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1.
Nat Rev Dis Primers ; 10(1): 74, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39362885

ABSTRACT

Scabies is one of the most common and highest-burden skin diseases globally. Estimates suggest that >200 million people worldwide have scabies at any one time, with an annual prevalence of 455 million people, with children in impoverished and overcrowded settings being the most affected. Scabies infection is highly contagious and leads to considerable morbidity. Secondary bacterial infections are common and can cause severe health complications, including sepsis or necrotizing soft-tissue infection, renal damage and rheumatic heart disease. There is no vaccine or preventive treatment against scabies and, for the past 30 years, only few broad-spectrum antiparasitic drugs (mainly topical permethrin and oral ivermectin) have been widely available. Treatment failure is common because drugs have short half-lives and do not kill all developmental stages of the scabies parasite. At least two consecutive treatments are needed, which is difficult to achieve in resource-poor and itinerant populations. Another key issue is the lack of a practical, rapid, cheap and accurate diagnostic tool for the timely detection of scabies, which could prevent the cycle of exacerbation and disease persistence in communities. Scabies control will require a multifaceted approach, aided by improved diagnostics and surveillance, new treatments, and increased public awareness.


Subject(s)
Ivermectin , Scabies , Scabies/epidemiology , Scabies/diagnosis , Scabies/drug therapy , Humans , Ivermectin/therapeutic use , Antiparasitic Agents/therapeutic use , Permethrin/therapeutic use , Prevalence
2.
PLoS Negl Trop Dis ; 18(10): e0012532, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39374184

ABSTRACT

Strongyloidiasis is a neglected tropical disease estimated to affect more than 600 million people worldwide. Recently, the World Health Organization road map on neglected tropical diseases 2021-2030 has put the focus on strongyloidiasis, including this disease within its mass drug administration campaigns. With the use of ivermectin in extensive treatment of all populations at-risk, identifying effective therapeutic alternatives is crucial in case ivermectin resistance arises. The objective of the present study was the development of a larval migration inhibition assay to evaluate the anthelmintic efficacy of commercial drugs and diamine and aminoalcohol derivatives against infective Strongyloides ratti third stage larvae. Through this technique, we successfully screened and estimated the in vitro anthelmintic efficacy of six commercial drugs, seven diamine derivatives and eight aminoalcohol derivatives. Unexpectedly, the half-maximal effective concentration of ivermectin and moxidectin (2.21 and 2.34 µM, respectively) were observed as the highest value obtained among all commercial drugs tested by this in vitro technique. Moreover, some diamine and aminoalcohol derivatives showed superior efficacy inhibiting S. ratti motility compared to ivermectin, with five compounds (AA23, AA34, AO2 AO7 and AO14b) also displaying selectivity indexes on HepG2 and Caco2 higher than 1. These findings underscore the potential of these derivatives as promising alternatives for strongyloidiasis treatment, warranting further investigation and in vivo efficacy assessment.


Subject(s)
Anthelmintics , Ivermectin , Larva , Strongyloides ratti , Strongyloidiasis , Animals , Larva/drug effects , Strongyloidiasis/drug therapy , Strongyloidiasis/parasitology , Ivermectin/pharmacology , Ivermectin/therapeutic use , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Humans , Strongyloides ratti/drug effects , Rats , Macrolides
3.
Rev Esp Sanid Penit ; 26(2): 72-76, 2024.
Article in English | MEDLINE | ID: mdl-39345041

ABSTRACT

OBJECTIVES: To review the homogeneity of pharmacological prescription and control measures applied in cases of scabies in prisons in Catalonia. MATERIAL AND METHOD: Observational, multicenter, and retrospective study. Cases of scabies from March 01, 2021 and March 01, 2022 were analyzed according to the International Alliance for the Control of Scabies (IACS) 2020 criteria: a) confirmed cases; b) clinically probable cases; and c) suspected cases.Epidemiological, clinical, therapeutic and regimental control variables were collected. We checked whether the interventions were homogeneous in each site. The mean and standard deviation were used as continuous variables and percentages and confidence interval (95%) for discrete variables. The Chi-square test was used to determine statistical association. RESULTS: 269 cases were detected (21.2% confirmed, 50.2% clinically probable and 28.6% suspected). 61.3% were treated with permethrin, 18.6% with ivermectin and 20.1% with both. 27.1% of the cases were withdrawn.There were no significant in-site differences in the study of contacts, isolation and treatment of clothing and belongings, but there were significant differences in the prescription of drugs (P <0.001), duration of treatment (P <0.001) and disinfection of the cell (P <0.001). DISCUSSION: The number of detected cases is estimated to be high, and the majority (71.4%) confirmed or clinically probable. Control measures are homogeneous, except for cell disinfection, which was conventional in 59.1%. Pharmacological treatment and its duration varied between prisons. It would be advisable to establish a protocol to standardize control measures applied to new cases in the centers of Catalonia and subsequently evaluate their efficacy.


Subject(s)
Ivermectin , Scabies , Scabies/drug therapy , Scabies/diagnosis , Humans , Spain , Retrospective Studies , Ivermectin/therapeutic use , Male , Female , Adult , Permethrin/therapeutic use , Prisoners/statistics & numerical data , Middle Aged , Insecticides/therapeutic use , Prisons
4.
PLoS Negl Trop Dis ; 18(9): e0012470, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39241094

ABSTRACT

INTRODUCTION: Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin. METHODS: This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6-11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400-950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population. RESULTS: 56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9-22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08-1.38), middle altitudes (OR = 2.34 [95%CI: 2.04-2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57-2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7-160.4) cases per 100,000 person-years. CONCLUSION: Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area.


Subject(s)
Epilepsy , Ivermectin , Onchocerciasis , Humans , Ivermectin/therapeutic use , Onchocerciasis/epidemiology , Onchocerciasis/drug therapy , Female , Male , Epilepsy/epidemiology , Epilepsy/drug therapy , Tanzania/epidemiology , Child , Cross-Sectional Studies , Prevalence , Adolescent , Adult , Young Adult , Animals , Child, Preschool , Onchocerca volvulus/drug effects , Middle Aged , Antiparasitic Agents/therapeutic use , Infant , Aged
5.
PLoS Negl Trop Dis ; 18(9): e0012461, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39226306

ABSTRACT

BACKGROUND: Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region. METHODS AND FINDINGS: We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development of an antigen capture ELISA to detect this antigen. This assay detected Ll-Bhp-1 in 74 of 116 (63.8%) loiasis patient sera. Ll-Bhp-1 levels were significantly correlated with L. loa microfilarial counts, and the sensitivity of the assay was highest for samples from people with high counts, (94% and 100% in people with ≥20,000 and ≥50,000 microfilaria per milliliter of blood, respectively). The antigen was not detected in 112 sera from people with other filarial infections, or in 34 control sera from the USA. CONCLUSIONS: This Ll-Bhp-1 antigen assay is specific for loiasis, and highly sensitive for identifying people with high L. loa microfilarial counts who are at increased risk for serious adverse events after ivermectin treatment. L. loa antigen detection has the potential to facilitate loiasis mapping efforts and programs to eliminate lymphatic filariasis and onchocerciasis in Central Africa.


Subject(s)
Antigens, Helminth , Biomarkers , Enzyme-Linked Immunosorbent Assay , Loa , Loiasis , Humans , Loa/immunology , Loa/isolation & purification , Loiasis/diagnosis , Loiasis/drug therapy , Loiasis/blood , Loiasis/parasitology , Animals , Antigens, Helminth/blood , Antigens, Helminth/immunology , Enzyme-Linked Immunosorbent Assay/methods , Biomarkers/blood , Africa, Central , Microfilariae/immunology , Sensitivity and Specificity , Ivermectin/therapeutic use , Female , Male
6.
PLoS Negl Trop Dis ; 18(9): e0012508, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39321251

ABSTRACT

BACKGROUND: The control of the Soil-Transmitted Helminths (STH) infections primarily relies on the school-based Preventive Chemotherapy (PCT) with mebendazole. Given the efficacy of ivermectin on STH, the control of the latter is expected to be potentialized in areas where ivermectin is also distributed for onchocerciasis and/or lymphatic filariasis control/elimination. This study aimed to assess the prevalence and intensity of STH in the Lomie Health District where annual school-based deworming campaigns and community-directed treatments with Ivermectin have been underway for almost two decades. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative cross-sectional study was conducted in 10 schools of the Lomie Health District, East Region, Cameroon. Stool samples were collected from school-aged children and analysed using the Kato-Katz technique. Semi-structured questionnaires were administered to enrolees to assess compliance with water, sanitation, and hygiene (WASH). Of the 491 children (median age: 9 years; IQR: 7-10) enrolled, 83.9% (95% CI: 80.3-87.1) were infected with at least one STH species. Trichuris trichiura was the predominant species (78.5%), and no hookworm was found. The prevalence trend slightly decreased between 1987 and 2010 (~8%) and remained unchanged since 2010 (p-value = 0.05). Overall, 46.8% and 41.8% of children were heavy-to-moderately infected with Ascaris lumbricoides and T. trichiura. Poor hand hygiene (OR: 2.24, 95% IC: 1.4-3.4, p-value = 0.0002) and the use of river as a source of drinking water (OR: 14.8, 95% IC: 6.9-33.3, p-value = 0.0001) were the main risk factors associated with the STH infection in Lomie Health District. CONCLUSIONS/SIGNIFICANCE: The persistent high prevalence and intensity of STH infection despite 16 years of mebendazole-based PCT and expected collateral impact of ivermectin mass distribution, points to plausible implementation gaps, poor compliance to WASH or sub-optimal efficacy of the anthelminthics used. This study highlights the need to further assess the cause of the persistent high prevalence and implement context-adapted control measures in order to curb STH transmission.


Subject(s)
Feces , Helminthiasis , Ivermectin , Mebendazole , Soil , Humans , Child , Cameroon/epidemiology , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Cross-Sectional Studies , Male , Female , Mebendazole/therapeutic use , Mebendazole/administration & dosage , Soil/parasitology , Helminthiasis/epidemiology , Helminthiasis/transmission , Helminthiasis/prevention & control , Helminthiasis/drug therapy , Animals , Feces/parasitology , Prevalence , Anthelmintics/therapeutic use , Anthelmintics/administration & dosage , Helminths/drug effects , Helminths/isolation & purification , Adolescent , Trichuris/drug effects , Trichuris/isolation & purification , Trichuriasis/epidemiology , Trichuriasis/transmission , Trichuriasis/drug therapy , Trichuriasis/prevention & control , Schools , Surveys and Questionnaires
7.
Arch Dermatol Res ; 316(8): 601, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225867

ABSTRACT

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.


Subject(s)
C-Reactive Protein , Ivermectin , Quality of Life , Scabies , Humans , Scabies/drug therapy , Scabies/immunology , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Male , Female , Middle Aged , Administration, Oral , Adult , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Aged , Young Adult , Adolescent , Antiparasitic Agents/administration & dosage , Antiparasitic Agents/therapeutic use , Sarcoptes scabiei/drug effects , Sarcoptes scabiei/immunology , Blood Sedimentation , Inflammation/immunology , Inflammation/drug therapy , Treatment Outcome , Animals
8.
Vet Parasitol ; 331: 110271, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39089177

ABSTRACT

The metastrongyloids Aelurostrongylus abstrusus and Troglostrongylus brevior are primary causes of feline clinical respiratory disease. The present field trial evaluated the clinical efficacy of a spot-on formulation containing eprinomectin, esafoxolaner and praziquantel (NexGard® Combo) administered per label recommendations to cats affected with aelurostrongylosis and/or troglostrongylosis. Overall, 36 naturally infected cats were randomly assigned to Group 1 (G1) or Group 2 (G2) of 18 cats each. The two groups included 6 cats with A. abstrusus, T. brevior and mixed infection, each. All cats completed the study. Cats in G1 were treated on study Days (SDs) 0 and 28±2. Cats in G2 served as negative control until SD 56±2 and were then treated on SD 56±2 and 84±2. On SD 0/-7, 28±2 and SD 56±2 all cats were subjected to parasitological (quali-quantitative Baermann) and clinical examinations (physical exams and thoracic X-rays). Hematology and biochemistry analyses were performed on SD 0/-7 and SD 56±2. On SD 84±2 quali-quantitative Baermann, clinical examination and thorax radiography were performed on all G2 cats and on two G1 cats that still had radiographic alterations on SD 56±2. On SD 112±2 all G2 cats were subjected to parasitological and clinical evaluations and one cat from G1 that still had radiographic signs at SD 84±2 was clinically and radiographically evaluated. Efficacy criteria were the reduction of larval shedding in faeces and the clinical response in terms of pathological and radiographic scores after treatment compared to the baseline. An efficacy of 100 % based on LPG reduction was recorded after one (20/24 cats) or two (all 24 cats) treatments in cats with single infection by A. abstrusus or T. brevior. For cats with mixed infections, larval shedding was stopped after one (11/12 cats) or two (all 12 cats) treatments. Statistically significant clinical and radiographic improvement was evident in all study cats after 2 treatments. The present data show that two monthly treatments with NexGard® Combo stopped larval shedding and led to a significant clinical recovery and a complete resolution of radiographic abnormalities in cats infected with A. abstrusus and/or T. brevior.


Subject(s)
Cat Diseases , Ivermectin , Metastrongyloidea , Praziquantel , Strongylida Infections , Animals , Cats , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Cat Diseases/drug therapy , Cat Diseases/parasitology , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Ivermectin/analogs & derivatives , Strongylida Infections/drug therapy , Strongylida Infections/veterinary , Strongylida Infections/parasitology , Metastrongyloidea/drug effects , Male , Female , Drug Combinations , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Feces/parasitology , Treatment Outcome
9.
Exp Parasitol ; 265: 108823, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39187057

ABSTRACT

Trichinosis is a common parasitic disease that affects the striated skeletal muscles, causing apoptotic and degenerative changes associated with myogenin expression in the affected myocytes. Hence, this study aimed to assess the ameliorative effects of stem cells and atorvastatin added to ivermectin on the infected myocytes during the muscular phase of murine trichinosis. 120 laboratory Swiss albino male mice were divided into 10 groups, and each group was subdivided into intestinal and muscular phases (each n = 6); uninfected control; untreated infected control; infected received ivermectin monotherapy; infected received atorvastatin monotherapy; infected received stem cells monotherapy; infected received ivermectin and atorvastatin dual therapy; infected received ivermectin and stem cells dual therapy; infected received atorvastatin and stem cells dual therapy; infected received ivermectin 0.2, atorvastatin 40, and stem cells triple therapy; and infected received ivermectin 0.1, atorvastatin 20, and stem cells triple therapy. Intestinal phase mice were sacrificed on the 5th day post-infection, while those of the muscular phase were sacrificed on the 35th day post-infection. Parasitological, histopathological, ultrastructural, histochemical, biochemical, and myogenin gene expression assessments were performed. The results revealed that mice that received ivermectin, atorvastatin, and stem cell triple therapies showed the maximum reduction in the adult worm and larvae burden, marked improvement in the underlying muscular degenerative changes (as was noticed by histopathological, ultrastructural, and histochemical Feulgen stain assessment), lower biochemical levels of serum NK-κB and tissue NO, and lower myogenin expression. Accordingly, the combination of stem cells, atorvastatin, and ivermectin affords a potential synergistic activity against trichinosis with considerable healing of the underlying degenerative sequel.


Subject(s)
Apoptosis , Atorvastatin , Ivermectin , Myogenin , Trichinellosis , Animals , Atorvastatin/pharmacology , Atorvastatin/therapeutic use , Male , Mice , Ivermectin/pharmacology , Ivermectin/therapeutic use , Trichinellosis/drug therapy , Trichinellosis/parasitology , Apoptosis/drug effects , Myogenin/genetics , Myogenin/metabolism , Muscle, Skeletal/parasitology , Muscle, Skeletal/pathology , Muscle, Skeletal/drug effects , Gene Expression/drug effects , Microscopy, Electron, Transmission , Stem Cell Transplantation , Trichinella spiralis/genetics , Trichinella spiralis/drug effects , Stem Cells/drug effects
10.
J Prev Med Public Health ; 57(5): 490-498, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39139093

ABSTRACT

OBJECTIVES: The aim of this study was to identify factors associated with coverage in community-directed treatment with ivermectin for onchocerciasis control in savannah and forest areas in the Central African Republic. METHODS: A cross-sectional study was conducted in 2 districts where onchocerciasis is endemic. We employed a pretested and validated questionnaire that included questions about the socio-demographic characteristics of the respondents and variables relevant to coverage assessment. Multivariate logistic regression analyses were performed to identify the associations between surveyed mass drug administration (MDA) coverage and the variables considered, while accounting for potential confounding factors. A p-value <0.05 was considered statistically significant. RESULTS: At the district level, the MDA program achieved a reach of 87.29% (95% confidence interval [CI], 86.03 to 88.55) in Bossangoa and 61.74% (95% CI, 59.56 to 63.92) in Kémo, compared to the reported rates of 90.02% and 91.70%, respectively. Women in both Bossangoa and Kémo were 1.28 times more likely to have taken ivermectin than men (95% CI, 1.12 to 1.47; p=0.008; 95% CI, 1.09 to 2.00; p=0.041, respectively). The age groups of 5-14, 15-24, and 25-34 were statistically associated with better distribution coverage in both districts. Individuals with knowledge of onchocerciasis were more likely to receive ivermectin compared to those without knowledge, with adjusted odds ratios of 1.41 (95% CI, 1.11 to 2.01; p=0.030) and 3.19 (95% CI, 2.91 to 4.08; p=0.001), respectively. CONCLUSIONS: The authors recommend implementing measures to improve MDA coverage in future campaigns. These measures should include allocating sufficient time for MDA activities, providing health education, and mobilising the entire population.


Subject(s)
Ivermectin , Onchocerciasis , Humans , Ivermectin/therapeutic use , Onchocerciasis/drug therapy , Onchocerciasis/prevention & control , Onchocerciasis/epidemiology , Cross-Sectional Studies , Female , Male , Adult , Central African Republic/epidemiology , Middle Aged , Adolescent , Young Adult , Forests , Surveys and Questionnaires , Mass Drug Administration/statistics & numerical data , Logistic Models
11.
Rev Bras Parasitol Vet ; 33(3): e003324, 2024.
Article in English | MEDLINE | ID: mdl-39140496

ABSTRACT

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.


Subject(s)
Ivermectin , Parasite Egg Count , Animals , Ivermectin/therapeutic use , Ivermectin/administration & dosage , Horses/parasitology , Brazil , Horse Diseases/parasitology , Horse Diseases/drug therapy , Horse Diseases/diagnosis , Female , Antiparasitic Agents/therapeutic use , Antiparasitic Agents/administration & dosage , Strongyle Infections, Equine/drug therapy , Strongyle Infections, Equine/parasitology , Strongyle Infections, Equine/diagnosis , Feces/parasitology
12.
Viral Immunol ; 37(6): 298-307, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39096169

ABSTRACT

The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).


Subject(s)
Antiviral Agents , Azithromycin , COVID-19 Drug Treatment , COVID-19 , Drug Repositioning , Hydroxychloroquine , Ivermectin , Lopinavir , Ritonavir , SARS-CoV-2 , Humans , Antiviral Agents/therapeutic use , SARS-CoV-2/drug effects , Hydroxychloroquine/therapeutic use , Ivermectin/therapeutic use , Ritonavir/therapeutic use , Azithromycin/therapeutic use , Lopinavir/therapeutic use , Male , Drug Therapy, Combination , Doxycycline/therapeutic use , Drug Combinations , Middle Aged , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Treatment Outcome , Aged , Pregnenediones/therapeutic use
13.
Parasite ; 31: 44, 2024.
Article in English | MEDLINE | ID: mdl-39109981

ABSTRACT

Amblyomma maculatum, the Gulf Coast tick, infests a wide range of vertebrate species including livestock, dogs, cats, and humans. It is a species of significant veterinary and public health importance, especially as a vector of diseases, for instance American canine hepatozoonosis or tidewater spotted fever. An experimental study was conducted to evaluate the efficacy of NexGard® Combo, a topical endectoparasiticide product for cats combining eprinomectin, praziquantel and esafoxolaner, against induced infestations of A. maculatum in cats. This Good Clinical Practice (GCP) study used a randomized, negative controlled, masked design. Ten cats were allocated to an untreated group and ten to a treated group, dosed once on Day 0 at the minimum label dose. On Days -2, 7, 14, 21, 28, 35, and 42, cats were infested with ~50 unfed adult A. maculatum. On Days 3, 10, 17, 24, 31, 38, and 45, i.e., 72 h after treatment and subsequent infestations, ticks were removed, counted and the numbers of live attached tick in each group were used for efficacy calculations. At each time-point, all untreated cats were adequately infested, demonstrating a vigorous tick population and an adequate study model. The curative efficacy after a single application against existing tick infestation, 72 h after treatment, was 98.7%. The preventive efficacy, 72 h after weekly infestations, over the following five weeks ranged from 93.8% to 99.4%.


Title: Efficacité d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les infestations par Amblyomma maculatum chez le chat. Abstract: Amblyomma maculatum, la tique de la Gulf Coast, infeste un large éventail d'espèces de vertébrés, notamment le bétail, les chiens, les chats et les humains. Il s'agit d'une espèce d'importance significative en médecine vétérinaire et en santé publique, notamment en tant que vecteur de maladies, par exemple l'hépatozoonose canine américaine ou la fièvre pourprée des marées. Une étude expérimentale a été menée pour évaluer l'efficacité de NexGard® Combo, un produit endectoparasiticide topique pour chats associant éprinomectine, praziquantel et esafoxolaner, contre les infestations par A. maculatum provoquées chez le chat. Cette étude de bonnes pratiques cliniques (BPC) a utilisé une conception randomisée, contrôlée négativement et masquée. Dix chats ont été répartis dans un groupe non traité et dix chats dans un groupe traité, traités une fois au jour 0 à la dose minimale indiquée sur l'étiquette. Aux jours −2, 7, 14, 21, 28, 35 et 42, les chats ont été infestés par environ 50 A. maculatum adultes non nourris. Les jours 3, 10, 17, 24, 31, 38 et 45, c'est-à-dire 72 heures après le traitement et les infestations ultérieures, les tiques ont été retirées, comptées et le nombre de tiques vivantes attachées dans chaque groupe a été utilisé pour les calculs d'efficacité. À chaque instant, tous les chats non traités étaient correctement infestés, démontrant une population de tiques vigoureuse et un modèle d'étude adéquat. L'efficacité curative après une seule application contre une infestation de tiques existante, 72 heures après le traitement, était de 98,7%. L'efficacité préventive, 72 heures après les infestations hebdomadaires, au cours des cinq semaines suivantes, variait entre 93,8% et 99,4%.


Subject(s)
Amblyomma , Cat Diseases , Ivermectin , Praziquantel , Tick Infestations , Animals , Praziquantel/administration & dosage , Praziquantel/therapeutic use , Cats , Cat Diseases/drug therapy , Cat Diseases/parasitology , Tick Infestations/veterinary , Tick Infestations/drug therapy , Tick Infestations/parasitology , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Ivermectin/analogs & derivatives , Female , Male , Administration, Topical , Drug Combinations , Treatment Outcome , Acaricides/administration & dosage , Acaricides/therapeutic use
15.
Am J Trop Med Hyg ; 111(3_Suppl): 137-140, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-38981465

ABSTRACT

The single onchocerciasis-endemic focus in the remote Amazon rainforest is shared by Brazil and Venezuela and affects primarily the indigenous Yanomami people. Regional elimination of onchocerciasis is challenged by the magnitude and inaccessibility of this area. In Brazil, 272 onchocerciasis-endemic communities are operationally organized through 21 health centers ("polos bases"). Mass drug administration of ivermectin began in 1995, with 36 effective biannual rounds (≥85% coverage of the eligible population) through 2022. The national on chocerciasis program maintains community-level monitoring to prioritize treatment activities and epidemiological surveys. The Onchocerciasis Elimination Program for the Americas and the WHO onchocerciasis elimination guidelines have helped Brazil move toward its goal of stopping ivermectin treatment by 2025 and verifying transmission elimination by 2030. Additional challenges to the Brazilian onchocerciasis program include cross-border movements and insecurity due to illegal mining and inter-community conflicts. The new government in Brazil offers hope given its commitment to the equity of indigenous people and preservation of the Amazon environment.


Subject(s)
Disease Eradication , Ivermectin , Onchocerciasis , Humans , Brazil/epidemiology , Onchocerciasis/prevention & control , Onchocerciasis/epidemiology , Onchocerciasis/drug therapy , Disease Eradication/methods , Ivermectin/therapeutic use , Mass Drug Administration , Filaricides/therapeutic use
16.
Am J Trop Med Hyg ; 111(3): 521-525, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-38981492

ABSTRACT

Loiasis is a rarely imported infectious disease that is often difficult to diagnose and treat. Here we describe clinical features and treatment outcomes of 11 patients with imported loiasis seen at a German reference center between 2013 and 2023. Clinical presentations varied by patient origin, with eye-worm migration and ophthalmological symptoms being more common among patients from endemic areas and Calabar swelling, subcutaneous swelling, and pruritus more prevalent among returning travelers from nonendemic regions. Eosinophil counts were higher in returning travelers. Diethylcarbamazine was most commonly used for treatment either as monotherapy in combination with ivermectin or with albendazole and ivermectin, respectively. In one patient, long-term follow-up indicated treatment failure after the first course of treatment. Another traveler was prescribed chemoprophylaxis with diethylcarbamazine after experiencing repeated infections due to long-term residence in a high-risk region in Cameroon.


Subject(s)
Ivermectin , Loiasis , Humans , Loiasis/drug therapy , Loiasis/epidemiology , Loiasis/diagnosis , Germany/epidemiology , Male , Female , Retrospective Studies , Adult , Middle Aged , Ivermectin/therapeutic use , Travel , Albendazole/therapeutic use , Diethylcarbamazine/therapeutic use , Communicable Diseases, Imported/drug therapy , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/parasitology , Communicable Diseases, Imported/diagnosis , Young Adult , Filaricides/therapeutic use , Animals , Aged
17.
Clin Ther ; 46(8): e15-e18, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38969585

ABSTRACT

PURPOSE: Global fears regarding future epidemics of new and re-emerging infections will prompt clinicians to try out unconventional treatments based on limited evidence, including the repurposing of existing drugs. The dilemma involves balancing clinical intuition with the need to rely on low-quality information because of the scarcity of definitive evidence. An example was ivermectin; with its potential antiviral properties, it was promoted for its efficacy in treating coronavirus disease 2019 despite conflicting outcomes in clinical trials and varying expert opinions. This article describes the development of a decision-making framework to resolve such dilemmas. METHODS: The case study from Sri Lanka illustrates multiple challenges faced by clinicians. As the horrific details of deaths in countries such as Italy spread on social media, there was panic and an unprecedented demand for clinicians and health services to provide effective treatment. This led to the popularity of drugs such as ivermectin and several herbal cures. However, there was no consensus among experts on the efficacy of ivermectin, which eventually led to the authorities to recommend limited approval for use under physician supervision. FINDINGS: The situation lent itself to a framework with 4 elements: prerequisites, applying an appropriate decision-making tool (eg, multiple criteria decision-making methods), ethical considerations, and sensitive communication. IMPLICATIONS: We propose this framework for clinicians when they face similar situations with demands to repurpose medicines with inconclusive evidence of efficacy to combat devastating infections from new or re-emerging infections.


Subject(s)
COVID-19 Drug Treatment , Drug Repositioning , Ivermectin , Humans , Ivermectin/therapeutic use , Sri Lanka , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Decision Making , SARS-CoV-2 , Clinical Decision-Making
18.
J Oral Sci ; 66(3): 202-205, 2024.
Article in English | MEDLINE | ID: mdl-39010170

ABSTRACT

The present work reports a case of a female patient complaining of itching and painful lesions affecting the oral mucosa for 7 months. Buccal and lip mucosa showed swelling and erythema, with serpiginous tracks. The patient was diagnosed with oral larva migrans, and the lesions resolved after ivermectin administration. At 18-month follow-up, no sign of recurrence was observed. Larva migrans can represent a pitfall in oral diagnosis and a stressful condition for the patient. Oral health care providers should be aware of this and keep this disease in mind as a possible differential diagnosis in oral mucosa lesions.


Subject(s)
Larva Migrans , Humans , Female , Larva Migrans/diagnosis , Diagnosis, Differential , Mouth Diseases/diagnosis , Mouth Diseases/parasitology , Ivermectin/therapeutic use , Adult , Mouth Mucosa/pathology , Mouth Mucosa/parasitology
19.
Health Aff (Millwood) ; 43(7): 959-969, 2024 07.
Article in English | MEDLINE | ID: mdl-38950300

ABSTRACT

Global supply chains for active pharmaceutical ingredients (APIs) are highly centralized in certain countries and are susceptible to supply-chain shocks. However, there is no systematic monitoring or global coordination to manage risk and ensure equitable supply continuity during public health emergencies. In this study, we applied quasi-experimental methods on shipment-level customs data to determine how prices and export volume for APIs exported from India were affected by the COVID-19 pandemic. We found that API prices for key essential medicines not used for COVID-19 did not change significantly in the year after the World Health Organization pandemic declaration, but volume decreased by 80 percent. Prices for medicines speculatively repurposed for COVID-19, such as hydroxychloroquine and ivermectin, increased by as much as 250 percent compared with prices for nonrepurposed medicines, but only ivermectin saw a decrease in volume. Systematic monitoring of API markets, investments to promote supply diversification, and legal and political reforms to disincentivize price speculation could support supply-chain resilience and safeguard access to medicines.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , India , Commerce , COVID-19 Drug Treatment , Global Health , Drugs, Essential/supply & distribution , Drugs, Essential/economics , Ivermectin/supply & distribution , Ivermectin/therapeutic use , Ivermectin/economics , Pandemics , Internationality , Bulk Drugs
20.
Vet Res Commun ; 48(5): 3365-3369, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39012470

ABSTRACT

Lamanema chavezi is an entero-hepatic strongylid parasite specific to South American camelids. It has been reported only on few occasions outside South America. Due to its hepatic migration, it can cause extensive liver damage, leading to granulomatous and fibrotic hepatitis and manifesting with lethargy, anorexia, and even death. We are reporting the second case of L. chavezi infection in Europe and the first in Switzerland. The patient was a three-year old neutered male llama (Lama glama). Clinical examination revealed bloody mucous discharge from the anus. Fecal sedimentation/flotation revealed strongylid eggs consistent with L. chavezi, which were molecularly confirmed by a PCR targeting the ITS2 plus 5.8S and 28S rDNA flanking regions and amplicon sequencing. Eighteen weeks after administration of a single dose of eprinomectin (0.2 mg/kg i.m.), no further L. chavezi eggs were detected in the feces. The source of infection could not be traced back. The entire herd consisted of llamas bred in Switzerland. L. chavezi has been rarely reported outside South America, but its potential for pathogenicity and establishment should not be underestimated. Fecal sedimentation/flotation techniques should be routinely performed to ensure early detection of the parasite.


Subject(s)
Camelids, New World , Animals , Camelids, New World/parasitology , Male , Switzerland , Strongylida Infections/veterinary , Strongylida Infections/diagnosis , Strongylida Infections/parasitology , Feces/parasitology , Ivermectin/therapeutic use , Ivermectin/analogs & derivatives , Anthelmintics/therapeutic use
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