Serious limitations of the current strategy to control Soil-Transmitted Helminths and added value of Ivermectin/Albendazole mass administration: A population-based observational study in Cameroon.

BACKGROUND: Soil-transmitted helminth (STH) infections remain a public health concern in sub-Saharan Africa. School-based mass drug administration (MDA) using the anthelminthic drug Mebendazole/Albendazole have succeeded in controlling morbidity associated to these diseases but failed to interrupt their transmission. In areas were filarial diseases are co-endemic, another anthelminthic drug (Ivermectin) is distributed to almost the entire population, following the community-directed treatment with ivermectin (CDTI) strategy. Since Ivermectin is a broad spectrum anthelmintic known to be effective against STH, we conducted cross-sectional surveys in two health districts with very contrasting histories of Ivermectin/Albendazole-based PC in order to investigate whether CDTI might have contributed in STH transmission interruption. METHODOLOGY: Cross-sectional surveys were conducted in two health districts with similar socio-environmental patterns but with very contrasting CDTI histories (Akonolinga health district where CDTI was yet to be implemented vs. Yabassi health district where CDTI has been ongoing for two decades). Stool samples were collected from all volunteers aged >2 years old and analyzed using the Kato-Katz technique. Infections by different STH species were compared between Akonolinga and Yabassi health districts to decipher the impact of Ivermectin/Albendazole-based MDA on STH transmission. PRINCIPAL FINDINGS: A total of 610 and 584 participants aged 2-90 years old were enrolled in Akonolinga and Yabassi health districts, respectively. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found, with prevalence significantly higher in Akonolinga health district (43.3%; 95% CI: 38.1-46.6) compared to Yabassi health district (2.5%; 95% CI: 1.1-5.1) (chi-square: 90.8; df: 1; p < 0.001). CONCLUSION/SIGNIFICANCE: These findings (i) suggest that Mebendazole- or Albendazole-based MDA alone distributed only to at-risk populations might not be enough to eliminate STH, (ii) support the collateral impact of Ivermectin/Albendazole MDA on A. lumbricoides and T. trichiura infections, and (iii) suggest that Ivermectin/Albendazole-based PC could accelerate STH transmission interruption.

The impact of four years of semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: A community-based study in the Democratic Republic of the Congo.

BACKGROUND: The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period. CONCLUSION/SIGNIFICANCE: These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.

The public health benefit and burden of mass drug administration programs in Vietnamese schoolchildren: Impact of mebendazole.

BACKGROUND: Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5-14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter. METHODOLOGY: Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment. PRINCIPAL FINDINGS: Compared to 'no treatment', the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs. CONCLUSIONS: The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain.

Use of quantitative PCR to assess the efficacy of albendazole against Necator americanus and Ascaris spp. in Manufahi District, Timor-Leste.

BACKGROUND: Soil-transmitted helminths (STHs) including Ascaris lumbricoides, Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of significant global morbidity. To mitigate their disease burden, at-risk groups in endemic regions receive periodic mass drug administration using anthelmintics, most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic drugs is important for confirming that these regimens are working effectively and that drug resistance has not emerged. In this study we aimed to characterise the therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for parasite detection and quantification. RESULTS: A total of 314 participants from 8 communities in Timor-Leste provided stool samples before and 10-14 days after the administration of a single 400 mg dose of albendazole. Helminth infection status and infection intensity (measured in Ct-values and relative fluorescence units) were determined using qPCR. Efficacy was determined by examining the cure rates and infection intensity reduction rates. Albendazole was found to be highly efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9-95.2%) and infection intensity reduction rate of 95.6% (95% CI: 88.3-100%). The drug was less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4-64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0-97.0%). CONCLUSIONS: The observed cure rates and infection intensity reduction rates obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the continued efficacy of albendazole against these species and its utility as a mass chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs. Additional research is necessary to translate Ct-values into eggs per gram in a systematic way. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry 12614000680662 (registered 27 June 2014).

Helminth lifespan interacts with non-compliance in reducing the effectiveness of anthelmintic treatment.

BACKGROUND: The success of mass drug administration programmes targeting the soil-transmitted helminths and schistosome parasites is in part dependent on compliance to treatment at sequential rounds of mass drug administration (MDA). The impact of MDA is vulnerable to systematic non-compliance, defined as a portion of the eligible population remaining untreated over successive treatment rounds. The impact of systematic non-compliance on helminth transmission dynamics - and thereby on the number of treatment rounds required to interrupt transmission - is dependent on the parasitic helminth being targeted by MDA. RESULTS: Here, we investigate the impact of adult parasite lifespan in the human host and other factors that determine the magnitude of the basic reproductive number R 0 , on the number of additional treatment rounds required in a target population, using mathematical models of Ascaris lumbricoides and Schistosoma mansoni transmission incorporating systematic non-compliance. Our analysis indicates a strong interaction between helminth lifespan and the impact of systematic non-compliance on parasite elimination, and confirms differences in its impact between Ascaris and the schistosome parasites in a streamlined model structure. CONCLUSIONS: Our analysis suggests that achieving reductions in the level of systematic non-compliance may be of particular benefit in mass drug administration programmes treating the longer-lived helminth parasites, and highlights the need for improved data collection in understanding the impact of compliance.

Controlling Taenia solium and soil transmitted helminths in a northern Lao PDR village: Impact of a triple dose albendazole regime.

Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the resident dog population. These results suggest that the triple dose albendazole 400mg treatment regime achieved a significant reduction in the level of taeniasis whilst simultaneously reducing the STH burden within the village. The increased STH prevalence detected between MDAs reflects the need for behavioural changes and a sustained chemotherapy programme, which may also need to include the resident dog population.

Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections.

BACKGROUND: Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections. METHODS: All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models. RESULTS: Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 µM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 µM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 µM) and adults (50 µM), and H. polygyrus L3 (200 µM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively. CONCLUSION: Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a starting point for drug discovery for STH.

The impact of two semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in the Republic of Congo.

Implementation of mass drug administration (MDA) with ivermectin plus albendazole (ALB) for lymphatic filariasis (LF) has been delayed in central Africa because of the risk of serious adverse events in subjects with high Loa loa microfilaremia. We conducted a community trial to assess the impact of semiannual MDA with ALB (400 mg) alone on LF and soil-transmitted helminth (STH) infections in the Republic of Congo. Evaluation at 12 months showed that ALB MDA had not significantly reduced Wuchereria bancrofti antigenemia or microfilaria (mf) rates in the community (from 17.3% to 16.6% and from 5.3% to 4.2%, respectively). However, the geometric mean mf count in mf-positive subjects was reduced from 202.2 to 80.9 mf/mL (60% reduction, P = 0.01). The effect of ALB was impressive in 38 subjects who were mf-positive at baseline and retested at 12 months: 37% had total mf clearance, and individual mf densities were reduced by 73.0%. MDA also dramatically reduced the hookworm infection rate in the community from 6.5% to 0.6% (91% reduction), with less impressive effects on Ascaris and Trichuris. These preliminary results suggest that semiannual community MDA with ALB is a promising strategy for controlling LF and STH in areas with coendemic loiasis.

Low-dose beta-carotene supplementation and deworming improve serum vitamin A and beta-carotene concentrations in preschool children of Bangladesh.

Despite the national vitamin A and antihelminthic prophylaxis programmes, both intestinal geohelminths and subclinical vitamin A deficiency continue to be prevalent among children in developing countries. Studies on potential synergistic effects of vitamin A supplementation and deworming on retinol status have inconsistent results. The purpose of the present study was to investigate the impacts of low-dose beta-carotene supplementation and antihelminthic therapy on serum retinol and beta-carotene concentrations in preschool children of Bangladesh. Two hundred and forty-four children, known to be infected with Ascaris lumbricoides, were randomized into four treatment groups: I-IV. Group I and II received two oral doses of 400 mg of albendazole each, the first dose at baseline and the second dose after four months; Group III and IV received placebo in place of albendazole. In addition, Group I and III received 1.2 mg of beta-carotene powder in capsule daily for six months, and Group II and IV received placebo in place of beta-carotene. Serum retinol and beta-carotene levels were measured before and after six months of the interventions. Serum retinol and beta-carotene increased significantly in Group I where both antihelminthic therapy and daily beta-carotene supplementation were given (p<0.05 and p<0.001 respectively). Antihelminthic therapy alone only improved serum beta-carotene concentration (p<0.0001). Low-dose beta-carotene supplementation, along with an antihelminthic therapy, synergistically improved vitamin A status. This finding has public-health implications for improving vitamin A status of children in developing countries.

Epidemiology and the effect of treatment of soil-transmitted helminthiasis in pregnant women in southern Thailand.

This study aimed to assess the current situation of STH in pregnant women, explore factors associated with STH and evaluate the effects of its treatment. A cohort study was conducted in four southernmost provinces. All pregnant women who presented at their first prenatal care visit at participating hospitals were interviewed by trained health care providers and their stool specimens were examined for Ascaris lumbricoides, Trichuris trichiura and hookworm eggs. Women with STH were treated with 400 mg of albendazole after 14 weeks of gestation and treatment outcomes were evaluated three weeks after treatment. Of 1,063 pregnant women, STH were detected in 190 patients (17.9%) without seasonal variation for a combined infection of 21.6%. Ascaris, hookworm and Trichuris were detected in 10.3, 5.7 and 6.3%, respectively. The cure rate with a single dose was 92% but was 100% when repeated treatment was given as a three-day course. The risk of infection was higher in Muslim women, those with a family income < or = USD300/month, those bathing outside the house and those with no knowledge of STH. These results showed that southern Thailand is still an endemic area for STH and there appears to be no seasonal variation in incidence. Although the cure rate for treatment with albendazole was good, the low cure rate and egg reduction rate for trichuriasis needs to be considered.

Treatment options in the management of Ascaris lumbricoides.

Infection with Ascaris lumbricoides constitutes one of the most common helmintic diseases in the world, especially in tropical and subtropical regions. Transmission of this disease involves environmental contamination with eggs, and therefore, is classified as a soil-transmitted disease. The public health importance of ascariasis is made evident by the high number of infected individuals suffering its consequences, which can become severe, depending on the worm burden. Since the introduction of benzimidazoles, chemotherapy has improved significantly, offering fast and direct effects at relatively low cost, as a result of the simple and safe application of these drugs. Unfortunately, the effects are not long-lasting or permanent. The intervention with chemotherapy alone constitutes a fast and efficient way to reduce the worm burden in a population of high prevalence, but does not avoid reinfection. Therefore, the option of integrated control programmes based on chemotherapy in combination with sanitation and health education, together with strong community involvement, must be considered in order to ensure the positive long-term effects of such programmes.

Anthelminthic efficacy of traditional herbs on Ascaris lumbricoides.

The ascaricidal efficacy of six commonly used traditional herbs. Artemesia santonica, Inula helenium, Cassia abutnsifolla, Albizzia lebbek, Acacia auriculoformis and oil of Apium graveolens, was tested in vitro against the eggs and larvae of Ascaris lumbricoides. Aqueous extracts of 1% Artemesia and 5% of Albizzia and Inula were effective in killing both the infective larvae ill less than 40 days and eggs in 20 days. The results showed that Artemesia, Albizzia and to less extent Inula were promising antihelmintics against Ascaris lumbricoides. Extracts of the other tested herbs were less or no value.

Pharmacotherapy of ascariasis.

Ascaris lumbricoides, the most frequent human intestinal nematode, is the causative agent of ascariasis, with an estimated worldwide prevalence of over one billion people, especially in moist tropical and subtropical regions, but also in cooler climates. Although characterised with low morbidity and mortality rates, the global prevalence of ascariasis still results in approximately 20,000 deaths annually, primarily as a consequence of intestinal obstruction. In humans, transmission usually occurs by hand-to-mouth route by way of contaminated agricultural products and food, or from dirty hands. Three phases of ascariasis may be present, namely, the pulmonary, intestinal and the complications stage. Although generally asymptomatic, heavy infestation may cause serious pulmonary disease, or partial or complete obstruction of biliary or intestinal tracts. Anthelminthic chemotherapy is required to eradicate the parasites and prevent potentially serious complications. Mebendazole, albendazole and pyrantel pamoate are the most widely used agents to treat ascariasis. Preventive chemotherapy delivered to communities in endemic regions may serve as an affordable and cost-effective strategy to reduce the prevalence and morbidity in endemic regions. Under unusual circumstances, Ascaris suum, the cause of helminthic infection in pigs, may also cause disease in humans.

In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India.

The in vitro activity of root-tuber-peel extract of Flemingia vestita, an indigenous plant consumed by the natives in Northeast India, was tested against helminth parasites. Live parasites (nematode: Ascaris suum from pigs, A. lumbricoides from humans, Ascaridia galli and Heterakis gallinarum from domestic fowl; cestode: Raillietina echinobothrida from domestic fowl; trematode: Paramphistomum sp. from cattle) were collected in 0.9 % physiological buffered saline (PBS) and maintained at 37 +/- 1 degrees C. In vitro treatment of the parasites with the crude extract (50 mg/ml) in PBS revealed complete immobilization of the trematode and cestode in about 43 and 20 min, respectively. However, the cuticle-covered nematodes did not show any change in physical activity and remained viable even after a long period of exposure to the extract. Exposure of R. echinobothrida to genistein (0.5 mg/ml), an active principle isolated from the root-tuber peel, caused spontaneous loss of movement (paralysis) in 4.5 h, which was slower than the time required for praziquantel, the reference flukicide and cestodicide. The treated parasites showed structural alteration in their tegumental architecture. This study suggests the vermifugal activity of this plant extract against trematodes and cestodes.