Effects of water, sanitation, handwashing and nutritional interventions on soil-transmitted helminth infections in young children: A cluster-randomized controlled trial in rural Bangladesh

Ercümen, Ayşe; Benjamin‐Chung, Jade; Arnold, Benjamin F.; Lin, Audrie; Hubbard, Alan; Stewart, Christine P; Rahman, Zahidur; Parvez, Sarker Masud; Unicomb, Leanne; Rahman, Mahbubur; Haque, Rashidul; Colford, John M.; Luby, Stephen P.

doi:10.1371/journal.pntd.0007323

Cited by 58 publications

(79 citation statements)

References 55 publications

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“…Our results further support the recommendation that qPCR be considered the new gold standard STH diagnostic (22). Importantly, using qPCR instead of Kato-Katz in intervention trials can also reduce misclassification and bias of intervention effect estimates (53). Taken together, our findings underscore that molecular methods of detecting STH infection are more appropriate than copromicroscopic methods in settings with predominantly low infection intensity or with a goal to interrupt STH transmission.…”

Section: Resultssupporting

confidence: 76%

“…For quality assurance, 10% of slides were evaluated independently by two technicians, and 5% were evaluated by an experienced parasitologist. The quality assurance results have previously been published elsewhere (28). In brief, agreement between laboratory technicians was high (Kappa statistic > 0.99 for each STH).…”

Section: Kato-katz Proceduresmentioning

confidence: 72%

“…These unexpected findings call into question the common assumption that Kato-Katz yields few false positives (16,22,46,47). The quality control assessment found minimal misclassification of A. lumbricoides between laboratory technicians and expert parasitologists (53), suggesting that Kato-Katz was performed with typical quality. Yet, experimental testing with two qPCR assays utilizing independent targets as well as sequencing analysis of a subset of samples confirmed that samples classified as A. lumbricoides negative by qPCR indeed contained no genomic targets for A. lumbricoides.…”

Section: Discussionmentioning

confidence: 98%

“…The trial delivered interventions to improve water, sanitation, handwashing, and nutrition and included single and combined intervention arms. Full details of interventions and user adherence have been published elsewhere (27,28). This study randomly selected 2,800 stool specimens collected from children aged 22 months to 12 years of age (mean = 57 months) enrolled in the individual improved water, sanitation, handwashing, and combined water+sanitation+handwashing (WSH) arms.…”

Section: Study Populationmentioning

confidence: 99%

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Comparison of multi-parallel qPCR and Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

Benjamin‐Chung

Pilotte

Ercümen

et al. 2019

Preprint

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An active area of research investigates whether soil-transmitted helminths (STH) can be locally eliminated in endemic settings. In such settings, highly sensitive diagnostics are needed to detect STH infection. We compared double-slide Kato-Katz, the most commonly used copromicroscopic detection method, to multi-parallel quantitative polymerase chain reaction (qPCR) in 2,800 stool samples from children 2-12 years in rural Bangladesh. We estimated the sensitivity and specificity of each diagnostic using Bayesian latent class analysis. Compared to Kato-Katz, STH prevalence using qPCR was almost 3-fold higher for hookworm species and nearly 2-fold higher for Trichuris trichiura. Ascaris lumbricoides prevalence was lower using qPCR, and 26% of samples classified as A. lumbricoides positive by Kato-Katz were negative by qPCR. Amplicon sequencing of the 18S rDNA from 10 samples confirmed that A. lumbricoides was absent in samples classified as positive by Kato-Katz and negative by qPCR. The sensitivity of Kato-Katz was 49% for A. lumbricoides, 32% for hookworm, and 52% for T. trichiura; the sensitivity of qPCR was 79% for A. lumbricoides, 93% for hookworm, and 90% for T. trichiura. Specificity was ³ 97% for both tests for all STH except for Kato-Katz for A. lumbricoides (specificity = 68%). There were moderate negative, monotonic correlations between qPCR cycle quantification values and eggs per gram quantified by Kato-Katz. While it is widely assumed that Kato-Katz has few false positives, our results indicate otherwise. Our findings suggest that qPCR is more appropriate than Kato-Katz in low intensity infection settings because of its higher sensitivity and specificity. Author summarySoil-transmitted helminth infections (STH) (e.g., Ascaris, hookworm, Trichuris) contribute to a large burden of disease among children in low-and middle-income countries. There is increasing interest in implementing large-scale deworming programs to eliminate STH in certain settings. Efforts to monitor whether local elimination has occurred require sensitive diagnostic tests that will not miss positive cases. Kato-Katz, a microscopy-based diagnostic test, has commonly been used to identify STH eggs in stool, but in settings where infection intensity is low, this method frequently misses positive samples because it requires visual identification of small numbers of eggs, and eggs may degrade prior to visualization. Quantitative polymerase chain reaction (qPCR) is a molecular diagnostic method that may miss fewer infections because it identifies STH DNA in stool, which can be detected in very small quantities and is less likely to degrade. This study compared the performance of Kato-Katz and qPCR using 2,800 stool samples from children aged 2-12 years in rural Bangladesh. qPCR detected substantially more hookworm and Trichuris infections than Kato-Katz. 26% of samples were classified as Ascaris positive by Kato-Katz and negative by qPCR. We conclude that qPCR is a more appropriate diagnostic method than Kato-Katz in low infection intensity...

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Section: Resultssupporting

confidence: 76%

Section: Kato-katz Proceduresmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Study Populationmentioning

confidence: 99%

See 2 more Smart Citations

Comparison of multi-parallel qPCR and Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

Benjamin‐Chung

Pilotte

Ercümen

et al. 2019

Preprint

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“…Another panel of 150 samples of human stool extracts, variously infected with the same species of STH (at least 500 mg of stool), was prepared at SC and was shipped to the Natural History Museum (NHM; London, UK). All samples utilized during phase II of this study were collected in Bangladesh as part of the WASH Benefits Bangladesh trial [31]. All samples were previously screened at SC via real-time PCR and the results for each individual sample were available.…”

Section: Phase Ii: Field-samples Experiment-sc and Natural History Mumentioning

confidence: 99%

Pooling as a strategy for the timely diagnosis of soil-transmitted helminths in stool: value and reproducibility

et al. 2019

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Background: The strategy of pooling stool specimens has been extensively used in the field of parasitology in order to facilitate the screening of large numbers of samples whilst minimizing the prohibitive cost of single sample analysis. The aim of this study was to develop a standardized reproducible pooling protocol for stool samples, validated between two different laboratories, without jeopardizing the sensitivity of the quantitative polymerase chain reaction (qPCR) assays employed for the detection of soil-transmitted helminths (STHs). Two distinct experimental phases were recruited. First, the sensitivity and specificity of the established protocol was assessed by real-time PCR for each one of the STHs. Secondly, agreement and reproducibility of the protocol between the two different laboratories were tested. The need for multiple stool sampling to avoid false negative results was also assessed. Finally, a cost exercise was conducted which included labour cost in low-and high-wage settings, consumable cost, prevalence of a single STH species, and a simple distribution pattern of the positive samples in pools to estimate time and money savings suggested by the strategy. Results: The sensitivity of the pooling method was variable among the STH species but consistent between the two laboratories. Estimates of specificity indicate a 'pooling approach' can yield a low frequency of 'missed' infections. There were no significant differences regarding the execution of the protocol and the subsequent STH detection between the two laboratories, which suggests in most cases the protocol is reproducible by adequately trained staff. Finally, given the high degree of agreement, there appears to be little or no need for multiple sampling of either individuals or pools. Conclusions: Our results suggest that the pooling protocol developed herein is a robust and efficient strategy for the detection of STHs in 'pools-of-five'. There is notable complexity of the pool preparation to ensure even distribution of helminth DNA throughout. Therefore, at a given setting, cost of labour among other logistical and epidemiological factors, is the more concerning and determining factor when choosing pooling strategies, rather than losing sensitivity and/or specificity of the molecular assay or the method.

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Interventions to improve water, sanitation, and hygiene for preventing soil-transmitted helminth infection

Garn

Wilkers

Meehan

et al. 2022

Cochrane Database of Systematic Reviews

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Background It is estimated that 1.5 billion people are infected with soil‐transmitted helminths (STHs) worldwide. Re‐infection occurs rapidly following deworming, and interruption of transmission is unlikely without complementary control efforts such as improvements in water, sanitation, and hygiene (WASH) access and behaviours. Objectives To assess the effectiveness of WASH interventions to prevent STH infection. Search methods We used standard, extensive Cochrane search methods. The latest search date was 19 October 2021. Selection criteria We included interventions to improve WASH access or practices in communities where STHs are endemic. We included randomized controlled trials (RCTs), as well as trials with an external control group where participants (or clusters) were allocated to different interventions using a non‐random method (non‐RCTs). We did not include observational study designs. Our primary outcome was prevalence of any STH infection. Prevalence of individual worms was a secondary outcome, including for Ascaris lumbricoides , Trichuris trichiura , hookworm ( Ancylostoma duodenale or Necator americanus ), or Strongyloides stercoralis . Intensity of infection, measured as a count of eggs per gram of faeces for each species, was another secondary outcome. Data collection and analysis Two review authors independently reviewed titles and abstracts and full‐text records for eligibility, performed data extraction, and assessed risk of bias using the Cochrane risk of bias assessment tool for RCTs and the EPOC tool for non‐RCTs. We used a random‐effects meta‐analysis to pool study estimates. We used Moran’s I² statistic to assess heterogeneity and conducted subgroup analyses to explore sources of heterogeneity. We assessed the certainty of the evidence using the GRADE approach. Main results We included 32 studies (16 RCTs and 16 non‐RCTs) involving a total of 52,944 participants in the review. Twenty‐two studies (14 RCTs (16 estimates) and eight non‐RCTs (11 estimates)) reported on our primary outcome, prevalence of infection with at least one STH species. Twenty‐one studies reported on the prevalence of A lumbricoides (12 RCTs and 9 non‐RCTs); 17 on the prevalence of T trichiura (9 RCTs and 8 non‐RCTs); 18 on the prevalence of hookworm (10 RCTs and 8 non‐RCTs); and one on the prevalence of S stercoralis (1 non‐RCT). Sixteen studies measured the intensity of infection for an individual STH type. Ten RCTs and five non‐RCTs reported on the intensity of infection of A lumbricoides ; eight RCTs and five non‐RCTs measured the intensity of infection of T trichiura ; an...

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Effects of water, sanitation, handwashing and nutritional interventions on soil-transmitted helminth infections in young children: A cluster-randomized controlled trial in rural Bangladesh

Cited by 58 publications

References 55 publications

Comparison of multi-parallel qPCR and Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

Comparison of multi-parallel qPCR and Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

Pooling as a strategy for the timely diagnosis of soil-transmitted helminths in stool: value and reproducibility

Interventions to improve water, sanitation, and hygiene for preventing soil-transmitted helminth infection

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