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.

Molecular Regulation of NLRP3 Inflammasome Activation During Parasitic Infection.

Parasitic diseases are a serious global health concern, causing many common and severe infections, including Chagas disease, leishmaniasis,and schistosomiasis. The NLRP3 inflammasome belongs to the NLR (nucleotide-binding domain leucine-rich-repeat-containing proteins) family, which are cytosolic proteins playing key roles in the detection of pathogens. NLRP3 inflammasomes are activated in immune responses to Plasmodium,Leishmania, Toxoplasma gondii, Entamoeba histolytica,Trypanosoma cruzi and other parasites. The role of NLRP3 is not fully understood, but it is a crucial component of the innate immune response to parasitic infections and its functions as a sensor triggering the inflammatory response to the invasive parasites. However, while this response can limit the parasites' growth, it can also result in potentially catastrophic host pathology. This makes it essential to understand how NLRP3 interacts with parasites to initiate the inflammatory response. Plasmodium hemozoin, Leishmania glycoconjugate lipophosphoglycan (LPG) and E. histolytica Gal/GalNAc lectin can stimulate NLRP3 activation, while the dense granule protein 9 (GRA9) of T. gondii has been shown to suppress it. Several other parasitic products also have diverse effects on NLRP3 activation. Understanding the mechanism of NLRP3 interaction with these products will help to develop advanced therapeutic approaches to treat parasitic diseases. This review summarizes current knowledge of the NLRP3 inflammasome's action on the immune response to parasitic infections and aims to determine the mechanisms through which parasitic molecules either activate or inhibit its action.

Searching for common patterns in parasite ecology: species and host contributions to beta-diversity in helminths of South African ungulates and fleas of South American rodents.

We searched for common patterns in parasite ecology by investigating species and host contributions to the beta-diversity of infracommunities (=assemblages of parasites harboured by a host individual) in helminths of three species of South African ungulates and fleas of 11 species of South American rodents, assuming that a comparison of patterns in distinctly different parasites and hosts would allow us to judge the generality or, at least, commonness of these patterns. We used data on species' composition and numbers of parasites and asked whether (i) parasite species' attributes (life cycle, transmission mode, and host specificity in helminths; possession of sclerotized combs, microhabitat preference, and host specificity in fleas) or their population structure (mean abundance and/or prevalence) and (ii) host characteristics (sex and age) affect parasite and host species' contributions to parasite beta-diversity (SCBD and HCBD, respectively). We found that parasite species' morphological and ecological attributes were mostly not associated with their SCBD. In contrast, parasite SCBD, in both ungulates and rodents, significantly increased with either parasite mean abundance or prevalence or both. The effect of host characteristics on HCBD was detected in a few hosts only. In general, parasite infracommunities' beta-diversity appeared to be driven by variation in parasite species rather than the uniqueness of the assemblages harboured by individual hosts. We conclude that some ecological patterns (such as the relationships between SCBD and parasite abundance/prevalence) appear to be common and do not differ between different host-parasite associations in different geographic regions, whereas other patterns (the relationships between SCBD and parasite species' attributes) are contingent and depend on parasite and host identities.

Efficacy of 400 mg albendazole against soil-transmitted helminthes among Salgy Primary School Children, Dembia district, Northwest Ethiopia, 2020. "Uncontrolled experimental study".

Background and Aims: Soil-transmitted helminths are one of the most prevalent causes of both intellectual and physical disability in the world. Albendazole (ALB) is a drug recommended for mass treatment of the high burden of soil-transmitted helminths in schoolchildren, particularly in developing countries. However, some researchers have reported that the efficacy of albedazole against soil-transmitted helminths is inconsistent. Monitoring the programs is crucial to evaluating the effectiveness of 400 mg of ALB against soil-transmitted helminths, as well as any changes in its therapeutic efficacy. Thus, the purpose of this study was to evaluate ALB effectiveness in treating soil-transmitted helminthes in Salgy Primary School Children. Methods: An uncontrolled experimental study was conducted at Salgy Primary School Children, Northwest Ethiopia, from March to May 2020. A total of 439 schoolchildren were enrolled and screened for soil-transmitted helminths by stratified proportionate systematic random sampling to get 228 positive schoolchildren. Students in grades one through eight were grouped based on their educational attainment. Using the Kato-Katz thick smear technique, the selected stool sample collected from school children was examined using the Kato-Katz thick smear technique to determine the cure and egg reduction rates. The statistical package for social science software, version 20, was used to analyze the data. To determine the relationship between CR (cure rate) and ERR (egg reduction rate) by age, a chi-square test (X 2) was employed and significance was considered at A 95% confidence interval and p Value (p < 0.05). Results: A 400 mg single dosage of ALB showed a 99.35% CR and a 97.30% egg reduction rate against Ascaris lumibricoides. Additionally, a 400 mg dose of ALB showed a 95.75% CR and an 82.07% egg reduction rate, suggesting questionable effectiveness against hookworm infections. Trichuris trichiura showed a decreased efficacy, with a 43.53% CR and a 23.12% egg reduction rate. Conclusion: A single dose of 400 mg ALB is effective (satisfactory), doubtful, and unsatisfactory against Ascaris lumbricoides, hookworm, and T. trichiura infections, respectively. Further studies using different brands, doses, and routes will be needed to treat hookworm and T. trichiura infections successfully by using a larger sample size.

Exploring factors associated with Trichuris trichiura infection in school children in a high-transmission setting in Kenya.

Objectives: Kenya has implemented a national school-based deworming program, which has led to substantial decline in the prevalence of soil-transmitted helminths (STHs), although some pockets of infections remain. To effectively design an STH control program that leads to significant reductions of Trichuris trichiura, there is a need to understand the drivers of persistent infection despite ongoing treatment programs. Methods: This study was conducted between July and September 2019 at the south coast of Kenya, using a two-stage sampling design. First, a school-based cross-sectional survey was conducted in 2265 randomly selected school children from selected schools in areas known to be endemic for T. trichiura. After this, we conducted a nested case-control study wherein all children positive for T. trichiura (142) were matched to 148 negative controls based on age and village. A household survey was then conducted with all household members of cases and controls. In addition, a subsample of 116 children found to be infected with T. trichiura were followed up to assess the efficacy of albendazole at day 21 post-treatment. The predictors of presence of T. trichiura were investigated through multilevel logistic regression, considering clustering of infection. Results: Overall, 34.4% of the children were infected with at least one STH species; T. trichiura was the most common (28.3%), 89.1% of those with T. trichiura had light-intensity infections. The prevalence of T. trichiura was significantly higher in male children and was positively associated with younger age and number of people infected with T. trichiura in a household. The parasitological cure rate and egg reduction rate of T. trichiura were 35% and 51%, respectively. Other STHs identified were hookworm (9.6%) and Ascaris lumbricoides (5.7%). Conclusions: T. trichiura remains a significant public health challenge in the study area with albendazole treatment efficacy against the parasite, remaining lower than the World Health Organization-recommended thresholds. Because of the observed focal transmission of T. trichiura in the current area, control efforts tailored to local conditions and targeting lower implementation units should be used to achieve optimal results on transmission.

Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis.

Helminth-derived proteins have immunomodulatory properties, influencing the host's immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn's disease.

Intestinal Parasitic Infections in People Referring to the Central Laboratory of Meshkin Shahr County, Ardabil Province, Iran.

Background: Intestinal parasitic infections are still a considerable global public health problem. We aimed to determine the frequency of intestinal parasitic infections among people referring to the central laboratory of Meshkin Shahr City, Ardabil Province, Iran. Methods: In this cross-sectional survey, 460 fecal samples were collected randomly from persons referred to the central laboratory of Meshkin Shahr City, from January to June 2022. The samples were examined by direct wet-mount, Trichrome and modified Ziehl-Neelsen staining, formalin ethyl acetate sedimentation, and agar plate culture. Results: The frequency of intestinal parasites was 15.7% (72 out of 460 cases), with some people with numerous intestinal parasites. The frequency of protozoan infections (13.9%) was higher than the helminthic infections (2.6%). Blastocystis spp. (8.1%) was the most prevalent detected intestinal protozoan. Entamoeba coli (5.7%), Dicrocoelium dendriticum (2.2%), Giardia lamblia (1.5%), Fasciola spp. (0.2%), and Hymenolepis nana (0.2%) were other detected parasites. Conclusion: In- spite of betterment of the health condition in Iran and reduction of parasitic infection, intestinal parasitic infections are still a considerable public health issue in some parts of Iran.

Dirofilaria immitis and Onchocercidae spp. in wild felids from Brazil.

Among the species described within the Onchocercidae family, Dirofilaria immitis is regarded as the most common worldwide, causing severe and often fatal conditions in dogs, cats, and occasionally humans. Dirofilaria spp. are vectored by mosquitoes, simulids, and culicoids, with their epidemiology dependent on the geographical distribution of competent vectors. Eight species of Dirofilaria have been reported so far in Brazil, of which six parasitize non-human primates, deer, procyonids, and marsupials. Here, we investigated the occurrence of Onchocercidae in wild felids (i.e., Panthera onca, Puma concolor, Herpailurus yagouaroundi, Leopardus geoffroyi, Leopardus guttulus, Leopardus pardalis, Leopardus wiedii, Leopardus munoai) from different locations in Brazil. Overall, 82 samples (n = 63 blood; n = 19 tissues) were molecularly screened for cytochrome c oxidase subunit-1 (cox1) gene. Four (i.e., 4.8%) wild felid samples were positive, and at BLAST analysis, the obtained sequences showed varying percentage of nucleotide identity with the genera Brugia (i.e., 87-88%), Setaria (i.e., 89%), and D. immitis (i.e., 94.4%). Phylogenetic analyses clustered sequences obtained into three distinct clades, one with D. immitis and the remaining two with other Onchocercidae spp. Data herein obtained highlight the need for a more comprehensive understanding of the diversity and biology of Onchocercidae in South America in order to assess the potential impact that these species may have for domestic and wild animals, as well as humans.

Geospatial analysis and prevalence of Schistosoma mansoni and soil-transmitted helminth infections in an endemic area in Eastern Brazilian Amazon.

OBJECTIVES: This study evaluated the occurrence of Schistosoma mansoni and soil-transmitted helminths in an endemic area in the Eastern Brazilian Amazon, analysing prevalence and spatial distribution. METHODS: The study was conducted in four localities of Primavera Municipality, in Pará state. Data was obtained from the Decit 40/2012 project and the participants were divided into five age range categories for evaluation: children, adolescents, young adults, adults and elderly individuals. For the diagnostic tests, Kato-Katz slides were prepared to detect S. mansoni and soil-transmitted helminths eggs. The spatial distribution map and the Kernel Density Estimation were performed to assess the presence and location of infections. RESULTS: Stool samples revealed the presence of hookworms, S. mansoni, Ascaris lumbricoides and Trichuris trichiura eggs. Mono-, bi- and poly-parasitic infections were observed, with a significant prevalence of hookworm monoparasitism. CONCLUSIONS: The high frequency of children infected with soil-transmitted helminths confirms their significance as an ongoing public health problem in the poorest municipalities of Brazil. The Geographic Information System plays a crucial role in environmental surveillance and in the control of epidemics and endemic diseases, enabling accurate assessment and informed decision-making for their control.

Modulation of intestinal epithelial permeability by chronic small intestinal helminth infections.

Increased permeability of the intestinal epithelial layer is linked to the pathogenesis and perpetuation of a wide range of intestinal and extra-intestinal diseases. Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed as a treatment for many of the same diseases. Helminths induce immunoregulatory changes in their host which could decrease epithelial permeability, which is highlighted as a potential mechanism through which helminths treat disease. Despite this, the influence of a chronic helminth infection on epithelial permeability remains unclear. This study uses the chronically infecting intestinal helminth Heligmosomoides polygyrus to reveal alterations in the expression of intestinal tight junction proteins and epithelial permeability during the infection course. In the acute infection phase (1 week postinfection), an increase in intestinal epithelial permeability is observed. Consistent with this finding, jejunal claudin-2 is upregulated and tricellulin is downregulated. By contrast, in the chronic infection phase (6 weeks postinfection), colonic claudin-1 is upregulated and epithelial permeability decreases. Importantly, this study also investigates changes in epithelial permeability in a small human cohort experimentally challenged with the human hookworm, Necator americanus. It demonstrates a trend toward small intestinal permeability increasing in the acute infection phase (8 weeks postinfection), and colonic and whole gut permeability decreasing in the chronic infection phase (24 weeks postinfection), suggesting a conserved epithelial response between humans and mice. In summary, our findings demonstrate dynamic changes in epithelial permeability during a chronic helminth infection and provide another plausible mechanism by which chronic helminth infections could be utilized to treat disease.

Concurrent Abdominal and Mediastinal Hydatid Cystic Disease: A Rare Case.

Hydatid disease in humans is caused by accidental ingestion of Echinococcus in its larval form. It mostly affects the liver and lungs, but rarely the mediastinum and other areas as well. The diagnosis is mostly confirmed intraoperatively in cases of mediastinal disease. The mainstay of treatment in such cases is surgery. This is a case report of a rare finding of hydatid disease in mediastinum along with the abdomen and its surgical management.

The Zoonotic Angiostrongylus cantonensis and the Veterinary Parasite Aelurostrongylus abstrusus Infecting Terrestrial Gastropods from Urban Areas of Macapá, Brazilian Amazon Region.

Metastrongyloidea includes nematodes that parasitize mammals, mainly infecting their respiratory and cardiovascular systems, and are responsible for emerging zoonosis in the world. Terrestrial mollusks are their main intermediate hosts, with few exceptions. Here we present the results of a malacological survey to know the distribution of Angiostrongylus cantonensis in Macapá, Amapá, in the Brazilian Amazon region, after the report of a case of eosinophilic meningitis in 2018. Mollusks were collected in 45 neighborhoods between March 2019 and February 2020. They were identified, parasitologically analyzed, and their nematodes parasites were identified based on the morphology and MT-CO1 sequencing. Infections of An. cantonensis were observed in Achatina fulica, Sarasinula linguaeformis and Subulina octona. These are the first records of the natural infection of the last two species by An. cantonensis in the Brazilian Amazon region. The angiostrongylid Aelurostrongylus abstrusus, which parasitizes cats, was also detected parasitizing A. fulica and Diplosolenodes occidentalis. This is also the first record of the slug D. occidentalis infected by Ae. abstrusus. The highest infection rates were recorded in neighborhoods where the environment conditions favor the proliferation of both mollusks and rodents. The results demonstrate the ample distribution of An. cantonensis in Macapá and the need for surveillance and mollusk vector control in Brazil and other countries.

Autochthonous Ascariasis, Mississippi, USA.

We describe a case of a 2-year-old child who expelled a single adult female Ascaris lumbricoides worm. The patient is from a rural county in Mississippi, USA, with no reported travel outside of the United States. The caregivers in the home practice good sanitation. Exposure to domestic pigs is the likely source of infection.

Role of Silver Nanoparticles for the Control of Anthelmintic Resistance in Small and Large Ruminants.

Helminths are considered a significant threat to the livestock industry, as they cause substantial economic losses in small and large ruminant farming. Their morbidity and mortality rates are also increasing day by day as they have zoonotic importance. Anthelmintic drugs have been used for controlling these parasites; unfortunately, due to the development of resistance of these drugs in helminths (parasites), especially in three major classes like benzimidazoles, nicotinic agonists, and macrocyclic lactones, their use is becoming very low. Although new anthelmintics are being developed, the process is time-consuming and costly. As a result, nanoparticles are being explored as an alternative to anthelmintics. Nanoparticles enhance drug effectiveness, drug delivery, and target specificity and have no resistance against parasites. Different types of nanoparticles are used, such as organic (chitosan) and inorganic (gold, silver, zinc oxide, iron oxide, and nickel oxide). One of them, silver nanoparticles (AgNPs), has unique properties in various fields, especially parasitology. AgNPs are synthesized from three primary methods: physical, chemical, and biological. Their primary mechanism of action is causing stress through the production of ROS that destroys cells, organs, proteins, and DNA parasites. The present review is about AgNPs, their mode of action, and their role in controlling anthelmintic resistance against small and large ruminants.

Investigating the effect of a school-based WASH intervention on soil-transmitted helminth and schistosome infections and nutritional status of school children in Ethiopia: a quasi-experimental study.

BACKGROUND: The impact of access to improved water, sanitation and hygiene (WASH) and health education on large-scale deworming programs aimed at controlling soil-transmitted helminth (STH) and schistosome (SCH) infections has not been well studied. We assessed the additional impact of improved WASH infrastructure and health education at schools on STH and SCH infections in Ethiopia. METHODS: The study used a quasi-experimental design under which 30 schools were assigned to either an intervention (15 schools) or control (15 schools) arm. Both arms received a standard deworming treatment and lunch. In the intervention arm, improved WASH and health education were provided. At three consecutive time points (baseline in 2013, 2014 and 2015), the prevalence and intensity of STH and SCH infections and the nutritional status [hemoglobin concentrations and physical growth (height and weight)] were determined. To verify whether interventions were successfully implemented, the WASH status at school and the student knowledge, attitudes and practices related to WASH (WASH-KAP) were recorded. Differences in metrics between arms at baseline (2013) and follow-up (2015) were assessed both within and between the arms. RESULTS: A significant increase in scores for both the school WASH and student KAP was found in the intervention arm, indicating successful implementation of the intervention. The prevalence of any STH infection was significantly reduced in the intervention arm but not in the control arm (F = 4.486, p = 0.034). There was a significantly greater reduction in the intensity of infection of hookworm and Ascaris lumbricoides compared to baseline in both arms. The intervention did not affect school children's height-for-age z-score (intervention arm * time coef = 0.12, p = 0.400) and body mass index-for-age z-scores (intervention * time coef = - 0.06, p = 0.526). Hemoglobin concentrations increased significantly more in the control than the intervention arm (coef = - 0.16, p = 0.006). CONCLUSIONS: Although the intervention did increase school WASH and student WASH-KAP, our study found poor evidence of the additional benefit of improved WASH and health education to deworming and school food programs on parasite re-infection and the health outcomes of children.

Albendazole metabolites excretion in human saliva as a biomarker to assess treatment compliance in mass drug administration (MDA) anthelmintic programs.

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.

Association between helminth infection and allergic disorders among children in Batu, Ethiopia.

BACKGROUND: Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy-related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths,  atopy and allergic conditions. METHODS: A total of 461 school children participated in this cross-sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer-led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme-linked immunosorbent assay and eosinophil count were also measured. RESULTS: Overall sensitivity to both allergens was 2.4%. Self-reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p = .052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p = .268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p = .268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. CONCLUSION AND CLINICAL RELEVANCE: This study found a non-significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders.

Parasites in ancient Egypt and Nubia: Malaria, schistosomiasis and the pharaohs.

The civilizations of ancient Egypt and Nubia played a key role in the cultural development of Africa, the Near East, and the Mediterranean world. This study explores how their location along the River Nile, agricultural practices, the climate, endemic insects and aquatic snails impacted the type of parasites that were most successful in their populations. A meta-analysis approach finds that up to 65% of mummies were positive for schistosomiasis, 40% for headlice, 22% for falciparum malaria, and 10% for visceral leishmaniasis. Such a disease burden must have had major consequences upon the physical stamina and productivity of a large proportion of the workforce. In contrast, the virtual absence of evidence for whipworm and roundworm (so common in adjacent civilizations in the Near East and Europe) may have been a result of the yearly Nile floods fertilising the agricultural land, so that farmers did not have to fertilise their crops with human faeces.

Phytochemical analysis and anthelmintic activity of Combretum mucronatum leaf extract against infective larvae of soil-transmitted helminths including ruminant gastrointestinal nematodes.

BACKGROUND: Soil-transmitted helminths (STH) infect more than a quarter of the world's human population. In the absence of vaccines for most animal and human gastrointestinal nematodes (GIN), treatment of infections primarily relies on anthelmintic drugs, while resistance is a growing threat. Therefore, there is a need to find alternatives to current anthelmintic drugs, especially those with novel modes of action. The present work aimed to study the composition and anthelmintic activity of Combretum mucronatum leaf extract (CMLE) by phytochemical analysis and larval migration inhibition assays, respectively. METHODS: Combretum mucronatum leaves were defatted with petroleum ether and the residue was extracted by ethanol/water (1/1) followed by freeze-drying. The proanthocyanidins and flavonoids were characterized by thin layer chromatography (TLC) and ultra-high performance liquid chromatography (UPLC). To evaluate the inhibitory activity of this extract, larval migration assays with STH and GIN were performed. For this purpose, infective larvae of the helminths were, if necessary, exsheathed (Ancylostoma caninum, GIN) and incubated with different concentrations of CMLE. RESULTS: CMLE was found to be rich in flavonoids and proanthocyanidins; catechin and epicatechin were therefore quantified for standardization of the extract. Data indicate that CMLE had a significant effect on larval migration. The effect was dose-dependent and higher concentrations (1000 µg/mL) exerted significantly higher larvicidal effect (P < 0.001) compared with the negative control (1% dimethyl sulfoxide, DMSO) and lower concentrations (≤ 100 µg/ml). Infective larvae of Ascaris suum [half-maximal inhibitory concentration (IC50) = 5.5 µg/mL], Trichuris suis (IC50 = 7.4 µg/mL), and A. caninum (IC50 = 18.9 µg/mL) were more sensitive to CMLE than that of Toxocara canis (IC50 = 310.0 µg/mL), while infective larvae of Toxocara cati were largely unaffected (IC50 > 1000 µg/mL). Likewise, CMLE was active against most infective larvae of soil-transmitted ruminant GIN, except for Cooperia punctata. Trichostrongylus colubriformis was most sensitive to CMLE (IC50 = 2.1 µg/mL) followed by Cooperia oncophora (IC50 = 27.6 µg/mL), Ostertagia ostertagi (IC50 = 48.5 µg/mL), Trichostrongylus axei (IC50 = 54.7 µg/mL), Haemonchus contortus (IC50 = 145.6 µg/mL), and Cooperia curticei (IC50 = 156.6 µg/mL). CONCLUSIONS: These results indicate that CMLE exhibits promising anthelmintic properties against infective larvae of a large variety of soil-transmitted nematodes.

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products.

Natural products (NPs) have played a vital role in human survival for millennia, particularly for their medicinal properties. Many traditional medicine practices continue to utilise crude plants and animal products for treating various diseases, including inflammation. In contrast, contemporary medicine focuses more on isolating drug-lead compounds from NPs to develop new and better treatment drugs for treating inflammatory disorders such as inflammatory bowel diseases. There is an ongoing search for new drug leads as there is still no cure for many inflammatory conditions. Various approaches and technologies are used in drug discoveries from NPs. This review comprehensively focuses on anti-inflammatory small molecules and describes the key strategies in identifying, extracting, fractionating and isolating small-molecule drug leads. This review also discusses the (i) most used approaches and recently available techniques, including artificial intelligence (AI), (ii) machine learning, and computational approaches in drug discovery; (iii) provides various animal models and cell lines used in in-vitro and in-vivo assessment of the anti-inflammatory potential of NPs.