Investigation of the effect of oral ivermectin on systemic inflammatory response and quality of life in scabies patients.

Scabies is a prevalent ectoparasitic infectious disease, caused by the mite Sarcoptes scabiei. As a consequence of the infestation, localised cutaneous inflammation, pruritus and polymorphic skin lesions develop. The primary symptoms of scabies manifest as hypersensitivity-like reactions and immune responses, the precise mechanisms of which remain poorly defined. The objective of this study was to evaluate the effects of oral ivermectin treatment in patients with scabies on the systemic immune response and the patient's quality of life (QoL). Patients admitted to the dermatology outpatient clinic and diagnosed with scabies were administered oral ivermectin treatment following diagnosis at week 0 and 2. Laboratory tests were conducted to measure complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels before treatment and at week 4. The systemic immune-inflammation index (SII) was calculated using the platelet, neutrophil and lymphocyte counts. Additionally, data pertaining to the Dermatological Life Quality Index (DLQI) were recorded. In 119 patients (51 males) diagnosed with scabies, increases in ESR, CRP, and SII values and decreases in inflammatory cell counts and DLQI scores were observed one month after treatment with oral ivermectin. The results of the study showed that the use of oral ivermectin, a scabicidal agent, triggered the inflammatory response and improved the QoL of the patients.

Reduction of egg reappearance period of cyathostomins in naturally infected horses after increasing doses of ivermectin in Brazil: a grim picture for sustainable parasite control.

Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.

Evaluating a Reduction in Treatment Duration of Ivermectin Diet for Fur Mite (Radfordia affinis) Eradication in Mice.

Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis -positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis, making successful eradication initiatives more achievable.

Anti-inflammatory and immunomodulatory effects of mesenchymal stem cell therapy on parasitic drug resistance.

INTRODUCTION: The emergence of antiparasitic drug resistance poses a concerning threat to animals and humans. Mesenchymal Stem Cells (MSCs) have been widely used to treat infections in humans, pets, and livestock. Although this is an emerging field of study, the current review outlines possible mechanisms and examines potential synergism in combination therapies and the possible harmful effects of such an approach. AREAS COVERED: The present study delved into the latest pre-clinical research on utilizing MSCs to treat parasitic infections. As per investigations, the introduction of MSCs to patients grappling with parasitic diseases like schistosomiasis, malaria, cystic echinococcosis, toxoplasmosis, leishmaniasis, and trypanosomiasis has shown a reduction in parasite prevalence. This intervention also alters the levels of both pro- and anti-inflammatory cytokines. Furthermore, the combined administration of MSCs and antiparasitic drugs has demonstrated enhanced efficacy in combating parasites and modulating the immune response. EXPERT OPINION: Mesenchymal stem cells are a potential solution for addressing parasitic drug resistance. This is mainly because of their remarkable immunomodulatory abilities, which can potentially help combat parasites' resistance to drugs.

Pharmacokinetics of Nitazoxanide Dry Suspensions After Single Oral Doses in Healthy Subjects: Food Effects Evaluation and Bioequivalence Study.

Nitazoxanide (NTZ) is an effective antiparasitic drug with potent antiviral and antimicrobial activity. This randomized, open-label, 2-sequence, 2-period crossover trial was designed to evaluate the bioequivalence (BE) of the NTZ dry suspension in healthy subjects and investigated the effect of food intake on the pharmacokinetic (PK) properties of tizoxanide (an active metabolite of NTZ, TIZ). Sixty healthy Chinese subjects were enrolled and received a single dose of 500 mg/25 mL of preparations on days 1 and 4 under overnight fasting or fed conditions, respectively. The plasma concentration of TIZ was determined using high-performance liquid chromatography/tandem mass spectrometry. PK parameters were calculated using WinNonlin 8.2 and BE was evaluated using SAS 9.4. The 90% confidence intervals for the geometric mean ratio (test/reference) of maximum concentration (Cmax), the area under the curve from time 0 to the time of the last quantifiable concentration (AUC0-t), and the area under the curve from time 0 to extrapolation to infinity (AUC0-∞) were all within the equivalent interval of 80%-125%, compliant with BE requirements. In comparison with fasting, on taking the reference and test preparations of the NTZ dry suspension after a meal, the AUC0-t increased by 48.9% and 47.3%, respectively, the AUC0-∞ increased by 48.4% and 48.3%, respectively, and the post-meal Tmax was prolonged by 1.8-2 hours. Our results demonstrate that the test and reference preparations were bioequivalent. High-fat meals significantly improve the degree of drug absorption and delay the rate of drug absorption.

Topical Dexamethasone Counters Intravitreal Ivermectin-Induced Ocular Toxicity in a Rabbit Model.

PURPOSE: Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone. METHODS: Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits (N = 4) with and without topical drops of Verapamil (N = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology.0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit (N = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay. RESULTS: Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis. CONCLUSIONS: Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin.

Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa. METHODS: For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986. FINDINGS: Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission. INTERPRETATION: Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission. FUNDING: The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking. TRANSLATIONS: For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC.

The feline MDR1 mutation (ABCB11930_1931delTC) has been associated with neurological toxicosis after topical application of eprinomectin products labeled for feline use. Information was collected from veterinarians who submitted samples for ABCB11930_1931delTC genotyping. In most cases, the submission form indicated an adverse event involving eprinomectin, in other cases submitting veterinarians were contacted to determine whether the patient had experienced an adverse drug event involving eprinomectin. If so, additional information was obtained to determine whether the case met inclusion criteria. 14 cases were highly consistent with eprinomectin toxicosis. Eight cats were homozygous for ABCB11930_1931del TC (3 died; 5 recovered). Six cats were homozygous wildtype (2 died; 4 recovered). The observed ABCB11930_1931delTC frequency (57%) was higher than the expected frequency (≤1%) in the feline population (Fisher Exact test, p < 0.01). Among wildtype cats, four were concurrently treated with potential competitive inhibitors of P-glycoprotein. Results indicate that topical eprinomectin products, should be avoided in cats homozygous for ABCB11930_1931delTC. This is a serious, preventable adverse event occurring in an identifiable subpopulation treated with FDA-approved products in accordance with label directions. Acquired P-glycoprotein deficiency resulting from drug interactions may enhance susceptibility to eprinomectin-induced neurological toxicosis in any cat, regardless of ABCB1 genotype.

Epidemia de escabiosis: los nuevos retos de una enfermedad ancestral / Epidemic Scabies: New Treatment Challenges in an Ancient Disease

La escabiosis es una de las enfermedades transmisibles más prevalentes en el mundo, actualmente en auge en nuestro entorno. Existen diferentes causas que explican la problemática de esta epidemia: una incorrecta aplicación o pauta del tratamiento; la disminución de la sensibilidad o la resistencia al tratamiento tópico y las carencias en el conocimiento del parásito y su transmisibilidad. Por este motivo es necesario un nuevo enfoque en el tratamiento de esta enfermedad que contemple los problemas y la evidencia actual. Si hay una persistencia de la clínica tras un correcto tratamiento es importante corroborar el fracaso terapéutico y estandarizar la actitud. Por último, ante un caso recalcitrante cabría plantear la posibilidad de priorizar el tratamiento oral, aumentar su dosis, realizar tratamientos combinados o plantear su uso fuera de ficha técnica en poblaciones especiales. La aparición de nuevos tratamientos, como el spinosad o, sobre todo, la moxidectina, aportan esperanza en el control de esta enfermedad (AU)

Scabies, which is among the most prevalent diseases worldwide, is becoming more frequent in Spain. The problems of this epidemic can be explained by several factors: improper application or prescription of treatments, resistance or reduced sensitivity to topical treatments, and poor understanding of the parasite and contagion. We require a new evidence-based approach to therapy that takes these problems into consideration. If symptoms persist after proper treatment, it is important to identify the reason for failure and standardize our approach. In refractory cases, the prescriber should prioritize oral medication, indicate a higher dose, combine treatments, or evaluate the use of off-label treatments in certain populations. The availability of new medications —such as spinosad or, especially, moxidectin— offer hope for bringing this disease under control (AU)

[Translated article] Epidemic Scabies: New Treatment Challenges in an Ancient Disease / Epidemia de escabiosis: los nuevos retos de una enfermedad ancestral

Scabies, which is among the most prevalent diseases worldwide, is becoming more frequent in Spain. The problems of this epidemic can be explained by several factors: improper application or prescription of treatments, resistance or reduced sensitivity to topical treatments, and poor understanding of the parasite and contagion. We require a new evidence-based approach to therapy that takes these problems into consideration. If symptoms persist after proper treatment, it is important to identify the reason for failure and standardize our approach. In refractory cases, the prescriber should prioritize oral medication, indicate a higher dose, combine treatments, or evaluate the use of off-label treatments in certain populations. The availability of new medications —such as spinosad or, especially, moxidectin— offer hope for bringing this disease under control (AU)

La escabiosis es una de las enfermedades transmisibles más prevalentes en el mundo, actualmente en auge en nuestro entorno. Existen diferentes causas que explican la problemática de esta epidemia: una incorrecta aplicación o pauta del tratamiento; la disminución de la sensibilidad o la resistencia al tratamiento tópico y las carencias en el conocimiento del parásito y su transmisibilidad. Por este motivo es necesario un nuevo enfoque en el tratamiento de esta enfermedad que contemple los problemas y la evidencia actual. Si hay una persistencia de la clínica tras un correcto tratamiento es importante corroborar el fracaso terapéutico y estandarizar la actitud. Por último, ante un caso recalcitrante cabría plantear la posibilidad de priorizar el tratamiento oral, aumentar su dosis, realizar tratamientos combinados o plantear su uso fuera de ficha técnica en poblaciones especiales. La aparición de nuevos tratamientos, como el spinosad o, sobre todo, la moxidectina, aportan esperanza en el control de esta enfermedad (AU)

Uso da miltefosina no tratamento clínico de cães com leishmaniose visceral: revisão de literatura / Use of miltefosin in the clinical treatment of dogs with visceral leishmaniosis / Uso de miltefosina en el tratamiento clínico de perros con leishmaniosis visceral: revisión de la literatura

A leishmaniose visceral canina é uma doença de caráter zoonótico, acometendo os seres humanos e diversas espécies de animais silvestres e domésticos. Objetivou-se com o presente estudo realizar uma revisão de literatura sobre o uso da miltefosina no tratamento clínico de cães com leishmaniose visceral. Trata- se de uma revisão de literatura, a qual foi realizada por meio de consultas à periódicos e livros presentes na biblioteca do Cesmac. Foram utilizadas bases de dados como: portal Capes, SCIELO, Google Acadêmico; pesquisa em monografias, teses e dissertações. Causada pelo protozoário Leishmania chagasi, sendo o cão doméstico o principal reservatório desse protozoário. Por representar um problema grave de saúde pública e ser considerada uma doença potencialmente fatal (quando não tratada precocemente e adequadamente), faz- se importante que o clínico esteja familiarizado com os sinais clínicos, exames complementares e principais protocolos terapêuticos, em especial a utilização da miltefosina no tratamento da leishmaniose visceral em cães. Por ser uma zoonose que causa graves problemas de saúde pública e que vem crescendo cada vez mais no Brasil, cabe aos médicos veterinários assumirem o compromisso na conscientização sobre a importância do diagnóstico precoce além de promoverem o bem-estar animal e a saúde pública.(AU)

Canine visceral leishmaniasis is a zoonotic disease, affecting humans and several species of wild and domestic animals. The objective of the present study was to carry out a literature review on the use of miltefosine in the clinical treatment of dogs with visceral leishmaniasis. This is a literature review, which was carried out through consultations with periodicals and books present in the Cesmac library. Databases such as: Capes portal, SCIELO, Google Scholar; research in monographs, theses and dissertations. Caused by the protozoan Leishmania chagasi, with the domestic dog being the main reservoir of this protozoan. As it represents a serious public health problem and is considered a potentially fatal disease (when not treated early and properly), it is important that the clinician is familiar with the clinical signs, complementary exams and main therapeutic protocols, especially the use of miltefosine in the treatment of visceral leishmaniasis in dogs. As it is a zoonosis that causes serious public health problems and that has been growing more and more in Brazil, it is up to veterinarians to make a commitment to raise awareness of the importance of early diagnosis in addition to promoting animal welfare and public health.(AU)

La leishmaniosis visceral canina es una enfermedad zoonótica que afecta a los seres humanos y a varias especies de animales salvajes y domésticos. El objetivo de este estudio fue realizar una revisión bibliográfica sobre el uso de la miltefosina en el tratamiento clínico de perros con leishmaniosis visceral. Se trata de una revisión bibliográfica, que se realizó mediante consultas a publicaciones periódicas y libros presentes en la biblioteca del Cesmac. Se utilizaron bases de datos como: portal Capes, SCIELO, Google Académico; investigación en monografías, tesis y disertaciones. Causada por el protozoo Leishmania chagasi, siendo el perro doméstico el principal reservorio de este protozoo. Dado que representa un grave problema de salud pública y se considera una enfermedad potencialmente mortal (cuando no se trata de forma temprana y adecuada), es importante que el clínico esté familiarizado con los signos clínicos, las pruebas adicionales y los principales protocolos terapéuticos, especialmente el uso de miltefosina en el tratamiento de la leishmaniosis visceral en perros. Siendo una zoonosis que causa graves problemas de salud pública y que viene creciendo cada vez más en Brasil, corresponde a los veterinarios asumir el compromiso de concienciar sobre la importancia del diagnóstico precoz y promover el bienestar animal y la salud pública.(AU)

Effects of deworming medication on anaemia among children aged 6-59 months in sub-Saharan Africa.

BACKGROUND: Despite the limited knowledge regarding the effects of deworming medication (DM) on nutritional indicators in sub-Saharan Africa (SSA), deworming programmes continue to be implemented in resource-limited countries. Therefore, the current study aimed to examine the effects of DM on anaemia among children aged 6-59 months in SSA. METHODS: The analysis was performed using data obtained from 17 demographic and health surveys (DHSs) conducted in SSA. Children were considered to be anaemic if their haemoglobin (Hb) concentration was less than 11.0 g/dl, adjusting for altitude. To account for both multiple measures at the cluster level and the clustering of children within the same country, generalized linear mixed models were used to analyse the anaemia outcomes in 50,075 children aged 6-59 months. RESULTS: Overall, anaemia was reported in 61.8% of the children, and their median Hb concentration was 10.5 g/dl (interquartile range 9.4-11.5). The prevalence of anaemia ranged from 34.5% in Rwanda to 81.1% in Mali. Multivariate analyses showed that children who did not receive DM had increased odds of being anaemic (adjusted odds ratio [aOR]: 1.11; 95% confidence interval [CI] 1.07-1.16). CONCLUSIONS: The current study revealed that DM can decrease the risk of anaemia among preschool-age children (pre-SAC) in SSA. Thus, tailored public health programmes aimed at reducing childhood anaemia need to consider deworming. However, longitudinal studies are needed to validate the association that has been reported in this cross-sectional study.