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The Korean Journal of Parasitology Jun 2021The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed.... (Review)
Review
The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.
Topics: Albendazole; Animals; Anthelmintics; Antineoplastic Agents; Ascariasis; Female; Humans; Male; Mebendazole; Parasites; Trichuriasis
PubMed: 34218593
DOI: 10.3347/kjp.2021.59.3.189 -
Tropical Medicine and Infectious Disease Nov 2022Intestinal parasitic infections are common infectious diseases causing many health problems and impaired growth and physical development.. Children under five years old... (Review)
Review
Intestinal parasitic infections are common infectious diseases causing many health problems and impaired growth and physical development.. Children under five years old are the most vulnerable to infections, due to their immature immunity and feeding and exploratory behaviours. This systematic review aimed to assess the relationship between intestinal parasitic infections and undernutrition among children under 5 years old. Fifteen studies met the inclusion and exclusion criteria and were classified as high-quality studies. Twelve parasites were reported, including , spp., , , , hookworm, , , spp. and . Ascariasis is the most reported infection, with a prevalence ranging from 10.77% in Ethiopia to 57.14% in Malaysia, and is correlated with stunting (OR 2.17 (95% CI 1.14, 4.13), = 0.02). Giardiasis is the second most reported infection, with a prevalence ranging from 4.43% in Ethiopia to 66.33% in the Central African Republic, and is related to an increased risk of stunting (OR 2.34 (95% CI 1.07, 5.10), = 0.03)), wasting (OR 2.90 (95% CI 1.12, 7.49, = 0.03)), and being underweight (OR 1.53 (95% CI 1.02, 2.29, = 0.04)). The third and fourth most prevalent infections are and hookworm infections. Intestinal parasitic infections can occur very early in life and cause significant growth retardation. It is important to understand the prevalence and effects of infection based on the parasite species in order to implement therapeutic interventions and prevention controls.
PubMed: 36422922
DOI: 10.3390/tropicalmed7110371 -
Nucleic Acids Research Mar 2022Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the...
Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.
Topics: Animals; Cattle; G-Quadruplexes; Genome; Helminths; Humans; Ligands; Nematoda; Parasites; Platyhelminths
PubMed: 35234933
DOI: 10.1093/nar/gkac129 -
Frontiers in Immunology 2023The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including...
INTRODUCTION
The COVID-19 pandemic has had devastating effects worldwide, but the trajectory of the pandemic has been milder in Low-and-Middle-Income Countries (LMICs), including those in Africa. Co-infection with helminths, such as Ascaris lumbricoides, has been suggested as a possible factor contributing to the reduced severity observed in these regions.
METHODS
The present study investigated the association between Ascaris-specific antibody levels and COVID-19 severity in 276 SARS-CoV-2-infected individuals in Benin. Participants were categorized into asymptomatic (n=100), mild (n=150), and severe (n=26) groups based on clinical disease severity. Sera were collected and analyzed using ELISA to measure Ascaris and SARS-CoV-2-specific antibodies, while Luminex was used to assess cytokines and SARS-CoV-2-specific neutralizing antibody expression.
RESULTS AND DISCUSSION
The results demonstrated that asymptomatic SARS-CoV-2 seropositive individuals expressed, on average, 1.7 and 2.2-times higher levels of Ascaris antibodies compared to individuals with mild and severe COVID-19, respectively. This finding suggests an inverse correlation between Ascaris antibody levels and COVID-19 severity. Notably, logistic regression analysis showed that Ascaris seropositivity was significantly associated with a reduced risk of severe COVID-19 (OR = 0.277, p = 0.021). Interestingly, COVID-19 patients with comorbidities such as type 2 diabetes and high blood pressure showed lower expression of Ascaris antibodies. Strikingly, no correlation was observed between Ascaris antibody levels and SARS-CoV-2-specific neutralizing antibodies. On the other hand, individuals seronegative for Ascaris displayed significantly higher levels of systemic pro-inflammatory markers compared to seropositive individuals. These findings suggest that higher expression of Ascaris antibodies is associated with asymptomatic SARS-CoV-2 infections and may contribute to the reduction of the risk to develop severe COVID-19. The beneficial effect of Ascaris seropositivity on COVID-19 outcomes in Benin may be attributed to a decrease in comorbidities and pro-inflammatory markers. These observations provide valuable insights into the milder COVID-19 trajectory observed in Africa and may have implications for future therapeutic strategies.
Topics: Humans; Animals; Ascaris lumbricoides; Benin; COVID-19; Diabetes Mellitus, Type 2; Pandemics; SARS-CoV-2; Ascaris; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37622109
DOI: 10.3389/fimmu.2023.1233082 -
Parasites & Vectors Dec 2022Ascaris lumbricoides causes human ascariasis, the most prevalent helminth disease, infecting approximately 1 billion individuals globally. In 2019 the global disease...
BACKGROUND
Ascaris lumbricoides causes human ascariasis, the most prevalent helminth disease, infecting approximately 1 billion individuals globally. In 2019 the global disease burden was estimated to be 754,000 DALYs and resulted in 2090 deaths. In the absence of a vaccination strategy, treatment of ascariasis has relied on anthelminthic chemotherapy, but drug resistance is a concern. The propensity for reinfection is also a major challenge to disease control; female worms lay up to 200,000 eggs daily, which contaminate surrounding environments and remain viable for years, resulting in high transmission rates. Understanding the molecular mechanisms of reproductive processes, including control of egg production, spermatogenesis, oogenesis and embryogenesis, will drive the development of new drugs and/or vaccine targets for future ascariasis control.
METHODS
Transcriptome profiles of discrete reproductive and somatic tissue samples were generated from adult male and female worms using Illumina HiSeq with 2 × 150 bp paired-end sequencing. Male tissues included: testis germinal zone, testis part of vas deferens, seminal vesicle and somatic tissue. Female tissues included: ovary germinal zone, ovary part of the oviduct, uterus and somatic tissue. Differentially expressed genes (DEGs) were identified from the fragments per kilobases per million reads (FPKM) profiles. Hierarchical analysis was performed to identify tissue-specific genes. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to identify significant terms and pathways for the DEGs.
RESULTS
DEGs involved in protein phosphorylation and adhesion molecules were indicated to play a crucial role in spermatogenesis and fertilization, respectively. Those genes associated with the G-protein-coupled receptor (GPCR) signaling pathway and small GTPase-mediated signal transduction pathway play an essential role in cytoskeleton organization during oogenesis. Additionally, DEGs associated with the SMA genes and TGF-β signaling pathway are crucial in adult female embryogenesis. Some genes associated with particular biological processes and pathways that were identified in this study have been linked to defects in germline development, embryogenesis and reproductive behavior. In the enriched KEGG pathway analysis, Hippo signaling, oxytocin signaling and tight junction pathways were identified to play a role in Ascaris male and female reproductive systems.
CONCLUSIONS
This study has provided comprehensive transcriptome profiles of discrete A. lumbricoides reproductive tissue samples, revealing the molecular basis of these functionally important tissues. The data generated from this study will provide fundamental knowledge on the reproductive biology of Ascaris and will inform future target identification for anti-ascariasis drugs and/or vaccines.
Topics: Animals; Male; Female; Humans; Ascaris lumbricoides; Gene Expression Profiling; Transcriptome; Ascariasis; Ovary
PubMed: 36539906
DOI: 10.1186/s13071-022-05602-2 -
Jornal de Pediatria Mar 2024Complications of ascariasis are a significant cause of abdominal pain in pediatric emergencies, especially where it is endemic. A literature review was conducted with... (Review)
Review
OBJECTIVE
Complications of ascariasis are a significant cause of abdominal pain in pediatric emergencies, especially where it is endemic. A literature review was conducted with the aim of improving diagnostic and therapeutic approaches for these patients.
DATA SOURCES
A PubMed search was conducted using the key terms "ascariasis complications" and "hepatobiliary ascariasis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, case reports, and reviews published up to December 2023.
SUMMARY OF FINDINGS
Obstruction of the small bowel is the most common complication. Others that are, rarer and more difficult to properly identify and treat, such as biliary, hepatic, and pancreatic complications, acute appendicitis, Meckel's diverticulitis, or peritoneal granulomas. Hepatic and pancreatic complications are rarer and more serious in children than in adults. While plain radiography is usually the only option in cases of intestinal obstruction, ultrasonography is the examination of choice in cases of hepatobiliary, pancreatic, and appendicular ascariasis complications in childhood. The treatment is clinical and conservative in most patients. Surgical treatment is indicated if conservative therapy fails, or if there are signs of complications. Laparoscopy has been used as an excellent technical alternative in adults with hepatobiliary complications of ascariasis, but further studies on its use in children are still needed.
CONCLUSION
The creation of protocols and greater debate on this subject should be encouraged for a better understanding of the disease and to establish an early diagnosis and adequate treatment for children with complications resulting from massive infestation by Ascaris lumbricoides.
PubMed: 38522478
DOI: 10.1016/j.jped.2024.02.001 -
Parasites, Hosts and Diseases May 2023In the l950s, under the legacy of traditional agriculture, Ascaris lumbricoides, spread epidemically in the war-bitten society of Korea. Consensus on the parasite... (Review)
Review
In the l950s, under the legacy of traditional agriculture, Ascaris lumbricoides, spread epidemically in the war-bitten society of Korea. Consensus on the parasite control was drafted in the Parasite Disease Prevention Act, which passed a parliamentary agreement in 1966, and established safe disposal of feces and mass chemotherapy as control strategies. Biannual stool examinations and treating infected schoolchildren were basic scheme of the control activity through which revenue could be secured for organized business. In the 27 years following 1969, a maximum of 16 million stool examinations had been done every year. Cellophane thick smear enabled the task. The infection declined remarkably in the 1970s when industrialization and green revolution proceeded. A population study of A. lumbricoides in the late 1970s helped us better understand its epidemiology. The data also settled down the understandable protest of teachers against the repeated stool examinations. In the 9 years following 1987, the target population was gradually reduced when the egg positive rate was below 0.1%. An article in the Korean Law, stipulating obligatory stool examinations, was made optional. Although the long-term Korean effort of Ascaris control was a success, the effect of mass chemotherapy was not as succinct in terms of lowering reinfection. In the period of control, Korean agricultural technology changed, and the economy grew and supplied sanitary facilities by which the vicious cycle was disconnected. Reduction of morbidity was a benefit of mass chemotherapy, which is the only control method feasible in economically difficult countries. The most important hurdle of parasite control in the 1960s was poverty of general population and limited financial resources in Korea but the society formed a consensus on the priority of intestinal helminthiasis control during the ordeal period. The national consensus in the 1960s was the critical milestone for Ascaris control in Korea. Under the social agreement, application of timely technical and research advancements in parasitology achieved the success of ascariasis elimination. The successful experience of ascariasis elimination in Korea can be a benchmark for countries where neglected tropical diseases are endemically recycled.
Topics: Animals; Humans; Child; Ascariasis; Helminthiasis; Intestinal Diseases, Parasitic; Ascaris; Republic of Korea
PubMed: 37258258
DOI: 10.3347/PHD.22152