Meta-analysis and public policy: Reconciling the evidence on deworming.

The WHO recommends mass drug administration (MDA) for intestinal worm infections in areas with over 20% infection prevalence. Recent Cochrane meta-analyses endorse treatment of infected individuals but recommend against MDA. We conducted a theory-agnostic random-effects meta-analysis of the effect of multiple-dose MDA and a cost-effectiveness analysis. We estimate significant effects of MDA on child weight (0.15 kg, 95% CI: 0.07, 0.24; P < 0.001), mid-upper arm circumference (0.20 cm, 95% CI: 0.03, 0.37; P = 0.02), and height (0.09 cm, 95% CI: 0.01, 0.16; P = 0.02) when prevalence is over 20% but not on Hb (0.06 g/dL, 95% CI: -0.01, 0.14; P = 0.1). These results suggest that MDA is a cost-effective intervention, particularly in the settings where it is recommended by the WHO.

Deworming and micronutrient status by community open defecation prevalence: An observational study using nationally representative data from India, 2016-2018.

BACKGROUND: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. METHODS AND FINDINGS: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. CONCLUSIONS: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study.

A 14-year review (2007-2020) of helminthiasis epidemiology in a hospital in Southern Madrid, Spain.

PURPOSE: Vast majority of helminth diseases remain neglected tropical diseases (NTDs), causing significant morbidity. The widespread and periodic distribution of antiparasitic drugs, remains the cornerstone for controlling these diseases. In Spain, most helminthiasis cases are imported, and suspicion and diagnosis have become increasingly important. Our primary objective is to present the epidemiological landscape of helminthiasis diagnoses within our facility, while also detailing the demographic characteristics of the affected population. METHODS: A retrospective study was conducted at the Hospital Universitario Severo Ochoa (HUSO) from January 1, 2007, to December 31, 2020, encompassing all diagnosed cases of helminthiasis during this period. Comprehensive epidemiological, clinical, and microbiological data were gathered for all diagnosed patients. The study population comprised patients receiving treatment at the HUSO, as well as those receiving treatment at the Leganés and Fuenlabrada Primary Care Units. Subsequently, descriptive and comparative statistics were performed, comparing Spanish and foreign patients. RESULTS: During this period, a total of 952 patients were diagnosed with some form of helminthiasis. Among them, 495 were Spanish, and 457 were foreign. The total number of helminths identified, including patients with multiple infections, was 1,010. Significant differences were observed between Africans and Americans in terms of age distribution, with a higher prevalence among Africans in the 0-15 age range and among Americans in the 31-60 age range. Variations were noted in the distribution of helminths, with S. stercoralis significantly affecting Americans. For Spanish patients, the presence of Trichuris trichiura and S. stercoralis was significantly associated with eosinophilia, whereas among foreign patients, it was associated with Trichuris trichiura, Ascaris lumbricoides among others. Regarding symptoms, skin manifestations were more frequent among Spanish, while digestive were more common among foreigners. CONCLUSIONS: This study offers crucial epidemiological insights into helminth infections observed over time in a Madrid hospital. Although the prevalence of helminth infections has been decreasing, there is still a need for screening and diagnosing foreign patients.

Twenty-year economic impacts of deworming.

Estimating the impact of child health investments on adult living standards entails multiple methodological challenges, including the lack of experimental variation in health status, an inability to track individuals over time, and accurately measuring living standards and productivity in low-income settings. This study exploits a randomized school health intervention that provided deworming treatment to Kenyan children, and uses longitudinal data to estimate impacts on economic outcomes up to 20 y later. The effective respondent tracking rate was 84%. Individuals who received two to three additional years of childhood deworming experienced a 14% gain in consumption expenditures and 13% increase in hourly earnings. There are also shifts in sectors of residence and employment: treatment group individuals are 9% more likely to live in urban areas, and experience a 9% increase in nonagricultural work hours. Most effects are concentrated among males and older individuals. The observed consumption and earnings benefits, together with deworming's low cost when distributed at scale, imply that a conservative estimate of its annualized social internal rate of return is 37%, a high return by any standard.

Management of paediatric soil-transmitted helminthiasis in a non-endemic area: experience in a reference international health unit.

Soil-transmitted helminth (STH) infections inflict disability worldwide, especially in the poorest communities. Current therapeutic options against STHs show limited efficacy, particularly against Trichuris trichiura. The empirical management of patients coming from high-prevalence areas has been suggested for non-endemic areas. This study aimed to describe the management of STH infections in a non-endemic setting using an individualised approach. We performed a retrospective, descriptive study of all patients up to 16 years of age with STH infections attended at an international health unit in a non-endemic area (2014-2018), including all T. trichiura, Necator americanus, Ancylostoma duodenale, and Ascaris lumbricoides infections diagnosed using a formol-ether concentration technique and direct visualisation. Patients were treated according to current international guidelines. Sixty-one stool samples from 48 patients testing positive for STHs were collected, with 96% (46/48) reporting a previous long-term stay in endemic areas. Cure rates with 3-day benzimidazole regimens were 72% for T. trichiura, 40% for hookworms, and 83% for A. lumbricoides. The results were not influenced by any reinfection risk due to the study being performed in a non-endemic area. Patients coming from STH-endemic areas should be evaluated with appropriate diagnostic tools and followed up until cure control results. Cure rates in our cohort were moderate to low, similar to those published in studies in endemic areas. The efficacy of current treatment options is insufficient to recommend a specific empirical approach in high-income countries' healthcare systems.

Reach and uptake of mass drug administration for worm infections through health facility-, school-, and community-based approaches in two districts of Zambia: a call for scale-up.

Helminthiases cause significant health deficiencies among children. Mass administration of anthelminthic drugs has had significant results to counter these effects. We assessed the effects on and determinants of treatment coverage of community-directed treatment among children in Zambia, using cross-sectional survey data, and using chi-square test and multilevel mixed-effects model. Of 1,416 children, 51.5% were males and 48.5% were females, while 52.7%, were school-age, and 47.3% were preschool-age. Overall treatment coverage was 53.7% (95% confidence interval (CI) 51.1, 56.4). More preschool-age children were treated compared to school-age ones, 65.2% versus 43.4%, P < 0.001. Similarly, more children under community-directed intervention were treated compared to regular mass drug administration (65.2% versus 51.1 %, P < 0.001). Treatment among school-age participants was associated with being male (Adjusted Odds Ratio (AOR 1.83, 95%CI 1.23-2.72), receiving community-directed treatment (AOR 5.53; 95%CI 3.41-8.97), and shorter distance to health facility (AOR 2.20; 95%CI 1.36-3.56). Among preschool-aged participants, treatment was associated with being residents of Siavonga district (AOR 0.03; 95%CI 0.01-0.04) and shorter distance to health facility (AOR 0.35; 95%CI 0.21-0.59). Community-directed treatment can be used to increase treatment coverage, thereby contribute to 2030 vision of ending epidemics of neglected tropical diseases.

Horse and donkey parasitology: differences and analogies for a correct diagnostic and management of major helminth infections.

In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed. Although these 2 species are genetically different, they can be challenged by a similar range of parasites (i.e. small and large strongyles, and Parascaris spp.). Although equids can demonstrate some level of resilience to parasites, they have quite distinct helminth biodiversity, distribution and intensity among different geographical locations and breeds. Heavily infected donkeys may show fewer clinical signs than horses. Although parasite control is primarily provided to horses, we consider that there may be a risk of drug-resistance parasitic infection through passive infection in donkeys when sharing the same pasture areas. Knowing the possible lack of drug efficacy (<90 or 80%), it is advocated the use of selective treatment for both species based on fecal egg counts. Adult horses should receive treatment when the threshold exceeds 200­500 eggs per gram (EPG) of small strongyles. Moreover, considering that there are no precise indications in donkeys, a value >300 EPG may be a safe recommendation. We have highlighted the main points of the discussion including the dynamics of helminth infections between the 2 species.

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.

Anthelmintic resistance in soil-transmitted helminths: One-Health considerations.

The One-Health approach recognizes the intricate connection between human, animal, and environmental health, and that cooperative effort from various professionals provides comprehensive awareness and potential solutions for issues relating to the health of people, animals, and the environment. This approach has increasingly gained appeal as the standard strategy for tackling emerging infectious diseases, most of which are zoonoses. Treatment with anthelmintics (AHs) without a doubt minimizes the severe consequences of soil-transmitted helminths (STHs); however, evidence of anthelmintic resistance (AR) development to different helminths of practically every animal species and the distinct groups of AHs is overwhelming globally. In this regard, the correlation between the application of anthelmintic drugs in both human and animal populations and the consequent development of anthelmintic resistance in STHs within the context of a One-Health framework is explored. This review provides an overview of the major human and animal STHs, treatment of the STHs, AR development and drug-related factors contributing towards AR, One-Health and STHs, and an outline of some One-Health strategies that may be used in combating AR.

Resistance to single dose albendazole and reinfection with intestinal helminths among children ages 2 to 11 years from the Peruvian Amazon region: a study protocol.

BACKGROUND: Deworming programs aimed at reducing morbidity and mortality from geohelminth infections are common in many countries where these infections are endemic, but data demonstrating increasing levels of resistance to albendazole and mebendazole are causes for concern. Studies to evaluate the clinical efficacy of deworming programs are critical to maintain high infection control goals. METHODS: We propose to assess the clinical efficacy of Peruvian national guidelines for deworming programs in a prospective observational study conducted in the Amazon River basin area near Iquitos, Peru. Major outcomes to be evaluated include (1) albendazole resistance of intestinal helminths (trichuriasis, ascariasis, hookworm), and (2) frequency of reinfection with intestinal helminths 4 months after treatment with albendazole. Children ages 2-11 years from the Belén District of Iquitos will be identified based on a community census. Following parental informed consent, demographic data, weight, and height will be recorded and a stool specimen for parasitological exam by direct observation and Kato-Katz concentration method, and helminthic egg counts will be collected prior to administration of albendazole, following Peruvian national guidelines. Follow-up stool specimens examined in the same manner will be collected at 20 days, 90 days, and 100 days following initial administration of albendazole, and based on parasites found repeat treatment will be administered in accordance with national guidelines. Real-time multiplex qPCR will be performed on helminth positive samples collected prior to initial deworming and on helminth-positive specimens detected on day 15-20. A total sample size of 380 participants was calculated based on total population in the target group and prevalence estimates of helminth infections and clinical resistance based on recent data. DISCUSSION: Data from observational clinical efficacy studies are important to guide geohelminth infection control programs. Trial registration https://www.researchregistry.com/ . Identification number: researchregistry7736; Registered retrospectively March 13, 2022; https://www.researchregistry.com/browse-the-registry#home/registrationdetails/622e024cf06132001e3327bf/.

Defining optimal implementation packages for delivering community-wide mass drug administration for soil-transmitted helminths with high coverage.

BACKGROUND: Recent evidence suggests that community-wide mass drug administration (MDA) may interrupt the transmission of soil-transmitted helminths (STH), a group of intestinal worms that infect 1.5 billion individuals globally. Although current operational guidelines provide best practices for effective MDA delivery, they do not describe which activities are most essential for achieving high coverage or how they work together to produce effective intervention delivery. We aimed to identify the various packages of influential intervention delivery activities that result in high coverage of community-wide MDA for STH in Benin, India, and Malawi. METHODS: We applied coincidence analysis (CNA), a novel cross-case analytical method, to process mapping data as part of the implementation science research of the DeWorm3 Project, a Hybrid Type 1 cluster randomized controlled trial assessing the feasibility of interrupting the transmission of STH using bi-annual community-wide MDA in Benin, India, and Malawi. Our analysis aimed to identify any necessary and/or sufficient combinations of intervention delivery activities (i.e., implementation pathways) that resulted in high MDA coverage. Activities were related to drug supply chain, implementer training, community sensitization strategy, intervention duration, and implementation context. We used pooled implementation data from three sites and six intervention rounds, with study clusters serving as analytical cases (N = 360). Secondary analyses assessed differences in pathways across sites and over intervention rounds. RESULTS: Across all three sites and six intervention rounds, efficient duration of MDA delivery (within ten days) singularly emerged as a common and fundamental component for achieving high MDA coverage when combined with other particular activities, including a conducive implementation context, early arrival of albendazole before the planned start of MDA, or a flexible community sensitization strategy. No individual activity proved sufficient by itself for producing high MDA coverage. We observed four possible overall models that could explain effective MDA delivery strategies, all which included efficient duration of MDA delivery as an integral component. CONCLUSION: Efficient duration of MDA delivery uniquely stood out as a highly influential implementation activity for producing high coverage of community-wide MDA for STH. Effective MDA delivery can be achieved with flexible implementation strategies that include various combinations of influential intervention components.

An assessment of implementation and effectiveness of mass drug administration for prevention and control of schistosomiasis and soil-transmitted helminths in selected southern Malawi districts.

BACKGROUND: Mass drug administration (MDA) is one of the key interventions recommended by WHO for prevention and control of neglected tropical diseases (NTD). In Malawi, MDA is widely carried out annually since 2009 for prevention and control of schistosomiasis and soil-transmitted helminths (STH). No study has been carried out to assess effectiveness of the MDA approach and to document perceptions of health providers and beneficiaries regarding use of MDA. This study was done to understand how well MDA is being implemented and to identify opportunities for improvement in MDA delivery in Malawi. METHODS: Designed as a cross-sectional and multi-methods research, the study was carried out in three southern Malawi districts of Chiradzulu, Mangochi and Zomba. In each district, four health centres and 16 villages were randomly selected to participate. A mixed-methods approach to data collection focusing on quantitative data for coverage and knowledge, attitudes and practices assessments; and qualitative data for assessing perceptions of health providers and beneficiaries regarding MDA was used. Quantitative data were processed and analyzed using IBM SPSS software version 26 while qualitative data were analysed using NVivo 12 for Windows. RESULTS: Knowledge levels about schistosomiasis and STH in the districts varied according to disease aspects asked about. Majority are more knowledgeable about what schistosomiasis is (78%) and whether STH are treatable with drugs (97%); with least knowledgeable about the organism that transmits schistosomiasis (18%), types of schistosomiasis (11%) and what causes STH (20%). In 2018 and 2019 the districts registered high coverage rates for praziquantel and albendazole using community-based MDA (73-100%) and using school-based MDA (75-91%). Both the health authorities and community members perceived the MDA approach as good because it brings treatment closer to people. CONCLUSION: With the high MDA coverage obtained in communities and schools, the effectiveness of MDA in the target districts is satisfactory. There are, however, several challenges including disproportionate knowledge levels, which are hampering progress towards attainment of the 2030 global NTD goals. There is a need for promotion of community participation and partnerships as well as implementation of other recommended interventions for sustainable prevention and control of schistosomiasis and STH.

Factors determining preventive chemotherapy uptake against soil-transmitted helminthiasis among school-age children in Ghana.

By 2020, the World Health Organization and the Ghana Neglected Tropical Diseases programme intended to treat 75% and 100% of school-age children, respectively, during preventative chemotherapy (PCT), to control soil-transmitted helminths. The performance of PCT was assessed, and the factors associated with albendazole uptake in 2019 were determined. This study comprised secondary data (2019 PCT) and a community-based cross-sectional study conducted among 352 children aged from 7 to 14 years and enrolled with their caregivers. Logistic regression was used to determine the factors hindering or favouring the PCT uptake. According to surveillance data (2019 PCT), Krachi East Municipal reported coverage of 83% in schools and 40.9% for all children between 5 and 14 years. The cross-sectional data showed that the median child age was 11 years (IQR: 9-12). There was no gap in the estimates for coverage and uptake, which were both 90.9% (95%CI: 87.4-93.5%). Christians made up the majority of the caregivers (87.5%), and 48.0% had completed secondary or higher education. After controlling for potential confounders, caregiver religion (aOR = 0.07 95%CI: 0.01-0.36) and the perception of a child's PCT risk (aOR = 0.33 95%CI: 0.13-0.84) were the significant barriers of PCT uptake, whereas the child's age (aOR = 1.49 95%CI: 1.19-1.88) and the perception of a child's PCT's benefit (aOR = 10.26 95%CI: 2.57-40.95) were the significant facilitators among children 7-14 years old. Although the performance of PCT was high, the national treatment target was not attained. Intensive and focused health education is therefore needed to improve positive perceptions towards PCT for school-age children.

Essential Oils as Novel Anthelmintic Drug Candidates.

Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health Organization to prevent helminth infection includes increasing hygienic awareness, providing better sanitation and preventative anthelmintic drug therapy in vulnerable populations. Nowadays, anthelmintic drugs are used heavily in livestock, both in case of infection and as a preventative measure. However, this has led to the development of resistance against several of the most common drugs, such as levamisole, ivermectin and thiabendazole. As many as 70% of the livestock in developed countries now has helminths that are drug resistant, and multiple resistance is common. Because of this, novel anthelmintics are urgently needed to help combat large-scale production losses. Prior to this review, no comprehensive review of the anthelmintic effects of essential oils and their components existed. Multiple review articles have been published on the uses of a single plant and its extracts that only briefly touch upon their anthelmintic activity. This review aims to provide a detailed overview of essential oils and their components as anthelmintic treatment against a wider variety of helminths.

Status of Helminthic Infections in Residents around River Basins in the Republic of Korea for 10 Years (2011-2020).

The positive rate of Clonorchis sinensis is the highest among intestinal parasites in the Republic of Korea (Korea). More than 1.2 million people were at risk of C. sinensis infection in Korea in 2012. An intensive control program is being implemented for residents of the 5 major river basins to reduce helminthic infections, including C. sinensis infection. This study evaluated the continuous intensive control program for parasitic diseases including clonorchiasis in areas near the 5 major river basins in Korea over the past 10 years (2011-2020). A total of 335,020 fecal samples (one sample per resident) prepared by the modified sedimentation technic were microscopically examined. Those who expelled helminth eggs were treated with anthelmintics through local health centers and re-examined 3 months later. The overall positive rate of helminths egg was 7.1%. The annual positive rates were dramatically decreased from 14.4% (2011) to 5.9% (2020). The egg positive rate was highest in C. sinensis (5.3%), followed by heterophyid flukes (1.5%) and Trichuris trichiura (0.2%). The prevalence of C. sinensis was significantly higher in males (7.6%) than in females (3.7%), and the highest in the 50-59 years (7.0%) age group. Our results are beneficial to establish prevention and control policies against helminthiases including clonorchiasis in endemic areas in this country.

Survey Design to Monitor Drug Efficacy for the Control of Soil-Transmitted Helminthiasis and Schistosomiasis.

BACKGROUND: Control of soil-transmitted helminthiasis and schistosomiasis relies heavily on regular preventive chemotherapy. Monitoring drug efficacy is crucial to provide early warning of treatment failures. The World Health Organization (WHO) recommends a survey design in which only egg-positive individuals are retested after treatment. Although this practice makes more efficient use of resources, it may lead to biased drug efficacy estimates. METHODS: We performed a simulation study to assess the potential for bias when evaluating drug efficacy using the World Health Organization-recommended survey design, and to identify alternative designs for evaluating drug efficacy that are less affected by bias. These designs were also based on selection of egg-positive individuals, but involve retesting them a second time at baseline and up to 2 times at follow-up. The utility of the different designs was compared fairly by constraining them to the same budget. RESULTS: The standard procedure of selecting egg-positive individuals can introduce a substantial positive bias in drug efficacy due to regression toward the mean, particularly when infection levels or drug efficacy are low. This bias was completely eliminated by using a second baseline sample, conditionally on the first sample being excluded from analysis. Precision of estimates can be improved by increasing the number of thick smears and/or samples per person at follow-up, despite fewer individuals being tested within the same budget. CONCLUSIONS: We present optimized survey designs to monitor drug efficacy in field settings, which are highly relevant for sustained control of soil-transmitted helminths and schistosomiasis, as well as onchocerciasis and lymphatic filariasis.

Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers.

Soil-transmitted-helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting preschool- and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to (i) evaluate the effect of type of diet (a heavy or light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and (ii) evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulfoxide (ALBSO) metabolite was enhanced more than 2-fold after food ingestion (a heavy or light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulfone (NHALBSO2) derivative and ALBSO for up to 96 h suggests that it may be feasible to develop a noninvasive tool to evaluate compliance/adherence to ALB treatment.

Coexistent Helminth Infection-Mediated Modulation of Chemokine Responses in Latent Tuberculosis.

Coexistent helminth infections are known to modulate T cell and cytokine responses in latent infection with Mycobacterium tuberculosis However, their role in modulating chemokine responses in latent tuberculosis (LTB) has not been explored. Because chemokines play a vital role in the protective immune responses in LTB, we postulated that coexistent helminth infection could modulate chemokine production in helminth-LTB coinfection. To test this, we measured the levels of a panel of CC and CXC chemokines at baseline and following mycobacterial Ag or mitogen stimulation in individuals with LTB with (Strongyloides stercoralis +LTB+) or without S. stercoralis (S. stercoralis -LTB+) infection and in individuals without both infections, healthy controls (HC). At baseline (in the absence of a stimulus), S. stercoralis +LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL9, CXCL10, and CXCL11 in comparison with S. stercoralis -LTB+ and/or HC individuals. Upon mycobacterial Ag stimulation, S. stercoralis +LTB+ individuals exhibited significantly diminished production of CCL1, CCL2, CCL4, CCL11, CXCL2, CXCL9, and CXCL10 in comparison with S. stercoralis -LTB+ and/or HC individuals. No differences were observed upon mitogen stimulation. Finally, after anthelmintic treatment, the baseline levels of CCL1, CCL2, CCL4, CCL11, and CXCL11 and mycobacterial Ag-stimulated levels of CCL1, CCL2, CCL11, CXCL2, and CXCL10 were significantly increased in S. stercoralis +LTB+ individuals. Thus, our data demonstrate that S. stercoralis +LTB+ individuals are associated with a compromised ability to express both CC and CXC chemokines and that this defect is at least partially reversible upon treatment. Hence, coexistent helminth infection induces downmodulation of chemokine responses in LTB individuals with likely potential effects on tuberculosis pathogenesis.

Effect of mass deworming with antihelminthics for soil-transmitted helminths during pregnancy.

BACKGROUND: Helminthiasis is an infestation of the human body with parasitic worms. It is estimated to affect 44 million pregnancies, globally, each year. Intestinal helminthiasis (hookworm infestation) is associated with blood loss and decreased supply of nutrients for erythropoiesis, resulting in iron-deficiency anaemia. Over 50% of the pregnant women in low- and middle-income countries (LMIC) suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hookworm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious, but evidence of their beneficial effect and safety when given during pregnancy has not been established. This is an update of a Cochrane Review last published in 2015. OBJECTIVES: To determine the effects of mass deworming with antihelminthics for soil-transmitted helminths (STH) during the second or third trimester of pregnancy on maternal and pregnancy outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (8 March 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included all prospective randomised controlled trials evaluating the effect of administration of antihelminthics versus placebo or no treatment during the second or third trimester of pregnancy; both individual-randomised and cluster-randomised trials were eligible. We excluded quasi-randomised trials and studies that were only available as abstracts with insufficient information. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, checked accuracy and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included a total of six trials (24 reports) that randomised 7873 pregnant women. All of the included trials were conducted in antenatal clinics within hospitals in LMICs (Uganda, Nigeria, Peru, India, Sierra Leone and Tanzania). Among primary outcomes, five trials reported maternal anaemia, one trial reported preterm birth and three trials reported perinatal mortality. Among secondary outcomes, included trials reported maternal worm prevalence, low birthweight (LBW) and birthweight. None of the included studies reported maternal anthropometric measures or infant survival at six months. Overall, we judged the included trials to be generally at low risk of bias for most domains, while the certainty of evidence ranged from low to moderate. Analysis suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia by 15% (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.72 to 1.00; I²= 86%; 5 trials, 5745 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on preterm birth (RR 0.84, 95% CI 0.38 to 1.86; 1 trial, 1042 participants; low-certainty evidence) or perinatal mortality (RR 1.01, 95% CI 0.67 to 1.52; 3 trials, 3356 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on hookworm (average RR 0.31, 95% CI 0.05 to 1.93; Tau² = 1.76, I² = 99%; 2 trials, 2488 participants; low-certainty evidence). Among other secondary outcomes, findings suggest that administration of antihelminthics during pregnancy may reduce the prevalence of trichuris (average RR 0.68, 95% CI 0.48 to 0.98; I²=75%; 2 trials, 2488 participants; low-certainty evidence) and ascaris (RR 0.24, 95% CI 0.19 to 0.29; I²= 0%; 2 trials, 2488 participants; moderate-certainty evidence). Antihelminthics during pregnancy probably make little or no difference to LBW (RR 0.89, 95% CI 0.69 to 1.16; 3 trials, 2960 participants; moderate-certainty evidence) and birthweight (mean difference 0.00 kg, 95% CI -0.03 kg to 0.04 kg; 3 trials, 2960 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia and worm prevalence when used in settings with high prevalence of maternal helminthiasis. Further data is needed to establish the benefit of antihelminthic treatment on other maternal and pregnancy outcomes. Future research should focus on evaluating the effect of these antihelminthics among various subgroups in order to assess whether the effect varies. Future studies could also assess the effectiveness of co-interventions and health education along with antihelminthics for maternal and pregnancy outcomes.