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1.
PLoS Negl Trop Dis ; 15(3): e0009088, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33661903

RESUMO

The neglected tropical diseases (NTDs) affect hundreds of millions of people, predominantly in rural, often difficult-to-access areas, poorly served by national health services. Here, we review the contributions of 4.8 million community-directed distributors (CDDs) of medicines over 2 decades in 146,000 communities in 27 sub-Saharan African countries to control or eliminate onchocerciasis and lymphatic filariasis (LF). We examine their role in the control of other NTDs, malaria, HIV/AIDS interventions, immunisation campaigns, and support to overstretched health service personnel. We are of the opinion that CDDs as community selected, trained, and experienced "foot soldiers," some of whom were involved in the Ebola outbreak responses at the community level in Liberia, if retrained, can assist community leaders and support health workers (HWs) in the ongoing Coronavirus Disease 2019 (COVID-19) crisis. The review highlights the improved treatment coverage where there are women CDDs, the benefits and lessons from the work of CDDs, their long-term engagement, and the challenges they face in healthcare delivery. It underscores the value of utilising the CDD model for strong community engagement and recommends the model, with some review, to hasten the achievement of the NTD 2030 goal and assist the health system cope with evolving epidemics and other challenges. We propose that, based on the unprecedented progress made in the control of NTDs directly linked to community engagement and contributions of CDDs "foot soldiers," they deserve regional and global recognition. We also suggest that the World Health Organization (WHO) and other international stakeholders promote policy and guidance for countries to adapt this model for the elimination of NTDs and to strengthen national health services. This will enhance the accomplishment of some Sustainable Development Goals (SDGs) by 2030 in sub-Saharan Africa.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Filariose Linfática/terapia , Administração Massiva de Medicamentos , Doenças Negligenciadas/terapia , Oncocercose/terapia , África ao Sul do Saara , Agentes Comunitários de Saúde , Filariose Linfática/prevenção & controle , Feminino , Humanos , Ivermectina/administração & dosagem , Doenças Negligenciadas/prevenção & controle , Oncocercose/prevenção & controle
2.
PLoS One ; 16(2): e0247163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33592050

RESUMO

BACKGROUND: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers. METHODS: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection. RESULTS: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection. CONCLUSION: Two-dose ivermectin prophylaxis at a dose of 300 µg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic.


Assuntos
/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Ivermectina/uso terapêutico , Adulto , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/uso terapêutico , Estudos de Casos e Controles , Quimioprevenção/métodos , Combinação de Medicamentos , Feminino , Humanos , Índia , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade
3.
Trials ; 22(1): 4, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397429

RESUMO

OBJECTIVES: We will evaluate the efficacy and safety of Ivermectin in patients with mild and moderately severe COVID-19. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design (1:1 ratio). PARTICIPANTS: The Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will screen for patients age ≥ 20 years and weight ≥35 kg for the following criteria: Inclusion criteria for patients with mild COVID-19 symptoms (outpatients) 1. Diagnosed mild pneumonia using computed tomography (CT) and/or chest X-ray (CX-R) imaging, not requiring hospitalization. 2. Signing informed consent. Inclusion criteria for patients with moderate COVID-19 symptoms (inpatients) 1. Confirmed infection using PCR. 2. Diagnosed moderate pneumonia using CT and/or CXR imaging, requiring hospitalization. 3. Hospitalized ≤ 48 hours. 4. Signing informed consent. Exclusion criteria 1. Severe and critical pneumonia due to COVID-19. 2. Underlying diseases, including AIDS, asthma, loiasis, and severe liver and kidney disease. 3. Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). 4. History of drug allergy to Ivermectin. 5. Pregnancy or breastfeeding. INTERVENTION AND COMPARATOR: Intervention groups: Outpatient and inpatient groups will receive the standard treatment regimen for mild and moderate COVID-19, based on the Iranian Ministry of Health and Medical Education's protocol, along with oral Ivermectin (MSD Company, France) at a single dose of 0.2 mg/kg. Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days. The inpatient group will receive 200/50 mg Lopinavir/Ritonavir (Heterd Company, India) twice a day for the seven days, plus five doses of 44 mcg Interferon beta-1a (CinnaGen, Iran) every other day. Other supportive and routine care will be the same in both outpatient and inpatient groups. MAIN OUTCOME: The primary outcomes are composite and include the improvement of clinical symptoms and need for hospitalization for outpatient groups, and the length of hospital stay until discharge, the need for ICU admission until discharge, and the need for mechanical ventilation for inpatient groups within seven days of randomization. The secondary outcome is the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Patients in both outpatient (mild) and inpatient (moderate) groups will be randomized into the treatment and control groups based on the following method. A simple randomization method and table of random numbers will be used. If the selected number is even, the patient is allocated to the treatment group, and if it is odd, the patient is allocated to the control group in a 1:1 ratio. BLINDING (MASKING): This is an open-label study, and there is not blinding. Numbers to be randomized (sample size) A total number of 120 patients (60 outpatients and 60 patients) will be randomized into two groups (30 patients in each of the intervention groups and 30 patients in each of the control groups). TRIAL STATUS: The protocol is Version 1.0, November 17, 2020. Recruitment began November 25, 2020, and is anticipated to be completed by February 25, 2021. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N6 ". The registration date is November 17, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Antivirais/administração & dosagem , Ivermectina/administração & dosagem , /isolamento & purificação , Administração Oral , Adulto , Antivirais/efeitos adversos , /virologia , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Unidades de Terapia Intensiva/estatística & dados numéricos , Interferon beta-1a/administração & dosagem , Interferon beta-1a/efeitos adversos , Irã (Geográfico) , Ivermectina/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença
7.
PLoS Negl Trop Dis ; 14(9): e0008642, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976514

RESUMO

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual rounds of MDA with similar compliance. The effects of MDA using ivermectin (IVM, 0.2 mg/kg) combined with albendazole (ALB, 400 mg) on the prevalence and intensity of hookworm infection were evaluated in the Abengourou (annual MDA) and Akoupé (semi-annual MDA) health Districts in eastern Côte d'Ivoire from 2014 to 2017. A cross-sectional approach was used together with mixed logistic regression, and mixed linear models. Subjects were tested for STH using the Kato-Katz technique before the first round of MDA and 12, 24, and 36 months after the first round of MDA. The mean self-reported MDA compliance assessed during the survey was 65%, and no difference was observed between treatment areas. These results were confirmed by an independent coverage survey as recommended by WHO. Hookworm was the most prevalent STH species in both areas (23.9% vs 12.4%) and the prevalence of other STH species was less than 1%. The crude prevalence of hookworm dropped significantly, from 23.9% to 5.5% (p <0.001, 77% reduction) in the annual MDA treatment area and from 12.4% to 1.9% (p <0.001, 85% reduction) in the semi-annual treatment area. The average intensity of hookworm infection decreased in the annual MDA area (406.2 epg to 118.3 epg), but not in the semi-annual MDA area (804.9 epg to 875.0 epg). Moderate and heavy infections (1% and 1.3% at baseline) were reduced to 0% and 0.4% in the annual and semi-annual treatment areas, respectively. Using a mixed logistic regression model, and after adjusting for baseline prevalence, only the year 2 re-examination showed a difference in prevalence between treatments (OR: 2.26 [95% CI: 1.03, 4.98], p = 0.043). Analysis of intensity of hookworm infection indicated also that treatment differences varied by follow-up visit. In conclusion twelve months after the last treatment cycle, three annual and five semi-annual rounds of community-wide MDA with the combination of IVM and ALB showed strong, but similar impact on hookworm prevalence and intensity in eastern Côte d'Ivoire. Therefore, an annual MDA regimen seems to be an efficient strategy to control hookworm infection in endemic areas with low and moderate infection prevalence. Trial registration: The study was registered at ClinicalTrial.gov under the number NTC02032043.


Assuntos
Filariose Linfática/tratamento farmacológico , Infecções por Uncinaria/tratamento farmacológico , Administração Massiva de Medicamentos/métodos , Oncocercose/tratamento farmacológico , Adolescente , Adulto , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Ancylostomatoidea , Animais , Criança , Costa do Marfim/epidemiologia , Estudos Transversais , Combinação de Medicamentos , Filariose Linfática/epidemiologia , Feminino , Infecções por Uncinaria/epidemiologia , Humanos , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oncocercose/epidemiologia , Prevalência , Adulto Jovem
8.
Exp Parasitol ; 218: 107998, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32941889

RESUMO

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations.


Assuntos
Inseticidas/uso terapêutico , Ivermectina/análogos & derivados , Infestações por Ácaros/veterinária , Psoroptidae/efeitos dos fármacos , Doenças dos Ovinos/tratamento farmacológico , Animais , Disponibilidade Biológica , Feminino , Meia-Vida , Injeções Subcutâneas/veterinária , Inseticidas/administração & dosagem , Inseticidas/sangue , Inseticidas/farmacologia , Ivermectina/administração & dosagem , Ivermectina/sangue , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Masculino , Infestações por Ácaros/tratamento farmacológico , Psoroptidae/crescimento & desenvolvimento , Ovinos , Doenças dos Ovinos/parasitologia
9.
J Pharm Sci ; 109(12): 3574-3578, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32891630

RESUMO

SARS-CoV-2 utilizes the IMPα/ß1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPß1 subunits as well as dissociating the IMPα/ß1 heterodimer and has in vitro efficacy against SARS-CoV-2. Plasma and lung ivermectin concentrations vs. time profiles in cattle were used to determine the apparent plasma to lung tissue partition coefficient of ivermectin. This coefficient, together with a simulated geometric mean plasma profile of ivermectin from a published population pharmacokinetic model, was utilized to develop a minimal physiologically-based pharmacokinetic (mPBPK) model. The mPBPK model accurately described the simulated ivermectin plasma concentration profile in humans. The mPBPK model was also used to simulate human lung exposure to ivermectin after 12, 30, and 120 mg oral doses. The simulated ivermectin lung exposures reached a maximum concentration of 772 ng/mL, far less than the estimated 1750 ng/mL IC50 reported for ivermectin against SARS-CoV-2 in vitro. Further studies of ivermectin either reformulated for inhaled delivery or in combination with other antivirals with differing mechanisms of action is needed to assess its therapeutic potential.


Assuntos
Antivirais/farmacocinética , Infecções por Coronavirus/tratamento farmacológico , Ivermectina/farmacocinética , Pulmão/metabolismo , Pneumonia Viral/tratamento farmacológico , Administração Oral , Animais , Antivirais/administração & dosagem , Antivirais/sangue , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/metabolismo , Bovinos , Simulação por Computador , Infecções por Coronavirus/metabolismo , Reposicionamento de Medicamentos , Humanos , Ivermectina/administração & dosagem , Ivermectina/sangue , Ivermectina/farmacologia , Modelos Biológicos , Pandemias , Pneumonia Viral/metabolismo
11.
PLoS One ; 15(8): e0236143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790679

RESUMO

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance.


Assuntos
Criação de Animais Domésticos/métodos , Anti-Helmínticos/administração & dosagem , Infecções por Nematoides/veterinária , Doenças dos Ovinos/tratamento farmacológico , Ovinos/parasitologia , Animais , Anti-Helmínticos/farmacocinética , Fazendas , Fezes/parasitologia , Feminino , Meia-Vida , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Ivermectina/farmacocinética , Larva , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Nematoides/isolamento & purificação , Infecções por Nematoides/diagnóstico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Período Pós-Parto , Gravidez , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/parasitologia
12.
Korean J Parasitol ; 58(3): 315-319, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32615745

RESUMO

In November 2019 a 5-month-old mixed-breed rabbit presented to Chungbuk National University Veterinary Teaching Hospital, Cheongju-si, Chungbuk, Republic of Korea (Korea) with symptoms comprising pruritus, crusts on skin, poor appetite and reduced defecation. The rabbit was purchased 2 months prior from a pet shop located in a big market, and that the symptoms were first observed about 2 weeks prior to the hospital visit. Physical examination revealed that the patient had crust formation and alopecia on the nose together with lesions on the digits. A skin scraping test was performed using mineral oil and a high density of mites was observed by microscopy. Each mite showed a round, tortoise-like body with 4 comparatively short pairs of legs. The anus was located at the terminal unlike with suspected pathogen, Notoedres cati. Based on morphological characteristics, we identified the mite as Sarcoptes sp. Ivermectin was administered weekly by subcutaneous injection at a dosage of 0.4 mg/kg, and 4 weeks of follow-up study revealed the patient was fully recovered. And no more mites were detected from the case. This is the first case report of sarcoptic mange in a pet rabbit in Korea.


Assuntos
Coelhos , Doenças dos Roedores/parasitologia , Escabiose/parasitologia , Escabiose/veterinária , Animais , Ivermectina/administração & dosagem , Ácaros , República da Coreia , Sarcoptes scabiei , Escabiose/tratamento farmacológico , Resultado do Tratamento
13.
PLoS Comput Biol ; 16(7): e1007506, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32692741

RESUMO

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps.


Assuntos
Erradicação de Doenças/estatística & dados numéricos , Filariose Linfática , Modelos Biológicos , Modelos Estatísticos , Antígenos de Helmintos/sangue , Biologia Computacional , Bases de Dados Factuais , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Filaricidas/administração & dosagem , Filaricidas/uso terapêutico , Humanos , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Nigéria
14.
PLoS Negl Trop Dis ; 14(6): e0008298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511226

RESUMO

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.


Assuntos
Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Dietilcarbamazina/administração & dosagem , Ivermectina/administração & dosagem , Adolescente , Adulto , Albendazol/efeitos adversos , Animais , Antiparasitários/efeitos adversos , Criança , Pré-Escolar , Dietilcarbamazina/efeitos adversos , Quimioterapia Combinada , Filariose Linfática/tratamento farmacológico , Feminino , Haiti , Humanos , Ivermectina/efeitos adversos , Modelos Logísticos , Masculino , Administração Massiva de Medicamentos/efeitos adversos , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
15.
Washington; Organización Panamericana de la Salud; jun. 23, 2020. 3 p.
Não convencional em Inglês, Espanhol, Português | LILACS | ID: biblio-1100598

RESUMO

Un estudio reciente (1) informó que la ivermectina se utilizó con éxito in vitro para el tratamiento del SARS-CoV-2 en células infectadas experimentalmente y dos publicaciones preimpresas (2,3) sobre estudios clínicos observacionales informaron la aparente utilidad de la ivermectina para tratar pacientes con COVID-19 que requirieron ventilación mecánica. Sin embargo, ninguno de estos estudios fue revisado por pares ni publicado formalmente y uno de ellos (3) fue retirado posteriormente.


A recent study reported that ivermectin was successfully used in vitro for the treatment of SARS-CoV-2 in experimentally infected cells, and two preprint publications reported observational clinical studies on the apparent utility of ivermectin to treat patients with COVID-19 needing mechanical ventilation. However, none of these studies was peer-reviewed nor formally published and one study was later retracted. The Pan American Health Organization (PAHO) compiled an evidence database of potential COVID-19 therapeutics for which a rapid review was conducted of all COVID-19 in vitro (lab) and in vivo (clinical) human studies published from January to May 2020. The review concluded that the studies on ivermectin were found to have a high risk of bias, very low certainty of the evidence, and that the existing evidence is insufficient to draw a conclusion on benefits and harms. Though the effectiveness of ivermectin is currently being evaluated in various randomized clinical trials, the World Health Organization (WHO) excluded ivermectin from its co-sponsored Solidarity Trial for COVID-19 treatments, a global effort to find an effective treatment for COVID-19. The Mectizan® (ivermectin) Expert Committee Statement on Potential Efficacy of Ivermectin on COVID-19 emphasized that the laboratory results showing efficacy of ivermectin to reduce viral loads in laboratory cultures, at dosage levels far beyond those approved by the FDA for treatment of parasitic diseases in humans, are not sufficient to indicate that ivermectin will be of clinical benefit to reduce viral loads in COVID-19 patients. Chaccour et al. caution against using in vitro findings as more than a qualitative indicator of potential efficacy and emphasize that "due diligence and regulatory review are needed before testing ivermectin in COVID-19.


Um estudo recente informou que a ivermectina foi usada com êxito, in vitro, para o tratamento do vírus SARS-CoV-2 em células infectadas experimentalmente. Duas publicações preprint sobre estudos clínicos observacionais relataram aparente utilidade da ivermectina no tratamento de pacientes com COVID-19, em ventilação mecânica. Nenhum desses estudos teve revisão por pares, nem foi publicado formalmente, e um deles se retratou depois. A Organização Pan-Americana da Saúde (OPAS) compilou um banco de dados de evidências sobre potenciais tratamentos para COVID-19, e fez uma revisão rápida de todos os estudos realizados em humanos, in vitro (laboratórios) ou in vivo (clínicos), publicados de janeiro a maio de 2020. A revisão concluiu que os estudos sobre ivermectina tinham um alto risco de viés, muito pouca certeza de evidências, e as evidências existentes eram insuficientes para se chegar a uma conclusão sobre benefícios e danos. Apesar da efetividade da ivermectina estar sendo avaliada atualmente em diversos ensaios clínicos randomizados, deve-se enfatizar que a Organização Mundial da Saúde (OMS) excluiu a ivermectina de seu ensaio "Solidarity Trial" para tratamentos da COVID-19, uma iniciativa co-patrocinada, para encontrar um tratamento efetivo para COVID-19.


Assuntos
Humanos , Pneumonia Viral/prevenção & controle , Ivermectina/administração & dosagem , Ivermectina/efeitos adversos , Ivermectina/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ventiladores Mecânicos , Resultado do Tratamento , Medicina Baseada em Evidências
16.
Clin Pharmacol Ther ; 108(4): 762-765, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32378737

RESUMO

Caly et al.1 reported that ivermectin inhibited severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in vitro for up to 48 hours using ivermectin at 5 µM. The concentration resulting in 50% inhibition (IC50 ; 2 µM) was > 35× higher than the maximum plasma concentration (Cmax ) after oral administration of the approved dose of ivermectin when given fasted. Simulations were conducted using an available population pharmacokinetic model to predict total (bound and unbound) and unbound plasma concentration-time profiles after a single and repeat fasted administration of the approved dose of ivermectin (200 µg/kg), 60 mg, and 120 mg. Plasma total Cmax was determined and then multiplied by the lung:plasma ratio reported in cattle to predict the lung Cmax after administration of each single dose. Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC50 , even for a dose level 10× higher than the approved dose. Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC50 in the lungs after single oral administration of the approved dose (predicted lung: 0.0873 µM) or at doses 10× higher that the approved dose administered orally (predicted lung: 0.820 µM). In summary, the likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Repurposing drugs for use in coronavirus disease 2019 (COVID-19) treatment is an ideal strategy but is only feasible when product safety has been established and experiments of repurposed drugs are conducted at clinically relevant concentrations.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Ivermectina/administração & dosagem , Modelos Biológicos , Pneumonia Viral/tratamento farmacológico , Administração Oral , Adulto , Animais , Bovinos , Infecções por Coronavirus/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Ivermectina/sangue , Masculino , Pandemias , Pneumonia Viral/sangue , Resultado do Tratamento , Adulto Jovem
17.
Hautarzt ; 71(6): 447-454, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32430543

RESUMO

BACKGROUND: The diagnosis of scabies has become surprisingly frequent in Germany in recent years and the use of scabicides has risen significantly. OBJECTIVE: The aim of our survey was to determine whether this trend can also be detected among military personnel of the German Armed Forces (Bundeswehr). METHODS: The study was conducted as a retrospective single-center study over a period of 8 years from 2012 to 2019 in the Department of Dermatology of the Armed Forces Hospital Berlin, Germany. Data were generated from the hospital information system (KIS), which was searched for all scabies-coded diagnoses according to ICD10 code B86 both as outpatients and inpatients. Only first presentations with scabies diagnosis confirmed by dermoscopy or microscopy by a dermatologist were included. Inpatient treatment was required if a patient was not cured after at least three antiscabies treatment cycles in the outpatient setting. RESULTS: The data show that there has been a steady increase in the diagnosis of scabies in Bundeswehr personnel. Moreover, our data show that the number of unsuccessfully treated outpatients increased and required in-hospital treatment. CONCLUSION: We observed an increase of scabies among German military personnel who represent a typical at-risk group. These results support the observations of an increased incidence of scabies in Germany in general and especially in an at-risk population. With the general increase in scabies cases, there are also increasing numbers of German military personnel who are refractory to treatment, which was largely attributed to inadequate treatment of contact persons and individual treatment errors. Nevertheless, the data also emphasize the low overall prevalence of scabies; therefore, all diagnoses should be confirmed by dermoscopy or microscopy after 14 days whenever possible to rule out the bias of overreporting due to false-positive cases diagnosed only by clinical examination.


Assuntos
Antiparasitários/administração & dosagem , Ivermectina/administração & dosagem , Militares/estatística & dados numéricos , Escabiose/epidemiologia , Administração Tópica , Animais , Antiparasitários/uso terapêutico , Alemanha/epidemiologia , Humanos , Ivermectina/uso terapêutico , Estudos Retrospectivos , Escabiose/diagnóstico , Escabiose/tratamento farmacológico , Resultado do Tratamento
19.
Naunyn Schmiedebergs Arch Pharmacol ; 393(7): 1153-1156, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32462282

RESUMO

Ivermectin is an antiparasitic drug that has shown also an effective pharmacological activity towards various infective agents, including viruses. This paper proposes an alternative mechanism of action for this drug that makes it capable of having an antiviral action, also against the novel coronavirus, in addition to the processes already reported in literature.


Assuntos
Antivirais/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Ivermectina/farmacologia , Pneumonia Viral/tratamento farmacológico , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Humanos , Ivermectina/administração & dosagem , Pandemias , Pneumonia Viral/virologia
20.
Cochrane Database Syst Rev ; 4: CD010599, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289194

RESUMO

BACKGROUND: Ascaris lumbricoides is a common infection, and mainly affects children living in low-income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity. OBJECTIVES: To compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019. SELECTION CRITERIA: Randomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed-effect model for studies with low heterogeneity and the random-effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups. MAIN RESULTS: We included 30 parallel-group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co-funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty-two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting). Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate-certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high-certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high-certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate-certainty evidence). Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%. The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity. No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate- to low-certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever. AUTHORS' CONCLUSIONS: Single-dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events.


Assuntos
Anti-Helmínticos/uso terapêutico , Ascaríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/administração & dosagem , Ascaris lumbricoides , Criança , Pré-Escolar , Humanos , Lactente , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Mebendazol/administração & dosagem , Mebendazol/uso terapêutico , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
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