Progress in controlling the transmission of schistosome parasites in Southern Ethiopia: the Geshiyaro Project in the Wolaita Zone.

BACKGROUND: This paper describes changes in the prevalence and intensity of schistosome parasite infections in a project integrating mass drug administration (MDA), water, sanitation, and hygiene (WaSH), and behavioral change interventions. METHODS: The Geshiyaro Project comprises three intervention arms. Arm 1 is subdivided into "Arm 1 pilot" (one district) and Arm 1 (four other districts), both receiving integrated community-wide MDA with intensive WaSH interventions. Arm 2 involves 17 districts with community-wide MDA interventions, while Arm 3 serves as a control with school-based MDA interventions in three districts. A total of 150 individuals, stratified by age group, were randomly selected from each of the 45 sentinel sites. Arm sizes were 584 (Arm 1 pilot), 1636 (Arm 1), 2203 (Arm 2), and 2238 (Arm 3). Statistical tests were employed to compare infection prevalence and intensity across the different arms. RESULTS: The prevalence of schistosome parasite infection ranged from 0% to 2.6% and from 1.7% to 25.7% across districts, employing the Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) diagnostics, respectively. The mean infection intensity level showed no marked difference between baseline and follow-up surveys when measured by KK, except in Arm 2 (t = 6.89, P < 0.0001). Infection prevalence decreased significantly in Arm 1 (t = 8.62, P < 0.0001), Arm 2 (t = 6.94, P < 0.0001), and Arm 3 (t = 8.83, P < 0.0001), but not in Arm 1 pilot (t = 1.69, P = 0.09) by POC-CCA, when trace was considered positive. The decrease was significant only in Arm 1 (t = 3.28, P = 0.0001) and Arm 2 (t = 7.62, P < 0.0001) when the trace was considered negative in POC-CCA. Arm 2 demonstrated a significant difference in difference (DID) compared to the control group, Arm 3, regardless of whether trace in POC-CCA was considered positive (DID = 3.9%, df = 8780, P = 0.025) or negative (DID = -5.2, df = 8780, P = 0.0004). CONCLUSIONS: The prevalence of schistosomiasis was low when employing the KK diagnostic but moderate in some locations by the POC-CCA diagnostic. The infection level had decreased across all arms of the Geshiyaro study at mid-term of the 7-year project, but further efforts are needed to reduce the rate of parasite transmission based on the POC-CCA diagnostic scores.

Spatial heterogeneity in mass drug administration from a longitudinal epidemiological study assessing transmission interruption of soil transmitted helminths in the Wolaita zone of southern Ethiopia (Geshiyaro Project).

OBJECTIVES: Deworming programmes of soil-transmitted helminths are generally monitored and evaluated by aggregating drug coverage and infection levels at a district level. However, heterogeneity in drug coverage at finer spatial scales means indicators may remain above thresholds for elimination as a public health problem or of transmission in some areas. This paper aims to highlight the misleading information that aggregating data at larger spatial scales can have for programme decision making. METHODS: Drug coverage data from the Geshiyaro project were compared at two spatial scales with reference to the World Health Organisation's targets. District (woreda) and village (kebele) level were compared. The association between infection levels and drug coverage was analysed by fitting a weighted least-squares function to the mean intensity of infection (eggs per gram of faeces) against drug coverage. RESULTS: The data show clearly that when the evaluation of coverage is aggregated to the district level, information on heterogeneity at a finer spatial scale is lost. Infection intensity decreases significantly (p = 0.0023) with increasing drug coverage. CONCLUSION: Aggregating data at large spatial scales can result in prematurely ceasing deworming, prompting rapid infection bounce-back. There is a strong need to define context-specific spatial scales for monitoring and evaluating intervention programmes.

Measuring heterogeneities in soil-transmitted helminth transmission and control.

The global effort over the past decade to control soil-transmitted helminths (STH) has resulted in communities with endemic infection reaching low prevalence levels suitable for the validation of elimination as a public health problem (EPHP), defined by the World Health Organisation (WHO) as <2% of infections classified as moderate or heavy intensity. The spatial scale in which this is validated is currently undefined. As the burden of STH infection decreases, the degree of aggregation of infection within individuals in a population increases. Identifying these remaining pockets of infection requires fine-scale monitoring and evaluation (M&E) programmes that are rarely implemented within current national neglected tropical disease (NTD) control. This review examines various heterogeneities that characterise the epidemiology of STH infections, and discusses their impact on control policy formulation.

Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.

BACKGROUND: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. METHODS: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. RESULTS: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). CONCLUSIONS: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.

Individual longitudinal compliance to neglected tropical disease mass drug administration programmes, a systematic review.

Repeated distribution of preventative chemotherapy (PC) by mass drug administration forms the mainstay of transmission control for five of the 20 recognised neglected tropical diseases (NTDs); soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. The efficiency of such programmes is reliant upon participants swallowing the offered treatment consistently at each round. This is measured by compliance, defined as the proportion of eligible participants swallowing treatment. Individually linked longitudinal compliance data is important for assessing the potential impact of MDA-based control programmes, yet this accurate monitoring is rarely implemented in those for NTDs. Longitudinal compliance data reported by control programmes globally for the five (PC)-NTDs since 2016 is examined, focusing on key associations of compliance with age and gender. PubMed and Web of Science was searched in January 2022 for articles written in English and Spanish, and the subsequent extraction adhered to PRISMA guidelines. Study title screening was aided by Rayyan, a machine learning software package. Studies were considered for inclusion if primary compliance data was recorded for more than one time point, in a population larger than 100 participants. All data analysis was conducted in R. A total of 89 studies were identified containing compliance data, 57 were longitudinal studies, of which 25 reported individually linked data reported by varying methods. The association of increasing age with the degree of systematic treatment was commonly reported. The review is limited by the paucity of data published on this topic. The varying and overlapping terminologies used to describe coverage (receiving treatment) and compliance (swallowing treatment) is reviewed. Consequently, it is recommended that WHO considers clearly defining the terms for coverage, compliance, and longitudinal compliance which are currently contradictory across their NTD treatment guidelines. This review is registered with PROSPERO (number: CRD42022301991).

Predisposition to soil-transmitted helminth reinfection after four rounds of mass drug administration: results from a longitudinal cohort in the Geshiyaro project, a transmission elimination feasibility study in the Wolaita zone of southern Ethiopia.

BACKGROUND: Current WHO strategies for reaching soil-transmitted helminths (STH) elimination as a public health problem excludes treating certain adult populations in endemic areas, creating infection reservoirs that drive 'bounce back' of STH infection to pretreatment levels post-mass drug administration (MDA). Predisposition is a widespread, but poorly understood phenomena among helminth infections where individuals are predisposed to reinfection after repeated treatments. METHODS: This analysis uses Geshiyaro project data, an STH control programme exploring transmission interruption by community-wide MDA and enhanced water, sanitation and hygiene during 2019-2023. Parasitological survey data from longitudinal cohorts are analysed using Kendall's Tau-b rank correlation to assess the evidence for predisposition to light or heavy infection between four consecutive rounds of MDA. RESULTS: Correlation analyses revealed the strongest evidence for predisposition to heavy or light Ascaris lumbricoides infection was between survey 1 and 2 (Tau-b 0.29; p<0.001). Overall patterns were not observed for Trichuris trichiura or hookworm infections, however, some significant and notable correlations were recorded for some stratifications and time points. CONCLUSIONS: Evidence for predisposition in endemic settings in southern Ethiopia with low STH prevalence suggests that more targeted approaches to MDA in those predisposed to infection may be a sensible control strategy if cheap, point of care diagnostics are available.

Association between water, sanitation, and hygiene access and the prevalence of soil-transmitted helminth and schistosome infections in Wolayita, Ethiopia.

BACKGROUND: The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing infection with soil-transmitted helminths (STH) and schistosome parasites in combination with deworming in Wolayita zone, Ethiopia. METHODS: A population-based, cross-sectional census and parasitological mapping activity was conducted between 2018 and 2019. Individuals in the census were identified using either a registered study ID card or biometric fingerprint to enable linkage of their household WaSH data with baseline STH and schistosome prevalence for risk analysis. RESULTS: Prevalence of STH was 15.5% for any STH species, 9.47% for Ascaris lumbricoides, 1.78% for Trichuris trichiura, and 7.24% for hookworm. Intestinal schistosomiasis (Schistosoma mansoni) infection prevalence was 0.85% by Kato Katz, 21.6% by POC-CCA trace positive (Tr +), and 13.3% trace negative (Tr-). Microhaematuria was 2.77%, with 0.13% of people examined with S. haematobium eggs detected by urine filtration. At the household level, increased (> 30 min) time taken to collect drinking water, sharing a latrine, and lack of handwashing facilities were all associated with a greater risk of A. lumbricoides, hookworm, and S. mansoni infection. Not disposing of infant stool at the household and clothes washing/recreational freshwater contact were significantly associated with higher risk of schistosomiasis infection. Aggregating WaSH data at the community level showed odds of A. lumbricoides, hookworm, and T. trichiura infection were significantly lower as both community sanitation coverage and access to improved drinking water improved. CONCLUSIONS: The principal finding of this study is that lack of access to WaSH, such as improved drinking water and shared toilet and hand-washing facilities, were linked to an increased risk of infection with STH and schistosome parasites. These associations are difficult to establish at an individual household level because of wide variability in access between houses but are detectable when coverage is aggregated at the community level. Maintenance of WaSH facilities as well as increased access within the whole community is important in influencing the community-wide prevalence of infection with STH and schistosome parasites.

Longitudinal monitoring of prevalence and intensity of soil-transmitted helminth infections as part of community-wide mass drug administration within the Geshiyaro project in the Bolosso Sore district, Wolaita, Ethiopia.

Mass drug administration (MDA), targeted at school-aged children (SAC) is recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds, and research suggests that only treating SAC will not be sufficient to interrupt transmission of STH. In countries with endemic infection, such as Ethiopia, the coverage, community-groups targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. In this paper, individually-linked longitudinal data from three epidemiological STH surveys conducted between November 2018 and November 2020 in the Wolaita region of Ethiopia are analysed to determine how STH prevalence and intensity changes according to individual level treatment data collected over two rounds of MDA. This study demonstrates that while community-wide MDA successfully reduces overall infection intensity across the villages treated, the observed levels of non-compliance to treatment by individuals acts to maintain levels of parasite abundance whereby transmission interruption is not possible at to, despite reasonable levels of MDA coverage in the communities studied (ranging from 65% to 84% of the village populations). This quantifies with substantial data the often-postulated difference between coverage (accepting treatment) and compliance (swallowing of treatment), the latter impacting the former to a previously unquantified level. The paper highlights the need to focus treatment to partially treated, or never treated groups of individuals within existing community wide MDA control activities to interrupt the transmission of STH, and to reduce the basic reproductive number, R0, of the parasites to less than unity in value.

Comparing the accuracy of two diagnostic methods for detection of light Schistosoma haematobium infection in an elimination setting in Wolaita Zone, South Western Ethiopia.

Reagent urinalysis dipstick and filtration have been recommended diagnostic methods for the detection of urogenital schistosomiasis. However, the accurate diagnosis of light infections using these methods presents a major challenge. This study evaluates the diagnosis accuracy of light infection with Schistosoma haematobium in study participants living in Wolaita Zone, an area targeted for sustainable control of Schistosomiasis, and ultimately interrupt transmission. Urine samples were collected from children and adults in surveys carried out during baseline and longitudinal sentinel site surveys conducted from 2018 to 2020. All urine samples were tested using a reagent urinalysis dipstick test (Haemastix) to detect microhaematuria with reference urine filtration technique as a proxy for S. haematobium infection. Sensitivity and specificity were determined in diagnosing urogenital schistosomiasis. Cohen's Kappa statistics was done for the agreement of these diagnostic methods. A total of 12,102 participants were enrolled in the current baseline study. Among them, 285 (2.35%) samples tested positive for microhaematuria and 21 (0.20%) positive for S. haematobium eggs. A total of 4,357 samples were examined in year 1 and year 2 using urine dipsticks, and urine filtration 172 (3.95%) and 2 (0.05%) were positive for microhaematuria and S. haematobium eggs. The reagent urinalysis dipsticks showed the highest sensitivity and specificity for diagnosing light intensity of infection,100% (95% CI:85.18-100.00) and 97.4% (95% CI: 97.10-97.60), respectively. There is a slight agreement between the two methods (Kappa = 0.09, 95% CI: 0.01-0.18). The present study revealed very low prevalence and light intensity of S. haematobium infections. The study also highlights that the dipstick test is considered a useful adjunct diagnostic tool for population-based control of urogenital schistosomiasis.

Genome-wide insights into adaptive hybridisation across the Schistosoma haematobium group in West and Central Africa.

Schistosomiasis remains a public health concern across sub-Saharan Africa; current control programmes rely on accurate mapping and high mass drug administration (MDA) coverage to attempt disease elimination. Inter-species hybridisation can occur between certain species, changing epidemiological dynamics within endemic regions, which has the potential to confound control interventions. The impact of hybridisation on disease dynamics is well illustrated in areas of Cameroon where urogenital schistosomiasis, primarily due to Schistosoma haematobium and hybrid infections, now predominate over intestinal schistosomiasis caused by Schistosoma guineensis. Genetic markers have shown the ability to identify hybrids, however the underlying genomic architecture of divergence and introgression between these species has yet to be established. In this study, restriction site associated DNA sequencing (RADseq) was used on archived adult worms initially identified as; Schistosoma bovis (n = 4), S. haematobium (n = 9), S. guineensis (n = 3) and S. guineensis x S. haematobium hybrids (n = 4) from Mali, Senegal, Niger, São Tomé and Cameroon. Genome-wide evidence supports the existence of S. guineensis and S. haematobium hybrid populations across Cameroon. The hybridisation of S. guineensis x S. haematobium has not been demonstrated on the island of São Tomé, where all samples showed no introgression with S. haematobium. Additionally, all S. haematobium isolates from Nigeria, Mali and Cameroon indicated signatures of genomic introgression from S. bovis. Adaptive loci across the S. haematobium group showed that voltage-gated calcium ion channels (Cav) could play a key role in the ability to increase the survivability of species, particularly in host systems. Where admixture has occurred between S. guineensis and S. haematobium, the excess introgressive influx of tegumental (outer helminth body) and antigenic genes from S. haematobium has increased the adaptive response in hybrids, leading to increased hybrid population fitness and viability.

The SARS-CoV-2 pandemic: remaining uncertainties in our understanding of the epidemiology and transmission dynamics of the virus, and challenges to be overcome.

Great progress has been made over the past 18 months in scientific understanding of the biology, epidemiology and pathogenesis of SARS-CoV-2. Extraordinary advances have been made in vaccine development and the execution of clinical trials of possible therapies. However, uncertainties remain, and this review assesses these in the context of virus transmission, epidemiology, control by social distancing measures and mass vaccination and the effect on all of these on emerging variants. We briefly review the current state of the global pandemic, focussing on what is, and what is not, well understood about the parameters that control viral transmission and make up the constituent parts of the basic reproductive number R 0. Major areas of uncertainty include factors predisposing to asymptomatic infection, the population fraction that is asymptomatic, the infectiousness of asymptomatic compared to symptomatic individuals, the contribution of viral transmission of such individuals and what variables influence this. The duration of immunity post infection and post vaccination is also currently unknown, as is the phenotypic consequences of continual viral evolution and the emergence of many viral variants not just in one location, but globally, given the high connectivity between populations in the modern world. The pattern of spread of new variants is also examined. We review what can be learnt from contact tracing, household studies and whole-genome sequencing, regarding where people acquire infection, and how households are seeded with infection since they constitute a major location for viral transmission. We conclude by discussing the challenges to attaining herd immunity, given the uncertainty in the duration of vaccine-mediated immunity, the threat of continued evolution of the virus as demonstrated by the emergence and rapid spread of the Delta variant, and the logistics of vaccine manufacturing and delivery to achieve universal coverage worldwide. Significantly more support from higher income countries (HIC) is required in low- and middle-income countries over the coming year to ensure the creation of community-wide protection by mass vaccination is a global target, not one just for HIC. Unvaccinated populations create opportunities for viral evolution since the net rate of evolution is directly proportional to the number of cases occurring per unit of time. The unit for assessing success in achieving herd immunity is not any individual country, but the world.

Coverage evaluation surveys following soil-transmitted helminthiasis and schistosomiasis mass drug administration in Wolaita Zone of Ethiopia-The Geshiyaro project.

INTRODUCTION: The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. METHODS: A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. RESULTS: The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9-82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). CONCLUSION: Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.

Soil-transmitted helminths and schistosome infections in Ethiopia: a systematic review of progress in their control over the past 20 years.

BACKGROUND: Ethiopia has set the ambitious national targets of eliminating soil-transmitted helminths (STH) and schistosomiasis (SCH) as public health problems by 2020, and breaking their transmission by 2025. This systematic review was performed to provide insight into the progress made by the national STH and SCH control programme purposed with reaching these targets. METHODS: Studies published on STH and SCH in Ethiopia were searched for using Web of Science, PubMed, Scopus, and the resulting references of selected studies. Prevalence and intensity were analysed, stratified by region, age, and diagnostics. RESULTS: A total of 231 papers published between 2000 and 2020 were included. Over the past two decades, Trichuris trichiura (TT) infection has shown the most statistically significant decrease (93%, p < 0.0001), followed by Schistosoma mansoni (SM) (69%, p < 0.0001), Ascaris lumbricoides (AL) (67%, p < 0.0001) and Schistosoma haematobium (83%, p = 0.038) infections. Geographically, parasite burden has only consistently shown a significant reduction in the Southern Nations, Nationalities and Peoples' Region of Ethiopia, where AL, TT, hookworm and SM significantly decreased by 80% (p = 0.006), 95% (p = 0.005), 98% (p = 0.009) and 87% (p = 0.031), respectively. Prevalence of STH was highest among adults across all species, contrary to typical age-infection profiles for TT and AL that peak among school-aged children. Expanding treatment to the whole community would target reservoirs of adult and preschool-aged infection within the community, assisting Ethiopia in reaching their national transmission break targets. There was substantial heterogeneity in diagnostic methods used across studies, the majority of which predominantly used single-slide Kato-Katz. This low slide frequency provides poor diagnostic sensitivity, particularly in low endemic settings. CONCLUSION: The prevalence of STH and SCH in Ethiopia has decreased over time due to the strategic use of anthelmintics. Both standardising and increasing the sensitivity of the diagnostics used, alongside the ubiquitous use of parasite intensity with prevalence, would enable a more accurate and comparable understanding of Ethiopia's epidemiological progress. Further work is needed on community-wide surveillance in order to understand the burden and subsequent need for treatment among those outside of the standard school-based control program.