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

Abstract

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.

Assessing the efficacy of albendazole against hookworm in Vietnam using quantitative PCR and sodium nitrate flotation

“…The ERR we calculated by qPCR is within this range, while the ERR calculated by SNF is somewhat lower. A previous study also found that arithmetic mean ERR was higher by qPCR compared with SNF at 72.5% and 40.8% respectively [20]. The lower ERR by SNF may be due to low-level infections being missed by SNF before treatment but detected by qPCR.…”

“…Quantitative PCR (qPCR) is emerging as the "gold standard" for STH diagnostics, especially in settings where infection intensity is lower after multiple rounds of preventative chemotherapy, because it is more sensitive and able to detect very low-level infections, and also allows differentiation between hookworm species [19]. However, only a few studies have used qPCR to determine efficacy of anthelmintic drugs, and only one has calculated infection intensity in eggs per gram of faeces [20][21][22]. As qPCR becomes more popular as a diagnostic tool for STH, more studies are needed that compare its diagnostic performance with microscopy, especially because WHO classification of heavy-, moderate-, and light-intensity infections are based on microscopy parameters [23].…”

Ancylostoma ceylanicum Hookworms in Dogs, Grenada, West Indies

“…Furthermore, although some circumstantial evidence indicates that A. caninum hookworms cause patent infections in humans ( 9 , 13 ), molecular evidence is lacking, which is particularly pertinent given the close genetic relatedness of A. caninum and A. duodenale hookworms ( 1 , 13 ). Thus, use of molecular methods to specifically detect, identify, and differentiate is crucial for surveillance of hookworm infections/disease in dogs and humans and for monitoring the success of control campaigns in hookworm-endemic areas ( 14 ).…”

“…Furthermore, although some circumstantial evidence indicates that A. caninum hookworms cause patent infections in humans (9,13), molecular evidence is lacking, which is particularly pertinent given the close genetic relatedness of A. caninum and A. duodenale hookworms (1,13). Thus, use of molecular methods to specifically detect, identify, and differentiate is crucial for surveillance of hookworm infections/disease in dogs and humans and for monitoring the success of control campaigns in hookworm-endemic areas (14). Molecular detection of A. ceylanicum and A. caninum and the absence of A. braziliense hookworms in dogs in Grenada demonstrates the value of using molecular techniques to accurately identify hookworm species in dogs and humans living in the Americas.…”

Establishing control and breaking transmission: the importance of accurately classifying cure following treatment for soil-transmitted helminths

“…In a recent issue of The Lancet Region Health – Western Pacific , Colella and colleagues describe the results of a survey conducted across ten villages in Cambodia in which samples were collected to ascertain hookworm infection prevalence [3] . While the results of the prevalence survey are limited by the sampling methodology, the data on cure rates is informative and of relevance to public health programs.…”