Repeated doses of Praziquantel in Schistosomiasis Treatment (RePST) - single versus multiple praziquantel treatments in school-aged children in Côte d'Ivoire: a study protocol for an open-label, randomised controlled trial.

BACKGROUND: Large scale administration of the anthelminthic drug praziquantel (PZQ) to at-risk populations is the cornerstone of schistosomiasis control, although persisting high prevalence of infections in some areas and growing concerns of PZQ resistance have revealed the limitations of this strategy. Most studies assessing PZQ efficacy have used relatively insensitive parasitological diagnostics, such as the Kato-Katz (KK) and urine-filtration methods, thereby overestimating cure rates (CRs). This study aims to determine the efficacy of repeated PZQ treatments against Schistosoma mansoni infection in school-aged children in Côte d'Ivoire using the traditional KK technique, as well as more sensitive antigen- and DNA-detection methods. METHODS: An open-label, randomised controlled trial will be conducted in school-aged children (5 to 18 years) from the region of Taabo, Côte d'Ivoire, an area endemic for S. mansoni. This 8-week trial includes four two-weekly standard doses of PZQ in the "intense treatment" intervention group and one standard dose of PZQ in the "standard treatment" control group. The efficacy of PZQ will be evaluated in stool samples using the KK technique and real-time PCR as well as in urine using the point-of-care circulating cathodic antigen test and the up-converting phosphor, lateral flow, circulating anodic antigen assay. The primary outcome of the study will be the difference in CR of intense versus standard treatment with PZQ on individuals with a confirmed S. mansoni infection measured by KK. Secondary outcomes include the difference in CR and intensity reduction rate between the intense and standard treatment groups as measured by the other diagnostic tests, as well as the accuracy of the different diagnostic tests, and the safety of PZQ. DISCUSSION: This study will provide data on the efficacy of repeated PZQ treatment on the clearance of S. mansoni as measured by several diagnostic techniques. These findings will inform future mass drug administration policy and shed light on position of novel diagnostic tools to evaluate schistosomiasis control strategies. TRIAL REGISTRATION: The study is registered at EudraCT (2016-003017-10, date of registration: 22 July 2016) and ( NCT02868385 , date of registration: 16 August 2016).

Contrasting the distribution of phenotypic and molecular variation in the freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni.

Population differentiation was investigated by confronting phenotypic and molecular variation in the highly selfing freshwater snail Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni. We sampled seven natural populations separated by a few kilometers, and characterized by different habitat regimes (permanent/temporary) and openness (open/closed). A genetic analysis based on five microsatellite markers confirms that B. pfeifferi is a selfer (s≈0.9) and exhibits limited variation within populations. Most pairwise FST were significant indicating marked population structure, though no isolation by distance was detected. Families from the seven populations were monitored under laboratory conditions over two generations (G1 and G2), allowing to record several life-history traits, including growth, fecundity and survival, over 25 weeks. Marked differences were detected among populations for traits expressed early in the life cycle (up to sexual maturity). Age and size at first reproduction had high heritability values, but such a trend was not found for early reproductive traits. In most populations, G1 snails matured later and at a larger size than G2 individuals. Individuals from permanent habitats matured at a smaller size and were more fecund than those from temporary habitats. The mean phenotypic differentiation over all populations (QST) was lower than the mean genetic differentiation (FST), suggesting stabilizing selection. However, no difference was detected between QST and FST for both habitat regime and habitat openness.

Spatio-temporal distribution of tsetse and other biting flies in the Mouhoun River basin, Burkina Faso.

In the Mouhoun River basin, Burkina Faso, the main vectors of African animal trypanosomoses are Glossina palpalis gambiensis Vanderplank and Glossina tachinoides Westwood (Diptera: Glossinidae), both of which are riverine tsetse species. The aim of our study was to understand the impact of landscape anthropogenic changes on the seasonal dynamics of vectors and associated trypanosomosis risk. Three sites were selected on the basis of the level of disturbance of tsetse habitats and predominant tsetse species: disturbed (Boromo, for G. tachinoides) and half-disturbed (Douroula for G. tachinoides and Kadomba for G. p. gambiensis). At each of these sites, seasonal variations in the apparent densities of tsetse and mechanical vectors and tsetse infection rates were monitored over 17 months. Tsetse densities differed significantly between sites and seasons. Of 5613 captured tsetse, 1897 were dissected; 34 of these were found to be infected with trypanosomes. The most frequent infection was Trypanosoma vivax (1.4%), followed by Trypanosoma congolense (0.3%) and Trypanosoma brucei (0.05%). The mean physiological age of 703 tsetse females was investigated to better characterize the transmission risk. Despite the environmental changes, it appeared that tsetse lived long enough to transmit trypanosomes, especially in half-disturbed landscapes. A total of 3021 other biting flies from 15 species (mainly Tabanidae and Stomoxyinae) were also caught: their densities also differed significantly among sites and seasons. Their relative importance regarding trypanosome transmission is discussed; the trypanosomosis risk in cattle was similar at all sites despite very low tsetse densities (but high mechanical vector densities) in one of them.

Contribution of Anopheles funestus, An. gambiae and An. nili (Diptera: Culicidae) to the perennial malaria transmission in the southern and western forest areas of Côte d'Ivoire.

The involvement of members of the Anopheles gambiae complex Giles and An. funestus Giles and An. nili Theobald groups in the transmission of Plasmodium falciparum was recently investigated in the villages of Gbatta and Kpéhiri, which lie, respectively, in forest areas in the west and south of Côte d'Ivoire. Adult female mosquitoes were collected, using human landing catches, inside and outside dwellings. After identification and dissection, the heads and thoraces of all the anopheline mosquitoes were tested, in an ELISA, for circumsporozoite protein (CSP). All the female anopheline mosquitoes collected and identified to species using PCR were found to be An. gambiae s.s., An. nili s.s. or An. funestus s.s., with An. gambiae s.s. and An. funestus s.s. predominant in Gbatta but An. nili s.s. the most common species in Kpéhiri. In Gbatta, 3·1% of the female An. gambiae collected, 5·0% of the female An. funestus and 1·8% of the female An. nili were found CSP-positive. The corresponding values in Kpéhiri were even higher, at 5·9%, 6·2% and 2·4%, respectively. The estimated entomological inoculation rates (EIR) were very high: 302 infected bites (139 from An. gambiae, 146 from An. funestus and 17 from An. nili)/person-year in Gbatta and 484 infected bites (204 from An. gambiae, 70 from An. funestus and 210 from An. nili)/person-year in Kpéhiri. In Gbatta, An. gambiae s.s. was responsible for most of the rainy-season transmission while An. funestus became the main malaria vector in the dry seasons. In Kpéhiri, however, An. nili appeared to be the main vector throughout the year, with An. gambiae of secondary importance and An. funestus only becoming a significant vector during the rainy season. Although, in both study sites, intense transmission was therefore occurring and the same three species of anopheline mosquito were present, the relative importance of each mosquito species in the epidemiology of the human malaria at each site differed markedly.

[Bio-ecological characteristics of Anopheles gambiae s.s. in irrigated rice fields of central Côte d'Ivoire]. / Caractéristiques bioécologiques d'Anopheles gambiae s.s. en zones de riziculture irriguée au centre de la Côte d'Ivoire.

This longitudinal entomological survey was conducted between September 2008 and September 2009 in the villages of Abokro and Yaokoffikro located in an irrigated rice farming area of central Côte d'Ivoire. The purpose was to investigate the bio-ecological characteristics of Anopheles gambiae s.s. during the gonotrophic cycle. In both villages, adult mosquitoes were captured in 72 light traps, collected on humans subjects at a rate of 72 man-night from 6 p.m. to 6 a.m., and knocked down using pyrethroid spray inside 60 sentinel houses in the early morning. A total of 10,312 adult mosquitoes were collected in Abokro and 7,662 in Yaokoffikro. Anopheles was the dominant genus at both locations. Light traps were three times more efficient in Abokro than in Yaokoffikro. In both places, An. gambiae s.s. biting rates increased gradually up to a peak observed between midnight and 1 a.m. In Abokro, most An. gambiae s.s. were collected inside sleeping rooms. The endophagic rate and indoor resting density was 67.4% (n = 4798) and 14.9 females per bedroom per night, respectively, in Abokro as compared to 49.3% (n = 6775) and 2.9 females per bedroom per day, respectively, in Yaokoffikro.

Population structuring of the tsetse Glossina tachinoides resulting from landscape fragmentation in the Mouhoun River basin, Burkina Faso.

The impact of landscape fragmentation resulting from human- and climate-mediated factors on the structure of a population of Glossina tachinoides Westwood (Diptera: Glossinidae) in the Mouhoun River basin, Burkina Faso, was investigated. Allele frequencies at five microsatellite loci were compared in four populations. The average distance between samples was 72 km. The sampling points traversed an ecological cline in terms of rainfall and riverine forest ecotype, along a river loop that enlarged from upstream to downstream. Microsatellite DNA demonstrated no structuring among the groups studied (F(ST) = 0.015, P = 0.07), which is contrary to findings pertaining to Glossina palpalis gambiensis Vanderplank in the same geographical area. The populations of G. tachinoides showed complete panmixia (F(IS) = 0, P = 0.5 for the whole sample) and no genetic differentiation among populations or global positioning system trap locations. This is in line with the results of dispersal studies which indicated higher diffusion coefficients for G. tachinoides than for G. p. gambiensis. The impact of these findings is discussed within the framework of control campaigns currently promoted by the Pan African Tsetse and Trypanosomosis Eradication Campaign.

Spatial dispersion and characterisation of mosquito breeding habitats in urban vegetable-production areas of Abidjan, Côte d'Ivoire.

Although urban agriculture (UA) in the developing world may enhance nutrition and local economies, it may also lead to higher densities of mosquito breeding sites and, consequently, to increased transmission of malarial parasites. If targeted interventions against malaria vectors are to be successful in urban areas, the habitats that support Anopheles breeding need to be identified and detected. Mosquito breeding sites have recently been characterised, and the factors associated with productive Anopheles habitats identified, in market gardens of Abidjan, Côte d'Ivoire. Two surveys were conducted in seven vegetable-production areas, one towards the end of the rainy season and one during the dry season. A standardized methodology was used for habitat characterisation and the detection of Anopheles larvae and mosquito pupae. Overall, 454 and 559 potential mosquito-breeding sites were recorded in the rainy-season and dry-season surveys, respectively. In the rainy season, Anopheles larvae and mosquito pupae were found in 29.7% and 5.5% of the potential breeding sites, respectively, whereas the corresponding percentages in the dry season were 24.3% and 8.6%. The potential breeding sites in an agricultural zone on the periphery of Abidjan were those least likely to be positive for Anopheles larvae and mosquito pupae whereas 'agricultural trenches' between seedbeds were the sites most likely to be positive. In a spatially-explicit Bayesian multivariate logistic-regression model, although one out of every five such wells was also found to harbour Anopheles larvae, irrigation wells were found to be the least productive habitats, of those sampled, for pupae. In the study area, simple and cost-effective strategies of larval control should be targeted at agricultural trenches, ideally with the active involvement of local stakeholders (i.e. urban farmers and urban agricultural extension services).

[Epidemiological baseline situation before the construction of a small dam in five villages of Bouaké, central Côte-d'Ivoire]. / Situation épidémiologique avant la mise en eau du barrage hydroagricole de cinq villages de Bouaké, centre Côte-d'Ivoire

Abstract From June 2007 to June 2008, entomological, malacological and parasitological investigations were carried out in five villages in close proximity to a small dam of Raf-fierkro in Bouaké, central Côte-d'Ivoire. The objective of the study was to identify vectors and intermediate host snails of parasitic diseases related to water, and to assess the prevalence of malaria, schistosomiasis and soil-transmitted helminthiasis before dam construction. Mosquitoes were caught by human landing catches, snails were collected in water bodies, and microscopic analyses of blood, stool and urine samples were carried out. Two malaria vector species were identified:Anopheles gambiae and Anopheles funestus. The average infective rate of An. gambiae ranged between 3.1 and 4.5 %. The infective rate of An. funestus was 1 % in all sites. The entomological inoculation rate ranged between 343.1 and 427.1 infective bites per person per year (ib/p/y)for An. gambiae and between 14.6 and 40.1 ib/p/y for An. funestus. Three species of were found: Plasmodium falciparum (predominant species), Plasmodium ovale and Plasmodium malariae. There were no intermediate host snails of schistosomiasis with the exception of Biomphalaria pfeifferi,intermediate host snail of Schistosoma mansoni in Ahougui. The prevalence of urinary and intestinal schistosomiasis and soil-transmitted helminthiasis was low. Our studies revealed important transmission of malaria, with the presence of three plasmodial species, whereas schistosomiasis and soil-transmitted helminthiasis were present, but only at low frequencies.

[Ticks of Cattle (Bos taurus and Bos indicus) and Grasscutters (Thryonomys swinderianus) in Savannas District of Côte-d'Ivoire]. / Tiques des bovins (Bos taurus et Bos indicus) et des aulacodes (Thryonomys swinderianus) dans le district des Savanes de Côte-d'Ivoire.

During dry season of 2014, some ticks were collected on cattle (Bos taurus and Bos indicus) and grasscutters (Thryonomys swinderianus) in sugar complex areas of Savanna District of Côte-d'Ivoire. Two localities were concerned; SUCAF 1 in Ferkessédougou and SUCAF 2 in Komborodougou. The main objective was to inventory tick species that parasite cattle and grasscutters in this region, then, to identify the shared species between these two groups of animals. To this end, ticks were collected from 70 cattle (35 females and 35 males) and 50 grasscutters (30 females and 20 males). Four tick species were found on cattle: Amblyomma variegatum, Hyalomma truncatum, Rhipicephalus annulatus and Rhipicephalus microplus. On grasscutters, three species of ticks were found: A. variegatum, Ixodes aulacodi and Rhipicephalus simpsoni. The species A. variegatum dominated cattle infestation and was the only tick present in the two groups of animals. But, only immature forms were found on grasscutters. This later specie was mainly infested by adults R. simpsoni.

Pendant la saison sèche de l'année 2014, des tiques ont été collectées sur des bovins (Bos taurus et Bos indicus) et sur des aulacodes (Thryonomys swinderianus), respectivement à Ferkessédougou et Komborodougou au niveau des complexes sucriers SUCAF 1 et 2, dans le district des Savanes de Côte-d'Ivoire. L'objectif principal recherché était d'inventorier les espèces de tiques parasitant les bovins et les aulacodes sauvages dans cette région puis de déterminer les espèces communes à ces deux groupes d'animaux. Au total, les prélèvements de tiques ont été effectués sur 70 bovins et 50 aulacodes. Après identification morphologique, quatre espèces ont été trouvées chez les bovins : Amblyomma variegatum, Hyalomma truncatum, Rhipicephalus annulatus et Rhipicephalus microplus, et trois espèces chez les aulacodes : A. variegatum, Ixodes aulacodi et Rhipicephalus simpsoni. La tique A. variegatum, la seule espèce commune aux deux types d'animaux, était majoritaire chez les bovins. Chez les aulacodes par contre, seules les formes immatures d'A. variegatum ont été trouvées, et les adultes de l'espèce R. simpsoni ont été trouvés en majorité.

Schistosomiasis and soil-transmitted helminthiasis control in Cameroon and Côte d'Ivoire: implementing control on a limited budget.

Schistosomiasis and soil-transmitted helminthiasis occur throughout the developing world and remain a major public health problem in the poorest communities with enormous consequences for development. The extent of the problem has long been neglected because these diseases rarely kill at a young age and also because of their insidious nature. Today there exists a momentum and an unprecedented opportunity for a cost-effective control of these neglected tropical diseases. The control of these diseases has become a priority on the agenda of many governments, donors and international agencies. This paper highlights the progress made and future control activities in Cameroon and Côte d'Ivoire, where schistosomiasis and soil-transmitted helminthiasis control measures have been implemented over the past decade with limited budgets. In Cameroon, deworming activities were increased to encompass all ten regions in 2007 as a result of a co-ordinated effort of the Ministry of Health and the Ministry of Education with national and international partners. In Côte d'Ivoire, focal control activities were achieved with support from various partners. Prospects, opportunities and challenges for the control of neglected tropical diseases in these two countries are discussed.

Bayesian geostatistical modelling for mapping schistosomiasis transmission.

Progress has been made in mapping and predicting the risk of schistosomiasis using Bayesian geostatistical inference. Applications primarily focused on risk profiling of prevalence rather than infection intensity, although the latter is particularly important for morbidity control. In this review, the underlying assumptions used in a study mapping Schistosoma mansoni infection intensity in East Africa are examined. We argue that the assumption of stationarity needs to be relaxed, and that the negative binomial assumption might result in misleading inference because of a high number of excess zeros (individuals without an infection). We developed a Bayesian geostatistical zero-inflated (ZI) regression model that assumes a non-stationary spatial process. Our model is validated with a high-quality georeferenced database from western Côte d'Ivoire, consisting of demographic, environmental, parasitological and socio-economic data. Nearly 40% of the 3818 participating schoolchildren were infected with S. mansoni, and the mean egg count among infected children was 162 eggs per gram of stool (EPG), ranging between 24 and 6768 EPG. Compared to a negative binomial and ZI Poisson and negative binomial models, the Bayesian non-stationary ZI negative binomial model showed a better fit to the data. We conclude that geostatistical ZI models produce more accurate maps of helminth infection intensity than the spatial negative binomial ones.

Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution.

In May 2001, the World Health Assembly (WHA) passed a resolution which urged member states to attain, by 2010, a minimum target of regularly administering anthelminthic drugs to at least 75% and up to 100% of all school-aged children at risk of morbidity. The refined global strategy for the prevention and control of schistosomiasis and soil-transmitted helminthiasis was issued in the following year and large-scale administration of anthelminthic drugs endorsed as the central feature. This strategy has subsequently been termed 'preventive chemotherapy'. Clearly, the 2001 WHA resolution led the way for concurrently controlling multiple neglected tropical diseases. In this paper, we recall the schistosomiasis situation in Africa in mid-2003. Adhering to strategic guidelines issued by the World Health Organization, we estimate the projected annual treatment needs with praziquantel among the school-aged population and critically discuss these estimates. The important role of geospatial tools for disease risk mapping, surveillance and predictions for resource allocation is emphasised. We clarify that schistosomiasis is only one of many neglected tropical diseases and that considerable uncertainties remain regarding global burden estimates. We examine new control initiatives targeting schistosomiasis and other tropical diseases that are often neglected. The prospect and challenges of integrated control are discussed and the need for combining biomedical, educational and engineering strategies and geospatial tools for sustainable disease control are highlighted. We conclude that, for achieving integrated and sustainable control of neglected tropical diseases, a set of interventions must be tailored to a given endemic setting and fine-tuned over time in response to the changing nature and impact of control. Consequently, besides the environment, the prevailing demographic, health and social systems contexts need to be considered.

[Identification of high risks regions of schistosomiasis in Côte d'lvoire]. / Identification des régions à haut risque de schistosomoses en Côte d'lvoire.

Regional and national epidemiological data being not available for coherent and efficient control strategies, the identification of high risk zones of schistosomiasis was set up in 5 regions of Côte d'lvoire in April 1999. The inquiry was conducted by questionnaire in 1291 primary schools including 119624 pupils. After less than 2 months, the results revealed blood in urines and in stools in respectively 22035 (18.6%) and 27555 (23.3%) pupils. Out of 1089 (99.8%) schools at risk of schistosomae, 358 (32.9%) are high risk schools. They are to be found especially in the Agnéby (30.8%) and the Marahoué (19.9%) regions identified as high risk areas where actions of control are then important to implement. They are followed by the Lakes regions (15%), the Middle-Comoé (12.6%) and Southern-Comoé (8.9%). These results should help to develop the schistosomiasis control in Côte d'lvoire.

[Malaria and intestinal parasitosis in pregnant woman at Abobo district (Abidjan, Côte d'Ivoire)]. / Paludisme et parasitoses digestives chez la femme enceinte de la commune d'Abobo (Abidjan, Côte d'Ivoire).

A prospective study was carried out from 2010 to 2012 at the Hôpital Général d'Abobo (HGA) in Abidjan, in order to determine the impact of infectious and parasitic diseases on child cognitive development. Blood samples were examined by means of thick drop and blood smear; as for stool by direct examination and concentration by formalin-ether method. We evaluated the prevalence, the parasite load of malaria and gastrointestinal parasites; then we investigated the risk factors for these disorders. Overall, 331 pregnant women in the last trimester of their pregnancy were enrolled. The plasmodic index was 3.9% with infestation specific rates of P. falciparum from 100%. Concerning digestive protozoa, it has been observed 71.3% of nonpathogenic, against 9.7 % of pathogens, either an overall prevalence of 51.4% of digestive parasites. The calculated average parasitic loads revealed 3089.2 tpz/µl of blood (95 % CI: 591.1-5587.3) for malaria, 6.5 eggs per gram of stool (95 % CI: 0.4-13.4) for intestinal helminths and one parasite by microscopic field for protozoa (common infestation). It has been shown that the occurrence of malaria has been linked to the non-use of impregnated mosquito nets (x2 = 0.012; p = 0.018), not to age. No link could be established between the presence of digestive parasites and the age of pregnant women, or socioeconomic conditions (level of education, profession, type of toilet). Malaria is less common in pregnant women while the rate of digestive parasites remains high.

[Prevalence, genetic diversity and multiplicity of Plasmodium falciparum infection in school children in central Cote d'Ivoire]. / Prevalence, diversité antigénique et multiplicité d'infections de Plasmodium falciparum en milieu scolaire au centre de la Côte d'Ivoire.

A study was carried out in the village of Taabo, located in the vicinity of a large man-made lake in central Côte d'Ivoire. The objectives were (i) to determine the level of prevalence, genetic diversity and multiplicity of Plasmodiumfakiparum infection in schoolchildren and (ii) to compare the diagnostic performance of light microscopy and polymerase chain reaction (PCR). A total of 424 schoolchildren ranging in age from 5 to 15 years underwent diagnostic testing using both light microscopy of blood smears and PCR. Multiplicity of P. falciparum infection was investigated in 196 children (46.2%). The prevalence of malaria was 54.7% based on light microscopy and 83.9% based on PCR. Genotyping based on polymorphism in the length of the restriction fragment of the gene encoding the merozoite surface protein-2 (msp2) showed that 86.5% of cases involved multiple infection with a geometric mean of 3.87 genotypes per positive child. There was a strong positive correlation between multipcity of infection and parasite density in the 56-year old age group. A total of 50 genotypes including six observed for the first time were identified and classified into families with similar-sized sequence groups: 26 x FC27 (52%) and 24 x 3D7 (48%). In comparison with PCR, the sensitivity and specificity of light microscopy for diagnosis of P. falciparum was 81.3% and 88.2% respectively. Data are discussed in the light of similar studies carried out in sub-Saharan Africa and elsewhere. These findings can serve as a basis for monitoring the longterm effect of major water resource management projects on the prevalence, genetic diversity and multiplicity of P. falciparum infection.

Combined stool-based multiplex PCR and microscopy for enhanced pathogen detection in patients with persistent diarrhoea and asymptomatic controls from Côte d'Ivoire.

Infectious diarrhoea ranks among the leading causes of morbidity worldwide. Although most acute diarrhoeal episodes are self-limiting, the diagnosis and treatment of persistent diarrhoea (≥2 weeks) are cumbersome and require laboratory identification of the causative pathogen. Stool-based PCR assays have greatly improved the previously disappointing pathogen detection rates in high-income countries, but there is a paucity of quality data from tropical settings. We performed a case-control study to elucidate the spectrum of intestinal pathogens in patients with persistent diarrhoea and asymptomatic controls in southern Côte d'Ivoire. Stool samples from 68 patients and 68 controls were obtained and subjected to molecular multiplex testing with the Luminex(®) Gastrointestinal Pathogen Panel (GPP), microscopy and rapid antigen detection tests for the diagnosis of diarrhoeagenic pathogens. Overall, 20 different bacteria, parasites and viruses were detected by the suite of diagnostic methods employed. At least one pathogen was observed in 84% of the participants, and co-infections were observed in >50% of the participants. Enterotoxigenic Escherichia coli (32%), Giardia intestinalis (29%) and Shigella species (20%) were the predominant pathogens, and Strongyloides stercoralis (10%) was the most prevalent helminth. Pathogen frequencies and numbers of co-infections were similar in patients and controls. Although the Luminex(®) GPP detects a broad range of pathogens, microscopy for helminths and intestinal protozoa remains necessary to cover the full aetiological spectrum in tropical settings. We conclude that highly sensitive multiplex PCR assays constitute a useful screening tool, but that positive results might need to be confirmed by independent methods to discriminate active infection from asymptomatic faecal shedding of nucleic acids.

Effect of artemether against Schistosoma haematobium in experimentally infected hamsters.

The drug, artemether, has been shown to be active against the juvenile stages of Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals, while it is less effective on adult worms. These findings have been confirmed in randomised controlled trials in humans. Consequently, it could be expected that artemether is also active against Schistosoma haematobium. We present here the first results from experiments assessing the effect of artemether on S. haematobium. Hamsters with a single infection received intra-gastrically an initial dose of 300 mg/kg artemether on day 14, 21 or 28, followed by further doses at varying treatment regimens. In all the treatment groups, the total and female worm reduction rates were highly significant, and ranged from 78 to 100% in hamsters harbouring juvenile schistosomes. Hamsters infected three times with S. haematobium, on days 0, 4 and 9, and repeatedly treated with artemether at the same dose as above, showed highly significant total and female worm reduction rates of between 94 and 99%. Artemether was also active against 77-day-old adult S. haematobium, since its administration on two consecutive days resulted in highly significant total and female worm reduction rates of 76-89%. Our findings confirm that artemether is also active against S. haematobium, especially the schistosomules. These results provide a basis for clinical trials in humans, for further assessment of the potential of artemether for schistosomiasis control.

The potential of artemether for the control of schistosomiasis.

Schistosomiasis continues to rank--following malaria--at the second position of the world's parasitic diseases in terms of the extent of endemic areas and the number of infected people. There is yet no vaccine available and the current mainstay of control is chemotherapy with praziquantel used as the drug of choice. In view of concern about the development of tolerance and/or resistance to praziquantel, there is a need for research and development of novel drugs for the prevention and cure of schistosomiasis. Interestingly, derivatives of artemisinin, which are already effectively used in the treatment of malaria, also exhibit antischistosomal properties. Significant advances have been made with artemether, the methyl ether derivative of artemisinin. We review the discovery of the antischistosomal activity of artemether by Chinese scientists two decades ago; the detailed laboratory studies of the susceptibility of, and effect on, the different developmental stages of Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium to artemether; the possible mechanism of action and the potential long-term toxicity. Finally, we look at the effect of combined treatment with artemether and praziquantel; and clinical findings thus far obtained from randomised controlled trials with oral artemether for the prevention of patent infections and morbidity. The review intends to create a forum for strategic discussion of how these laboratory and clinical findings could be translated into public health actions. We conclude that artemether--as part of integrated current control measures and adapted to specific socio-ecological and epidemiological settings--has considerable potential to significantly reduce the current burden of schistosomiasis in many parts of the world.

Simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection among schoolchildren in western Côte d'Ivoire.

A study to determine the diagnostic performance of simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infection was carried out in western C te d'Ivoire. A total of 322 schoolchildren were screened over four consecutive days with the Kato-Katz technique to assess S. mansoni and concurrent geohelminth infections. Children were individually interviewed by teachers using a standardized questionnaire asking about symptoms, reported diseases, and water-contact patterns. The cumulative infection prevalence of S. mansoni was 76.4%. Univariate statistics revealed a significant association between the level of S. mansoni infection and three recalled water contact patterns: (1) fishing with nets, (2) swimming/bathing and (3) crossing rivers, but no significant association with reported symptoms and/or reported diseases. Multivariate analysis revealed significant adjusted odds ratios (OR) for crossing the river Tchéorbour (OR = 3.90, P = 0.007), crossing the river Sonbour (OR = 3.90, P = 0.008) and swimming/bathing in the latter (OR = 3.28, P = 0.017). The diagnostic performance of these water-contact patterns was characterized by high specificities but low sensitivities, hence negative predictive values. In the village studied here, recalled water-contact patterns were more useful variables than anamnestic questions for schoolchildren's self-diagnosis of S. mansoni infection, but no generalization of these findings beyond this population is possible at this time.

Intestinal amoebiasis, giardiasis and geohelminthiases: their association with other intestinal parasites and reported intestinal symptoms.

In order to determine reported signs and symptoms that may predict an intestinal parasitic infection, 241 schoolchildren in western Côte d'Ivoire were interviewed with a simple questionnaire and their stool specimens were examined over several consecutive days. Special emphasis was placed on (i) assessing infections by Entamoeba histolytica/E. dispar, Giardia duodenalis and by intestinal worms, (ii) looking for associations between these parasites, and (iii) looking for associations between these parasites and commonly perceived intestinal signs and symptoms. Complete questionnaire results, intestinal helminth infections derived from 4 Kato-Katz thick smears, and intestinal protozoa infections assessed on a single day by a formalin-ether concentration procedure were obtained from 209 children (87%). A logistic regression modelling approach showed that an infection with E. histolytica/E. dispar was significantly associated with an Entamoeba coli infection. However, for G. duodenalis, hookworm and Ascaris lumbricoides, no association was found between any of these parasites and other intestinal parasites. In a multivariate analysis reported diarrhoea was the only symptom positively associated with an E. histolytica/E. dispar infection (P = 0.028). Its diagnostic performance showed a low sensitivity (28%), a high specificity (85%) and moderate positive and negative predictive values (52% and 67%, respectively). Surprisingly, reported 'turning stomach' was less often reported by children infected with G. duodenalis (borderline significance, P = 0.057). It is concluded that reported diarrhoea could be a symptom worth exploring further for the rapid identification of schoolchildren infected with E. histolytica/E. dispar.