Regression of Schistosoma mansoni associated morbidity among Ugandan preschool children following praziquantel treatment: A randomised trial.

Preschool children suffer from morbidity attributable to Schistosoma mansoni. We compared a single and double dose of praziquantel treatment on the regression of S. mansoni associated morbidity in children less than six years in Uganda. We measured the sizes of spleen and liver as well as liver fibrosis before treatment and 8 months after treatment among children who either received one dose (n = 201) or two doses (n = 184) of praziquantel (standard oral dose of 40 mg/kg body weight). Heamoglobin measurements were also taken. Overall, liver enlargement reduced from 52.2% (95% CI (Confidence interval) 45.1, 59.3) to 17.9% (95% CI 12.9, 23.9) with a single dose and from 48.4 (95% CI 40.9, 55.8) to 17.9% (95% CI 12.7, 24.3) with a double dose and there was no significant difference between the changes in proportion of children with enlarged liver between the two treatment groups. The proportion of children with enlarged spleen was not significantly reduced in the group treated with either one or two doses, 47.8% (95% CI 41.7, 54.9) to 45.3% (95% CI 38.3, 52.4) and 48.4% (95% CI 40.9,55.8) to 40.8% 95% CI 33.6, 48.2), respectively. Liver fibrosis detected among children getting single dose (n = 9) or double doses (n = 13) resolved after treatment with praziquantel. The number of children with low heamoglobin significantly reduced from 51.2% (95% CI 44.1, 58.3) to 0.5% (0.2, 0.8) and 61.4% (95% CI 53.9,68.5) to 1.1% (95% CI 0.1, 3.9) after single and double dose treatment, respectively. These results suggest that there is no evidence of a difference in effect between one dose of praziquantel and two doses in reversing morbidity attributable to S. mansoni among children less than six years of age.

Schistosoma mansoni-Associated Morbidity among Preschool-Aged Children along the Shores of Lake Victoria in Uganda.

Schistosoma mansoni causes morbidity in human beings, with the highest prevalence in rural sub-Saharan Africa. Prolonged S. mansoni infection with egg deposition in intestinal blood vessels leads to liver and spleen enlargement, and thus chronic morbidity. The objective of this study was to assess whether preschool-aged children develop severe S. mansoni-related morbidity. Parasitological, clinical, and ultrasonographic examinations were carried out in 916 preschool-aged children in five schistosomiasis-endemic districts (Bugiri, Buikwe, Jinja, Mayuge, and Namayingo) along the Lake Victoria shoreline in east-central Uganda. Anaemia and anthropometry measurements were also taken. Using the Kato-Katz technique on one stool sample collected on three consecutive days, 74.9% (686/916) were found infected with S. mansoni; the majority were lightly infected (57.9%), while 22.7% and 19.4% were moderately and heavily infected, respectively. The overall geometric mean intensity (GMI) of infected children was 294.2 eggs per gram faeces. Mayuge and Jinja districts had the highest (51.2%) and lowest (2.2%) number of infected children, respectively. Hookworm infection was found in 7.8% (71/916) of the children. Both liver and spleen were significantly more enlarged in the infected children than in the uninfected children (p < 0.0005), as measured by ultrasonography. Physical palpation of the spleen was more often detected in the uninfected children. A significantly (p < 0.0005) higher proportion of S. mansoni-positive children were anaemic (359/686; 52.3%) compared to the children who had no eggs in their stool samples (81/230; 35.2%). Schistosoma mansoni infection did not have any severe effect on the nutrition status of preschool-aged children. Neither infected nor uninfected children were found to be underweight or stunted. Liver fibrosis with distinct Symmer's 'pipe stems' was found in a few heavily-infected children (0.3%). In a linear multivariable regression analysis, age of the child, anaemia, liver fibrosis, and size of the left liver lobe were associated with S. mansoni intensity of infection (adjusted R² = 0.11; p < 0.0005). Our results demonstrate that S. mansoni-related morbidity does develop in children less than six years of age, and that older children (37⁻60 months) are at higher risk (regression coefficient 0.33; p <0.0005) compared to younger ones (12⁻36 months). We recommend that preschool-aged children be included in the target population for schistosomiasis mass treatment so as to prevent the childhood chronic form of schistosomiasis.

Single Versus Double Dose Praziquantel Comparison on Efficacy and Schistosoma mansoni Re-Infection in Preschool-Age Children in Uganda: A Randomized Controlled Trial.

BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two treatments was assessed and compared 1 month after the second treatment. Re-infection with S. mansoni was assessed in the same children 8 months following the second treatment. CRs were non-significantly higher in children treated with two 40 mg/kg PZQ doses (85.5%; 290/339) compared to a single dose (83.2%; 297/357). ERRs were significantly higher in the double dose with 99.3 (95%CI: 99.2-99.5) compared with 98.9 (95%CI: 98.7-99.1) using a single dose, (P = 0.01). Side effects occurred more frequently during the first round of drug administration and were mild and short-lived; these included vomiting, abdominal pain and bloody diarrhea. Overall re-infection rate 8 months post treatment was 44.5%. CONCLUSIONS: PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children. Two PZQ doses lead to significant reduction in egg excretion compared to a single dose. Re-infection rates with S. mansoni 8 months post treatment is the same among children irrespective of the treatment regimen.

The ITS2 of the genus Bulinus: novel secondary structure among freshwater snails and potential new taxonomic markers.

The freshwater snail genus Bulinus has been intensively investigated due to its role as intermediate host for trematode blood flukes that cause the debilitating disease schistosomiasis in man and livestock. Owing to taxonomic ambiguities within Bulinus, attention has often focused upon species delineation and several molecular methods have recently been used for identification and characterization purposes. Inspection of compensatory base changes (CBCs) in the secondary structure of the nuclear ribosomal internal transcribed spacer (ITS) has been used to differentiate species in other genera, and here we present a study investigating the presence of CBCs between species in the species groups within Bulinus. CBCs were present within B. forskalii and B. globosus indicating that these widely distributed taxa might constitute cryptic species complexes. However, other currently recognized species could not be distinguished by CBC analysis. The putative secondary structure of the very long ITS2 sequence of the B. reticulatus species group had an additional helix (DIIa) between DII and DIII not seen in other species groups of Bulinus. The accumulation and inspection of further ITS2 sequences will no doubt reveal additional variation between Bulinus populations, and CBCs should be incorporated in future taxonomic work in this group.

Bulinus globosus (Planorbidae; Gastropoda) populations in the Lake Victoria basin and coastal Kenya show extreme nuclear genetic differentiation.

Bulinus globosus, a key intermediate host for Schistosoma haematobium that causes urinary schistosomiasis, is a hermaphroditic freshwater Planorbid snail species that inhabits patchy and transient water bodies prone to large seasonal variations in water availability. Although capable of self-fertilizing, this species has been reported to be preferentially out crossing. In this study, we characterized the population genetic structure of 19 B. globosus populations sampled across the Lake Victoria basin and coastal Kenya using four polymorphic microsatellite loci. Population genetic structure was characterized and quantified using FST statistics and Bayesian clustering algorithms. The four loci used in this study contained sufficient statistical power to detect low levels of population genetic differentiation and were highly polymorphic with the number of alleles per locus across populations ranging from 16 to 22. Average observed and expected heterozygosities across loci in each population ranged from 0.13 to 0.69 and from 0.39 to 0.79, respectively. Twenty-five of the seventy-six possible population-locus comparisons significantly deviated from Hardy-Weinberg equilibrium proportions after Bonferroni corrections, mostly due to the deficiency of heterozygotes. Significant genetic differentiation was observed between populations and Bayesian inferences identified 15 genetic clusters. The excess homozygosity, significant inbreeding and population genetic differentiation observed in B. globosus populations are likely to be due to the habitat patchiness, mating system and the proneness to cyclic extinction and recolonization in transient habitats.