International Journal for Parasitology: Drugs and Drug Resistance最新文献

{"title":"Ring stage dormancy of Plasmodium falciparum tolerant to artemisinin and its analogues – A genetically regulated “Sleeping Beauty”","authors":"Saranya Auparakkitanon ,&nbsp;Prapon Wilairat","doi":"10.1016/j.ijpddr.2023.01.002","DOIUrl":"10.1016/j.ijpddr.2023.01.002","url":null,"abstract":"<div><p>The appearance in 2008 in western Cambodia of <em>Plasmodium falciparum</em> tolerant to artemisinin, defined by longer parasite clearance time following drug administration and <em>in vitro</em> by a slightly higher survival rate of the ring stage after a 3-h treatment with 700 nM artemisinin (or analogues, collectively termed ART), has raised concerns of the possible loss of this frontline antimalarial [used in the form of an artemisinin combination therapy (ACT)], with its low IC₅₀ value against the ring stage and pleiotropic pro-drug/poison property. The key genetic marker of ART tolerance phenotype is a number of non-synonymous mutations in <em>Pfkelch13</em> propeller domain. This results in defective assembly at the ring stage of a cytostome structure located at cytoplasmic side of the parasite membrane required for invagination of a double-membrane endosome carrying host cytosol haemoglobin to the digestive vacuole. The consequential deprivation of amino acids initiates ring stage parasites bearing the causal mutations in <em>Pf</em>K13 (or other key cytostome components) entry into a dormant state (“Sleeping Beauty”), which, after a duration longer than that the short-lived ART, “Sleeping Beauty” ring parasite resumes its normal, but accelerated, development to maintain the 48-h intra-erythrocytic life-cycle. We posit that when ART-tolerant <em>P</em>. <em>falciparum</em> has acquired under ART stress the causative <em>Pf</em>K13 mutation (not obligatory if mutations occur in other critical cytostome components), together with other necessary mutations to adjust to the new normalcy and to provide survival competitiveness, ART-tolerant parasite has now evolved into a genetically programmed “Sleeping Beauty”. The onus of preventing the spread of ART-tolerant <em>P</em>. <em>falciparum</em> lies with the efficacy of ACT partner drug, hence the recommendation of a triple ACT (TACT). Nevertheless, attention should also be focussed on understanding the mechanisms of dormancy, such as induction, maintenance and recovery, to enable discovery and development of novel antimalarials targeting this unique parasite stage.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 61-64"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/5c/main.PMC9883618.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9810589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiophene derivatives activity against the protozoan parasite Leishmania infantum","authors":"Sophia Bigot ,&nbsp;Philippe Leprohon ,&nbsp;Abimael Vasquez ,&nbsp;Rohit Bhadoria ,&nbsp;Rachid Skouta ,&nbsp;Marc Ouellette","doi":"10.1016/j.ijpddr.2022.11.004","DOIUrl":"10.1016/j.ijpddr.2022.11.004","url":null,"abstract":"<div><p>Treatments against leishmaniasis are limited and the development of new molecules is crucial. One class of developmental drug that has shown activity against the parasite <em>Leishmania</em> are thiophene derivatives. Here we synthetized thirty-eight novel thiophene compounds and characterized their activity and potential for resistance against <em>L. infantum</em>. Half of the molecules had an EC₅₀ in the low micromolar range, the piperidine derivatives being more potent than the tetramethylpyran derivatives. Resistance was challenging to select for, and resistant cells could only be raised against one (GC1-19) of the four most active compounds. Using chemogenomic screens we show that a gene conversion event at the <em>ABCG2</em> locus as well as the overexpression of a tryparedoxin peroxidase are responsible for a weak but significant resistance to the GC1-19 drug candidate. Together, our results suggest that thiophene is a scaffold of interest for further drug development against leishmaniasis.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 13-20"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/1f/main.PMC9772499.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9439988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic diversity in the metronidazole metabolism genes nitroreductases and pyruvate ferredoxin oxidoreductases in susceptible and refractory clinical samples of Giardia lamblia","authors":"Christina S. Saghaug ,&nbsp;Astrid L. Gamlem ,&nbsp;Kirsti B. Hauge ,&nbsp;Juha Vahokoski ,&nbsp;Christian Klotz ,&nbsp;Toni Aebischer ,&nbsp;Nina Langeland ,&nbsp;Kurt Hanevik","doi":"10.1016/j.ijpddr.2022.12.003","DOIUrl":"10.1016/j.ijpddr.2022.12.003","url":null,"abstract":"<div><p>The effectiveness of metronidazole against the tetraploid intestinal parasite <em>Giardia lamblia</em> is dependent on its activation/inactivation within the cytoplasm. There are several activating enzymes, including pyruvate ferredoxin reductase (PFOR) and nitroreductase (NR) 1 which metabolize metronidazole into toxic forms, while NR2 on the other hand inactivates it. Metronidazole treatment failures have been increasing rapidly over the last decade, indicating genetic resistance mechanisms. Analyzing genetic variation in the PFOR and NR genes in susceptible and refractory <em>Giardia</em> isolates may help identify potential markers of resistance.</p><p>Full length <em>PFOR1</em>, <em>PFOR2</em>, <em>NR1</em> and <em>NR2</em> genes from clinical culturable isolates and non-cultured clinical <em>Giardia</em> assemblage B samples were cloned, sequenced and single nucleotide variants (SNVs) were analyzed to assess genetic diversity and alleles.</p><p>A similar ratio of amino acid changing SNVs per gene length was found for the NRs; 4.2% for <em>NR1</em> and 6.4% for <em>NR2</em>, while the <em>PFOR1</em> and <em>PFOR2</em> genes had less variability with a ratio of 1.1% and 1.6%, respectively. One of the samples from a refractory case had a nonsense mutation which caused a truncated <em>NR1</em> gene in one out of six alleles. Further, we found three <em>NR2</em> alleles with frameshift mutations, possibly causing a truncated protein in two susceptible isolates. One of these isolates was homozygous for the affected <em>NR2</em> allele. Three nsSNVs with potential for affecting protein function were found in the ferredoxin domain of the <em>PFOR2</em> gene. The considerable variation and discovery of mutations possibly causing dysfunctional NR proteins in clinical <em>Giardia</em> assemblage B isolates, reveal a potential for genetic link to metronidazole susceptibility and resistance.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 51-60"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9433400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic and pharmacodynamic considerations for treating sarcoptic mange with cross-relevance to Australian wildlife","authors":"Kotaro Takano ,&nbsp;Lachlan de Hayr ,&nbsp;Scott Carver ,&nbsp;Robert J. Harvey ,&nbsp;Kate E. Mounsey","doi":"10.1016/j.ijpddr.2023.02.004","DOIUrl":"10.1016/j.ijpddr.2023.02.004","url":null,"abstract":"<div><p><em>Sarcoptes scabiei</em> is the microscopic burrowing mite responsible for sarcoptic mange, which is reported in approximately 150 mammalian species. In Australia, sarcoptic mange affects a number of native and introduced wildlife species, is particularly severe in bare-nosed wombats (<em>Vombatus ursinus</em>) and an emerging issue in koala and quenda. There are a variety of acaricides available for the treatment of sarcoptic mange which are generally effective in eliminating mites from humans and animals in captivity. In wild populations, effective treatment is challenging, and concerns exist regarding safety, efficacy and the potential emergence of acaricide resistance. There are risks where acaricides are used intensively or inadequately, which could adversely affect treatment success rates as well as animal welfare. While reviews on epidemiology, treatment strategies, and pathogenesis of sarcoptic mange in wildlife are available, there is currently no review evaluating the use of specific acaricides in the context of their pharmacokinetic and pharmacodynamic properties, and subsequent likelihood of emerging drug resistance, particularly for Australian wildlife. This review critically evaluates acaricides that have been utilised to treat sarcoptic mange in wildlife, including dosage forms and routes, pharmacokinetics, mode of action and efficacy. We also highlight the reports of resistance of <em>S. scabiei</em> to acaricides, including clinical and <em>in vitro</em> observations.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 97-113"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/68/main.PMC10023865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9440544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase","authors":"Agriana Rosmalina Hidayati ,&nbsp;Melinda ,&nbsp;Hilkatul Ilmi ,&nbsp;Takaya Sakura ,&nbsp;Miako Sakaguchi ,&nbsp;Junko Ohmori ,&nbsp;Endah Dwi Hartuti ,&nbsp;Lidya Tumewu ,&nbsp;Daniel Ken Inaoka ,&nbsp;Mulyadi Tanjung ,&nbsp;Eri Yoshida ,&nbsp;Fuyuki Tokumasu ,&nbsp;Kiyoshi Kita ,&nbsp;Mihoko Mori ,&nbsp;Kazuyuki Dobashi ,&nbsp;Tomoyoshi Nozaki ,&nbsp;Din Syafruddin ,&nbsp;Achmad Fuad Hafid ,&nbsp;Danang Waluyo ,&nbsp;Aty Widyawaruyanti","doi":"10.1016/j.ijpddr.2022.12.001","DOIUrl":"10.1016/j.ijpddr.2022.12.001","url":null,"abstract":"<div><p>Nearly half of the world's population is at risk of being infected by <em>Plasmodium falciparum,</em> the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of <em>Artocarpus altilis</em> leaves have previously been reported to exhibit <em>in vitro</em> antimalarial activity against <em>P. falciparum</em> and <em>in vivo</em> activity against <em>P. berghei</em>. Despite these initial promising results, the active compound from <em>A. altilis</em> is yet to be identified. Here, we have identified 2-geranyl-2′, 4′, 3, 4-tetrahydroxy-dihydrochalcone (<strong>1</strong>) from <em>A. altilis</em> leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (<strong>1</strong>) were investigated. In the presence of (<strong>1</strong>), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (<strong>1</strong>) inhibited the mitochondrial malate: quinone oxidoreductase (<em>Pf</em>MQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as <em>bc</em>₁ complex activities. Our study suggests that (<strong>1</strong>) has a dual mechanism of action affecting the food vacuole and inhibition of <em>Pf</em>MQO-related pathways in mitochondria.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 40-50"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/56/main.PMC9798170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OBITUARY- Ian Fairweather","authors":"Mark W. Robinson ,&nbsp;Bob Hanna ,&nbsp;Philip Skuce ,&nbsp;Gerry Brennan","doi":"10.1016/j.ijpddr.2023.02.003","DOIUrl":"10.1016/j.ijpddr.2023.02.003","url":null,"abstract":"","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Page 96"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42453788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of Ancylostoma caninum parasites with the benzimidazole resistance F167Y polymorphism in the US dog population","authors":"Christian M. Leutenegger ,&nbsp;Cecilia E. Lozoya ,&nbsp;Jeffrey Tereski ,&nbsp;Christian Savard ,&nbsp;Jennifer Ogeer ,&nbsp;Rene Lallier","doi":"10.1016/j.ijpddr.2023.01.001","DOIUrl":"10.1016/j.ijpddr.2023.01.001","url":null,"abstract":"<div><h3>Background</h3><p>Anthelmintic resistance to benzimidazole has been detected in the canine hookworm, <em>Ancylostoma caninum</em>. Benzimidazole resistance is believed to have developed originally in greyhounds, but has also been detected in non-greyhound pet dogs. The aim of this study was to validate a probe-based allele-specific real-time PCR tests for the F167Y polymorphism on the β-tubulin isotype-1 gene and to determine the geographic distribution.</p></div><div><h3>Methods</h3><p>Allele-specific real-time PCR tests were established and validated to detect the codon 167 polymorphism in the <em>Ancylostoma caninum</em> β-tubulin isotype-1gene. Additionally, real-time PCR tests were validated for <em>Ancylostoma</em> spp. and <em>Uncinaria stenocephala</em>. Two nucleic acid extraction protocols were validated including mechanical disruption of parasite structures in stool. The frequency of the F167Y single nucleotide polymorphism (SNP) was determined in hookworm confirmed stool samples. Samples with the resistant 167Y genotype were confirmed by β-tubulin gene sequencing and allele frequencies were determined.</p></div><div><h3>Results</h3><p>The <em>Ancylostoma</em> spp. and <em>A. caninum</em> F167Y allele-specific real-time PCR tests were highly sensitive and specific when tested against synthetic DNA, spiked samples, and characterized parasites. Using an optimized total nucleic acid extraction protocol, 54 of 511 (10.6%) were found to contain the benzimidazole resistance allele. All 55 samples containing hookworms with the resistance mutation were confirmed by β-tubulin gene sequencing. The majority of resistant hookworms (44 resistant, 183 tested; 24.4%) originated from Florida, five from California (103 tested, 4.9%), three from Idaho (40 tested, 7.5%), two from Nevada (22 tested, 9.1%), and one sample from Hawaii (13 tested, 7.7%). Resistant genotypes were found in 14 different dog breeds including eight in Greyhounds. Allele-frequency determination revealed resistance allele frequencies between 1 and 100% with 58% above 50%.</p></div><div><h3>Conclusions</h3><p>This data strongly supports recent findings of benzimidazole resistant canine hookworms present throughout the general US pet dog population.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 131-140"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068012/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the oxamniquine in vitro-in vivo paradox to facilitate a new generation of anti-schistosome treatments","authors":"Katalin Toth ,&nbsp;Sevan Alwan ,&nbsp;Susan Khan ,&nbsp;Stanton F. McHardy ,&nbsp;Philip T. LoVerde ,&nbsp;Michael D. Cameron","doi":"10.1016/j.ijpddr.2023.01.003","DOIUrl":"10.1016/j.ijpddr.2023.01.003","url":null,"abstract":"<div><p>The antischistosomal drug oxamniquine, OXA, requires activation by a sulfotransferase within the parasitic worm to enable killing. Examination of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for OXA identified an <em>in vitro-in vivo</em> paradox with the maximal clinical plasma concentrations five-to ten-times lower than the efficacious concentration for <em>in vitro</em> schistosomal killing. The parasite resides in the vasculature between the intestine and the liver, and modeling the PK data to determine portal concentrations fits with <em>in vitro</em> studies and explains the required human dose. <em>In silico</em> models were used to predict murine dosing to recapitulate human conditions for OXA portal concentration and time course. Follow-up PK studies verified in mice that a 50–100 mg/kg oral gavage dose of OXA formulated in acetate buffer recapitulates the 20–40 mg/kg dose common in patients. OXA was rapidly cleared through a combination of metabolism and excretion into bile. OXA absorbance and tissue distribution were similar in wild-type and P-gp efflux transporter knockout mice. The incorporation of <em>in vitro</em> efficacy data and portal concentration was demonstrated for an improved OXA-inspired analog that has been shown to kill <em>S. mansoni, S. haematobium,</em> and <em>S. japonicum</em>, whereas OXA is only effective against <em>S. mansoni.</em> Second-generation OXA analogs should optimize both <em>in vitro</em> killing and physiochemical properties to achieve high portal concentration via rapid oral absorption, facilitated by favorable solubility, permeability, and minimal intestinal metabolism.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 65-73"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/a7/main.PMC9929523.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9830092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo","authors":"Jiao Mo ,&nbsp;Hongfei Si ,&nbsp;Siyang Liu ,&nbsp;Qingyuan Zeng ,&nbsp;Minghao Cai ,&nbsp;Zhendi Liu ,&nbsp;Jiyu Zhang ,&nbsp;Jingjing Fang ,&nbsp;Jili Zhang","doi":"10.1016/j.ijpddr.2023.02.001","DOIUrl":"10.1016/j.ijpddr.2023.02.001","url":null,"abstract":"<div><p>Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome <em>bc</em>1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The <em>in vitro</em> effects of HQNO were determined by plaque assay and qPCR assay. To determine the <em>in vivo</em> effect of HQNO, pharmacokinetic experiments and <em>in vivo</em> infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited <em>T. gondii</em> invasion and proliferation with an EC₅₀ of 0.995 μM. Pharmacokinetic experiments showed that the C_max of HQNO (20 mg/kg·bw) was 3560 ± 1601 ng/mL (13.73 μM) in healthy BALB/c mouse plasma with no toxicity <em>in vivo</em>. Moreover, HQNO induced a significant decrease in the parasite burden load of <em>T. gondii</em> in mouse peritoneum. TEM revealed alterations in the mitochondria of <em>T. gondii</em>. Further assays verified that HQNO also decreased the mitochondrial membrane potential (ΔΨm) and ATP levels and enhanced the level of reactive oxygen species (ROS) in <em>T. gondii</em>. Hence, HQNO exerted <em>anti-T. gondii</em> activity, which may be related to the damage to the mitochondrial electron transport chain (ETC).</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 74-80"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/b8/main.PMC9929485.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9433828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poor adherence is a major barrier to the proper treatment of cutaneous leishmaniasis: A case-control field assessment in Iran","authors":"Mehdi Bamorovat ,&nbsp;Iraj Sharifi ,&nbsp;Setareh Agha Kuchak Afshari ,&nbsp;Ali Karamoozian ,&nbsp;Amirhossein Tahmouresi ,&nbsp;Amireh Heshmatkhah ,&nbsp;Ehsan Salarkia ,&nbsp;Ahmad Khosravi ,&nbsp;Maryam Hakimi Parizi ,&nbsp;Maryam Barghi","doi":"10.1016/j.ijpddr.2022.11.006","DOIUrl":"10.1016/j.ijpddr.2022.11.006","url":null,"abstract":"<div><p>Leishmaniasis is an overlooked, poverty-stricken, and complex disease with growing social and public health problems. In general, leishmaniasis is a curable disease; however, there is an expansion of unresponsive cases to treatment in cutaneous leishmaniasis (CL). One of the effective and ignored determinants in the treatment outcome of CL is poor treatment adherence (PTA). PTA is an overlooked and widespread phenomenon to proper <em>Leishmania</em> treatment. This study aimed to explore the effect of poor adherence in unresponsiveness to treatment in patients with anthroponotic CL (ACL) by comparing conventional statistical modalities and machine learning analyses in Iran. Overall, 190 cases consisting of 50 unresponsive patients (case group), and 140 responsive patients (control group) with ACL were randomly selected. The data collecting form that included 25 queries (Q) was recorded for each case and analyzed by R software and genetic algorithm (GA) approaches. Complex treatment regimens (Q11), cultural and lay views about the disease and therapy (Q8), life stress, hopelessness and negative feelings (Q22), adverse effects of treatment (Q13), and long duration of the lesion (Q12) were the most prevalent significant variables that inhibited effective treatment adherence by the two methods, in decreasing order of significance. In the inherent algorithm approach, similar to the statistical approach, the most significant feature was complex treatment regimens (Q11). Providing essential knowledge about ACL and treatment of patients with chronic diseases and patients with misconceptions about chemical drugs are important issues directly related to the disease's unresponsiveness. Furthermore, early detection of patients to prevent the long duration of the disease and the process of treatment, efforts to minimize side effects of treatment, induction of positive thinking, and giving hope to patients with stress and anxiety by medical staff, and family can help patients adhere to the treatment.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"21 ","pages":"Pages 21-27"},"PeriodicalIF":4.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9445251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}