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S9 Fig Sensitivity analysis Forest Plot of the impact of therapy on blood in stool prevalence. Reversibility of urinary tract abnormalities due to Schistosoma haematobium infection. Main portal vein Four studies assessed the prevalence of portal vein dilation before and after chemotherapy for schistosomiasis see Table D in S1 Text.

Only studies delivering two chemotherapeutic interventions and those having a follow-up time greater than 24 months were associated with significant reductions in the diameter of the portal vein.

In addition, like hydronephrosis in urogenital schistosomiasis, splenic enlargement in intestinal schistosomiasis is likely a marker of more severe and more prolonged chronic intestinal schistosomiasis, and it may be more difficult to achieve regression with late treatment [ 4647 ]. Reduction of heterogeneity was observed, but heterogeneity remained high among studies that included the entire population, studies that included only infected individuals, studies with follow-up greater than 12 months, and studies performed in West Africa.

This finding likely reflects a more advanced stage of disease with a smaller chance of a beneficial chemotherapy effect from a single dose. Color circles indicate summary odds ratios estimated by random effects meta-analysis for morbidity prevalences after treatment, as compared to pre-treatment levels.

Significant heterogeneity was observed among the included studies Fig 2which decreased somewhat when grouped among the studies performed in South Africa and in the subgroup with individuals selected for some specific morbidity Table B in S3 Text.

Associations between egg reduction rate and treatment-related reductions in morbidity level To examine the hypothesis that post-treatment intensity of Schistosoma infection remains a correlate of morbidity risk after therapy, we performed meta-regression of the odds of having infection-related morbidities post-treatment as a function of post-treatment ERR achieved in an individual study population.

With respect to hemoglobin levels, it was only possible to identify statistically significant changes when the follow-up was performed at an interval greater than twelve months after treatment. Evaluation and application of potential schistosome-associated morbidity markers within large-scale mass chemotherapy programmes.

Panel A, Forest plot and meta-analysis for the difference in mean hemoglobin levels, pre-intervention vs. Tables A-K indicating the main characteristics of included studies evaluating the impact of chemotherapy on different Schistosoma infection-related morbidities.

Of importance to public health, it appears that monitoring of schistosomiasis-associated anemia impact should be planned for a period at one year or more after treatment. Log odds ratio of hematuria, proteinuria, and bladder abnormalities according to post-treatment egg reduction rate. Thirteen studies evaluated school age children and three evaluated adult males.


The meta-analysis of outcomes of cognitive performance and school achievement will be published in a separate paper. Log 0s07 ratio of periportal fibrosis according to post-treatment egg reduction rate.

As the time of follow-up increased, the chances of reversal of lesions decreased Table I in S3 Text. S13 Fig Sensitivity analysis Forest Plot of the impact of therapy on urinary tract abnormality prevalence.

The population studied, their ages and infection status, and the interval for follow-up all influenced the magnitude of morbidity reductions noted in a given study cohort. The chances of observing reductions in hepatomegaly, diarrhea, proteinuria, and bladder abnormalities were higher when the studies were performed on subjects who were definitely infected, i. Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren.

To test for outliers or the effects ch larger influential studies in our analysis, sensitivity analysis by exclusion of one study at a time from the meta-analysis did not affect the outcome performance of the odds ratio, Z, and p-values, and the significance of observed associations did not change S2 — S4 Figs.

As outlined in Fig 1of these study reports were excluded after second stage screening, leaving a total of reports for inclusion in the systematic review.

Overall, our results suggest that drug treatment significantly reduces but does not eliminate these common pathologic consequences of Schistosoma infection, and that the odds of improvement are linked to the magnitude of treatment-related reductions in adult worm burden of parasitic infection.

The reduction in prevalence was highly significant after chemotherapy for S. Endoscopic findings and clinicopathologic characteristics of colonic schistosomiasis: Forest plot showing sensitivity analysis, performed by removing one study at a time, for the effect of treatment on blood hemoglobin.

In clinical studies, portal vein diameter is an indicator that correlates with portal vein pressure and risk for hemorrhage [ 47 ]. Nevertheless, it was observed that even near-total reduction in egg counts by drug treatment was unlikely to lead to complete reduction of all morbidity risk. These were the prevalence of portal vein dilation and change in mean hemoglobin level. S2 Fig Sensitivity analysis Forest Plot of the impact of therapy on left lobe hepatomegaly prevalence.

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Ultrasound and clinical investigation of hepatosplenic schistosomiasis: Sensitivity analysis Forest Plot of the impact of therapy on splenomegaly prevalence. Not all morbidities had such stratifying data for all studies. Forest plot showing sensitivity analysis, performed by removing one study at a time, for the effect of treatment on prevalence of ultrasound abnormalities in the upper urinary tract.


Forest plot showing sensitivity analysis, performed by removing one study at a time, for the effect of treatment on prevalence of right hepatic lobe hepatomegaly. Bull World Health Organ.

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Moreover, the evidence may be chl in terms of generalizability because of the limitations in the design of included studies, and because the diverse populations selected for analysis yielded a high degree of heterogeneity across studies. Overall, for each of the three types of outcome, the population surveyed experienced a significant reduction in the odds of hepatomegaly after treatment, compared to pre-treatment levels.

For the sensitivity analysis, each meta-analysis was retested with the exclusion of one study at a time to assess s00 possibility of a disproportionate impact of any individual study on summary estimates.

Blood in the urine The presence of microhematuria was evaluated in 17 studies see Table G in Ck Text. Quantitative pooled analysis of treatment effects catalogued from the eligible studies was performed using Comprehensive Meta-Analysis software, v.

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Eight studies evaluated the cessation of episodes of diarrhea after anti-schistosomal chemotherapy see Table E in S1 Text. Sensitivity analysis by exclusion of a single study at a time from the meta-analysis did not affect the results S11 Fig. The data analyzed in this study may have been influenced by confounders such as uneven sex distributions, the presence of co-infections, and variation in local reinfection rates that could not be controlled for in the meta-analysis.

Publication bias Assessment for potential publication bias was carried out by visual inspection of funnel plots, and statistically by calculating the Egger test [ 32 ]. No restrictions were placed in terms of location of the s0077, Schistosoma species, or publication date. While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.

Nine studies assessed the reversal of lesions s0077 the upper urinary tract see Table J in S1 Text.