Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of (ABZSO (+)-®- and (-)-(S)- enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-®- and (-)-(S)- enantiomers were evaluated in vitro against T. solium cysts. Parasites were collected from naturally infected pigs, cultured and exposed to the racemic mixture or to each enantiomer (range 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound on cysts was assayed by measuring ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-®-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time- dependent manner, indicating that most of the activity of ABZSO resides in the (+)-®-enantiomer. Use of this enantiomer alone may lead increased efficacy and/or less toxicity compared to albendazole.
Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT).
Soil-transmitted helminth (STH) infections with Ascaris lumbricoides, hookworm and Trichuris trichiura affect large parts of the world’s population. For the implementation of national STH control programs, e.g. preventive chemotherapy (treatment with albendazole and mebendazole), the spatial distribution and prevalence of STH infections must be known. However, for Lesotho only little data were available and the STH distribution remains largely unknown.
Infections with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) are widespread and often occur concomitantly. These parasitic-worm infections are typically treated with albendazole or mebendazole, but both drugs show low efficacy against T. trichiura. Albendazole is the drug of choice against hookworm.
The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.
Worm infections continue to be among the most common diseases affecting children from low and middle income countries. Major worm infections of public health importance include Ascariasis, Trichuriasis, Hookworm, and Enterobiasis, which are transmitted through contaminated soil. In India, combined prevalence rates of worm infestation as per pooled data of 127 surveys is over 20%. Although most helminthic infections are mild and are often asymptomatic, but moderate to heavy worm infestations are generally associated with growth faltering, nutritional compromise, anemia and suboptimal academic performance among children from endemic regions. Migration of larval or adult worms also underpins pulmonary and gastrointestinal morbidity in affected children. Some of the distinctive life cycle and clinical features of various worms are discussed in the review. The gold standard diagnostic technique for evaluation of worm infestation includes stool microscopy for direct egg detection and species identification. Most of the community based surveys for detecting soil transmitted helminths (STH) use Kato-Katz technique. The drug armamentarium against worm infestation has evolved tremendously in last three to four decades with the availability of more efficacious and broad spectrum anthelminthics. The key strategies of a multi-component integrated management of worm infestation include individualized treatment, community management (mass drug administration) as well as preventive measures. Finally, barriers to diagnosis, treatment and prevention of worm infestations need to be identified and aggressively managed at individual, family and societal levels so that WHO’s 75% coverage target can be achieved to eliminate soil transmitted helminthiasis in children by 2020.
Objective To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates.Design Systematic review and network meta-analysis.Data Sources PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016.Study selection Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against Ascaris lumbricoides, hookworm (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura. The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models.Results 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against A lumbricoides Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against T trichiura, with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against T trichiura: by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027).Conclusions All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against T trichiura The decrease in efficacy of albendazole against T trichiura over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura.
Hookworm infections are rare causes of acute gastrointestinal bleeding. We report a middle aged man with primary nephrotic syndrome and pulmonary embolism. During the treatment with steroids and anticoagulants, the patient presented acute massive hemorrhage of the gastrointestinal tract. The results of gastroscopy showed red worms in the duodenum. Colonoscopy and CT angiogram of abdomen were unremarkable. Capsule endoscopy revealed fresh blood and multiple hookworms in the jejunum and ileum. Hookworms caused the acute intestinal bleeding. The patient responded well to albendazole. Hematochezia was markedly ameliorated after eliminating the parasites. Hence, hookworm infection should be considered in the differential diagnosis of a patient with obscure gastrointestinal bleeding. Capsule endoscopy may offer a better means of diagnosis for intestinal hookworm infections.
Hookworm infections are widely prevalent in tropical and subtropical areas, especially in low income regions. In the body, hookworms parasitize the proximal small intestine, leading to chronic intestinal hemorrhage and iron deficiency anemia. Occasionally, hookworms can cause overt gastrointestinal bleeding, but this is often ignored in heavily burdened individuals from endemic infectious areas. A total of 424 patients with overt obscure gastrointestinal bleeding were diagnosed by numerous blood tests or stool examinations as well as esophagogastroduodenoscopy, colonoscopy, capsule endoscopy or double-balloon enteroscopy. All of the patients lived in hookworm endemic areas and were not screened for hookworm infection using sensitive tests before the final diagnosis. The patients recovered after albendazole treatment, blood transfusion, and iron replacement, and none of the patients experienced recurrent bleeding in the follow-up. All the 31 patients were diagnosed with hookworm infections without other concomitant bleeding lesions, a rate of 7.3% (31/424). Seventeen out of 227 patients were diagnosed with hookworm infections in the capsule endoscopy (CE), and 14 out of 197 patients were diagnosed with hookworm infections in the double balloon enteroscopy (DBE). Hookworm infections can cause overt gastrointestinal bleeding and should be screened in patients with overt obscure gastrointestinal bleeding (OGIB) in endemic infectious areas with sensitive methods. Specifically, the examination of stool specimens is clinically warranted for most patients, and the proper examination for stool eggs relies on staff’s communication.
Intestinal helminth infections constitute a major health problem in low socio-economic communities worldwide. A cross-sectional study was conducted in children aged between 12 and 60 months. A structured questionnaire was used to collect socio-demographic data and stool samples were subjected to direct smear, stained with Lugol’s iodine, and formaldehyde-ether concentration techniques to determine the prevalence of intestinal helminth infections. The circumference of each child’s left mid upper arm (MUAC) was measured using standard procedures. Two hundred and six children with a mean MUAC of 14.7 cm (SD ± 1.1) were assessed from September to December 2014. The prevalence of acute energy undernutrition was 6.3% (13/206). All of them had moderate acute undernutrition and no cases of severe acute undernutrition. Paternal occupation was significantly associated with MUAC. Intestinal helminth infections were detected in 12.6% of children. Four species of parasites were identified; Ascaris lumbricoides (9.7%) followed by Enterobius vermicularis (1.5%), Trichuris trichiura (1.0%) and hookworms (1.0%). Uninfected children aged between 1 and 2 years showed significantly higher MUAC than infected children. No statistically significant association was detected between the severity of intestinal helminth infections and MUAC. Although intestinal helminth infections are a major public health problem in this community, they are not related to MUAC. Future research, providing more insight into the nutritional impact of intestinal helminth infections, is required to determine the association between parasitic infections and physical growth in this community.