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.

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.

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.

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.

Non-essential heavy metals and protective effects of selenium against mercury toxicity in endangered Australian sea lion (Neophoca cinerea) pups with hookworm disease.

The endangered Australian sea lion, Neophoca cinerea, faces ongoing population decline. Identification of key threats to N. cinerea population recovery, including disease and pollutants, is an objective of the species' recovery plan. Previous studies have identified Uncinaria sanguinis, an intestinal nematode, as a significant cause of disease and mortality in N. cinerea pups. Given the impact of heavy metals on the immune response, investigation of these pollutants is critical. To this end, the concentrations of arsenic (As), total mercury (Hg), cadmium (Cd), chromium (Cr), lead (Pb) and selenium (Se) were determined in blood collected from N. cinerea pups sampled during the 2017/18, 2019 and 2020/21 breeding seasons at Seal Bay Conservation Park, South Australia. Significant differences (p < 0.05) in Hg, As, Cr, and Se concentrations and molar ratio of Se:Hg were seen between breeding seasons. Pup age, maternal parity and inter-individual foraging behaviour were considered factors driving these differences. The concentrations of Hg (357, 198 and 241 µg/L) and As (225, 834 and 608 µg/L) were high in 2017/18, 2019 and 2020/21 respectively with Hg concentrations in the blood of N. cinerea pups above toxicological thresholds reported for marine mammals. The concentration of Se (1332, 647, 763 µg/L) and molar ratio of Se:Hg (9.47, 7.98 and 6.82) were low compared to other pinniped pups, indicating potential vulnerability of pups to the toxic effects of Hg. Significant (p < 0.05) negative associations for Pb and Cd with several red blood cell parameters suggest they could be exacerbating the anaemia caused by hookworm disease. Temporal (age-related) changes in element concentrations were also seen, such that pup age needs to be considered when interpreting bioaccumulation patterns. Further investigation of the role of elevated heavy metal concentrations on N. cinerea pup health, disease and development is recommended, particularly with respect to immunological impacts.

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.

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.

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.

Impact of hookworm infection and preventive chemotherapy on haemoglobin in non-pregnant populations.

OBJECTIVE: To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas. METHOD: Systematic review and meta-analysis searching PubMed and Web of Science for articles published since 2010 reporting either hookworm prevalence and Hb concentration (cross-sectional studies) or Hb concentration before and after the implementation of preventive chemotherapy (before-after studies and randomised controlled trials [RCTs]). For papers published before 2010, data were extracted from a previously published systematic review. Random effects meta-analyses were conducted to examine the relationship between Hb concentration and hookworm infection intensity (from cross-sectional studies) and the effect of preventive chemotherapy on Hb concentration (from before-after studies and RCTs). Sensitivity analyses investigated the impact of malaria endemicity and combined interventions for schistosomiasis and nutrition status on Hb concentration. RESULTS: Among cross-sectional studies, both light- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children. School-aged children with heavy hookworm infection in settings of high malaria endemicity had lower mean Hb than those in settings of low malaria endemicity. In non-pregnant populations, deworming with albendazole was associated with an increase in Hb of 3.02 g/L (95% CI 0.1, 6.0 g/L). No additional benefit was seen with deworming using albendazole co-administered with praziquantel for schistosomiasis infection or iron supplementation for nutrition status. CONCLUSION: Our findings confirm the benefits of preventive chemotherapy as a public health intervention.

Epidemiology of soil-transmitted helminths following sustained implementation of routine preventive chemotherapy: Demographics and baseline results of a cluster randomised trial in southern Malawi.

Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this study aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a community census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional parasitological survey was then conducted between March-May 2018 in the censused area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level, and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. Trial registration: NCT03014167.

The Effect of Drug Pricing on Outpatient Payments and Treatment for Three Soil-Transmitted Helminth Infections in the United States, 2010-2017.

The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.

Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans.

Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole anthelmintics. However, benzimidazole efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold chain, and massively scalable. Bacillus thuringiensis crystal protein 5B (Cry5B) has anthelmintic properties that could fill this void. Here, we developed an active pharmaceutical ingredient (API) containing B. thuringiensis Cry5B compatible with MDA. We expressed Cry5B in asporogenous B. thuringiensis during vegetative phase, forming cytosolic crystals. These bacteria with cytosolic crystals (BaCC) were rendered inviable (inactivated BaCC [IBaCC]) with food-grade essential oils. IBaCC potency was validated in vitro against nematodes. IBaCC was also potent in vivo against human hookworm infections in hamsters. IBaCC production was successfully scaled to 350 liters at a contract manufacturing facility. A simple fit-for-purpose formulation to protect against stomach digestion and powdered IBaCC were successfully made and used against GINs in hamsters and mice. A pilot histopathology study and blood chemistry workup showed that five daily consecutive doses of 200 mg/kg body weight Cry5B IBaCC (the curative single dose is 40 mg/kg) was nontoxic to hamsters and completely safe. IBaCC is a safe, inexpensive, highly effective, easy-to-manufacture, and scalable anthelmintic that is practical for MDA and represents a new paradigm for treating human GINs.

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.

An in-depth report of quality control on Kato-Katz and data entry in four clinical trials evaluating the efficacy of albendazole against soil-transmitted helminth infections.

BACKGROUND: Efforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality. METHODOLOGY: During four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections. RESULTS: Across the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets. In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected. CONCLUSION/SIGNIFICANCE: In these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality.

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.

Sustained preventive chemotherapy for soil-transmitted helminthiases leads to reduction in prevalence and anthelminthic tablets required.

BACKGROUND: The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed. METHODS: We selected countries from World Health Organization (WHO)'s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed. RESULTS: Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1-64.7%) for any STH, 23.2% (13.7-32.7%) for Ascaris lumbricoides, 21.01% (9.7-32.3%) for Trichuris trichiura and 18.2% (10.9-25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3-21.3%) for any STH, 6.9% (1.3-12.5%) for A. lumbricoides, 5.3% (1.06-9.6%) for T. trichiura and 8.1% (4.0-12.2%) for hookworm infections. CONCLUSIONS: Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.

Micronutrient levels of tuberculosis patients during the intensive phase, a prospective cohort study.

INTRODUCTION: The objectives of this study were to estimate the micronutrient deficiency levels of tuberculosis patients at the start and end of the intensive phase, and to identify the predictors of micronutrient deficiencies in tuberculosis patients. METHODS: A prospective cohort study design was implemented. The sample size was calculated using Epi-info software. Systematic sampling technique was used. Descriptive statistics were used to estimate the micronutrient levels. The general linear model was used to predict the determinants of micronutrient level. RESULTS: At the start of DOTS (directly observed treatment strategy), 64% of tuberculosis patients had a serum iron level less than 60 µg/dl, 41.9% of tuberculosis patients had serum zinc level less than 52 µg/dl, 29.7% of tuberculosis patients had serum selenium level less than 70 ng/dl, 40.5% of tuberculosis patients had serum vitamin d level less than 20 ng/ml, and 60.4% of tuberculosis patients had urine iodine level of less than 60.4 µg/dl. At the end of the intensive phase, 16.7% of tuberculosis patients had a serum iron level less than 60 µg/dl, <1% of tuberculosis patients had serum zinc level less than 52 µg/dl, <1% of tuberculosis patients had serum selenium level less than 70 ng/dl, 20.4% of tuberculosis patients had serum vitamin d level less than 20 ng/ml, and 53% of tuberculosis patients had urine iodine level of less than 60.4 µg/dl. Serum iron level was affected by HIV infection, hookworm infection, and site of tuberculosis infection: serum vitamin d level was affected by HIV infection: and alcohol dependency affected the serum zinc level of tuberculosis patients during the course of tuberculosis treatments. CONCLUSION: Antituberculosis drugs were effective in normalizing the serum zinc and selenium level, but the serum level of iron, vitamin d and iodine were not normalized by the anti-tuberculosis drugs.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.

Ovicidal and larvicidal effects of extracts from leaves of Andrographis paniculata (Burm. f.) Wall.ex Nees against field isolates of human hookworm (Ancylostoma duodenale).

ETHNOPHARMACOLOGICAL RELEVANCE: The whole plant of Andrographis paniculata (Burm. f.) Wall.ex Nees is used traditionally in different forms by the local people of Asian countries owing to its myriad medicinal properties. Its use as an anthelmintic has been mentioned in literature but has not been well elucidated. AIM OF THE STUDY: To determine anthelmintic effects of extracts from leaves of A.paniculata against human hookworm species based on a standard assay system and to establish the effects of major active compounds responsible for the effects. MATERIALS AND METHODS: Ovicidal and larvicidal activities of extracts of leaves of A.paniculata in different solvents ethanol (Et), methanol (Met), ethyl acetate (EA) and petroleum ether (PE) was studied against field isolates of Ancylostoma duodenale collected and cultivated from hookworm infected human stool samples by egg hatch and larval motility assays. Major active compounds namely andrographolide (AP1), neoandrographolide (AP2) and andrograpanin (AP3) were estimated quantitatively in all the extracts by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) analysis. Anthelmintic effects (ED50, LC50) and presence of the marker compounds in each extract was statistically analyzed by principal component analysis (PCA). Further, biological activities of pure compounds of AP1, AP2, AP3 were assessed to validate the results of the study. RESULTS: Extracts in ethanol and methanol showed highest activity in inhibition of egg hatching with lowest ED50 values (0.017 and 0.02 mg/mL respectively) while ethyl acetate extract had the highest activity against larval motility (0.001 mg/mL) followed by ethanol (0.019 mg/mL). On HPLC analysis, andrographolide content (%), the major diterpene compound, in Met and Et was 0.85 and 1.43 respectively. On PCA, andrographolide component in the extracts was associated with significant inhibitory effects both on egg hatching and larval motility. Pure compound AP1 also showed significant ovicidal and larvicidal activities at concentrations 0.125 µg/mL and 0.019 mg/mL respectively. CONCLUSION: Andrographolide is one of the main phytochemical responsible for significant ovicidal and larvicidal activity against field isolates of A.duodenale from human infections and can be developed as a potential therapeutic choice.

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar.

BACKGROUND: Mass drug administration (MDA), targeted at school-aged children (SAC) is the method recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds and research suggests that only treating SAC will not be sufficient to bring prevalence to low levels and possibly interrupt transmission of STH. In countries with endemic infection, such as Myanmar, the coverage, who is targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term. METHODS/PRINCIPAL FINDINGS: In this paper, data from an epidemiological study on STH, comprising three surveys conducted between June 2015 and June 2016 in the delta region of Myanmar, are analysed to determine how STH prevalence and intensity in the study community changes over the course of a year, including reinfection after two MDA rounds in which the whole study sample (all age groups, n = 523) were treated with albendazole. Prevalence in the first survey (August 2015) was 27.92% for any STH, 5.54% for Ascaris lumbricoides, 17.02% for Trichuris trichiura and 9.75% for hookworm. Over the year (survey one to survey three), prevalence of any STH decreased by 8.99% (P < 0.001) and mean EPG significantly decreased for T. trichiura (P < 0.01) and hookworm (P < 0.001). Risk ratios (RRs) for a four-month reinfection period (August to December) were statistically significant and were below one, indicating that STH prevalence had not bounced back to the prevalence levels recorded immediately prior to the last round of treatment (any STH RR = 0.67, 95% CI 0.56-0.81; A. lumbricoides RR = 0.31, 95% CI 0.16-0.59; T. trichiura RR = 0.70, 95% CI 0.55-0.88; hookworm RR = 0.69, 95% CI 0.50-0.95). The only statistically significant RR for the six-month reinfection period (December to June) was for A. lumbricoides infection in SAC (RR = 2.67, 95% CI 1.37-5.21). All six-month RRs were significantly higher than four-month RRs (P < 0.05). Evidence of predisposition to infection (low and high), as measured by the Kendall Tau-b statistic, was found for all species overall and within most age groups stratifications, except for hookworm infection in preschool-aged children. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that, for certain demographic groups, a six-month gap between MDA in these communities is enough time for STH infection to return to STH prevalence levels recorded immediately before the previous MDA round, and that on average the same individuals are being consistently infected between MDA rounds.