Adama D. Keita

The impact of single versus mixed schistosome species infections on liver, spleen and bladder morbidity within Malian children pre- and post-praziquantel treatment

BackgroundIn the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology.MethodsThe current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children.ResultsResults suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities.ConclusionsWhilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity.

Use of High-Dose, Twice-Yearly Albendazole and Ivermectin to Suppress Wuchereria bancrofti Microfilarial Levels

BACKGROUND Annual mass treatment with albendazole and ivermectin is the mainstay of current strategies to interrupt transmission of Wuchereria bancrofti in Africa. More-effective microfilarial suppression could potentially reduce the time necessary to interrupt transmission, easing the economic burden of mass treatment programs in countries with limited resources. METHODS To determine the effect of increased dose and frequency of albendazole-ivermectin treatment on microfilarial clearance, 51 W. bancrofti microfilaremic residents of an area of W. bancrofti endemicity in Mali were randomized to receive 2 doses of annual, standard-dose albendazole-ivermectin therapy (400 mg and 150 μg/kg; n = 26) or 4 doses of twice-yearly, increased-dose albendazole-ivermectin therapy (800 mg and 400 μg/kg; n = 25). RESULTS Although microfilarial levels decreased significantly after therapy in both groups, levels were significantly lower in the high-dose, twice-yearly group at 12, 18, and 24 months. Furthermore, there was complete clearance of detectable microfilariae at 12 months in the 19 patients in the twice-yearly therapy group with data available at 12 months, compared with 9 of 21 patients in the annual therapy group (P < .001, by Fishers exact test). This difference between the 2 groups was sustained at 18 and 24 months, with no detectable microfilariae in the patients receiving twice-yearly treatment. Worm nests detectable by ultrasonography and W. bancrofti circulating antigen levels, as measured by enzyme-linked immunosorbent assay, were decreased to the same degree in both groups at 24 months, compared with baseline. CONCLUSIONS These findings suggest that increasing the dosage and frequency of albendazole-ivermectin treatment enhances suppression of microfilariae but that this effect may not be attributable to improved adulticidal activity.

Significantly Reduced Intensity of Infection but Persistent Prevalence of Schistosomiasis in a Highly Endemic Region in Mali after Repeated Treatment

Background Preventive chemotherapy against schistosomiasis has been implemented since 2005 in Mali, targeting school-age children and adults at high risk. A cross-sectional survey was conducted in 2010 to evaluate the impact of repeated treatment among school-age children in the highly-endemic region of Segou. Methodology/Principal Findings The survey was conducted in six sentinel schools in three highly-endemic districts, and 640 school children aged 7–14 years were examined. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Overall prevalence of S. haematobium infection was 61.7%, a significant reduction of 30% from the baseline in 2004 (p<0.01), while overall prevalence of S. mansoni infection was 12.7% which was not significantly different from the baseline. Overall mean intensity of S. haematobium and S. mansoni infection was 180.4 eggs/10 ml of urine and 88.2 epg in 2004 respectively. These were reduced to 33.2 eggs/10 ml of urine and 43.2 epg in 2010 respectively, a significant reduction of 81.6% and 51% (p<0.001). The proportion of heavy S. haematobium infections was reduced from 48.8% in 2004 to 13.8% in 2010, and the proportion of moderate and heavy S. mansoni infection was reduced from 15.6% in 2004 to 9.4% in 2010, both significantly (p<0.01). Mathematical modelling suggests that the observed results were in line with the expected changes. Conclusions/Significance Significant reduction in intensity of infection on both infections and modest but significant reduction in S. haematobium prevalence were achieved in highly-endemic Segou region after repeated chemotherapy. However, persistent prevalence of both infections and relatively high level of intensity of S. mansoni infection suggest that more intensified control measures be implemented in order to achieve the goal of schistosomiasis elimination. In addition, closer monitoring and evaluation activities are needed in the programme to monitor the drug tolerance and to adjust treatment focus.

Impact of Schistosoma haematobium infection on urinary tract pathology, nutritional status and anaemia in school-aged children in two different endemic areas of the Niger River Basin, Mali

The aim of the present study was to contribute to define urinary schistosomiasis-related morbidity indicators and to understand the relationship between infection intensity and disease burden among school-aged children in different endemic areas of Mali. A cross sectional study was undertaken in two different endemic settings: Koulikoro district, along the river and Selingué dam area in the Niger River Basin in order to compare and describe morbidity related to Schistosoma haematobium infection. A total of 667 children aged 7-14 were enrolled in the study. Among these, 333 were from Koulikoro district (175 boys and 158 girls) and 334 from Selingué dam area (169 boys and 165 girls). The overall prevalence of S. haematobium in the two areas was 91.5%; Koulikoro (97.0%) and Selingué (85.9%) and this difference was significant after adjusting for age, sex and clustering within villages. Prevalence of heavy infection (≥ 50 eggs per 10 ml of urine), 57.6% in Koulikoro and 43.8% in Selingué, did not differ significantly after adjusting for age, sex and clustering within villages. The transmission of Schistosoma mansoni was mainly confined to Selingué dam area (12.5%) and was nearly absent in Koulikoro district (1.1%). Blood in urine was the most frequently reported clinical symptom, more common in Koulikoro (76.8%) than in Selingué (57.6%). In a multivariable logistic regression model adjusting for sex, age group, egg intensity category and clustering within villages, Selingué had higher prevalence of macro-haematuria, urinary tract pathology, upper urinary tract pathology and total pathology than Koulikoro, while micro-haematuria did not differ between the two areas. Morbidity measures increased to some extent with egg intensity category, especially micro-haematuria. The results obtained from this study are of importance for planning intervention as for monitoring and evaluation of control in different endemic settings in Mali.

Prevalence of schistomasiasis lesions detected by ultrasonography in children in Molodo, Mali

AIM To study schistomasiasis infection in school children in Molodo, an irrigated rice growing region of Mali, by determining the prevalence of schistomasiasis and lesions identified by ultrasonography among children living in this region. METHODS This cross sectional study included 346 children aged 7 to 14 years selected at random from five schools in Molodo. We tested for hematuria using urine dipsticks and searched for Schistosoma haematobium eggs in urine and S. mansoni eggs in stools. Ultrasonography of the liver, spleen and urinary tract was performed. RESULTS The prevalences of Schistosoma haematobium and S. mansoni infection were 72% (range: 66.9-76.6%) and 68.2% (range: 60.9-71.2%) respectively; 55.1% of the children had co-infection. Ultrasonography of the urinary tract revealed an irregular bladder wall as the most frequent abnormality (3.4% of children). Abdominal ultrasonography demonstrated type B hepatic fibrosis in four children (1.1%), type C in one (0.3%) and type D in one (0.3%). CONCLUSION Few schistosomiasis lesions were detected by ultrasonography compared with the prevalence of S. haematobium and S. mansoni infections. This observation is probably related to mass treatment programs conducted during a national anti-schistosomiasis program.

Inflammation dynamics after praziquantel treatment of Schistosoma haematobium reflected by urinary eosinophil cationic protein.

Background This cohort study assessed urinary eosinophil cationic protein (ECP) as an indicator for urinary tract morbidity and inflammation indication related to single-dose or dual-dose praziquantel (PZQ) treatment. Methods Urinary ECP was measured at baseline, 24 h and 9 weeks after treatment (baseline 305, follow-up 204 participants, ages 2-40 years). Results ECP was significantly associated with the intensity of infection at baseline (p<0.05). Levels at baseline were 8.31 times higher (p<0.01) in participants with bladder morbidity than in those without. There was no correlation with kidney morbidity and no significant effect of a repeated dose of PZQ 40 mg/kg. Baseline ECP and ECP after 9 weeks were associated with microhaematuria (geometric mean ratio at baseline 7.56 [95% confidence limit {CL} 2.34-24.45]; p<0.01) and macrohaematuria (geometric mean ratio at baseline 6.22 [95% CL 2.71-14.24]; p<0.001). Mean levels of ECP dropped significantly during the first follow-up period and far less so in the second follow-up period (mean ECP at baseline: 70.8 ng/mL; ECP at 24 h: 24.5 ng/mL; ECP at 9 weeks: 14.6 ng/mL). Conclusion The urine ECP decrease happened immediately after treatment, reflecting the rapid action of PZQ on eggs in the bladder tissue. ECP in urine can be used as an indirect marker of the degree of local inflammatory reaction in the bladder and is not significantly affected by a repeated dose of PZQ.

Anemia and growth retardation associated with Schistosoma haematobium infection in Mali: a possible subtle impact of a neglected tropical disease

Background The aim of this cross-sectional study was to investigate a possible association of Schistosoma haematobium with child growth development and describe a plausible schistosomiasis-related anemia in children and adults in a highly schistosomiasis endemic area of Mali. Methods Urine, feces and blood samples from 399 participants of both sexes (2-40 years of age) were analyzed and supplemented by anthropometric measurements. Results S. haematobium prevalence was 79.8%, S. mansoni 13.2% and Plasmodium falciparum 80.2%. S. haematobium infection intensity as five categories was significantly associated with anemia; i.e., odds of having anemia in the highest and the next highest category was 3.25 (95% CL 1.61-6.55; p<0.01) and 2.45 (95% CL 1.28-4.70; p<0.01), respectively, of that in the three lower categories combined after adjusting for age group and gender and the interaction between the two factors. Anemia was most pronounced in the 2-5 year olds males (55.5%, n=98). P. falciparum infection was not significantly associated with anemia. Stunting (body mass index [BMI] for age z-score<-2.00) was observed in 2.6% (2/78) of the 2-5 years olds and in 7.7% (14/182) in the 6-19 years age group. Lower BMI-z-scores (as continuous variable) were associated with anemia (p<0.05) while high intensity of S. haematobium infection was not significant when adjusting for age group and anemia. Participants with malaria infection had lower z-scores (as continuous variables) of weight and height for age. Lower height for age z-scores were also associated with anemia. Conclusions S. haematobium infection is likely to impact on child growth and possibly also anemia in all age groups and advocates for inclusion of whole populations into future control programes.

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17–1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages.