Biology subjects

Pullan, R. L.

Publications and source records attributed to Pullan, R. L..

3 recordsLinked to original sources

bioRxiv2026

Determination of diagnostic cycle threshold (Ct) cut-offs for qPCR-based prevalence surveys of soil-transmitted helminth infections

WHO guidelines for control of soil-transmitted helminths (STH) rely on coproscopic methods to assess population prevalence. In low-prevalence and light-intensity STH settings, quantitative PCR (qPCR) has higher sensitivity and specificity for detection. For qPCR to accurately identify transmissible infections of public health significance, it is essential to interpret the qPCR cycle threshold (Ct) results. As part of the DeWorm3 community-based cluster randomized trial on interrupting STH transmission, we conducted population-based surveys using high-throughput qPCR and aimed to establish appropriate Ct cut-offs to detect transmissible infections. Experimental approaches including egg and genome-equivalent spiking experiments were hindered by inefficient fecal DNA extraction despite optimization efforts. The Ct results for 29,980 samples (pre-intervention, cross-sectional surveys) revealed a bimodal distribution for two of the four species tested, N. americanus and A. lumbricoides. The first peak was assumed to represent transmissible infections, and the second peak to represent indeterminate or non-transmissible infections. Using a finite mixture model, we defined true qPCR positivity as any Ct result with a [≥]5% chance of belonging to the first peak. This approach yielded Ct cut-offs of 34.4398 for N. americanus and 28.57587 for A. lumbricoides. For hookworms, sensitivity of qPCR was 96.7%, compared to 73.2% for Kato-Katz and moderate- to heavy-intensity infections (median Ct: 19.1, interquartile range [IQR]: 17.9-19.8) were differentiated from light-intensity infections and Kato-Katz negative samples (25.3, IQR: 22.5-27.9). Our findings demonstrate the feasibility and utility of evidence-based Ct cut-offs to identify transmissible STH infections in large scale surveys, and to categorize infection intensity as programmatically relevant. Author SummaryQuantitative PCR (qPCR) has been used for the detection of soil-transmitted helminths but with limited emphasis on determining cycle threshold (Ct) cut-offs to accurately identify transmissible infections which are of public health significance. When qPCR is used to assess interventions, or, in the future, to potentially make programmatic decisions, it will be crucial to validate positivity criteria to avoid underestimation (false negatives) or overestimation (false positives) of results. As part of the DeWorm3 trial, a community-based cluster randomized trial on interrupting transmission of STH, we developed and applied a validated STH qPCR to test 29,980 samples collected pre-intervention and explored experimental approaches to establish assay-specific Ct cut-offs. The Ct values from these samples showed a bimodal distribution for N. americanus and A. lumbricoides, suggesting the presence of two distinct groups. For this reason, a statistical approach with a finite mixture model was employed to determine Ct cut-offs that differentiated epidemiologically relevant, transmissible, egg-positive STH infections from those that are likely to represent detection of non-transmissible DNA or indeterminate results. While our data were applied in three different country settings, India, Benin and Malawi, it is important to note that no single Ct cut-off may be applicable across all epidemiological scenarios. Our findings demonstrate the feasibility of developing evidence-based Ct cut-offs with high sensitivity to accurately detect transmissible STH infections in large scale surveys.

microbiology↗

bioRxiv2020

Predicting the Environmental Suitability and Population at Risk of Podoconiosis in Africa

BackgroundPodoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa is uncertain. MethodsWe applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the suitability and human population at risk. ResultsIn Africa, environmental suitability for podoconiosis was predicted in 29 countries. By 2020, the total population in areas suitable for podoconiosis was estimated at 114.5 million people, (95% confidence interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units defined by WHO in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of IUs with high environmental suitability are located in Angola (80 IUs), Cameroon (170 IUs), the DRC (244 IUs), Ethiopia (495 IUs), Kenya (217 IUs), Uganda (116 IUs) and Tanzania (112 IUs). Of the 1,655 environmental suitable IUs, 960 (58.0%) require more detailed community-level mapping ConclusionsOur estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes.

ecology↗

bioRxiv2019

Domains of transmission and association of community, school, and household sanitation with soil-transmitted helminth infections among children in coastal Kenya

IntroductionFew studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) and estimated the association of sanitation in each domain with STH infection.\n\nMethodsUsing data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village, school, and household sanitation with STH infection.\n\nFindingsWe found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains.\n\nConclusionFindings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.\n\nAuthor SummaryInfection by whipworm and hookworm results from either ingestion of eggs or larvae or through skin exposure to larvae. These eggs and larvae develop in suitable soils contaminated with openly-deposited human faeces. Safe disposal of faeces should reduce transmission of these soil-transmitted helminths (STH), yet evidence of the impact of sanitation on STH transmission remains limited. We used data collected during a large, community-wide survey to measure prevalence of STH infections in coastal Kenya in 2015 to examine the relationship between sanitation conditions at home, school, and village and the presence of STH infection among 4,104 children who reported attending schools. We found that sanitation access at home and school sanitation coverage, but not the overall level of village sanitation coverage, was protective against hookworm infection. In contrast, only high village sanitation coverage, but not home or school sanitation, was protective against whipworm infection. Current STH control strategies emphasise periodic deworming through mass drug administration (MDA) of at-risk populations, including school-age children. Our findings highlight the need for continued efforts, alongside MDA, to extend access to good sanitation facilities at homes, schools, and across communities.

epidemiology↗