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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 -
Trends in Parasitology Jul 2022Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of transmission (EoT) of onchocerciasis. Modelling suggests that EoT... (Review)
Review
Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of transmission (EoT) of onchocerciasis. Modelling suggests that EoT may not be reached in all endemic foci using annual MDA alone. Onchocerciasis and loiasis are coendemic in forest areas of Central Africa where ivermectin treatment can lead to severe adverse events in individuals with heavy loiasis load, rendering MDA inappropriate. Vector control has been proposed as a complementary intervention strategy. Here, we discuss (i) achievements and pitfalls of previous interventions; (ii) epidemiological impact, feasibility, and combination with MDA to accelerate and/or protect EoT; (iii) role of modelling; (iv) opportunities for innovative methods of vector monitoring and control; and (v) strengthening entomological capacity in endemic countries.
Topics: Humans; Ivermectin; Loiasis; Mass Drug Administration; Onchocerciasis
PubMed: 35379556
DOI: 10.1016/j.pt.2022.03.003 -
Journal of Global Health Jun 2018Loiasis is a vector-borne disease in Central and West Africa. While there is still uncertainty to what extent loiasis is responsible for population morbidity,...
BACKGROUND
Loiasis is a vector-borne disease in Central and West Africa. While there is still uncertainty to what extent loiasis is responsible for population morbidity, individuals having both loiasis and onchocerciasis have a high risk of fatal encephalopathy when treatment (ie, ivermectin) for onchocerciasis is given. Therefore it is current policy that communities of high loiasis-burden are excluded from mass drug administration programmes of ivermectin. To address this treatment gap we present diagnostic scores, based on clinical and behavioural predictors that may help to rapidly identify sub-groups with loiasis within high-burden communities.
METHODS
A cross-sectional survey was performed in the province of la Ngounie, Gabon between December 2015 and Februrary 2016 and 947 participants of all ages were recruited. Clinical parameters and behavioural exposure factors were ascertained by questionnaire-based interviews. Parasitological analysis of blood samples was performed for detection. Diagnostic scores consisting of clinical and behavioural factors were modelled to predict loiasis in sub-groups residing in endemic regions.
RESULTS
Increasing sylvan exposure was identified as important risk factor for loiasis with adjusted odds ratios of 5.1 (95% confidence interval CI 2.6-9.9) for occasional forest exposure, 11.1 (95% CI 5.4-22.6) for frequent forest exposure and 25.7 (95% CI 12.5-52.9) for intensive forest exposure. Individuals with loiasis were 7.7 (95% CI 5.4-11.0) times more likely to report recurrent pruritus than those without loiasis. Reporting of regular daily exposure to the deep rain forest and recurrent pruritus was 9-fold (positive likelihood ratio 9.18; 95% CI: 6.39-13.18) more prevalent in individuals with loiasis than in controls. Concordantly, the absence of regular weekly forest exposure was associated with extremely low disease-likelihood (negative likelihood ratio 0.09; 95% CI 0.05-0.16).
CONCLUSIONS
These composite scores may serve as a simple tool to rapidly identify both those most and those least at risk of disease and may simplify loiasis control activities as well as screening procedures for studies on loiasis. Further, they may aid policy-makers to tailor the delivery of ivermectin mass drug administration for onchocerciasis control programmes more effectively and safely in regions of high loiasis-burden.
Topics: Adolescent; Adult; Aged; Animals; Child; Child, Preschool; Cross-Sectional Studies; Environmental Exposure; Female; Gabon; Humans; Loa; Loiasis; Male; Middle Aged; Rainforest; Risk Assessment; Risk Factors; Rural Population; Surveys and Questionnaires; Young Adult
PubMed: 29497506
DOI: 10.7189/jogh.08.010413 -
Biomedicine & Pharmacotherapy =... May 2021Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high... (Review)
Review
Human filarial infections are vector-borne nematode infections, which include lymphatic filariasis, onchocerciasis, loiasis, and mansonella filariasis. With a high prevalence in developing countries, filarial infections are responsible for some of the most debilitating morbidities and a vicious cycle of poverty and disease. Global initiatives set to eradicate these infections include community mass treatments, vector control, provision of care for morbidity, and search for vaccines. However, there are growing challenges associated with mass treatments, vector control, and antifilarial vaccine development. With the emergence of genome editing tools and successful applications in other infectious diseases, the integration of genetic editing techniques in future control strategies for filarial infections would offer the best option for eliminating filarial infections. In this review, we briefly discuss the mechanisms of the three main genetic editing techniques and explore the potential applications of these powerful tools to control filarial infections.
Topics: Animals; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Filariasis; Filaricides; Filarioidea; Gene Editing; Genetic Therapy; Humans; Protozoan Vaccines
PubMed: 33581654
DOI: 10.1016/j.biopha.2021.111292 -
PLoS Neglected Tropical Diseases Sep 2022Loiasis-a filarial disease endemic in Central and West Africa-is increasingly recognized as significant individual and public health concern. While the understanding of...
BACKGROUND
Loiasis-a filarial disease endemic in Central and West Africa-is increasingly recognized as significant individual and public health concern. While the understanding of the disease characteristics remains limited, significant morbidity and excess mortality have been demonstrated. Here, we characterize clinical and hematological findings in a large cohort from Gabon.
METHODS
Loiasis-related clinical manifestations and microfilaremia, hemoglobin and differential blood counts were recorded prospectively during a cross-sectional survey. For analysis, participants were categorized into distinct infection states by the diagnostic criteria of eye worm history and microfilaremia.
RESULTS
Analysis of data from 1,232 individuals showed that occurrence of clinical and hematological findings differed significantly between the infection states. Eye worm positivity was associated with a wide range of clinical manifestations while microfilaremia by itself was not. Loa loa infection was associated with presence of eosinophilia and absolute eosinophil counts were associated with extent of microfilaremia (p-adj. = 0.012, ß-estimate:0.17[0.04-0.31]).
CONCLUSIONS
Loiasis is a complex disease, causing different disease manifestations in patients from endemic regions. The consequences for the affected individuals or populations as well as the pathophysiological consequences of correlating eosinophilia are largely unknown. High-quality research on loiasis should be fostered to improve patient care and understanding of the disease.
Topics: Animals; Cross-Sectional Studies; Gabon; Loa; Loiasis; Morbidity
PubMed: 36121900
DOI: 10.1371/journal.pntd.0010793 -
Emerging Infectious Diseases 2013An epidemic illness characterized by head nodding associated with onchocerciasis has been described in eastern Africa since the early 1960s; we summarize published...
An epidemic illness characterized by head nodding associated with onchocerciasis has been described in eastern Africa since the early 1960s; we summarize published reports and recent studies. Onset of nodding occurs in previously healthy 5-15-year-old children and is often triggered by eating or cold temperatures and accompanied by cognitive impairment. Its incidence has increased in Uganda and South Sudan over the past 10 years. Four case-control studies identified modest and inconsistent associations. There were nonspecific lesions seen by magnetic resonance imaging, no cerebrospinal fluid inflammation, and markedly abnormal electroencephalography results. Nodding episodes are atonic seizures. Testing has failed to demonstrate associations with trypanosomiasis, cysticercosis, loiasis, lymphatic filariasis, cerebral malaria, measles, prion disease, or novel pathogens; or deficiencies of folate, cobalamin, pyridoxine, retinol, or zinc; or toxicity from mercury, copper, or homocysteine. There is a consistent enigmatic association with onchocerciasis detected by skin snip or serologic analysis. Nodding syndrome is an unexplained epidemic epilepsy.
Topics: Adolescent; Adult; Africa; Age Factors; Case-Control Studies; Child; Child, Preschool; Electroencephalography; Female; Geography, Medical; Humans; Incidence; Infant; Magnetic Resonance Imaging; Male; Nodding Syndrome; Young Adult
PubMed: 23965548
DOI: 10.3201/eid1909.130401 -
PLoS Neglected Tropical Diseases Feb 2023Onchocerciasis (river blindness) caused by the filarial worm Onchocerca volvulus is a neglected tropical disease that affects the skin and eyes of humans. Mass drug...
BACKGROUND
Onchocerciasis (river blindness) caused by the filarial worm Onchocerca volvulus is a neglected tropical disease that affects the skin and eyes of humans. Mass drug administration with ivermectin (IVM) to control the disease often suffers from severe adverse events in individuals co-injected with high loads of Loa loa microfilariae (mf). Thus loiasis animal models for counter-screening of compounds effective against onchocerciasis are needed, as are the corresponding onchocerciasis screening models. The repertoire of such models is highly limiting. Therefore, this study was aimed at developing and validating mf immunocompetent small animal models to increase tools for onchocerciasis drug discovery.
METHODOLOGY/PRINCIPAL FINDINGS
O. ochengi mf from cattle skin and L. loa mf from human blood were used to infect BALB/c mice and Mongolian gerbils, and IVM was used for model validation. O. ochengi mf were given subcutaneously to both rodents while L. loa mf were administered intravenously to mice and intraperitoneally to gerbils. IVM was given orally. In an 8-day model of O. ochengi mf in BALB/c mice, treatment with IVM depleted all mf in the mice, unlike the controls. Also, in a 2.5-day model of L. loa mf in BALB/c, IVM significantly reduced mf in treated mice compared to the untreated. Furthermore, the gerbils were very susceptible to O. ochengi mf and IVM eradicated all mf in the treated animals. In the peritoneal L. loa mf gerbil model, IVM reduced mf motility in treated animals compared to the controls. In a 30-day gerbil co-injection model, IVM treatment cleared all O. ochengi mf and reduced motility of L. loa mf. Both mf survived for up to 50 days in a gerbil co-injection model.
CONCLUSIONS/SIGNIFICANCE
We have developed two immunocompetent small animal models for onchocerciasis and loiasis that can be used for microfilaricide discovery and to counter-screen onchocerciasis macrofilarides.
Topics: Humans; Cattle; Animals; Mice; Onchocerciasis; Gerbillinae; Loiasis; Filaricides; Ivermectin; Models, Animal; Loa; Microfilariae
PubMed: 36827447
DOI: 10.1371/journal.pntd.0011135 -
Trends in Parasitology Apr 2018Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and... (Review)
Review
Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.
Topics: Animals; Anthelmintics; Humans; Loa; Loiasis; Models, Biological
PubMed: 29331268
DOI: 10.1016/j.pt.2017.12.003 -
International Maritime Health 2020Travelling has been growing in popularity over the last several decades. Eye diseases, e.g. decreased visual acuity, inflammatory or degenerative lesions, chronic... (Review)
Review
Travelling has been growing in popularity over the last several decades. Eye diseases, e.g. decreased visual acuity, inflammatory or degenerative lesions, chronic diseases or eye trauma, affect all groups of travelers. The main risk factors contributing to the manifestation or exacerbation of common ocular diseases include exposure to dry air (inside the airplane cabin or in air-conditioned hotel rooms), exposure to chlorinated or salty water (swimming/bathing in swimming pools or in the sea), and sudden changes in the weather conditions. In addition, travelers to tropical destinations are at risk of ocular diseases which are rarely seen in temperate climate, e.g. onchocerciasis, loiasis, gnatostomosis, African trypanosomosis, or trachoma. The most common condition of the eye seen in travelers is conjunctivitis; it may be either of cosmopolitan (bacterial or viral infections, allergic inflammation) or tropical etiology, e.g. arboviral infections (zika, chikungunya). Given the fact that a large proportion of the general population have decreased visual acuity and many of them wear contact lenses rather than glasses, keratitis has become a common health problem among travelers as well; the major risk factors in such cases include sleeping in contact lenses, prolonged exposure to air-conditioning, working with a computer or swimming/bathing in microbiologically contaminated water (e.g. Acanthoamoeba protozoa). Conditions affecting the cornea, conjunctiva or lens may also occur due to excessive exposure to solar radiation, especially if travelers wear glasses without a UV protection.
Topics: Contact Lenses; Eye Diseases; Humans; Risk Factors; Sunlight; Swimming; Travel
PubMed: 32212152
DOI: 10.5603/IMH.2020.0015