Dealing with schistosomiasis: Current drug discovery strategies
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Neglected Tropical Diseases
Tropical disease
Mass drug administration
Parasitic Disease
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Disease Control
The World Health Organization (WHO) currently classifies 20 diseases and conditions as neglected tropical diseases (NTDs). However, since its inception in 2007, PLOS Neglected Tropical Diseases has considered an expanded list that includes additional diseases with the chronic and/or debilitating, and poverty-promoting features of NTDs. Described here is an update of our current scope, which attempts to embrace all of the NTDs, and a discussion of the status of some of the more debated medical conditions in terms of whether or not they constitute an NTD.
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In 2011, the World Health Organization (WHO) determined that more than 700 million people were treated with at least one essential medicine for neglected tropical diseases (NTDs) under the auspices of a global preventive chemotherapy initiative [1,2]. However, a total of at least 1.9 billion people require annual preventive chemotherapy [1,2], so these efforts will need to be greatly expanded in order to meet NTD control and elimination targets as outlined in the 2012 London Declaration and the 2013 World Health Assembly resolution for these diseases [3]. The original ‘‘rapid-impact’’ package of NTD interventions targeted up to seven NTDs highly endemic to sub-Saharan Africa, including the three soil-transmitted helminthiases, schistosomiasis, lymphatic filariasis, onchocerciasis, and trachoma, and was comprised of up to four essential NTD medicines that could include a benzimidazole anthelminthic drug (i.e., mebendazole or albendazole), ivermectin, praziquantel, and/or azithromycin [4,5]. However, it was quickly noted that either the entire rapid-impact package or some component thereof had applicability outside of Africa (with modifications depending on the specific NTDs being targeted) [6]. By controlling or eliminating the seven major NTDs, this approach could potentially effect a global disease burden reduction almost as important as HIV/ AIDS, tuberculosis, or malaria control [7,8]. As global preventive chemotherapy efforts expanded, it also became apparent that they could produce important collateral public health benefits that were not originally anticipated, including overall reductions in child mortality from the azithromycin component [9] and coverage for additional NTDs such as food-borne trematodiases, scabies, and yaws [3,10,11]. There are equally important efforts underway to broaden the interventions to include water, sanitation, and hygiene (WASH) initiatives [12]. Thus, in the decade since rapid impact was originally proposed, there are new uses and approaches for preventive chemotherapy. In the last year, two important studies were published that could alter how we think about current preventive chemotherapy approaches. The first, known as the Global Enteric Multicenter Study (GEMS) for diarrheal diseases, made the surprising finding that cryptosporidiosis is one of the most important causes of infectious diarrhea in children in developing countries [13]. The second is the Global Burden of Disease Study 2010 (GBD 2010), which found that, together, cryptosporidiosis and amoebiasis exceed the disease burden–as measured in disability-adjusted life years (DALYs) or in deaths—of any helminth infection now currently being targeted for preventive chemotherapy (Table 1) [14,15]. Although there are important disagreements in the NTD community about whether the DALYs for helminth infections (and other NTDs) were underestimated [16], both GEMS and GBD 2010 provide important information to our community that we need to consider in deciding whether it is possible to add coverage for cryptosporidiosis and amoebiasis as part of global preventive chemotherapy efforts. A potential candidate drug for use in mass drug administration programs to target intestinal protozoa is the nitrothiazole benzamide drug, nitazoxanide (Figure 1) [17]. The development program for nitazoxanide was led by Jean Francois Rossignol in the 1970s, initially as a veterinary anthelminthic agent, but the drug was subsequently shown to be active against intestinal protozoa and some human helminths, as well as anaerobic bacteria [17]. It was approved in 2002 by the United States Food and Drug Administration, initially as an oral suspension for pediatric use (100 mg/5 ml) against cryptosporidiosis and giardiasis, and subsequently as 500 mg tablets for adults [17]. According to The Medical Letter, the recommended therapeutic dosage is administered over three days [18]. Although the initial indication for nitazoxanide was for cryptosporidiosis and giardiasis, subsequent investigative research has revealed that the drug is effective for amoebiasis caused by Entamoeba histolytica and could be used to treat both invasive intestinal amoebiasis and colonization with E. histolytica [19]. Moreover, nitazoxanide is active against a number of nonprotozoan parasites, including the
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Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections.We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments.Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts for each of the five neglected tropical diseases, highlighting the opportunity for integrating drug distributions.
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The neglected diseases, which involve diverse etiological agents, such as viruses (chikungunya, dengue, rabies), bacteria (anthrax, bovine tuberculosis, brucellosis, leprosy, leptospirosis, plague), fungi (chromoblastomycosis), protozoa (leishmaniasis
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Ghana is exhibiting impressive economic gains that may compare with the growth rates expected in India or China. With economic development, there is an expectation that the prevalence and disease burden of the neglected tropical diseases (NTDs) and other poverty-related neglected diseases will decline. Indeed, guinea worm, human African trypanosomiasis, and trachoma recently have been eliminated in Ghana, and there have been steep declines in the prevalence of onchocerciasis and lymphatic filariasis (as well as oesophogostomiasis and yaws), with the prospect of eliminating these diseases as well in the not-too-distant future. In contrast, progress toward disease prevalence reductions for schistosomiasis, hookworm, and other soil-transmitted helminth infections, as well as other NTDs, including cysticercosis, cystic echinococcosis, scabies, Buruli ulcer, and leprosy, have been more modest. Snake bite envenoming, an important regional noninfectious NTD, also requires a different strategic approach. Arbovirus infections are emerging and thus remain a significant and under-recognized public health threat. For some of these NTDs, new technologies, including vaccines, will be required. Health-system strengthening with mobile health-activities are expected to continue furthering NTD disease reductions, with the hope that Ghana could become the first highly populated Sub-Saharan African nation to achieve its NTD elimination targets.
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Journal Article Potential for integrated control of neglected tropical diseases in Ethiopia Get access Zerihun Tadesse, Zerihun Tadesse aDisease Prevention and Control Department, Federal Ministry of Health, Addis Ababa, Ethiopia Search for other works by this author on: Oxford Academic PubMed Google Scholar Afework Hailemariam, Afework Hailemariam bMalaria Consortium Ethiopia, Addis Ababa, Ethiopia Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan H. Kolaczinski Jan H. Kolaczinski ⁎ cMalaria Consortium Africa, Kampala, UgandadLondon School of Hygiene & Tropical Medicine, London, UK ⁎Corresponding author. Tel.: +256 (0)312 300420; fax: +256 (0)312 300425. E-mail address:j.kolaczinski@malariaconsortium.org (J.H. Kolaczinski). Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 102, Issue 3, March 2008, Pages 213–214, https://doi.org/10.1016/j.trstmh.2007.09.005 Published: 01 March 2008
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The concept of a technological quick fix or 'magic-bullet' for control and elimination of Neglected Tropical Diseases (NTDs) is flawed. NTDs are embedded within complex biological and social systems that are shaped by ecological and political contexts. This commentary emphasises the need for implementation research to address implementation gaps in the control of NTDs. With a specific focus on sub-Saharan Africa and helminth diseases amenable to preventive chemotherapy through mass drug administration, we explore the important role of context, programme partnerships and community in achieving equitable and effective NTD control.
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Introduction: Schistosomiasis is one of the Neglected Tropical Diseases (NTDs) targeted for elimination in Uganda by 2025 through Mass Drug Administration (MDA) using praziquantel. To achieve this, WHO estimates indicate that MDA coverage and uptake of 75% is required. However, coverage remains suboptimal with insufficient knowledge and inadequate drug supply often cited as key reasons. There is a need to add to the body of knowledge in various settings to enable more robust mitigation measures. This study aimed to assess the uptake of praziquantel for MDA and associated factors in Butiaba sub-county along the shores of Lake Albert in Uganda.
Methods: A cross-sectional study was conducted in five randomly selected villages within Butiaba sub-county between July and September 2021 using quantitative and qualitative approaches. Semi-structured questionnaires were administered to 450 adults, with additional two Focus Group Discussions and Key Informant interviews held with implementation structures from the village to district level.
Results: Self-reported uptake of praziquantel within twelve months of the most recent MDA exercise was 71.56% (95% CI: 67.14 – 75.68). Of all the participants, 5.78% reported have never swallowed praziquantel in their lifetime, and 75% (96/128) of participants who didn’t swallow praziquantel in the last twelve months reported having at least swallowed the drug in the last ten years. Respondents were less likely to have swallowed praziquantel if they had no knowledge about schistosomiasis signs (AOR= 0.18, 95% CI: 0.08–0.39) and more likely if they were between the ages 30-39years (AOR= 2.31, 95% CI: 1.35–3.95) or 40 years and above (AOR= 2.86, 95% CI: 1.45 – 4.95). Operational challenges such as the inadequate supply of praziquantel and financial constraints also influence the uptake of praziquantel during MDA in Butiaba sub-county.
Conclusion: The uptake of praziquantel during MDA in Butiaba sub-county was high but still below the WHO target of 75%. People with limited knowledge of schistosomiasis symptoms and those aged 18 – 29 years were less likely to take Praziquantel. Irregular drug supply was also a key challenge.
Recommendation: Rigorous health education and ensuring a continuous supply of Praziquantel are key to improving MDA uptake.
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