Identification and localization of hookworm platelet inhibitor in Ancylostoma ceylanicum

Huang, Yanfang; Abuzeid, Asmaa M.I.; Liu, Yunqiu; He, Long; Zhao, Qi; Yan, Xinxin; Hang, Jianxiong; Ran, Rongkun; Sun, Yongxiang; Li, Xiu; Liu, Jumei; Li, Guoqing

doi:10.1016/j.meegid.2019.104102

Cited by 6 publications

(3 citation statements)

References 38 publications

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“… 15 , 50 Recent work shows that the morbidity of A. ceylanicum is linked to a platelet inhibitor in adult parasites involved in the pathogenesis of hookworm-associated intestinal haemorrhage and iron deficiency anaemia. 51 However, to date, no data have been available on the efficacy of anthelminthic drugs against A. ceylanicum , despite an estimated 100 million people estimated to be infected with this parasite. 14 Similarly, despite report of infections in humans showing clinical signs such as eosinophilia, diarrhoea, melena, dyspnoea, and anaemia, studies elucidating A. ceylanicum -associated morbidity at a population scale have not yet been performed.…”

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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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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“…Ace-hpi transcripts were most abundant in adults, followed by ssL3s and L3 stages, with a significant difference. Unlike Ac-HPI, E. colli-expressed recombinant Ace-HPI protein inhibited the platelet aggregation [61], supporting the role of Ace-HPI in hookworm blood-feeding.…”

Section: Hookworm Platelet Inhibitorsmentioning

confidence: 61%

Twenty-five-year research progress in hookworm excretory/secretory products

et al. 2020

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Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.

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“…Huang et al (33) estudiaron el inhibidor plaquetario de A. ceylanicum asumiendo su relación con la manifestación de hemorragia intestinal causada por uncinarias, previamente vinculada con el inhibidor plaquetario (HPI) aislado de la especie homóloga A. caninum. Por medio de técnicas bioquímicas y moleculares demostraron la expresión diferencial de este gen en todos los estadios del nematodo, que es mayor en fase adulta; determinaron su localización en esófago y glándulas cefálicas y estudiaron su actividad anticoagulante.…”

Section: Ciencias óMicasunclassified

Desarrollo de fármacos antihelmínticos: actualización de candidatos a fármacos y dianas terapéuticas en el manejo de las geohelmintiasis

Uribe Herrera,

Rojas,

Reyes Harker

et al. 2023

Rev. Med.

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Se estima que 1500 millones de personas en el mundo están infectadas por algún geohelminto. La disminución de la eficacia de los medicamentos antihelmínticos utilizados en la estrategia de quimioterapia preventiva, reportada particularmente para la especie Trichuris trichiura, motiva la búsqueda de otros antihelmínticos para enfrentar esta situación y evitar la posible resistencia ante este grupo de fármacos. Objetivos: esta revisión se centra en conocer el estado actual de la investigación en dianas terapéuticas y candidatos a fármacos antihelmínticos reportados en la literatura desde 2013 hasta 2021. Resultados: se recopiló la información de 28 trabajos de investigación que comprenden desarrollos desde la fase in silico hasta la fase de investigación clínica. La mayoría de los trabajos corresponde a desarrollos en las ciencias ómicas; desde la corrección en anotaciones de genomas hasta la identificación de familias proteicas fundamentales para los mecanismos de patogenicidad. Conclusión: la información referente a dianas y candidatos a fármacos, disponible en esta revisión, es una aproximación para seguir explorando las posibles aplicaciones y el desarrollo experimental de estos fármacos para el control de las geohelmintiasis.

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Identification and localization of hookworm platelet inhibitor in Ancylostoma ceylanicum

Cited by 6 publications

References 38 publications

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

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

Twenty-five-year research progress in hookworm excretory/secretory products

Desarrollo de fármacos antihelmínticos: actualización de candidatos a fármacos y dianas terapéuticas en el manejo de las geohelmintiasis

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