Novel Approaches in the Control of Schistosomiasis: from Rapid Identification to Chemoprophylaxis

Human schistosomiasis is the second most prevalent parasitic disease in the tropics, and has a huge impact on public health and socio-economic development. It is estimated that 652 million people live at risk of infection and that 193 million people are actually infected. Of the 120 million symptomatic cases, 20 million are suffering from severe disease. At present, 85% of all these cases are concentrated in sub-Saharan Africa and they cause an estimated morbidity burden of 3.5 million disability adjusted live years (DALYs). Since the advent of safe, effective, single dose drugs, the emphasis in schistosomiasis control has been on morbidity control. Since praziquantel is active against all schistosome species and has become relatively inexpensive, it is used as the drug of choice. For effective control of schistosomiasis, it is now of central importance to make the drug available to the communities at highest risk of infection. The distribution of schistosomiasis is extremely focal and since resources for health are seriously limited in most schistosomiasis endemic countries, there is a great need to identify high risk communities, so that resources can be better allocated. Due to the focal nature of the disease, neighbouring villages often show different patterns of schistosomiasis morbidity, resulting in large inter-village variation in perceived disease and actual public health importance. A simple procedure using questionnaires has been developed for rapid screening for Schistosoma haematobium infection and it proved to be reliable, non-intrusive and highly cost-effective in 8 African countries. Based on these experiences, WHO published guidelines for district health managers to be used as a first stage in the process of schistosomiasis control. Côte d’Ivoire is now the first country, that has taken advantage of these guidelines and translated them into direct application. In a first step, the feasibility and diagnostic performance of the questionnaire was rigorously validated in an S. haematobium endemic area in central Côte d’Ivoire. Correctly completed questionnaires were obtained from 124 schools (return rate: 91%), with 12,479 children interviewed. Following, previously trained teachers screened 5,959 children with reagent sticks. The questionnaire showed a good diagnostic performance with sensitivity and specificity values between 79% and 96% to detect correctly those schools where the pupils were at high risk of infection. These findings were in agreement with previous studies from other African countries, and the questionnaire approach was recommended for use at the national level. At present, the questionnaires are already being applied in 5 out of 16 districts. The active involvement of University students in distributing and collecting questionnaires in this survey, is a promising innovative approach. Based on the excellent performance of questionnaires for rapid screening of S. haematobium and linked to the ongoing process in Côte d’Ivoire, there was a demand asking for support with implementing this technique also in the Niger State of north-western Nigeria. Questionnaires were returned from 58 schools (return rate: 97%). A total of 3,033 children were interviewed and 2,479 children were screened with reagent sticks by previously trained teachers. Questionnaires also proved to be reliable in this setting, and identified schools at high risk of S. haematobium with sensitivity and specificity values ranging between 64% and 96%. The identification of high risk communities is an important component in the management and implementation of cost-effective schistosomiasis control programmes. For S. mansoni infection, reliable rapid methods have not yet been developed. Therefore possible ways of extending the questionnaire method for S. mansoni were assessed in Côte d’Ivoire. In a first study, perceived signs and symptoms for intestinal morbidity were assessed in focus group discussions with schoolchildren in an area highly endemic for S. mansoni. The most frequently perceived signs and symptoms were then used in a preliminary questionnaire in three schools. Comparison of the results with levels of S. mansoni infection revealed that reported blood in stool was the most reliable symptom to predict an infection (adjusted odds ratio: 2.87; 95% confidence interval (CI): 1.56-5.31). Based on these findings, a questionnaire was developed and distributed to 134 schools. Correctly filled-in questionnaires were returned from 121 schools (90%), with 12,227 children interviewed. 5,047 children were screened by a biomedical team with two consecutive Kato- Katz thick smears. For an individual diagnosis, the two symptoms “blood in stool” and “bloody diarrhoea” were significantly correlated with an S. mansoni infection: adjusted odds ratio 1.59 (95% CI: 1.38-1.83) and 1.34 (95% CI: 1.14-1.58), respectively. For community diagnosis, these two symptoms showed a high sensitivity (88%) and a moderate specificity (58%). Subsequently, it was assessed whether the diagnostic performance of the questionnaire could be improved by asking questions about water contact patterns. Although a positive response to a particular water contact pattern correlated significantly with an infection with S. mansoni, the diagnostic performance was again only moderate. In view of these findings, it was concluded that there is still a considerable amount of research needed before questionnaires can be adopted as a tool to screen for S. mansoni at the community level. Morbidity control in schistosomiasis requires effective initial treatment and the prevention of re-infection. In view of recent concern that praziquantel-tolerance/resistance might develop, there is a great need for research and development of novel substances with antischistosomal properties. Artemether has been identified in China as a promising product for early treatment and prophylaxis. It showed prophylactic effects in animals experimentally infected with S. japonicum, and was a successful prophylactic agent in humans exposed to S. japonicum. Further laboratory experiments showed a prophylactic effect also against S. mansoni. We conducted the first randomised double-blind placebo-controlled trial of oral artemether to prevent S. mansoni infections. 354 schoolchildren were enrolled. Stool samples were examined over four consecutive days, followed by two mass treatments with praziquantel four weeks apart. All S. mansoni negative children were randomly assigned to receive 6 repeated doses of a placebo (n=151) or artemether (n=138) at a dose of 6 mg/kg, spaced by 3 weeks. At the end of the study, the incidence and mean intensity of S. mansoni infection were assessed by examining four consecutive stool samples from the children. The group that received artemether had a significantly lower incidence of S. mansoni infection (31/128 vs. 68/140, relative risk: 0.50, 95% CI: 0.35-0.71, p<0.001). Furthermore, the geometric mean egg output among positive children in the artemether group (19 eggs/g stool) was significantly lower than in placebo recipients (32 eggs/g, p=0.017). Oral artemether was found to be safe and no adverse events occurred. Since artemether is already widely and effectively used against malaria, the use of artemether against schistosomiasis should not be recommended for widespread application in areas where malaria is endemic because of the potential risk of developing drug resistance in the malaria parasite. However, the use of artemether might contribute to a more effective schistosomiasis control in particular epidemiological settings. The findings of the present investigations clearly contributed to means of rapid identification of high risk areas of urinary and intestinal schistosomiasis in general and to the development and management of a national schistosomiasis control programme in Côte d’Ivoire in particular. We are optimistic that in the years to come considerable progress will be seen with the use of artemether (and hopefully also other drugs yet to be discovered) and that these products will take a promising place in a comprehensive strategy for schistosomiasis control

Editorial: Swiss TPH: 30 Years of R&D Towards New Drugs for Tropical Diseases

The year 2023 marks the 80th anniversary of the Swiss Tropical and Public Health Institute (Swiss TPH). Associated with the University of Basel, Swiss TPH combines research, education and services, working across a value chain from innovation and validation to application to improve people’s health and well-being. Around 700 staff and students work in Swiss TPH’s new headquarters in an emerging life-science cluster in Allschwil, Switzerland, focusing on infectious and non-communicable diseases, environment, society and health as well as health systems and interventions. In this special issue of Chimia, we highlight 30 years of research and development (R&amp;D) at Swiss TPH, deeply grounded in partnership, towards new drugs for tropical diseases

Trends in the core literature on tropical medicine: a bibliometric analysis from 1952-2002

Summary: We present empirical data on frequency and pattern of misprints in citations to twelve high-profile papers. We find that the distribution of misprints, ranked by frequency of their repetition, follows Zipf&apos;s law. We propose a stochastic model of citation process, which explains these findings, and leads to the conclusion that about 70-90&percnt; of scientific citations are copied from the lists of references used in other paper

Control of Neglected Tropical Diseases: Integrated Chemotherapy and Beyond

Utzinger and de Savigny discuss the implications of a new policy paper, which argues that the control of "the big three" diseases (HIV, TB, and malaria) should be integrated with control of the neglected tropical diseases

Antiparasitic drugs for paediatrics: systematic review, formulations, pharmacokinetics, safety, efficacy and implications for control

Drug development for paediatric applications entails a number of challenges, such as the wide age spectrum covered - from birth to adolescence - and developmental changes in physiology during biological maturation that influence the efficacy and toxicity of drugs. Safe and efficacious antiparasitic drugs for children are of pivotal importance given the large proportion of burden attributable to parasitic diseases in this age group, and growing efforts to administer, as widely as possible, antiparasitic drugs to at-risk populations, such as infants and school-aged children, often without prior diagnosis. The purpose of this review is to investigate whether antiparasitic drugs have been adequately studied for use in paediatrics. We approached this issue through a systematic review using PubMed and the Cochrane Central Register of Trials covering a period of 10 years and 8 months until the end of August 2010 to identify trials that investigated efficacy, safety and pharmacokinetic (PK) parameters of antiparasitic drugs for paediatrics. Overall, 269 clinical drug trials and 17 PK studies met our inclusion criteria. Antimalarial drugs were the most commonly studied medicines (82·6%). Most trials were carried out in Africa and children aged 2-11 years were the age group most often investigated. Additionally, we critically examined available drug formulations for anthelminthics and identified a number of shortcomings that are discussed. Finally, we shed new light on current proposals to expand ‘preventive chemotherapy' to preschool-aged children and emphasise that new research, including risk-benefit analyses, are needed before such a strategy can be adopted more widel

Surveillance and response systems for elimination of tropical diseases : summary of a thematic series in infectious diseases of poverty

The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured - i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme "Elimination of tropical disease through surveillance and response". The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors' affiliations reveals that scientists from the People's Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China's growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond

Spatial microhabitat selection by Biomphalaria pfeifferi in a small perennial river in Tanzania

A study was carried out in the Mlali river in south-central Tanzania with two aims. First, to determine microhabitat availability in two sites (A and B) with respect to water depth, water velocity and dominant substratum type. Second, to assess microhabitat use by Biomphalaria pfeifferi, the intermediate host snail of intestinal schistosomiasis and to investigate whether these snails show preferences for certain microhabitats. The two sites differed significantly with respect to width, water depth, water velocity and substratum composition. It is suggested that the absence of B. pfeifferi from site B is mainly associated with the high water velocities at that site, where 62% of the measurements exceeded30 cm s-1. In site A, the microhabitat use by 327 B. pfeifferi snails was assessed by means of direct observation. No significant relationships were found between snail size and the habitat variables investigated, indicating that snail size appeared to be of no importance in spatial microhabitat selection. B. pfeifferi snails showed statistically significant preferences for shallow water (depth: 2-7 cm) and the preferred water velocities ranged between 12 and 21 cm s-1 with an estimated optimum at13.3 cm s-1. No statistically significant preferences for substratum type were foun

Artesunate and artemether are effective fasciolicides in the rat model and in vitro

Objectives: To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro. Methods: Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 µg/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment. Results: F. hepatica exposed for 72 h to10 µg/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 µg/mL resulted in the death of all F. hepatica by 72 h. One hundred per cent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines. Conclusions: Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the host