Effect of intensive versus standard anthelminthic treatment on growth and cognition among children living in a high Schistosoma mansoni transmission setting: a study nested within a cluster-randomised trial

Background: Schistosomiasis and other worm infections have been associated with growth and cognitive impairments; however, whether treatment reverses these effects is uncertain. Moreover, mechanisms linking these infections to cognition are not clear. We aimed to compare growth and cognitive benefits of intensive versus standard anthelminthic treatment in school-aged-children and explore processes that might be involved. We hypothesised that intensive treatment would have greater benefits than standard treatment. Methods: The study was nested within a cluster-randomised trial of either quarterly single-dose praziquantel of 40mg/kg to treat Schistosoma mansoni plus triple dose albendazole of 400mg (intensive treatment) to treat soil-transmitted worms including Ascaris lumbricoides, hookworm and Trichuris trichiura, or annual single-dose praziquantel 40mg/kg plus six-monthly single-dose albendazole 400mg (standard treatment) conducted in the Koome islands in Lake Victoria, Uganda (ISRCTN47196031). Children aged 5-9 years (N=384) were assessed on primary outcomes (height, weight and eight measures of cognitive ability), worm infection, and proposed mediators of worm effects (cytokines, iron status, physical activity) at one year (intensive n=85; standard n=64) and at two years (intensive n=158; standard n=128) of the intervention. Linear regression was used to examine intervention effects on height, weight and cognitive performance. Linear mixed effects models were used to study changes in growth and cognitive performance between the two arms across the two time-points. Results: Intensive treatment resulted in lower Schistosoma mansoni prevalence than standard treatment (at one year, 41% versus 70%; adjusted odds ratio (aOR)=0.24, 95% CI: 0.12, 0.49; at two years, 39% versus 69%; aOR=0.27; 95% CI: 0.16, 0.43) but there were no significant differences in growth and cognitive outcomes at either time-point. Worms and treatment showed no consistent association with the proposed mediators of worm effects. Conclusion: Reduction in worm burden may not improve growth and cognitive outcomes in high S. mansoni transmission settings. Possible implications are discussed.

Human Ascariasis: An Updated Review

Background: Ascaris lumbricoides is the most common helminthic infection. More than 1.2 billion people have ascariasis worldwide. Objective: This article aimed to provide an update on the evaluation, diagnosis, and treatment of ascariasis. Methods: A PubMed search was conducted in February 2020 in Clinical Queries using the key terms “ascariasis” OR "Ascaris lumbricoides". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. The search was restricted to the English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term “ascariasis” OR "Ascaris lumbricoides" in www.freepatentsonline.com. Results: Ascaris lumbricoides is transmitted through ingestion of embryonated eggs from fecal-contaminated material. Ascariasis has high endemicity in tropical and subtropical areas. Predisposing factors include poverty, poor sanitation, inadequate sewage disposal, and poor personal hygiene. The prevalence is greatest in children younger than 5 years of age. The majority of patients with intestinal ascariasis are asymptomatic. For those with symptoms, anorexia, nausea, bloating, abdominal discomfort, recurrent abdominal pain, abdominal distension, and intermittent diarrhea are not uncommon. Other clinical manifestations vary widely, depending on the underlying complications. Complications include Löeffler syndrome, intestinal obstruction, biliary colic, recurrent pyogenic cholangitis, cholecystitis, acalculous cholecystitis, obstructive jaundice, cholelithiasis, pancreatitis, and malnutrition. The diagnosis is best established by microscopic examination of fecal smears or following concentration techniques for the characteristic ova. Patients with A. lumbricoides infection warrant anthelminthic treatment, even if they are asymptomatic, to prevent complications from migration of the parasite. Albendazole and mebendazole are the drugs of choice for children and nonpregnant individuals with ascariasis. Pregnant women with ascariasis should be treated with pyrantel pamoate. Recent patents related to the management of ascariasis are also discussed. Conclusion: The average cure rate with anthelminthic treatment is over 95%. Unfortunately, most treated patients in endemic areas become re-infected within months. Health education, personal hygiene, improved sanitary conditions, proper disposal of human excreta, and discontinuing the use of human fecal matter as a fertilizer are effective long-term preventive measures. Targeting deworming treatment and mass anthelminthic treatment should be considered in regions where A. lumbricoides is prevalent.

Acquisition of resistance after continuous infection with Ascaridia galli in chickens

SUMMARYAcquired resistance against Ascaridia galli infection was studied in seventy-two 18-week-old white Leghorn chickens allocated to six groups (G1–G6). In order to understand the population dynamics following trickle-infection (100 eggs per chicken twice weekly), chickens of subgroups of G1 were necropsied 3 days after 1, 6 or 12 inoculations (G1A, G1B and G1C respectively), while G2–G4 were inoculated for 6 weeks. G2 was necropsied 4 weeks after the last inoculation. The number of established larvae increased initially (between G1A and G1B) but decreased after repeated inoculations (G1C, G2). G3, G4 and G5 were used to measure the efficacy of anthelminthic treatment and to monitor the acquisition of resistance following a challenge infection. At week 7 G3, G4 and G5 were treated with flubendazole for 7 days in the feed. Two weeks after treatment the chickens in G4 and G5 were challenged with 500 eggs. G6 was left as uninfected control. Necropsy at week 10 after first inoculation revealed a lower establishment rate, an impaired development and a more posterior localization of the larvae in G4 (trickle-infected-treated-challenged) compared with G5 (treated-challenged). IgY level in serum reached noticeable level at 14 dpi in G2 and G4 chickens, and in G4 chickens IgY level further increased after challenge infection. The study provides evidence that acquired resistance against A. galli in chickens leads to a significant yet incomplete protection against re-infection.