Anthelmintic screening of Bangladeshi medicinal plants and related phytochemicals using in vitro and in silico methods: An ethnobotanical perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. AIM OF THE STUDY: The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt ß-tubulin function in helminths. METHODS: The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the ß-tubulin protein target (PDB ID: 1SA0). RESULTS: The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol. CONCLUSION: Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.

The effectiveness of albendazole against hookworm infections and the impact of bi-annual treatment on anaemia and body mass index of school children in the Kpandai district of northern Ghana.

The impact of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) (initiated in 2000 in Ghana and ran for 12 years) in mitigating soil-transmitted helminth (STH) infections in LF-endemic areas is unknown. During a 1-year hiatus which ensued between 2011 and 2012, a longitudinal study was conducted to determine GPELF effect on hookworm infections in selected communities involved in the programme since its inception, while measuring the effectiveness of biannual ALB treatments on schoolchildren living in such communities. A total of 399 school children aged 3 to 18 years were randomly selected from four communities in the Kpandai district of northern Ghana. Each presented a single stool sample at baseline, 21 days post-treatment, at the 3rd and 6th months, 21 days post-second intervention (i.e. following sample collection and treatment with ALB in the 6th month), and in the ninth month of the study period. Haemoglobin (hb) levels were also measured at all time points using finger prick blood samples and a URIT digital test kit. Each participant submitting a sample, was treated with a single-dose ALB (400mg) at baseline and in the sixth month. Stool samples were processed by preparing duplicate Kato-Katz slides per sample, and examined by microscopy. The Body Mass Index-for-age z-scores (BAZ) of participants were assessed following the determination of BMIs at each time point by measuring their height and weight with a stadiometer and weighing scale. Overall hookworm prevalences were 25.68% (95% CI = 20.51-31.75) at baseline, 11.18% (95% CI = 7.87-15.41) 21 days post-treatment, 11.78% (95% CI = 8.38-16.11) and 6.95% (95% CI = 4.41-10.43) in the 3rd and 6th months, 0.91% (95% CI = 0.19-2.65) 21 days post-second intervention, and 8.46% (95% CI = 5.62-12.23) in the ninth month. Observed overall faecal egg count reduction rates (ERRs) were 94.21% (95% CI = 81.50%- 100.00%) 21 days after baseline treatment, 97.70% (95% CI = 85.08-100.00) and 96.95% (95% CI = 84.18%- 100.00%) in the 3rd and 6th months, 99.98% (95% CI = 86.42%- 100.00%) 21 days post-second intervention, and 17.18% (95% CI = 14.07%- 20.67%) in the 9th month. Respective cure rates (CRs) were 62.35% (95% CI = 46.71-81.56%), 85.88% (95% CI = 67.32-100.00%), 87.06% (95% CI = 68.36%- 100.00%), 98.82% (95% CI = 78.83%- 100.00%), and 36.36% (95% CI = 9.91%- 93.11%). Additionally, increases in the percent frequency of 'normal hb' (p < 0.01) were observed across the study time points, whilst 'normal BAZ' cases remained high (from 94.87% to 98.87%) throughout the study period. These findings primarily indicate satisfactory effectiveness of ALB which may be maintainable in mass drug administration programmes by the modification of treatment strategies from annual to bi-annual regimes. This could minimize the likelihood of emerging poorly-responding hookworm phenotypes in Ghana. Additionally, a positive impact of bi-annual treatment on participant anaemia status is herein indicated with particular regard to the school children in our cohort.

Zinc status or supplementation and its relation to soil-transmitted helminthiasis in children: A systematic review.

Soil-transmitted helminths (STHs) parasitic infection is known as one of the most common infections around the world affecting more than a quarter of the world's population. The relationship between STH infections and micronutrient deficiencies are closely related and often coexist among the affected population. The study, therefore, aimed to summarise the available literature focusing on the effect of zinc status/deficiency or supplementation on STH infection or reinfection in children. For this purpose, we adopted a systematic approach and searched the existing literature on PubMed, Scopus, and Cochrane Library databases. A search term was entered to retrieve the available data. A total of 12 articles were included in this review after applying the inclusion/exclusion criteria. Most of the included studies reported a lower zinc status in children affected with any parasitic infection. Regarding the effect of zinc status and supplementation on parasitic infection in children, we found only a few studies (n = 4) with inconsistent result findings. This review reported that children infected with STH have lower zinc levels; however, a limited number of studies showed the effect of zinc supplements on the risk of STH warrants the need for further studies in this regard.

PRESCRIBING PATTERNS AND THE USE OF ANTHELMINTIC DRUGS IN COLOMBIAN PATIENTS: A CROSS-SECTIONAL STUDY.

Intestinal parasites continue to be a public health problem in low- and middle-income countries. Broad use of anthelmintics during deworming programs is still necessary in many regions. However, description of the usage of these medications in general medical practice has been limited. The objective of this study was to determine the use of anthelmintic drugs and their indications in a group of Colombian patients. This was a descriptive study from a drug-dispensing database, identifying patients with prescriptions for anthelmintic drugs. A total of 381 cases were randomly selected, and their medical records were reviewed, analyzing sociodemographic, clinical, and pharmacological variables (indication of use). The lack of diagnosis registration or clinical manifestations of parasites was determined as a prescription without indication. In total, 50.9% (n = 194) of patients were female, and 67.4% of all patients were under 18 yr of age. The diagnosis of helminthiases was clearly stated in 114 (29.9%) patients, and only 4.2% (n = 16) of these had microbiological confirmation. The most commonly used anthelmintic drug was albendazole (70.4% of all prescriptions). The use of anthelmintics was not indicated in 266 cases (69.8%). Nutritional supplements or vitamin prescriptions were associated with using anthelmintics without indication (odds ratio: 2.25; 95% confidence interval: 1.26-4.03). A high proportion of patients lacked symptoms or diagnoses in their clinical records that supported the use of anthelmintic drugs.

Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data.

BACKGROUND: In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. METHODOLOGY: Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. PRINCIPAL FINDINGS: The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. CONCLUSIONS/SIGNIFICANCE: For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.

Prevalence of Soil-Transmitted Helminths at Baseline and after Albendazole Treatment in the School-Age Children of Forcibly Displaced Myanmar Nationals in Bangladesh.

The forcibly displaced Myanmar nationals (FDMNs) known as Rohingya refugees are the largest group of stateless individuals globally. According to the emergencies humanitarian actors at the United Nations Office for the Coordination of Humanitarian Affairs, the worldwide refugee crisis involving FDMNs is intensifying at the fastest rate in history. Growing public health demands are being exacerbated by current difficulties in addressing poor access to health services, severe food shortages, and a lack of adequate housing. Infectious diseases constitute a major public health emergency in this vulnerable population. A study was carried out in FDMN children to investigate common soil-transmitted helminth (STH) infection at the time of enrollment and prospectively followed-up to 12 months after 2 doses albendazole treatment. At baseline, the prevalence of STH infection with at least one species was found to be 91.7% and 87.3% for Kato-Katz (KK) and quantitative polymerase chain reaction (qPCR) methods, respectively. Similarly, for follow-up children, the overall infection rate was 95.3% and 91.5%, respectively. Trichuris trichiura was the most predominant STH infection by both KK (baseline 87%, follow-up 89.1%) and qPCR (baseline 77.5%, follow-up 82.9%). The overall prevalence of stunting in the children was 37.8% at baseline and rose to 51.3% at 12 months. Alpha-1 antitrypsin (r = 0.13, P = 0.01) and myeloperoxidase (r = 0.12, P = 0.01) levels showed a positive correlation with Aascaris lumbricoides egg count per gram at baseline. An in-depth investigation is urgently needed to identify the underlying protective measures and the root cause of STH infections to improve the health of FDMN children.

Anthelmintic activity of European fern extracts against Haemonchus contortus.

Most drugs used in the treatment of helminthiasis in humans and animals have lost their efficacy due to the development of drug-resistance in helminths. Moreover, since anthelmintics, like many pharmaceuticals, are now recognized as hazardous contaminants of the environment, returning to medicinal plants and their products represents an environmentally friendly way to treat helminthiasis. The goal of the present study was to test the anthelminthic activity of methanol extracts of eight selected European ferns from the genera Dryopteris, Athyrium and Blechnum against the nematode Haemonchus contortus, a widespread parasite of small ruminants. Eggs and adults of H. contortus drug-susceptible strain ISE and drug-resistant strain WR were isolated from experimentally infected sheep. The efficacy of fern extracts was assayed using egg hatch test and adults viability test based on ATP-level measurement. Among the ferns tested, only Dryopteris aemula extract (0.2 mg/mL) inhibited eggs hatching by 25% in comparison to control. Athyrium distentifolium, Dryopteris aemula and Dryopteris cambrensis were effective against H. contortus adults. In concentration 0.1 mg/mL, A. distentifolium, D. aemula, D. cambrensis significantly decreased the viability of females from ISE and WR strains to 36.2%, 51.9%, 32.9% and to 35.3%, 27.0%, 23.3%, respectively in comparison to untreated controls. None of the extracts exhibited toxicity in precise cut slices from ovine liver. Polyphenol's analysis identified quercetin, kaempferol, luteolin, 3-hydroxybenzoic acid, caffeic acid, coumaric acid and protocatechuic acid as the major components of these anthelmintically active ferns.

A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.

Ethnobotanical knowledge on native Brazilian medicinal plants traditionally used as anthelmintic agents - A review.

Intestinal helminthiasis is a neglected disease that affects a significant portion of the global population, specifically in developing countries, where medicinal plants are widely used for therapeutic purposes. With the purpose to identify the native species used in traditional Brazilian medicine for the management of helminthiasis, ethnopharmacological books edited in Brazil documenting the folk use of medicinal plants were analyzed. The native species cited in at least three studies were selected, and bibliographic research was performed using electronic databases to identify their scientifically validated anthelmintic properties. The search retrieved 133 native species belonging to 88 genera and 43 families from all six Brazilian biomes. Fabaceae (14 Genera and 25 Species) and Asteraceae (7 Genera and 8 Species) were the most frequently cited families. The most reported native species were Baccharis crispa Spreng., Hymenaea courbaril L., Senna occidentalis (L.) Link, Carapa guianensis Aubl., Stachytarpheta cayennensis (Rich.) Vahl, Annona glabra L., Hymenaea stigonocarpa Mart. ex Hayne, Spigelia anthelmia L., Simarouba versicolor A.St.-Hil. and Anacardium occidentale L. Bark (19%) and leaves (17%) were the most commonly used plant parts, and decoction (27%) was the most preferred method of preparation. Evidence of the anthelmintic properties of most species was confirmed using in vitro assays for key human and animal parasites, including Haemonchus contortus, Hymenolepis diminuta, Schistosoma mansoni and Trichostrongylus spp. The species S. alata, S. occidentalis, A. occidentale, and S. anthelmia have been the subject of many biological studies, supporting their use as vermicides. The overall results obtained in this review revealed that Brazil is rich in traditional herbal medicines used to manage helminthiasis; however pharmacological investigations are lacking to confirm their therapeutic properties. Thus, this study could serve as a baseline to validate their use and encourage further clinical investigation of their vermifuge potential.

Red palm olein-enriched biscuit supplementation lowers Ascaris lumbricoides reinfection at 6-month after anthelmintic treatment among schoolchildren with vitamin A deficiency (VAD).

Notwithstanding the global efforts made to control intestinal parasitic infections, soil-transmitted helminth (STH) infections are still one of the most prevalent infections globally, especially in developing countries. A double-blinded, randomized controlled trial was conducted on 343 primary schoolchildren (8-12 years old) with vitamin A deficiency (VAD) in rural areas of Malaysia to investigate the effects of red palm olein (RPO)-enriched biscuits on STH reinfection rates and infection intensities. The effects of the RPO-enriched biscuits (experimental group, n = 153) and palm olein (PO)-enriched biscuits (control group, n = 190), were assessed at 3- and 6-month after the administration of complete triple-dose albendazole (one dose of 400 mg for three consecutive days). The overall STH infection rate at baseline was recorded at 65.6%. At 6-month, a significantly lower reinfection rate of A. lumbricoides was observed in the experimental group (35.3%) compared to the control group (60.0%) (P< 0.05), and a significant reduction in fecal egg count (epg) of A. lumbricoides was observed in the experimental group from baseline (P< 0.001), but no significant reduction was observed in the control group. No significant differences in the reduction of infection intensities of T. trichiura and hookworm were observed between experimental and control groups at 3- and 6-month (P>0.05). These findings suggest the potential beneficial effects of RPO-enriched biscuit supplementation on the reinfection of A. lumbricoides, which could be attributed to its high carotenoids content by enhancing host immune response and mucosal epithelium integrity. However, further studies are warranted to confirm whether RPO supplementation could result in similar parasite-specific beneficial effects in other community settings, as well as to explore the underlying mechanisms.

Micronutrients deficiencies and its correlation with the soil-transmitted helminthic infections among children and non-pregnant women in Nepal: findings from Nepal national micronutrient status survey.

Despite having a high risk of soil-transmitted helminths (STHs) infection, no national level study has been conducted to assess incidence and correlates of STHs in Nepal. Thus, we hypothesized that micronutrients and social status are linked with incidence of STHs infection among 6-59 months children and 15-49 years non-pregnant women in Nepal and Kato-Katz technique was adopted to measure the type and intensity of STHs infections using fresh stool specimens and venous blood was used to examine micronutrients biomarkers. Anthropometric measurements such as height and weight, sociodemographic and health status were determined using structured questionnaire. Logistic regression was used to assess unadjusted and adjusted odds ratio (AOR) and the 95% CIs of ORs. The bivariate association of STHs was assessed with the covariates variables. Overall, 12% children and 19% non-pregnant women had STHs infection; A. lumbricoides was the predominant helminth in both study participants. In multivariate model; age, ethnicity, anaemia and zinc deficiency were associated with STHs infections in children. Similarly, higher odds of STHs occurrence was observed among non-pregnant women with vitamin A deficiency. Findings from this study suggest that high-risk population, with a focus on those of lower socioeconomic status should be on priority of deworming program, nutrition intervention, and mass administration of preventive chemotherapy and sanitation champions supplement to reduce the STHs infections in Nepal.

A systematic review and meta-analysis of human and zoonotic dog soil-transmitted helminth infections in Australian Indigenous communities.

Soil-transmitted helminths (STH) infect 1.5 billion people and countless animals worldwide. In Australian Indigenous communities, STH infections have largely remained endemic despite control efforts, suggesting reservoirs of infection may exist. Dogs fulfil various important cultural, social and occupational roles in Australian Indigenous communities and are populous in these settings. Dogs may also harbour zoonotic STHs capable of producing morbidity and mortality in dogs and humans. This review provides an overview of human and zoonotic STH infections, identifies the Australian Indigenous locations affected and the parasite species and hosts involved. The meta-analysis provides estimates of individual study and pooled true prevalence of STH infections in Australian Indigenous communities and identifies knowledge gaps for further research on zoonotic or anthroponotic potential. A systematic literature search identified 45 eligible studies documenting the presence of Strongyloides stercoralis, Trichuris trichiura, Ancylostoma caninum, Ancylostoma duodenale, Ancylostoma ceylanicum, undifferentiated hookworm, and Ascaris lumbricoides. Of these studies, 26 were also eligible for inclusion in meta-analysis to establish true prevalence in the light of imperfect diagnostic test sensitivity and specificity by Rogan-Gladen and Bayesian methods. These studies revealed pooled true prevalence estimates of 18.9% (95% CI 15.8-22.1) for human and canine S. stercoralis infections and 77.3% (95% CI 63.7-91.0) for canine A. caninum infections indicating continued endemicity, but considerably more heterogenous pooled estimates for canine A. ceylanicum infections, and A. duodenale, undifferentiated hookworm and T. trichiura in humans. This review suggests that the prevalence of STHs in Australian Indigenous communities has likely been underestimated, principally based on imperfect diagnostic tests. Potential misclassification of hookworm species in humans and dogs due to outdated methodology, also obscures this picture. High-quality contemporary studies are required to establish current true prevalence of parasite species in all relevant hosts to guide future policy development and control decisions under a culturally sound One Health framework.

Prevalence and factors associated with anaemia in children aged 6-24 months living a high malaria transmission setting in Burundi.

BACKGROUND: In very young children, anaemia has been linked to increased morbidity, mortality and poor cognitive development. Although Burundi has a high burden of anaemia, which may be worsened by the high burden of malaria, little is known about the extent of the problem in very young children who are most at risk of severe disease. We estimated the prevalence, and assessed the factors associated with anaemia in children aged 6-24 months using baseline data collected as part of an on-going study evaluating the effect of Micronutrient supplementation on anaemia and cognition among children in high malaria transmission settings in Burundi. METHODS: Between February and March 2020, surveys were conducted in 498 households within the catchment area of Mukenke Health Center. One child aged 6-24 months was selected per household to participate in the survey. Following written informed consent, we administered a questionnaire to the child's primary caregiver to capture information on child's demographics, nutritional status, food intake, health (status, and morbidity and treatment-seeking practices), as well as the household markers of wealth. A physical exam was conducted, and a blood sample was collected to: 1) assess for presence of plasmodium infection using a rapid diagnosis test; 2) estimate the haemoglobin levels using a portable haemocue machine. A stool sample was also collected to examine for the presence of helminth infections. RESULTS: The prevalence of anaemia was 74.3% (95% confidence interval [CI] 61.5%-84.0%), with most of the anaemic study participants classified as having moderate anaemia (59.2%). A total of 62 (12.5%) participants had positive malaria rapid diagnosis tests. Factors significantly associated with higher odds of developing anaemia included not receiving deworming medication (adjusted Odd ratio [aOR] = 3.54, 95% CI 1.79-6.99, p<0.001), the child's home location (Mukenke II: aOR = 2.22, 95% CI 1.89-2.62, p<0.001; Mukenke: aOR = 2.76, 95% CI 2.46-3.10, p<0.001 and Budahunga: aOR = 3.12, 95% CI 2. 94-3.31, p<0.001) and the child's age group (Children aged 6-11 months: aOR = 2.27, 95% CI 1.32-3.91, p<0.001). Education level was inversely associated with less odds of anaemia: child's primary care giver with a secondary (aOR = 0.67; 95% CI: 0.47-0.95, p = 0,024) and tertiary education level (aOR = 0.48; 95% CI: 0.38-0.61, p<0.001). CONCLUSION: Anaemia is highly prevalent among young children in high malaria transmission setting. Anaemia is more prevalent among children who not dewormed and those with malaria. To prevent the long-term adverse outcomes of the anaemia in children, policy makers should focus on improving uptake of the deworming and malaria prevention programs, promote preventive interventions and improve the education of women especially in families with very young children.

Efficacy of triple dose albendazole treatment for soil-transmitted helminth infections.

In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment.

BACKGROUND: Periodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments. METHODOLOGY: We built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14-21 and 22-45 days) after drug administration. PRINCIPAL FINDINGS: The 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14-21 days and 22-45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14-21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%. CONCLUSIONS/SIGNIFICANCE: Combining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.

Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of communicable diseases affecting the poorest populations around the world. OBJECTIVE: To assess the effectiveness of interventions, including mass drug administration (MDA), water, sanitation, and hygiene (WASH), vector control, health education, and micronutrients supplementation, for NTDs among children and adolescents. METHODS: We conducted a literature search on the Cochrane Controlled Trials Register, Medline, and other databases until December 2020. We included randomized controlled trials and quasi-experimental studies conducted among children and adolescents. Two authors independently screened studies for relevance. Two authors independently extracted data, assessed the risk of bias, performed metaanalysis, and rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 155 studies (231 articles) involving 262 299 participants. For soil-transmitted helminthiasis, MDA may reduce the prevalence of Ascaris, Trichuris, and hookworm by 58%, 36%, and 57%, respectively. We are uncertain of the effect of health education, WASH, and iron supplementation on soil-transmitted helminthiasis prevalence. For Schistosomiasis, health education probably reduces the intensity and prevalence of S. mansoni, whereas micronutrient supplementation may reduce anemia prevalence and the infection intensity of S. hematobium compared with no supplementation. We are uncertain of the effect of MDA and vector control on Schistosomiasis outcomes. For trachoma, health education probably reduces the prevalence of active Trachoma, whereas we are uncertain of the effect of MDA, WASH, and vector control on Trachoma outcomes. There is limited data on the effectiveness of interventions for NTDs targeting children and adolescents. CONCLUSION: Future studies are needed to evaluate the relative effectiveness and cost-effectiveness of various interventions specifically targeting children and adolescents.

"Using the same hand": The complex local perceptions of integrated one health based interventions in East Africa.

BACKGROUND: Neglected Tropical Diseases (NTDs) such as soil transmitted helminths (STH) and human rabies represent a significant burden to health in East Africa. Control and elimination remains extremely challenging, particularly in remote communities. Novel approaches, such as One Health based integrated interventions, are gaining prominence, yet there is more to be learned about the ways in which social determinants affect such programmes. METHODOLOGY: In 2015 a mixed method qualitative study was conducted in northern Tanzania to determine community perceptions towards integrated delivery of two distinct healthcare interventions: treatment of children for STH and dog vaccination for rabies. In order to assess the effectiveness of the integrated approach, villages were randomly allocated to one of three intervention arms: i) Arm A received integrated mass drug administration (MDA) for STH and mass dog rabies vaccination (MDRV); ii) Arm B received MDA only; iii) Arm C received MDRV only. PRINCIPLE FINDINGS: Integrated interventions were looked upon favourably by communities with respondents in all arms stating that they were more likely to either get their dogs vaccinated if child deworming was delivered at the same time and vice versa. Participants appreciated integrated interventions, due to time and cost savings and increased access to essential health care. Analysis of qualitative data allowed deeper exploration of responses, revealing why people appreciated these benefits as well as constraints and barriers to participation in integrated programmes. CONCLUSIONS/SIGNIFICANCE: An interdisciplinary One Health approach that incorporates qualitative social science can provide key insights into complex local perceptions for integrated health service delivery for STH and human rabies. This includes providing insights into how interventions can be improved while acknowledging and addressing critical issues around awareness, participation and underlying health disparities in remote pastoralist communities.

Impact of Semi-Annual Albendazole on Lymphatic Filariasis and Soil-Transmitted Helminth Infection: Parasitological Assessment after 14 Rounds of Community Treatment.

Between October 2012 and October 2015, we conducted a community trial to assess the impact of semi-annual (twice yearly) community treatment with albendazole on lymphatic filariasis in Seke Pembe, a village in the Republic of the Congo. Semi-annual community treatment with albendazole has been continued in the community since October 2015. We conducted an additional parasitological assessment survey in October 2019, 6 months after the 14th round of semi-annual treatment. Between October 2012 and October 2015, Wuchereria bancrofti antigenemia and microfilaremia rates in the community had decreased from 17.3% to 4.7% and from 5.3% to 0.3%, respectively. In October 2019, the antigenemia rate had decreased further to 2.8% (19 of 687). No microfilariae were found in night blood smears from persons with circulating filarial antigenemia (0 of 16), suggesting that W. bancrofti transmission has been interrupted in Seke Pembe. Semi-annual albendazole treatments also reduced significantly infection rates with soil-transmitted helminths.

The yin and yang of human soil-transmitted helminth infections.

The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products.