Dataset Information

Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel.

ABSTRACT: Schistosomiasis control programs rely heavily on mass drug administration (MDA) campaigns with praziquantel for preventative chemotherapy. Areas where the prevalence and/or intensity of schistosomiasis infection remains high even after several rounds of treatment, termed "persistent hotspots" (PHSs), have been identified in trials of MDA effectiveness conducted by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) in Kenya, Mozambique, Tanzania, and Côte d'Ivoire. In this analysis, we apply a previously developed set of criteria to classify the PHS status of 531 study villages from five SCORE trials. We then fit logistic regression models to data from SCORE and publically available georeferenced datasets to evaluate the influence of local environmental and population features, pre-intervention infection burden, and treatment scheduling on PHS status in each trial. The frequency of PHS in individual trials ranged from 35.3% to 71.6% in study villages. Significant relationships between PHS status and MDA frequency, distance to freshwater, rainfall, baseline schistosomiasis burden, elevation, land cover type, and village remoteness were each observed in at least one trial, although the strength and direction of these relationships was not always consistent among study sites. These findings suggest that PHSs are driven in part by environmental conditions that modify the risk and frequency of reinfection.

SUBMITTER: Walker JW

PROVIDER: S-EPMC7008331 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel.

Walker Joseph W JW Kittur Nupur N Binder Sue S Castleman Jennifer D JD Drake John M JM Campbell Carl H CH King Charles H CH Colley Daniel G DG

The American journal of tropical medicine and hygiene 20200201 2

Schistosomiasis control programs rely heavily on mass drug administration (MDA) campaigns with praziquantel for preventative chemotherapy. Areas where the prevalence and/or intensity of schistosomiasis infection remains high even after several rounds of treatment, termed "persistent hotspots" (PHSs), have been identified in trials of MDA effectiveness conducted by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) in Kenya, Mozambique, Tanzania, and Côte d'Ivoire. In ...[more]

PMID: 31889506

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Project description:Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.

Project description:BACKGROUND:schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The current study, therefore, assessed whether persistent schistosomiasis, with its associated morbidity among children living in endemic areas within the Greater Accra Region of Ghana, is as a result of reinfection or suspected praziquantel resistance. METHODOLOGY:this was a longitudinal study involving a baseline and follow-up sampling after praziquantel treatment. Urine samples were collected from school children (whose parents had also consented) for the detection of S. haematobium ova using a sedimentation technique. The morbidity parameters were examined with urine chemistry strips, as well as microscopy. Viability was assessed using a modified hatchability technique, vital staining (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) microscopy. Infected individuals were treated with a single dose of praziquantel (40mg/kg). Resampling to determine reinfection was done sixth months post-treatment, after evidence of total egg clearance. For possible resistance assessment, egg counts and viability testing were conducted on the positive samples at the baseline, as well as weekly post-treatment follow-ups for 12 weeks. RESULTS:out of the 420 school children sampled, 77 were initially positive but, after the sixth month sampling for reinfection assessment, eight out of the initial positives were infected again, giving a reinfection percentage of 10.4%. No suspected praziquantel resistance was recorded in the 21 positives detected out of the 360 sampled for suspected resistance assessment. The egg reduction rate increased weekly in the follow-up samples with a gradual reduction in the egg count. The study also recorded a gradual decrease in the percentage of live eggs after the first week; with all viability testing methods used complimenting each other. The morbidity parameters (proteinuria, haematuria and pyuria) changed between the baseline and post-treatment samples, eventually reducing to zero. CONCLUSIONS:the outcome of this study suggests that the persistent schistosomiasis, with its associated morbidity observed in these endemic communities, is not likely to be as a result of praziquantel resistance, but reinfection. Even though there was no suspected resistance observed in the study, there remains the need to continuously intensify the monitoring of praziquantel in other endemic communities.

Project description:Historic data and baseline surveys showed schistosomiasis as highly/moderately endemic in 7 of 14 districts in Sierra Leone, justifying annual/biennial mass drug administration (MDA) with praziquantel. MDA commenced in 2009 and reported treatment coverage had been above the World Health Organization recommended 75% of target population. Assessment in 2012 showed significant reduction in infection. In 2016, another national school-based survey was conducted to evaluate the progress. Two schools from each category (high, moderate or low) of endemic communities in each MDA district and five schools in non-MDA districts were selected. Fifty children (25 boys and 25 girls) aged 9-14 years were randomly selected per school. Parasitological examination of 1,980 stool and 1,382 urine samples were conducted. Overall Schistosoma mansoni prevalence in the seven MDA districts decreased to 20.4% (95% CI: 18.7-22.3%) in 2016 from 42.2% (95% CI: 39.8-44.5%) at baseline (p < 0.0001). Mean overall S. mansoni intensity of infection reduced to 52.8 epg (95% CI: 43.2-62.4 epg) in 2016 from 100.5 epg (95% CI: 88.7-112.3 epg) at baseline (p < 0.001). The prevalence of Schistosoma haematobium in the five MDA districts that had baseline prevalence data decreased to 2.2% (95% CI: 1.5-3.1%) in 2016 from 18.3% (95% CI: 16.3-20.5%) at baseline (p < 0.0001). Mean overall intensity of infection increased to 1.12 e/10 ml (95% CI: 0.55-0.1.70 e/10 ml) in 2016 compared to 0.47 e/10 ml (95% CI: 0.16-0.78 e/10 ml) in 2012 (p < 0.05) (no baseline data). No district was highly endemic in 2016 compared to three at baseline and there was no significant difference in prevalence or intensity of infection by sex for both species. This survey illustrated the significant progress made in controlling schistosomiasis in Sierra Leone. The fact that prevalence and intensity of infection showed an increase from the 2010 level suggested a detrimental effect of missing MDA due to the Ebola toward schistosomiasis control. The national program needs to continue the treatment and adopt a comprehensive approach including water, hygiene, and sanitation measures to achieve control and elimination of schistosomiasis.

Project description:BackgroundIn 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months-7 years old) in lakeshore settings of Uganda.Methodology/principal findingsFrom a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment.Conclusion/significanceOur findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial.

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Dataset Information

Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel.

Publications

Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel.

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