Comparison of School-Based and Community-Wide Mass Drug Administration for Schistosomiasis Control in an Area of Western Kenya with High Initial Schistosoma mansoni Infection Prevalence: A Cluster Randomized Trial

Abstract

We conducted a cluster randomized trial comparing the target population and timing of mass drug administration (MDA) with praziquantel for control of schistosomiasis in villages in western Kenya with high initial prevalence (> 25%) according to a harmonized protocol developed by the Schistosomiasis Consortium for Operational Research and Evaluation. A total of 150 villages were randomized into six treatment arms (25 villages per arm), were assessed at baseline, and received two or four rounds of MDA using community-wide (CWT) or school-based (SBT) treatment over 4 years. In the fifth year, a final evaluation was conducted. The primary outcomes were prevalence and intensity of Schistosoma mansoni infections in children aged 9-12 years, each year their village received MDA. Baseline and year 5 assessments of first-year students and adults were also performed. Using Poisson and negative binomial regression with generalized estimating equations, we found similar effects of CWT and SBT MDA treatment strategies in children aged 9-12 years: significant reductions of prevalence of infection in all arms and of heavy-intensity (³ 400 eggs/gram) infections in most arms but no significant differences between arms. Combined arms of villages that received four rounds of treatment had greater reduction than villages in arms that only received two rounds of treatment. Surprisingly, we also found benefits of SBT for first-year primary students and adults, who never received treatment in those arms. Our data support the use of annual SBT for control programs when coupled with attention to infections in younger children and occasional treatment of adults.

Challenges in Protocol Development and Interpretation of the Schistosomiasis Consortium for Operational Research and Evaluation Intervention Studies

“…Given appropriate caveats in performing post hoc secondary analysis, it does appear that four rounds of treatment over 5 years offers advantages over two rounds of treatment in terms of reducing SAC infection prevalence and/ or intensity in higher prevalence S. haematobium-and S. mansoni-endemic communities. 24,36,37 Similarly, after post hoc adjustment for starting prevalence, 4 years of CWT appears likely to yield better control of S. mansoni-related morbidity than every-other-year SBT. 37 Addition of snail control or structured behavior change intervention may also improve outcomes beyond those obtained with intensive (biannual) MDA alone.…”

“…This supported the choice of using 25 communities per treatment study arm, with sampling of 100 9-to-12-year-old children per community each year. In the final analysis, based on our formalized statistical analysis plan, the variance in communitylevel responses turned out to be substantially greater than expected, 24,29 which ultimately limited our ability to claim clear-cut advantages to any given implementation strategy (see Kittur et al 30 in this issue regarding the problem of "persistent hotspots"). Because of this large variance and the limited advance information on potential confounders, our ability to stratify communities by risk and our power to detect statistically significant differences in infection and morbidity outcomes was more limited than we had anticipated.…”

“…A larger sample size, with fewer study intervention arms may have avoided this problem. 24 It has been suggested that an initial re-randomization to obtain better balance in known risk factors might have allowed the 25 villages/arm study design to provide more convincing evidence of a differences in endpoint outcomes among the study arms. However, the information available on community-level factors was relatively limited at the time of randomization at the beginning of the SCORE studies.…”

Impact of Different Mass Drug Administration Strategies for Gaining and Sustaining Control of Schistosoma mansoni and Schistosoma haematobium Infection in Africa

“…Mass drug administration with praziquantel reduced community-level prevalence and the mean intensity of Schistosoma infection across all study arms and in all SCORE study countries (AE Phillips, et al, personal communication and M Ouattara et al, personal communication). [22][23][24][25][26][27][28] Figure 3 shows the Year 1 (baseline) and Year 5 prevalence values by treatment study arm for the sustaining control studies for S. mansoni in Côte d'Ivoire and Kenya, the gaining control studies for S. mansoni in Kenya and Tanzania, and the gaining control study for S. haematobium in Mozambique. Prevalence by intensity of infection (light, moderate, or heavy) 9 are also indicated in Figure 3.…”

Lessons Learned in Conducting Mass Drug Administration for Schistosomiasis Control and Measuring Coverage in an Operational Research Setting

“…9 A number of articles have been published describing the baseline characteristics of the study populations and some of the main study outcomes, including changes in infection prevalence and intensity among children aged 9-12 years after 4 years of intervention. [10][11][12][13][14][15][16] To ensure that our findings would have relevance to ongoing schistosomiasis control and elimination efforts, the SCORE gaining and sustaining control studies were conducted in the context of country neglected tropical disease (NTD) programs, with MDA coordinated by or aligned with national NTD programs. However, the studies also involved aspects of field trial research, with random assignment of groups of people (i.e., villages) to different interventions.…”