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.

How tapeworms interact with cancers: a mini-review.

Cancer is one of the leading causes of death, with an estimated 19.3 million new cases and 10 million deaths worldwide in 2020 alone. Approximately 2.2 million cancer cases are attributed to infectious diseases, according to the World Health Organization (WHO). Despite the apparent involvement of some parasitic helminths (especially trematodes) in cancer induction, there are also records of the potential suppressive effects of helminth infections on cancer. Tapeworms such as Echinococcus granulosus, Taenia crassiceps, and more seem to have the potential to suppress malignant cell development, although in a few cases the evidence might be contradictory. Our review aims to summarize known epidemiological data on the cancer-helminth co-occurrence in the human population and the interactions of tapeworms with cancers, i.e., proven or hypothetical effects of tapeworms and their products on cancer cells in vivo (i.e., in experimental animals) or in vitro. The prospect of bioactive tapeworm molecules helping reduce the growth and metastasis of cancer is within the realm of future possibility, although extensive research is yet required due to certain concerns.

Prevalence and correlates of soil-transmitted helminths in schoolchildren aged 5 to 18 years in low- and middle-income countries: a systematic review and meta-analysis.

Background: According to the Global Burden of Disease (GBD) 2019 report, up to 1.5 million disability-adjusted life years (DALYs) are lost due to soil-transmitted helminths (STHs), and 5.9 million people are at risk of acquiring STHs. Regions with the highest prevalence of STH infections include Sub-Saharan Africa, China, South America, and Asia. While there are numerous fragmented studies on STH, comprehensive information on the prevalence and geographic distribution of different species, as well as their regional variations in the context of STHs is limited. The present systematic review and meta-analysis study attempts to provide a summary of the prevalence, geographical variation, and determinants of STHs among schoolchildren aged 5 to 18 years. Methods: An extensive literature search was carried out using PubMed, Embase, Cinhal, and Psychinfo for studies published between 1999 and 2022 that reported the rate of STH infection in school-going children aged 5-18 years. A random effects model was employed in this meta-analysis due to expected heterogeneity. Subgroup analysis was carried out based on sex and STH species because of expected geographical variation. Results: A total of 19,725 of the 49,630 children examined were infected with STH, yielding an overall pooled prevalence of 37.16% (95% CI: 29.74-44.89). The prevalence was highest in the Western Pacific region at 50.41% (95% CI: 33.74-67.04) followed by Europe at 39.74% (95% CI: 20.40-61.0) and Africa at 37.10% (95% CI: 26.84-47.95). Ascaris lumbricoides was found to be the most prevalent helminth with a prevalence of 24.07% (95% CI: 17.07-31.83). Conclusion: The Western Pacific region is classified as a High-risk Zone (HRZ), while Southeast Asia, Africa, Europe, and the Eastern Mediterranean are classified as moderate-risk zones (MRZs). We found a 12% reduction in the pooled prevalence of STH infection from 1999 to 2012. Ascaris lumbricoides was the predominant species among schoolchildren. Mass Drug Administration (MDA) of Albendazole tablets and improved water, sanitation, and hygiene (WASH) practices are effective in controlling and preventing STH. Ensuring their implementation and access is crucial to addressing the problem. Systematic review registration: https://www.crd.york.ac.uk/prospero/#loginpage, CRD42022333341.

Diagnosis of soil-transmitted helminth infections with digital mobile microscopy and artificial intelligence in a resource-limited setting.

BACKGROUND: Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples. However, the diagnostic accuracy of AI-based analysis of entire microscope slides, so called whole-slide images (WSI), has previously not been evaluated on a sample-level in primary healthcare settings in STH endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: Stool samples (n = 1,335) were collected during 2020 from children attending primary schools in Kwale County, Kenya, prepared according to the Kato-Katz method at a local primary healthcare laboratory and digitized with a portable whole-slide microscopy scanner and uploaded via mobile networks to a cloud environment. The digital samples of adequate quality (n = 1,180) were split into a training (n = 388) and test set (n = 792) and a deep-learning system (DLS) developed for detection of STHs. The DLS findings were compared with expert manual microscopy and additional visual assessment of the digital samples in slides with discordant results between the methods. Manual microscopy detected 15 (1.9%) Ascaris lumbricoides, 172 (21.7%) Tricuris trichiura and 140 (17.7%) hookworm (Ancylostoma duodenale or Necator americanus) infections in the test set. Importantly, more than 90% of all STH positive cases represented light intensity infections. With manual microscopy as the reference standard, the sensitivity of the DLS as the index test for detection of A. lumbricoides, T. trichiura and hookworm was 80%, 92% and 76%, respectively. The corresponding specificity was 98%, 90% and 95%. Notably, in 79 samples (10%) classified as negative by manual microscopy for a specific species, STH eggs were detected by the DLS and confirmed correct by visual inspection of the digital samples. CONCLUSIONS/SIGNIFICANCE: Analysis of digitally scanned stool samples with the DLS provided high diagnostic accuracy for detection of STHs. Importantly, a substantial number of light intensity infections were missed by manual microscopy but detected by the DLS. Thus, analysis of WSIs with image-based AI may provide a future tool for improved detection of STHs in a primary healthcare setting, which in turn could facilitate monitoring and evaluation of control programs.

Serological diagnosis of soil-transmitted helminth (Ascaris, Trichuris and hookworm) infections: A scoping review.

BACKGROUND: The World Health Organization emphasizes the importance of integrated monitoring and evaluation in neglected tropical disease (NTD) control programs. Serological assays offer a potential solution for integrated diagnosis of NTDs, particularly for those requiring mass drug administration (MDA) as primary control and elimination strategy. This scoping review aims (i) to provide an overview of assays using serum or plasma to detect infections with soil-transmitted helminths (STHs) in both humans and animals, (ii) to examine the methodologies used in this research field and (iii) to discuss advancements in serological diagnosis of STHs to guide prevention and control programs in veterinary and human medicine. METHODOLOGY: We conducted a systematic search in the Ovid MEDLINE, Embase and Cochrane Library databases, supplemented by a Google search using predefined keywords to identify commercially available serological assays. Additionally, we performed a patent search through Espacenet. PRINCIPAL FINDINGS: We identified 85 relevant literature records spanning over 50 years, with a notable increased interest in serological assay development in recent years. Most of the research efforts concentrated on diagnosing Ascaris infections in both humans and pigs, primarily using ELISA and western blot technologies. Almost all records targeted antibodies as analytes, employing proteins and peptides as analyte detection agents. Approximately 60% of sample sets described pertained to human samples. No commercially available tests for Trichuris or hookworms were identified, while for Ascaris, there are at least seven different ELISAs on the market. CONCLUSIONS: While a substantial number of assays are employed in epidemiological research, the current state of serological diagnosis for guiding STH prevention and control programs is limited. Only two assays designed for pigs are used to inform efficient deworming practices in pig populations. Regarding human diagnosis, none of the existing assays has undergone extensive large-scale validation or integration into routine diagnostics for MDA programs.

Adolescents' Perspective Regarding a Community-Wide Mass Drug Administration Program for Soil-Transmitted Helminths in India.

This study was undertaken to understand the perspective of adolescents in endemic communities of India regarding soil-transmitted helminth (STH) infections and community-wide mass drug administration (cMDA). A multicountry community-based cluster-randomized trial, the Deworm3 trial, tested the feasibility of interrupting STH transmission with cMDA, where all individuals aged 1-99 are treated empirically with albendazole. Using a guideline based on the Consolidated Framework for Implementation Research, eight focus group discussions were conducted among 57 adolescents from the trial site in India and analyzed on ATLAS.ti 8.0 software using an a priori thematic codebook. Adolescents believed that adults could be a source of STH infection because they were not routinely dewormed like the children through the national deworming program. Perceived benefits of cMDA for all were better health and increased work efficiency. Perceived barriers to adults' participation in cMDA was their mistrust about the program, fear of side effects, perceived low risk of infection, and absence during drug distribution. To encourage adult participation in cMDAs, adolescents suggested community outreach activities, engaging village influencers and health workers, and tailoring drug distribution to when adults would be available. Adolescents were confident in their ability to be change agents within their households for treatment compliance. Adolescents provided insights into potential barriers and solutions to improve adult participation in cMDA, identified best practices of cMDA delivery, and suggested that they have unique roles as change agents to increase their household participation in cMDA.

The association of 25(OH)D, interleukin-4, interleukin-5, and interleukin-13 levels with the burden of soil-transmitted helminth infection in stunted children aged 24-59 months.

Soil-transmitted helminth (STH) among children aged 24-59 months is one cause of chronic infection that could lead to stunting. The association of 25(OH)D and immune responses during chronic infection in stunted populations has not yet been well established. An association study of case-control data was conducted in Bandung district from October 2019 to January 2023. Sociodemographic factors, stool samples, and serum levels of 25(OH)D, interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) were assessed. Statistical analysis was performed to evaluate the prevalence and association of 25(OH)D, IL-4, IL-5, and IL-13 with the burden of STH infection in stunted children. In total, 401 stunted children were recruited. A higher burden of STH infection was found for lower levels of IL-5 (r = -0.477; p = 0.004) and IL-13 (r = -0.433; p = 0.028). Thus, 25(OH)D, IL-4, IL-5, and IL-13 play a role in the burden of STH infection.

Gastrointestinal helminths infection of free-roaming cats (Felis catus) in Southeast Iran.

BACKGROUND: Cats in Iran are definitive hosts for several zoonotic intestinal helminths, such as Toxocara cati, Dipylidium caninum, Toxascaris leonina, Physaloptera praeputialis and Diplopylidium nolleri. OBJECTIVE: This study aimed to determine the prevalence of intestinal helminth infection in free-roaming cats in southeast Iran, a region with a high free-roaming cat population. METHODS: From January 2018 to December 2021, 153 cadavers of free-roaming cats from Southeast Iran were necropsied for intestinal helminth infections. The carcasses were dissected, and the digestive systems were removed. The esophagus, stomach, small intestine, caecum and colon were tightly ligated. All adult helminths were collected, preserved and identified. RESULTS: The prevalence of gastrointestinal helminth infections was 80.39% (123/153). Of the cats from Kerman, 73% (73/100) were infected with at least one helminth, including D. caninum 70% (70/100), T. leonina 8% (8/100) and P. praeputialis 17% (17/100). Concurrent infection with two helminth species was found in 16% (16/100) and of three species infections was found in 3% (3/100) of the cats. Of the cats from Zabol, 94.33% (50/53) were infected with at least one of the helminths, including D. caninum 69.81% (37/53), T. leonina 11.32% (6/53), P. praeputialis 37.73% (20/53) and T. cati 5.66% (3/53). Concurrent infection with two helminth species was found in 28.3% (15/53), and three species were found in 1.88% (1/53) of the cats. Helminth infections were more prevalent in older cats. There was no association between sex and infection rate. CONCLUSION: Based on the very high prevalence of zoonotic intestinal helminth infections in free-roaming cats in southeast Iran, the potential public health risk emphasizes the need for intersectoral collaboration, particularly the provision of health and hygiene education to high-risk populations, such as pre-school and school-age children.

A review of health education activities targeting schoolchildren for the control of soil-transmitted helminthiasis in Southeast Asia, with emphasis upon the Magic Glasses approach.

Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region.

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.

Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatment.

BACKGROUND: Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date. METHODS: Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy. RESULTS: Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively. CONCLUSIONS: Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections. TRIAL REGISTRATION: NCT03527732.

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.

"Our desire is to make this village intestinal worm free": Identifying determinants of high coverage of community-wide mass drug administration for soil transmitted helminths in Benin, India, and Malawi.

BACKGROUND: Soil-transmitted helminth infections (STH) are associated with substantial morbidity in low-and-middle-income countries, accounting for 2.7 million disability-adjusted life years annually. Current World Health Organization guidelines recommend controlling STH-associated morbidity through periodic deworming of at-risk populations, including children and women of reproductive age (15-49 years). However, there is increasing interest in community-wide mass drug administration (cMDA) which includes deworming adults who serve as infection reservoirs as a method to improve coverage and possibly to interrupt STH transmission. We investigated determinants of cMDA coverage by comparing high-coverage clusters (HCCs) and low-coverage clusters (LCCs) receiving STH cMDA in three countries. METHODS: A convergent mixed-methods design was used to analyze data from HCCs and LCCs in DeWorm3 trial sites in Benin, India, and Malawi following three rounds of cMDA. Qualitative data were collected via 48 community-level focus group discussions. Quantitative data were collected via routine activities nested within the DeWorm3 trial, including annual censuses and coverage surveys. The Consolidated Framework for Implementation Research (CFIR) guided coding, theme development and a rating process to determine the influence of each CFIR construct on cMDA coverage. RESULTS: Of 23 CFIR constructs evaluated, we identified 11 constructs that differentiated between HCCs and LCCs, indicating they are potential drivers of coverage. Determinants differentiating HCC and LCC include participant experiences with previous community-wide programs, communities' perceptions of directly observed therapy (DOT), perceptions about the treatment uptake behaviors of neighbors, and women's agency to make household-level treatment decisions. CONCLUSION: The convergent mixed-methods study identified barriers and facilitators that may be useful to NTD programs to improve cMDA implementation for STH, increase treatment coverage, and contribute to the successful control or elimination of STH. TRIAL REGISTRATION: The parent trial was registered at clinicaltrials.gov (NCT03014167).

Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy.

Control of soil-transmitted helminths relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human soil-transmitted helminths, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. Here we predict the population dynamics of human soil-transmitted helminth infections and drug resistance during 20 years of regular preventive chemotherapy, using an individual-based model. With the current preventive chemotherapy strategy of mainly targeting children in schools, drug resistance may evolve in soil-transmitted helminths within a decade. More intense preventive chemotherapy strategies increase the prospects of soil-transmitted helminths elimination, but also increase the speed at which drug efficacy declines, especially when implementing community-based preventive chemotherapy (population-wide deworming). If during the last decade, preventive chemotherapy against soil-transmitted helminths has led to resistance, we may not have detected it as drug efficacy has not been structurally monitored, or incorrectly so. These findings highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.

Beyond schistosomiasis: unraveling co-infections and altered immunity.

Schistosomiasis is a neglected tropical disease caused by the helminth Schistosoma spp. and has the second highest global impact of all parasites. Schistosoma are transmitted through contact with contaminated fresh water predominantly in Africa, Asia, the Middle East, and South America. Due to the widespread prevalence of Schistosoma, co-infection with other infectious agents is common but often poorly described. Herein, we review recent literature describing the impact of Schistosoma co-infection between species and Schistosoma co-infection with blood-borne protozoa, soil-transmitted helminths, various intestinal protozoa, Mycobacterium, Salmonella, various urinary tract infection-causing agents, and viral pathogens. In each case, disease severity and, of particular interest, the immune landscape, are altered as a consequence of co-infection. Understanding the impact of schistosomiasis co-infections will be important when considering treatment strategies and vaccine development moving forward.

Protocol for spatial prediction of soil transmitted helminth prevalence in the Western Pacific region using a meta-analytical approach.

BACKGROUND: Soil transmitted helminth (STH) infections are estimated to impact 24% of the world's population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR). METHODS: The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps. DISCUSSION: This protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence's and can be used to inform resource allocation in combating this neglected tropical disease. TRIAL REGISTRATION: Open Science Framework: osf.io/qmxcj.

Pattern and Prevalence of Intestinal Helminthiasis among Human Immunodeficiency Virus-Infected Children at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State.

BACKGROUND: Children infected with the human immunodeficiency virus (HIV) may be more prone to helminthic infestation because they have depleted immunity, which increases their susceptibility to infection and infestations, even with minimally pathogenic organisms such as helminths. AIM: The prevalence and pattern of intestinal helminthiasis among children living with HIV attending the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu. PATIENTS AND METHODS: A cross-sectional study in which 70 HIV-infected children were consecutively recruited from the Pediatric HIV clinic and matched for age and sex with 70 children recruited from the children outpatient clinic (CHOP) of UNTH Ituku-Ozalla. Stool samples of study participants were collected and analyzed using the Kato-Katz method and subsequently examined under the microscope for helminths' eggs and larvae. The worm intensity was determined using the theoretical analytic sensitivity (TAS) of 24 eggs per gram (EPG) to obtain the number of eggs per gram of feces. The CD4+ count, which describes the severity of immunosuppression in HIV-positive children was determined using the PARTEC Cyflow counter for the CD4+ lymphocyte count, whereas HIV screening was performed using the rapid diagnostic tests for HIV (Determine, Statpack and Unigold). Data were analyzed using IBM SPSS. RESULTS: The prevalence of intestinal helminthiasis among HIV-infected and non-infected children was 27.1% and 12.9%, respectively (P = 0.038). HIV-positive children were more likely to have intestinal helminthiasis than HIV-negative children (odds ratio [OR] =2.525, 95% confidence interval [CI]: 1.052-6.063). Ascaris lumbricoides was the predominant helminthic species in both HIV-infected and non-infected groups; however, there was no statistical significance between intestinal helminthic species and HIV status (P = 0.655) but the severity of intestinal helminthiasis was significantly associated with decreasing CD4+ count (P = 0.028). The risk factors for intestinal helminthic infestation examined were similar in both HIV-positive and HIV-negative children (P > 0.05). CONCLUSION: There was a significantly higher prevalence of helminthic infestation among HIV-infected children compared to their HIV-negative counterparts. The severity of intestinal helminthiasis was significantly associated with decreasing CD4+ count.

Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis.

BACKGROUND: Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations. METHODS: We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219). RESULTS: A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96-94.66) across five studies and 81.37% (95% CI 61.62-90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23-69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66-95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I2 > 65%). CONCLUSIONS: This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs.

Spatial heterogeneity in mass drug administration from a longitudinal epidemiological study assessing transmission interruption of soil transmitted helminths in the Wolaita zone of southern Ethiopia (Geshiyaro Project).

OBJECTIVES: Deworming programmes of soil-transmitted helminths are generally monitored and evaluated by aggregating drug coverage and infection levels at a district level. However, heterogeneity in drug coverage at finer spatial scales means indicators may remain above thresholds for elimination as a public health problem or of transmission in some areas. This paper aims to highlight the misleading information that aggregating data at larger spatial scales can have for programme decision making. METHODS: Drug coverage data from the Geshiyaro project were compared at two spatial scales with reference to the World Health Organisation's targets. District (woreda) and village (kebele) level were compared. The association between infection levels and drug coverage was analysed by fitting a weighted least-squares function to the mean intensity of infection (eggs per gram of faeces) against drug coverage. RESULTS: The data show clearly that when the evaluation of coverage is aggregated to the district level, information on heterogeneity at a finer spatial scale is lost. Infection intensity decreases significantly (p = 0.0023) with increasing drug coverage. CONCLUSION: Aggregating data at large spatial scales can result in prematurely ceasing deworming, prompting rapid infection bounce-back. There is a strong need to define context-specific spatial scales for monitoring and evaluating intervention programmes.

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.