoS Negl Trop Dis 9.12 (2015): e0004290.

  82. Tennessen, JA. "PMC - NCBI - National Institutes of Health." 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361660/>

  83. "PAF: Gene Drive Report — Effective Altruism at Harvard." 2016. 28 Jun. 2016 <http://www.harvardea.org/blog/2016/3/2/paf-gene-drive-report>

  84. Grimes, Jack ET et al. "The roles of water, sanitation and hygiene in reducing schistosomiasis: a review." Parasit Vectors 8 (2015): 156.

  85. Worrell, Caitlin M et al. "A Cross-Sectional Study of Water, Sanitation, and Hygiene-Related Risk Factors for Soil-Transmitted Helminth Infection in Urban School-and Preschool-Aged Children in Kibera, Nairobi." PloS one 11.3 (2016): e0150744.

  86. Campbell, Suzy J et al. "A Critical Appraisal of Control Strategies for Soil-Transmitted Helminths." Trends in Parasitology (2016).

  87. Blair, Paul, and David Diemert. "Update on prevention and treatment of intestinal helminth infections." Current infectious disease reports 17.3 (2015): 1-8.

  88. Merrifield, Maureen, et al. "Advancing a vaccine to prevent human schistosomiasis." Vaccine 34.26 (2016): 2988-2991.

  89. Bartsch, Sarah M., et al. "Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting." Vaccine 34.19 (2016): 2197-2206.

  90. Except in the case in which vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%.

  91. Lo, Nathan C et al. "Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study." The Lancet Global Health 3.10 (2015): e629-e638.

  92. "WHO | Deworming to combat the health and nutritional …" 2012. 29 Mar. 2016 <http://www.who.int/elena/titles/bbc/deworming/en/>

  93. Midzi, N et al. "Efficacy and side effects of praziquantel treatment against Schistosoma haematobium infection among primary school children in Zimbabwe." Transactions of the Royal Society of Tropical Medicine and Hygiene 102.8 (2008): 759-766.

  94. Nontasut, Ponganant et al. "Comparison of ivermectin and albendazole treatment for gnathostomiasis." Southeast Asian journal of tropical medicine and public health 31.2 (2000): 374-377.

  95. "GiveWell's Cost-Effectiveness Analyses | GiveWell." 2014. 22 Feb. 2016 <http://www.givewell.org/international/technical/criteria/cost-effectiveness/cost-effectiveness-models>

  96. Turner, Hugo C et al. "Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses." The Lancet Infectious Diseases (2016).

  97. "Cost-effectiveness of community-wide treatment for … - The Lancet." 2016. 28 Jun. 2016 <http://thelancet.com/journals/langlo/article/PIIS2214-109X(15)00278-8/fulltext>

  98. Turner, Hugo C et al. "Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses." The Lancet Infectious Diseases (2016).

  99. Turner, Hugo C et al. "Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses." The Lancet Infectious Diseases (2016).

  100. Kramer, CV. "Drugs for treating urinary schistosomiasis | Cochrane." 2014. <http://www.cochrane.org/CD000053/INFECTN_drugs-for-treating-urinary-schistosomiasis>

  101. Saconato, Humberto, and A Atallah. "Interventions for treating schistosomiasis mansoni." Cochrane Database of Systematic Reviews 3 (1999).

  102. Bennett, Andrew, and Helen Guyatt. "Reducing intestinal nematode infection: efficacy of albendazole and mebendazole." Parasitology Today 16.2 (2000): 71-77.

  103. Turner, Hugo C., et al. "Cost and cost-effectiveness of soil-transmitted helminth treatment programmes: systematic review and research needs."Parasites & vectors 8.1 (2015): 1.

  104. Miguel E, Kremer M. Worms: Identifying impacts on education and health in the presence of treatment externalities. Econometrica. 2004;72(1):159–217

  105. Warren KS, Bundy DAP, Anderson RM, Davis AR, Henderson DA, Jamison DT, et al. Helminth infections. In: Jamison DT, Mosley WH, Measham AR, Bobadilla JL, editors. Disease Control Priorities in Developing Countries. Oxford: Oxford University Press; 1993. p. 131–60.

  106. Hotez PJ, Bundy DAP, Beegle K, Brooker S, Drake L, de Silva N, et al. Helminth Infections: Soil-transmitted Helminth Infections and Schistosomiasis. Disease Control Priorities in Developing Countries. 2nd ed. New York: Oxford University Press; 2006 http://www.who.int/management/referralhospitals.pdf

  107. GiveWell, Errors in DCP2 cost-effectiveness estimate for deworming http://blog.givewell.org/2011/09/29/errors-in-dcp2-cost-effectiveness-estimate-for-deworming/

  108. "Cost-Effectiveness in $/DALY for Deworming Interventions | GiveWell." 2011. 16 Jun. 2016 <http://www.givewell.org/international/technical/programs/deworming/cost-effectiveness>

  109. GiveWell, Combination deworming (mass drug administration targeting both schistosomiasis and soil-transmitted helminthiasis), http://www.givewell.org/international/technical/programs/deworming#Howcosteffectiveismassdeworming

  110. Lo, Nathan C et al. "Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study." The Lancet Global Health 3.10 (2015): e629-e638.

  111. Lo, Nathan C et al. "Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study." The Lancet Global Health 3.10 (2015): e629-e638. Note that this analysis tested the effect of varying key model parameters on the incremental cost-effectiveness ratio (ICER) of expanding mass drug administration to entire communities compared with only treatment of school-aged children. The horizontal bar represents the range of ICER values for the specified range of the tested parameter. All strategies left of the dashed vertical line at US$1521 per disability-adjusted life-year (DALY) averted (2013 gross domestic product per capita in Côte d’Ivoire) are regarded as highly cost effective. *Relative environmental contribution refers to the relative rate of excretion of eggs into the environment among preschool-aged children and school-aged children when compared with adults.

  112. Mbah, Martial L Ndeffo et al. "Potential cost-effectiveness of schistosomiasis treatment for reducing HIV transmission in Africa–the case of Zimbabwean women." PLoS neglected tropical diseases 7.8 (2013): e2346.

  113. Mbah, Martial L Ndeffo et al. "Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa." Proceedings of the National Academy of Sciences 110.19 (2013): 7952-7957.

  114. Murray, Christopher JL, and Alan D Lopez. "Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study." The Lancet 349.9064 (1997): 1498-1504.

  115. These are uniformly weighted with a 3 percent discount rate as per DCP convention.

  116. Neves, Bruno J, Carolina H Andrade, and Pedro VL Cravo. "Natural products as leads in schistosome drug discovery." Molecules 20.2 (2015): 1872-1903.

  117. Kasinathan, Ravi S, William M Morgan, and Robert M Greenberg. "Genetic knockdown and pharmacological inhibition of parasite multidrug resistance transporters disrupts egg production in Schistosoma mansoni." PLoS Negl Trop Dis 5.12 (2011): e1425.

  118. "Frequently asked questions | Imperial College London." 2016. 22 Jun. 2016 <http://www.imperial.ac.uk/schistosomiasis-control-initiative/support-us/frequently-asked-questions/>

  119. "Frequently asked questions | Imperial College London." 2016. 22 Jun. 2016 <http://www.imperial.ac.uk/schistosomiasis-control-initiative/support-us/frequently-asked-questions/>

  120. Scientists receive $3.5 million to study drug resistance in a global parasitic disease, EurekAlert! June 2016

  121. McCreesh, Nicky, Grigory Nikulin, and Mark Booth. "Predicting the effects of climate change on Schistosoma mansoni transmission in eastern Africa." Parasites & vectors 8.1 (2015): 1-9.

  122. Cavalli, Anna et al. "Interactions between global health initiatives and country health systems: the case of a neglected tropical diseases control program in Mali." PLoS Negl Trop Dis 4.8 (2010): e798.

  123. Bowser, Diana et al. "Global Fund investments in human resources for health: innovation and missed opportunities for health systems strengthening." Health Policy and Planning 29.8 (2014): 986-997.

  124. Strunz, Eric C., et al. "Water, sanitation, hygiene, and soil-transmitted helminth infection: a systematic review and meta-analysis." PLoS Med 11.3 (2014): e1001620.

  125. Strunz, Eric C., et al. "Water, sanitation, hygiene, and soil-transmitted helminth infection: a systematic review and meta-analysis." PLoS Med 11.3 (2014): e1001620.

  126. Grimes, Jack ET, et al. "The roles of water, sanitation and hygiene in reducing schistosomiasis: a review." Parasites & vectors 8.1 (2015): 1.

  127. "Weekly epidemiological record Relevé épidémiologique …" 2015. 29 Feb. 2016 <http://www.who.int/wer/2015/wer9010.pdf >

  128. Mtethiwa, Austin HN et al. "Extent of morbidity associated with schistosomiasis infection in Malawi: a review paper." Infectious diseases of poverty 4.1 (2015): 1.

  129. WHO The Weekly Epidemiological Record http://www.who.int/wer/en/

  130. World Health Organization. "investing to overcome the global impact of neglected …" 2015. <http://apps.who.int/iris/bitstream/10665/152781/1/9789241564861_eng.pdf?ua=1>

  131. Note that the upper graph’s x-axis starts 25 Million SAC, school-age children; STH, soil-transmitted helminthiases. The dots indicate the number of people treated in 2012; the solid lines are targets not forecasts. Targets assume integrated delivery of preventive chemotherapy for LF and onchocerciasis in Africa, schistosomiasis and STH among school-age children, and LF and STH outside Africa. Pending further evidence, they do not yet assume further integration of LF and onchocerciasis in Africa with schistosomiasis and STH.

  132. This excludes medicine prices, which are donated by the pharmaceutical companies. Figure adapted from (Fig. 2.4 Investment targets for universal coverage against NTDs from recent WHO report on NTDs)  World Health Organization. "investing to overcome the global impact of neglected …" 2015. <http://apps.who.int/iris/bitstream/10665/152781/1/9789241564861_eng.pdf?ua=1>

  133. This excludes medicine prices, which are donated by the pharmaceutical companies. Figure adapted from a recent WHO report, World Health Organization. "investing to overcome the global impact of neglected …" 2015. <http://apps.who.int/iris/bitstream/10665/152781/1/9789241564861_eng.pdf?ua=1> Notes: Shaded areas reflect the range determined by low and high values of the unit cost benchmarks; they do not reflect uncertainty about future rates of scale-up and scale-down of interventions. The dots in 2012 are actual numbers reported (when available) multiplied by the unit cost benchmarks, which is the approximate cost of delivering one treatment; these are not actual expenditures, but can be thought of as a benchmark for actual expenditures. All numbers expressed in US$ are constant (real) US$, adjusted to reflect purchasing power in the United States of America in 2015.