SCORE Operational Research on Moving toward Interruption of Schistosomiasis Transmission

Abstract. As part of its diverse portfolio, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) included two cluster-randomized trials evaluating interventions that could potentially lead to interruption of schistosomiasis transmission (elimination) in areas of Africa with low prevalence and intensity of infection. These studies, conducted in Zanzibar and Côte d’Ivoire, demonstrated that multiyear mass drug administration (MDA) with praziquantel failed to interrupt the transmission of urogenital schistosomiasis, even when provided biannually and/or supplemented by small-scale implementation of additional interventions. Other SCORE activities related to elimination included a feasibility and acceptability assessment of test–treat–track–test–treat (T5) strategies and mathematical modeling. Future evaluations of interventions to eliminate schistosomiasis should recognize the difficulties inherent in conducting randomized controlled trials on elimination and in measuring small changes where baseline prevalence is low. Highly sensitive and specific diagnostic tests for use in very low–prevalence areas for schistosomiasis are not routinely available, which complicates accurate measurement of infection rates and assessment of changes resulting from interventions in these settings. Although not encountered in these two studies, as prevalence and intensity decrease, political and community commitment to population-wide MDA may decrease. Because of this potential problem, SCORE developed and funded the T5 strategy implemented in Egypt, Kenya, and Tanzania. It is likely that focal MDA campaigns, along with more targeted approaches, including a T5 strategy and snail control, will need to be supplemented with the provision of clean water and sanitation and behavior change communications to achieve interruption of schistosome transmission.


Figure 2: Flow diagram for progress of schools and individuals through ZEST cross-sectional studies (baseline in 2012 to Y6 in 2017)
* Kiongwe school belongs to Mafufuni shehia, which was originally randomized, but the school was only surveyed from 2013 onwards. A wrong school, Makoba school in Makoba shehia, was surveyed instead in 2012. We keep Kiongwe school but not Makoba school in the primary analysis. Since no baseline data are available for Kiongwe, we only have 14 schools in the snail arm at baseline and 15 at follow-ups. **Regeza Mwendo schools belongs to Mwera shehia, which was originally randomized, but the school was only surveyed from 2013 onwards. A wrong school, Machui school in Koani shehia, was surveyed instead in 2012. We keep Regeza Mwendo school but not Machui school in the primary analysis. Since no baseline data are available for Regeza Mwendo, we only have 14 schools in the snail arm at baseline and 15 at follow-ups. Hence, for all children that had no urine filtration result but a haemastix result, a microhaematuria result >0 was considered as S. haematobium-positive. The number of children with prevalence results is thus different from the number of children with intensity results. Table 1a. Baseline characteristics of participants by study arm: individual level data summarized by study arm.

Table 1b. Baseline characteristics of participants by study arm: village level results summarized by study arm.
Kiongwe school belongs to Mafufuni shehia, which was originally randomized, but the school was only surveyed from 2013 onwards. A wrong school, Makoba school in Makoba shehia, was surveyed instead in 2012. We keep Kiongwe school but not Makoba school in the primary analysis. Since no baseline data are available for Kiongwe, we only have 14 schools in the snail arm at baseline and 15 at follow-ups.

Island
Study arm

Issues and concerns related to MDA coverage: Pemba
• SBT was only introduced in 2013, in round 4. It was not conducted in 2014, round 5, due to a lack of funds. Subsequently, SBT was added to CWT in round 6, 7, 8, 9, and 10.
• In 2013, SBT round 4, behavior arm: no MoH SBT data were available from Shungi and Mchangamdodo, hence we show data from 13shehias only.
• In 2014, SBT round 6, snail arm: no MoH SBT data were available from Makanagale, hence we show data from 14 shehias only.
• In 2012, a national census was conducted. The annual growth factor is indicated at 2.8. Hence, we are able to calculate population numbers for the subsequent years.
• In 2012, in CWT round 1, it is not clear whether the population recorded by the CDDs is the total or eligible population. It is not differentiated by sex, adult or school-aged population.
• In 2012, in CWT round 2, it is mentioned that the total population is the total population in the households. It is not differentiated by sex, adult or school-aged population.
• In 2014, in CWT round 6, health posts instead of CDDs were implemented. No coverage was assessed.
• In all CWT rounds implemented from 2012-2017: o Tumbe shehia was split in Tumbe East and Tumbe West; MoH coverage data include both ( 16 shehias) o Msuka shehia was split in Msuka East and Msuka West; MoH coverage data include both ( 16 shehias) • General: Pujini shehia was split in Dodo and Kumvini; MoH coverage data were combined as Pujini.
• Post-MDA surveys were conducted within the SCORE parasitology surveys in 2014, 2015 and 2016, hence for round 4, 6 and 8.
• In 2014, in SBT round 4, schools in Chanjaani shehia have more children treated than children registered, hence the coverage is >100% (MoH data).
• In 2015, in SBT round 6, schools in Shungi and Kiwanie shehias have more children treated than children registered, hence the coverage is >100% (MoH data).
• In 2016, in CWT round 10, Kisiwani shehia has more people treated than total population, hence the coverage is >100% (MoH data).
• In 2016, SBT round 10, schools in Konde, Chambani, Kangani, Kiwani, Mtambile, Ngombeni, Ukutini shehias have more children treated than children registered (MoH data). • In 2012, in CWT round 1 and CWT round 2, it is not clear whether the population recorded by the CDDs is the total or eligible population. It is not differentiated by sex, adult or schoolaged population.
• In 2013, in CWT round 4, no data are recorded for Gamba shehia (MoH data).
• In 2015, in CWT round 7, Fujoni shehia has more people treated than total population, hence the coverage is >100% (MoH data).
• In 2016, in CWT round 10, Kama and Mwakaje shehias hav more people treated than total population.

Details on method of collecting demographic data, both islands
The Ministry of Health (MoH) data were collected in the frame of community wide treatment (CWT) by community drug distributors (CDDs). CDDs followed a door to door approach registering the people living in the households of their responsibility and recording the number of people they provided drugs with. The approach was not directly observed treatment (DOT). Summary data for each shehia were provided to the MoH. The MoH data were collected in the frame of school based treatment (SBT) by teachers, who recorded the number and sex of children registered in school and the number and sex of treated children. Summary data for each school were provided to the MoH. In 2012, a national census was conducted. The annual growth factor is indicated at 2.8. Hence, we are able to calculate population numbers for the subsequent years. The SCORE post-MDA surveys with questionnaires on drug compliance were conducted within the frame of the parasitology surveys, as described in the study protocol.

Listing of serious adverse events or harms, both islands:
• 2012, round 1: No single case of severe reaction, which needed hospitalization, was reported.
• 2012, round 2: No case of severe reaction, which needed hospitalization, was reported. Cases of nausea and vomiting were observed in some areas.
• 2013, round 3: No major adverse reactions were reported in any area. All reported cases were simple and most of them were due to nausea and vomiting and some few cases experienced body weakness.
• 2013, round 4: Two cases of severe reactions, which needed hospitalisation, were reported: one from each island. In Unguja, a girl of 13 years old developed body weakness and was hospitalised at Kivunge Hospital for six hours for IV fluid, then discharged, but remained weak and unable to walk without assistance for two weeks, then she recovered fully. Also a girl of 16 years from Pemba was hospitalised at Chake Chake Hospital and then referred to Mnazi Mmoja Hospital following severe swelling of both eye lids. The diagnosis at Mnazi Mmoja was Cavernous Thrombosis. The patient was referred to Muhimbili Hospital in Dar es Salaam, where the final diagnosis was a tumour.
• 2014, round 5: No major adverse reactions were reported in any area. All reported cases were simple and most of them were due to nausea and vomiting and some few cases experienced body weakness.
• 2014, round 6: No major adverse reactions were reported in any area. All reported cases were simple and most of them were due to nausea and vomiting and some few cases experienced body weakness.
• 2015, round 7: No case of severe reaction, which needed hospitalization, was reported. Cases of nausea and vomiting were observed in some areas.
• 2016, round 9: No major adverse reactions needing hospitalization were reported in any area. About 33 cases were reported, 13 in Pemba and 20 in Unguja, all with abdominal symptoms such as nausea, vomiting and some few cases experiencing body weakness.
• 2016, round 10: no case of severe reaction which needed hospitalization, was reported. However, cases of nausea and vomiting were common in most areas, especially among school children. The most fear observed reaction, which is a challenge to the programme and general population is the development of body weakness plus minus loss of consciousness. Three cases have been observed in Unguja and two in Pemba during this round.