Impact of seven years of mass drug administration and recrudescence of Schistosoma haematobium infections after one year of treatment gap in Zanzibar: Repeated cross-sectional studies

Abstract

Background: Considerable progress towards the elimination of urogenital schistosomiasis was made by the Zanzibar Elimination of Schistosomiasis Transmission project from 2012 till 2016, when biannual praziquantel mass drug administration (MDA) alone or with additional snail control or behaviour change interventions were implemented. Annual MDA was continued in 2017 and 2018, but not in 2019, imposing a 16-month treatment gap. We monitored the Schistosoma haematobium prevalence from 2012 till 2020 and assessed recrudescence patterns with focus on 2020.

Methodology: Repeated cross-sectional surveys were conducted from 2011/12 till 2020 in 90 communities and 90 schools in Zanzibar. Annually, around 4,500 adults and up to 20,000 schoolchildren were surveyed. The S. haematobium prevalence was detected by urine filtration and reagent strips. In 2020, risk factors for infection were investigated using generalized estimated equation models.

Principal findings: In adults, the apparent S. haematobium prevalence was 3.9% in 2011 and 0.4% in 2020. In schoolchildren, the prevalence decreased from 6.6% in 2012 to 1.2% in 2019 with vicissitudes over the years. Prominent recrudescence of infection from 2.8% in 2019 to 9.1% (+225%) in 2020 was observed in 29 schools with historically moderate prevalences (≥10%). Compared with 2019, reinfection in 2020 was particularly striking in boys aged 9-16 years. Being male was a risk factor for infection in 2020 (adults: odds ratio (OR): 6.24, 95% confidence interval (95% CI): 1.96-19.60; schoolchildren: OR: 2.06, 95% CI: 1.52-2.78). Living near to a natural freshwater body significantly increased the odds of infection in adults (OR: 2.90, CI: 1.12-7.54).

Conclusions/significance: After 11 rounds of MDA over 7 years and a 16-month treatment gap, the urogenital schistosomiasis prevalence considerably rebounded in hotspot areas. Future elimination efforts in Zanzibar should focus on re-intensifying MDA plus additional interventions in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted surveillance-response.

Fig 1. Flowchart of study design.

Fig 2. Prevalence and intensity of S. haematobium infections, microhematuria levels, and implementation of MDAs in Zanzibar from 2011/12 until 2020.

The data show the S. haematobium prevalence and infection intensity, the levels of microhematuria, and implementation of MDA per annual quartile (Q). A: 20- to 55-year old adults; B: 9- to 12-year old schoolchildren. Blue: light intensity infection prevalence; red: heavy intensity infection prevalence. Very light brown: microhematuria graded trace; light brown: microhematuria graded 1; brown: microhematuria graded 2; dark brown: microhematuria graded 3. Dark green: community-wide treatment (CWT) only; dark and light green: community-wide (CWT) and school-based treatment (SBT).

Fig 3

Maps indicating prevalence of S. haematobium infections from 2011/12 till 2020 in spatial clusters in Pemba (A) and Unguja (B). Data are S. haematobium prevalence in 45 schools/shehias (clusters) per island, stratified by population group and island. A: Pemba; B: Unguja. Data are presented per year starting from 2011/12 (12 o`clock position) to 2020. Inner circle: 20- to 55-year old adults; outer circle: 9- to 12-year old schoolchildren. The colors show the prevalence from dark green as lowest prevalence to dark red as highest prevalence, and grey indicates missing. The * represents a hotspot school and/or community. Maps containing information about the spatial distribution of prevalence were created with R version 4.0.3. Coordinates of schools were collected with a handheld Garmin GPSMAP 62sc device (Garmin, Kansas City, USA). Shape files of shehias were provided by the Zanzibar Health Management Information System to the Neglected Diseases Program of the Zanzibar Ministry of Health.

Fig 4

Prevalence of S. haematobium infections stratified by infection intensity levels in Zanzibar from 2011/12 until 2020 per spatial cluster in Pemba (A) and Unguja (B). Data are proportion of S. haematobium infection intensity in schoolchildren and adults in each surveyed cluster on each island. A: Shehias and schools in Pemba; B: Shehias and schools in Unguja. X-axis: year of survey (2011/12 to 2020); y-axis: proportion infection intensity. Dark blue: heavy intensity infection among 20- to 55-year old adults; light blue: light intensity infection among 20- to 55-year old adults. Dark red: heavy intensity infection among 9- to 12-year old schoolchildren; light red: light intensity infection among 9- to 12-year old schoolchildren.

Fig 5

S. haematobium prevalence across all ages, stratified by sex, after 11 rounds of MDA in 2019 (A) and a 16-month treatment gap in 2020 (B). The blue (male) and red (female) dots in the upper part (pos) of each figure, each represent a S. haematobium-positive urine sample from an individual of a certain age (x-axis). The blue (male) and red (female) dots in the lower part (neg) of each figure, each represent a S. haematobium-negative urine sample prom an individual of a certain age (x-axis). The blue (male) and red (female) lines in the middle part of each figure represent the predicted S. haematobium age-prevalence. The shading around the lines represent 95% confidence bands.

Fig 6

Multivariable analysis of risk factors for S. haematobium infections in adults (A) and schoolchildren (B) in Zanzibar in 2020. The figure shows the odds ratios for a S. haematobium infection adjusted for different risk factors. Grey dots indicate the reference categories. N: total number of participants analyzed per group; Prev [%]: S. haematobium prevalence per group.