The increased sensitivity of qPCR in comparison to Kato-Katz is required for the accurate assessment of the prevalence of soil-transmitted helminth infection in settings that have received multiple rounds of mass drug administration

Dunn, Julia C.; Papaiakovou, Marina; Han, Kay Thwe; Chooneea, Darren; Bettis, Alison A.; Wyine, Nay Yee; Lwin, Aye Moe Moe; Maung, Nay Soe; Misra, Raju; Littlewood, D. Tim J.; Anderson, Roy M.

doi:10.1186/s13071-020-04197-w

Cited by 35 publications

(49 citation statements)

References 41 publications

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“…We found that qPCR results indicate higher sensitivity for all species across all examination days compared to Kato-Katz, which substantiates previous findings [17,27,30,34,[44][45][46]. Interestingly, follow-up Kato-Katz results differ significantly compared to the baseline results in the case of A. lumbricoides, indicating a time-dependent difference.…”

Section: Discussionsupporting

confidence: 89%

Performance of the Kato-Katz method and real time polymerase chain reaction for the diagnosis of soil-transmitted helminthiasis in the framework of a randomised controlled trial: treatment efficacy and day-to-day variation

et al. 2020

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Background Accurate, scalable and sensitive diagnostic tools are crucial in determining prevalence of soil-transmitted helminths (STH), assessing infection intensities and monitoring treatment efficacy. However, assessments on treatment efficacy comparing traditional microscopic to newly emerging molecular approaches such as quantitative Polymerase Chain Reaction (qPCR) are scarce and hampered partly by lack of an established diagnostic gold standard. Methods We compared the performance of the copromicroscopic Kato-Katz method to qPCR in the framework of a randomized controlled trial on Pemba Island, Tanzania, evaluating treatment efficacy based on cure rates of albendazole monotherapy versus ivermectin-albendazole against Trichuris trichiura and concomitant STH infections. Day-to-day variability of both diagnostic methods was assessed to elucidate reproducibility of test results by analysing two stool samples before and two stool samples after treatment of 160 T. trichiura Kato-Katz positive participants, partially co-infected with Ascaris lumbricoides and hookworm, per treatment arm (n = 320). As negative controls, two faecal samples of 180 Kato-Katz helminth negative participants were analysed. Results Fair to moderate correlation between microscopic egg count and DNA copy number for the different STH species was observed at baseline and follow-up. Results indicated higher sensitivity of qPCR for all three STH species across all time points; however, we found lower test result reproducibility compared to Kato-Katz. When assessed with two samples from consecutive days by qPCR, cure rates were significantly lower for T. trichiura (23.2 vs 46.8%), A. lumbricoides (75.3 vs 100%) and hookworm (52.4 vs 78.3%) in the ivermectin-albendazole treatment arm, when compared to Kato-Katz. Conclusions qPCR diagnosis showed lower reproducibility of test results compared to Kato-Katz, hence multiple samples per participant should be analysed to achieve a reliable diagnosis of STH infection. Our study confirms that cure rates are overestimated using Kato-Katz alone. Our findings emphasize that standardized and accurate molecular diagnostic tools are urgently needed for future monitoring within STH control and/or elimination programmes.

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Section: Discussionsupporting

confidence: 89%

Performance of the Kato-Katz method and real time polymerase chain reaction for the diagnosis of soil-transmitted helminthiasis in the framework of a randomised controlled trial: treatment efficacy and day-to-day variation

et al. 2020

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“…This is the case of people living in communities that have received multiple treatments within MDA, during post-MDA surveillance, or when large worm burden in the host results in a decreased production of eggs. [41] , [42] , [43] Therefore, qPCR should be used instead of conventional coproscopic techniques to better estimate the distribution and intensity of STH infections in endemic areas and to monitor the effectiveness of deworming programs. This holds true for hookworms, but not for other STHs, for the tendency of their eggs to collapse and disappear when using conventional techniques, such as the Kato Katz thick smear.…”

Section: Discussionmentioning

confidence: 99%

Risk profiling and efficacy of albendazole against the hookworms Necator americanus and Ancylostoma ceylanicum in Cambodia to support control programs in Southeast Asia and the Western Pacific

Colella

Khieu

Worsley

et al. 2021

The Lancet Regional Health - Western Pacific

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Background: Hookworm disease is endemic throughout many parts of the Asia Pacific, despite targeted control programs of at-risk populations. The success of these programs has been hindered by the limited efficacy of widely-used mebendazole, rapid re-infection rates linked to persistent reservoirs of untreated people and dogs, and the low sensitivity of conventional coprodiagnostic techniques employed. Methods: Here, we used standard faecal flotation (SFF) and a multiplex qPCR (mqPCR) assay to calculate and compare species-specific cure and egg reduction rates of single dose albendazole (400 mg) against hookworm infections at community level. Data from a cross-sectional survey in 1,232 people from Cambodia were used to inform a generalised linear mixed model to identify risk factors linked to hookworm infection(s) at baseline. Furthermore, we calculated risk factors associated to the probability of being cured after albendazole administration. Findings: Overall, 13·5% of all 1,232 people tested by SFF were positive for hookworm infection(s). Most (80·1%) infected people were >12 years of age, hence above the age targeted by the WHO control program. We estimate that as age increases, the odds of being infected increases at a faster rate for females than for males. We revealed a substantial difference in cure rate of hookworm infection(s) following albendazole treatment using the SFF (81·5%) and mqPCR (46·4%) assays, and provide the first data on the efficacy of this drug against the zoonotic hookworm Ancylostoma ceylanicum . We estimated that as age increases by one year, the odds of being cured decreases by 0·4%–3·7%. Similarly, the odds of being cured for people who boiled drinking water was estimated to be between 1·02 and 6·82. Interpretation: These findings show that the adoption of refined diagnostic techniques is central to monitoring hookworm infection(s) and the success of control strategies, which can ultimately aid in reducing associated morbidity in human populations. The approach taken is likely to be directly applicable to other parts of Southeast Asia and the Western Pacific, where specific epidemiological conditions might hamper the success of targeted treatment programs. Funding: Faculty of Veterinary and Agricultural Sciences Strategic Research Funds, The University of Melbourne.

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“…This study has some limitation. Although we used Kato-Katz, the most widely used diagnostic method recommended by WHO for epidemiologic surveys and anthelminthic drug efficacy studies against schistosomiasis and STH [ 37 , 39 ], its sensitivity decreases in low prevalence and low-intensity settings [ 40 ]. Low sensitivity of Kato-Katz for detection of hookworm infection may be related to rapid degeneration of delicate hookworm eggs with time [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda

et al. 2020

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Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5–15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda.

show abstract

The increased sensitivity of qPCR in comparison to Kato-Katz is required for the accurate assessment of the prevalence of soil-transmitted helminth infection in settings that have received multiple rounds of mass drug administration

Cited by 35 publications

References 41 publications

Performance of the Kato-Katz method and real time polymerase chain reaction for the diagnosis of soil-transmitted helminthiasis in the framework of a randomised controlled trial: treatment efficacy and day-to-day variation

Performance of the Kato-Katz method and real time polymerase chain reaction for the diagnosis of soil-transmitted helminthiasis in the framework of a randomised controlled trial: treatment efficacy and day-to-day variation

Risk profiling and efficacy of albendazole against the hookworms Necator americanus and Ancylostoma ceylanicum in Cambodia to support control programs in Southeast Asia and the Western Pacific

Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda

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