Five-Year Impact of Different Multi-Year Mass Drug Administration Strategies on Childhood Schistosoma mansoni-Associated Morbidity: A Combined Analysis from the Schistosomiasis Consortium for Operational Research and Evaluation Cohort Studies in the Lake Victoria Regions of Kenya and Tanzania

Abstract

The WHO recommends mass treatment with praziquantel as the primary approach for Schistosoma mansoni-related morbidity control in endemic populations. The Schistosomiasis Consortium for Operational Research and Evaluation implemented multi-country, cluster-randomized trials to compare effectiveness of community-wide and school-based treatment (SBT) regimens on prevalence and intensity of schistosomiasis. To assess the impact of two different treatment schedules on S. mansoni-associated morbidity in children, cohort studies were nested within the randomized trials conducted in villages in Kenya and Tanzania having baseline prevalence ≥ 25%. Children aged 7-8 years were enrolled at baseline and followed to ages 11-12 years. Infection intensity and odds of infection were reduced both in villages receiving four years of annual community-wide treatment (CWT) and those who received biennial SBT over 4 years. These regimens were also associated with reduced odds of undernutrition and reduced odds of portal vein dilation at follow-up. However, neither hemoglobin levels nor the prevalence of the rare abnormal pattern C liver scores on ultrasound improved. For the combined cohorts, growth stunting worsened in the areas receiving biennial SBT, and maximal oxygen uptake as estimated by fitness testing scores declined under both regimens. After adjusting for imbalance in starting prevalence between study arms, children in villages receiving annual CWT had significantly greater decreases in infection prevalence and intensity than those villages receiving biennial SBT. Although health-related quality-of-life scores improved in both study arms, children in the CWT villages gained significantly more. We conclude that programs using annual CWT are likely to achieve better overall S. mansoni morbidity control than those implementing only biennial SBT.

Figure 1.

Flow diagram of the cohort study. In the upper arm, children lived in communities randomized to receive annual community-wide mass drug administration treatment (CWT). The children in the lower study arm lived in communities randomized to receive only biennial (every other year) school-based treatment (SBT), with drug “holidays” in Year 2 and in Year 4. Final assessment for both groups was performed in Year 5 of the study.

Figure 2.

Comparison of Year 1 and Year 5 Schistosoma mansoni prevalence for participating children in each of the combined cohort study arms (annual community-wide treatment (CWT) vs. biennial school-based treatment [SBT]). Dark circles indicate baseline and Year 5 prevalence values for the annual CWT arm. Open squares indicate corresponding prevalence values for the children in the biennial SBT arm. Error bars indicate 95% CI.

Figure 3.

Comparison of Year 1 and Year 5 Schistosoma mansoni infection intensities by the cohort study arm. Shown here are Year 1 baseline intensity values (dark bars) and 95% CI for participating children in the two study arms receiving either annual community-wide treatment (CWT) or biennial school-based treatment (SBT), calculated either as arithmetic mean intensity for egg-positive children (individual-level intensity, left side), or as mean intensity for all children, including those with zero egg counts (cohort-level intensity, right side). Corresponding values for participating children in Year 5, after MDA, are shown by the light bars.