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1.
PLoS Negl Trop Dis ; 15(3): e0009302, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33780461

RESUMO

BACKGROUND: Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). METHODS: For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression. RESULTS: We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041-0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001-2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368-1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021-0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244-1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020-0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections. CONCLUSION: Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.


Assuntos
Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/mortalidade , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antimônio/efeitos adversos , Antimônio/uso terapêutico , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Humanos , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico
2.
Am J Ophthalmol ; 223: 75-82, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33045218

RESUMO

PURPOSE: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy. DESIGN: Descriptive, retrospective multicenter case series. METHODS: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease. RESULTS: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect. CONCLUSIONS: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/administração & dosagem , Fosforilcolina/análogos & derivados , Ceratite por Acanthamoeba/diagnóstico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiprotozoários/efeitos adversos , Biguanidas/uso terapêutico , Feminino , Humanos , Ceratoplastia Penetrante , Masculino , Pessoa de Meia-Idade , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
3.
Rev. Soc. Bras. Med. Trop ; 54: e20200208, 2021. graf
Artigo em Inglês | LILACS, Coleciona SUS, Sec. Est. Saúde SP | ID: biblio-1143878

RESUMO

Abstract Post-kala-azar dermal leishmaniasis is a skin disorder occurring in 5-10% of visceral leishmaniasis patients after treatment with miltefosine,the first-line drug for this skin disorder. We reported a case of acute anterior uveitis,a rare adverse effect, experienced by a patient treated with miltefosine for post-kala-azar dermal leishmaniasis. This adverse effect developed after 15 days of miltefosine consumption, and the patient himself discontinued the treatment. The ophthalmic complication was completely resolved with antibiotics and steroid eye drops. After recovery from the ophthalmic complication, the patient was successfully treated with liposomal amphotericin B for the skin lesions.


Assuntos
Humanos , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Antiprotozoários/efeitos adversos , Fosforilcolina/análogos & derivados
4.
Rev Soc Bras Med Trop ; 54: e20200208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338118

RESUMO

Post-kala-azar dermal leishmaniasis is a skin disorder occurring in 5-10% of visceral leishmaniasis patients after treatment with miltefosine,the first-line drug for this skin disorder. We reported a case of acute anterior uveitis,a rare adverse effect, experienced by a patient treated with miltefosine for post-kala-azar dermal leishmaniasis. This adverse effect developed after 15 days of miltefosine consumption, and the patient himself discontinued the treatment. The ophthalmic complication was completely resolved with antibiotics and steroid eye drops. After recovery from the ophthalmic complication, the patient was successfully treated with liposomal amphotericin B for the skin lesions.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Leishmaniose Visceral , Uveíte , Antiprotozoários/efeitos adversos , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico
5.
Acta Derm Venereol ; 100(18): adv00322, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205828

RESUMO

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Antiprotozoários/efeitos adversos , Criança , Humanos , Israel , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Estudos Retrospectivos
6.
Acta Derm Venereol ; 100(18): adv00322, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074340

RESUMO

Cutaneous leishmaniasis poses a therapeutic challenge in the paediatric population. The aim of this study was to assess the efficacy and safety of miltefosine treatment for Old World cutaneous leishmaniasis in paediatric patients. A multicentre retrospective review of 10 children (≤ 18 years of age) with cutaneous leishmaniasis treated with miltefosine in Israel was performed. Mean ± standard deviation age at diagnosis was 9.1 ± 5.0 years. The Leishmania species diagnosed was L. tropica in 8 cases and Leishmania major in 2 cases. Mean ± standard deviation duration of treatment was 44.8 ± 20.6 days, with a mean follow-up period of 12.1 ± 17.1 months. Complete response was noted in 8 (80%) patients. Treatment failure was noted in 2 (20%) cases. Side-effects related to the medication were minimal. In conclusion, oral miltefosine may be an effective and safe treatment for Old World cutaneous leishmaniasis caused by Leishmania tropica or Leishmania major in children. However, further studies are warranted to draw a definite conclusion.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Antiprotozoários/efeitos adversos , Criança , Humanos , Israel , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Estudos Retrospectivos
7.
Cochrane Database Syst Rev ; 8: CD004834, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853410

RESUMO

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.


Assuntos
Leishmaniose Cutânea/terapia , Administração Oral , Adulto , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Vacina BCG/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Imunocompetência , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/uso terapêutico , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Mucocutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Expert Opin Ther Pat ; 30(8): 633-641, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32602760

RESUMO

INTRODUCTION: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Worldwide, approximately 1.5-2 million new cases of leishmaniasis and 20,000-30,000 deaths occurs each year. Effective treatment for all forms of leishmaniasis have numerous adverse effects contributing to poor adherence and/or treatment interruption by the patient. Development of novel therapies, as multitarget drugs, for example, can contribute to accelerate discover safer, more active, and patient-compliant drugs for leishmaniasis treatment. AREAS COVERED: In this review, authors summarize pharmaceutical agents for treatment of leishmaniasis developed between 2014 and 2019, which includes synthetic and natural drugs for specific treatments, as well as considering new approaches and strategies using drug delivery system. EXPERT OPINION: Universities or public research institutes produced most of the patents related to pharmaceutical agents for treatment of leishmaniasis in this review, and the majority of the inventions disclosed did not conduct clinical trials. In other words, there is still a lot of investment to be done for the identification of new drugs.


Assuntos
Antiprotozoários/administração & dosagem , Desenvolvimento de Medicamentos , Leishmaniose/tratamento farmacológico , Animais , Antiprotozoários/efeitos adversos , Antiprotozoários/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Leishmaniose/parasitologia , Adesão à Medicação , Patentes como Assunto
9.
Expert Opin Ther Targets ; 24(9): 915-922, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32552166

RESUMO

Introduction Cryptosporidium species are protozoan parasites that are important causes of diarrheal disease including waterborne outbreaks, childhood diarrhea in resource-poor countries, and diarrhea in compromised hosts worldwide. Recent studies highlight the importance of cryptosporidiosis in childhood diarrhea, malnutrition, and death in resource-poor countries. Despite this, only a single drug, nitazoxanide, has demonstrated efficacy in human cryptosporidiosis and its efficacy is limited in malnourished children and patients with HIV. Areas covered In this review, we highlight work on potential targets for chemotherapy and review progress on drug development. A number of new targets have been identified for chemotherapy and progress has been made at developing drugs for these targets. Targets include parasite kinases, nucleic acid synthesis and processing, proteases, and lipid metabolism. Other groups have performed high-throughput screening to identify potential drugs. Several compounds have advanced to large animal studies. Expert opinion Development of drugs for cryptosporidiosis has been plagued by a lack of success. Barriers have included poor correlations between in vitro activity and clinical success as well as frequent unanticipated adverse effects. Without a clear pathway forward, it is wise to maintain a diverse development pipeline. Drug developers should also realize that success will likely require a sustained, methodical effort.


Assuntos
Antiprotozoários/farmacologia , Criptosporidiose/tratamento farmacológico , Terapia de Alvo Molecular , Animais , Antiprotozoários/efeitos adversos , Criança , Transtornos da Nutrição Infantil/complicações , Criptosporidiose/parasitologia , Diarreia/tratamento farmacológico , Diarreia/parasitologia , Desenvolvimento de Medicamentos , Infecções por HIV/complicações , Ensaios de Triagem em Larga Escala , Humanos
10.
Medicine (Baltimore) ; 99(20): e20198, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443341

RESUMO

RATIONALE: Metronidazole is widely used for treating infection of anaerobic bacteria and protozoa. Metronidazole is generally well tolerated, although metronidazole-associated peripheral neuropathy (PN) and metronidazole-induced encephalopathy (MIE) have been reported as rare side effects. The most common sites of MIE involve the bilateral dentate nucleus of the cerebellum. Herein, we present a rare case of MIE with isolated corpus callosum involvement, with concomitant metronidazole-associated PN. PATIENT CONCERNS: A middle-aged man with ulcerative colitis was diagnosed with amoebic dysentery because of unhygienic eating. After receiving metronidazole (1.8 g/d, cumulative dose 61.2 g) for >1 month, he started to complain of continuous paresthesia of the limbs, and intermittent speech problems. Magnetic resonance imaging demonstrated an isolated lesion in the splenium of the corpus callosum. DIAGNOSIS: A diagnosis of reversible splenial lesion syndrome and PN was made. Given the patient's medical history, MIE and metronidazole-associated PN were considered. INTERVENTIONS: Metronidazole was stopped. Mecobalamine and vitamin B1 were used for adjuvant treatment. OUTCOMES: At 1.5 months after stopping metronidazole, his symptoms of numbness and hyperesthesia had not improved, although he felt less ill. The isolated lesion disappeared on follow-up magnetic resonance imaging. At 6 months later, the hyperesthesia symptoms remained, and he was unable to resume his previous work. CONCLUSIONS: Physicians should consider MIE in their differentials for reversible splenial lesion syndrome when encountering a patient with a history of metronidazole medication and symptoms of encephalopathy, especially with concomitant PN. Early identification of this metronidazole-related complication and early cessation of the drug are essential for treatment.


Assuntos
Antiprotozoários/efeitos adversos , Encefalopatias/induzido quimicamente , Disenteria Amebiana/tratamento farmacológico , Metronidazol/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adulto , Idoso , Encefalopatias/diagnóstico , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/efeitos dos fármacos , Corpo Caloso/patologia , Disenteria Amebiana/complicações , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Resultado do Tratamento , Vitamina B 12/administração & dosagem , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico , Suspensão de Tratamento
11.
Hautarzt ; 71(6): 437-442, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32394080

RESUMO

Here we describe two complicated cases of complex Old World cutaneous Leishmaniasis due to L. infantum and L. aethiopica. Both of our patients infected with the Leishmania parasite presented with a completely different clinical picture, course of disease, and treatment response. Clinical healing was achieved after multiple courses of treatment with a variety of different antileishmanial drugs. Nephrotoxity was a limiting side effect.


Assuntos
Leishmania infantum/isolamento & purificação , Leishmania/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/uso terapêutico , Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Progressão da Doença , Humanos , Leishmania/classificação
12.
Expert Rev Anti Infect Ther ; 18(4): 381-387, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32067521

RESUMO

Objectives: Cutaneous leishmaniasis is a neglected disease, associated with high morbidity, which is partially due to the toxicity of available therapies. The pentavalent antimonial derivatives intralesional infiltration has proven to be as effective as the intravenous drug-based therapy, however, there is a lack of robust safety data.Methods: Phase II, uncontrolled, unicenter clinical trial to assess the safety profile of a standardized meglumine antimionate intralesional therapy, based on weekly infiltrations.Results: Fifty-three patients were studied, predominantly men (60%) and young adults (43.7 ± 17.1 years). Overall, 86.9% of the patients had at least one clinical adverse event. Local events were the most frequent (83%), followed by systemic ones (47.3%). Fourteen participants (26%) presented biochemical abnormalities. In all cases, laboratorial alterations were classified as mild and treatment discontinuation was not required. Differently, the two hypersensitivity (3.8%) reactions observed led to permanent treatment interruption. QTc interval prolongation was recorded in 14 patients (25.5%). The following risk associations to adverse events were identified in the multiple analysis: hypertension with systemic clinical events and smoking with QT interval prolongation.Expert commentary: In general, MA-IL was well tolerated and although associated with local and systemic adverse events, there was a low risk of high intensity or severe complications.


Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Adulto , Antiprotozoários/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Feminino , Humanos , Injeções Intralesionais , Masculino , Antimoniato de Meglumina/efeitos adversos , Pessoa de Meia-Idade , Risco
13.
Trop Doct ; 50(2): 165-166, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32019474

RESUMO

Related neurological adverse effects to metronidazole are rarely encountered in clinical practice despite its wide use as an antibacterial or antiparasitic agent. The neurotoxicity is not dose-dependent and is fully reversible with discontinuation of the drug. We describe a young man who was receiving metronidazole for an amoebic liver abscess and developed encephalopathy and seizures. Brain magnetic resonance imaging showed characteristic bilateral symmetrical cerebellar dentate hyperintensities.


Assuntos
Antiprotozoários/efeitos adversos , Abscesso Hepático Amebiano/tratamento farmacológico , Metronidazol/efeitos adversos , Síndromes Neurotóxicas/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndromes Neurotóxicas/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Adulto Jovem
14.
Nihon Shokakibyo Gakkai Zasshi ; 117(1): 72-77, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31941859

RESUMO

Peripheral neuropathy reportedly develops after a long period of metronidazole administration. Here, we report a case of amoebic colitis in which peripheral neuropathy occurred approximately 24 hours after administering metronidazole. A 76-year-old man presented with mucous and bloody stool. Initially, lower gastrointestinal endoscopy and stool analysis confirmed the occurrence of amoebic colitis, and metronidazole was then intravenously administered. The following day, however, the patient experienced a diminished sensation in a glove-and-stocking distribution in his extremities, followed by bilateral burning foot pain. After the withdrawal of metronidazole, the symptoms improved and finally disappeared 3 months later.


Assuntos
Antiprotozoários/efeitos adversos , Disenteria Amebiana , Metronidazol/efeitos adversos , Doenças do Sistema Nervoso Periférico , Idoso , Antiprotozoários/uso terapêutico , Hemorragia Gastrointestinal , Humanos , Masculino , Metronidazol/uso terapêutico
15.
J Vet Med Sci ; 82(2): 184-187, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31904004

RESUMO

Toxoplasma gondii can cause severe encephalitis in immunocompromised patients. Although pyrimethamine and sulphadiazine have been standard therapeutic agents for the treatment of acute toxoplasmosis, they have toxic side effects. Therefore, there is a need to identify new drugs that are less toxic. Some traditional Chinese medicines (TCMs) have shown good efficacy in controlling T. gondii replication in mouse models. Here, we screened a natural product library comprising TCMs with the aim of identifying compounds and extracts with anti-toxoplasmosis activities. We found several hit compounds and extracts that could be candidates for new drugs against T. gondii infection.


Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Toxoplasma/efeitos dos fármacos , Animais , Antiprotozoários/efeitos adversos , Antiprotozoários/farmacologia , Linhagem Celular , Chlorocebus aethiops , Humanos , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose/tratamento farmacológico , Células Vero
16.
Curr Opin Infect Dis ; 33(1): 73-77, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31789671

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to update information on treatment of Trichomonas vaginalis. T. vaginalis is estimated to be the most common treatable sexually transmitted infection. In the world and is associated with poor birth outcomes, cervical cancer, sperm motility and morphology issues, and HIV acquisition and transmission. RECENT FINDINGS: The efficacy of the recommended 2-g oral single-dose metronidazole (MTZ) for the treatment of T. vaginalis in women has recently been challenged. Two recent multicentered randomized trials and a meta-analysis have demonstrated that the 7-day dose of MTZ 500 mg twice daily was nearly two times more efficacious at clearing infection compared with the 2-g dose. Partner treatment is also essential, since up to 70% of male sexual partners can be infected and rescreening of treated women at 3 months is also recommended given the high repeat infection rates. Future studies should examine the importance of treating asymptomatic T. vaginalis, best treatment for men, the influence of the microbiome on treatment efficacy and different formulations of intravaginal treatments for hypersensitivity. SUMMARY: 7-day 500 mg twice daily MTZ should be used as the first line treatment for T. vaginalis-infected women.


Assuntos
Antiprotozoários/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Nitroimidazóis/efeitos adversos , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Tricomoníase/tratamento farmacológico , Antiprotozoários/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/efeitos adversos , Nitroimidazóis/administração & dosagem , Recidiva , Trichomonas vaginalis/efeitos dos fármacos
17.
Trop Doct ; 50(1): 37-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31610724

RESUMO

A 12-week course of miltefosine (MF) is recommended in India for the treatment of post-kala-azar dermal leishmaniasis (PKDL). We report a case series of four patients with PKDL, across three districts of Bihar state, who developed eye complications during treatment. They presented with acute scleritis and corneal infiltration with or without corneal ulceration. One patient solely with corneal infiltration recovered completely. The three others with corneal ulceration healed with corneal opacificity. One patient with bilateral eye involvement underwent corneal transplantation to prevent blindness. All adverse events were graded as certain using the World Health Organization-Uppsala Monitoring Centre causality assessment scale. There is need to counsel patients regarding possible adverse ocular events during MF treatment, to expand pharmacovigilance to all primary health centres in kala-azar endemic areas, and to update drug safety information considering the emerging evidence.


Assuntos
Antiprotozoários/efeitos adversos , Oftalmopatias/induzido quimicamente , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adulto , Antiprotozoários/uso terapêutico , Criança , Oftalmopatias/patologia , Oftalmopatias/fisiopatologia , Oftalmopatias/terapia , Feminino , Humanos , Índia/epidemiologia , Leishmaniose Visceral/epidemiologia , Masculino , Pessoa de Meia-Idade , Fosforilcolina/efeitos adversos , Fosforilcolina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
18.
Am J Trop Med Hyg ; 102(2): 274-279, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31820708

RESUMO

Cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) are endemic diseases in America, especially in some countries such as Colombia. Among the therapeutic options is amphotericin B (AB). Nevertheless, its lipid-associated formulations have better safety profiles and effectiveness in other diseases, so far with no comparative studies in CL or MCL. We conducted a retrospective descriptive study describing the effectiveness and adverse effects of AB deoxycholate (ABD), AB colloidal dispersion (ABCD), and liposomal AB (LAB) as third-line treatments for CL and MCL. The effectiveness of LAB (88.5%) was greater than those of ABCD (66.6%) and ABD (80.8%). There were also fewer adverse effects in the LAB group (46.2%) than in the ABD (96.1%) and ABCD (80.9%) groups. LAB is an alternative for the treatment of CL and MCL in patients with therapeutic failure to first- and second-line drugs; findings suggest it might be less toxic and more effective than ABD and ABCD.


Assuntos
Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Ácido Desoxicólico/uso terapêutico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Mucocutânea/tratamento farmacológico , Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Coloides , Colômbia/epidemiologia , Ácido Desoxicólico/efeitos adversos , Combinação de Medicamentos , Humanos , Leishmaniose Cutânea/epidemiologia , Leishmaniose Mucocutânea/epidemiologia , Estudos Retrospectivos
19.
J Infect Dis ; 221(4): 608-617, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-31854451

RESUMO

BACKGROUND: No satisfactory canonical treatment is available for post-kala-azar dermal leishmaniasis (PKDL), clinical sequela of visceral leishmaniasis. Confined treatment options and substantial increase in relapse rate after miltefosine (MIL) treatment warrant the need to adapt resilient combination therapies. In this study, we assessed the safety and efficacy of combination therapy using liposomal amphotericin B (LAmB) and MIL for treating PKDL. METHODS: Thirty-two PKDL patients, confirmed by microscopy or quantitative polymerase chain reaction (qPCR), were included in the study. An equal number of cases (n = 16) were put on MIL monotherapy (100 mg/day for 90 days) or MIL and LAmB combination for 45 days (3 injections of LAmB, 5 mg/kg body weight, and 100 mg/day MIL). Parasite load in slit aspirate was monitored using qPCR. RESULTS: Patients treated with combination therapy demonstrated a rapid decline in parasite load and achieved 100% cure, with no reports of relapse. Those treated with MIL monotherapy attained clinical cure with a gradual decrease in parasite load; however, 25% relapsed within 18 months of follow-up. CONCLUSIONS: Liposomal amphotericin B and MIL combination for treating PKDL is efficacious and safe, with high tolerability. Furthermore, this study established the utility of minimally invasive slit aspirate method for monitoring of parasite load and assessment of cure in PKDL.


Assuntos
Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Leishmania donovani/genética , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Anfotericina B/efeitos adversos , Antiprotozoários/efeitos adversos , Criança , DNA de Protozoário/genética , Quimioterapia Combinada , Feminino , Humanos , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/parasitologia , Lipossomos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Fosforilcolina/efeitos adversos , Fosforilcolina/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Resultado do Tratamento , Adulto Jovem
20.
Res Vet Sci ; 126: 131-138, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491669

RESUMO

This study examines correlations among serum proteins, clinical score, body weight and kidney function biomarkers after a standard treatment course (meglumine antimoniate plus allopurinol) in twelve Canine leishmaniosis (CanL) patients at the three times points pre treatment, after treatment and after the end of treatment. The laboratory variables measured were those used for the follow-up of sick dogs along with biomarkers of kidney function: glomerular filtration rate (GFR), creatinine (Cr), urea, calcium, inorganic phosphorus, urine specific gravity (USG) and urine protein to creatinine ratio (UPC). Arterial blood pressure (systolic blood pressure, SBP), clinical score (CS) and weight were also monitored over the study period. At Tp0, GFR was within the normal range in most dogs. Hyperfiltration was detected in three patients and hypofiltration in one. In dogs showing hyperfiltration, this factor remained in the non-azotemic range over the whole study period. After treatment normal filtration values were recovered. Meglumine antimoniate did not modify GFR or USG. A significant reduction in UPC was recorded. In all dogs, clinical scores improved. Negative correlation was found between GFR and Cr, UPC and albumin (Alb) and CS and Alb, while positive correlation was detected between UPC and total globulins (GlobT), CS and GlobT, UPC and total solids (TS), SBP and CS and SBP and UPC. Our findings indicate no impacts on kidney function of the treatment of CanL with meglumine antimoniate, as no effects were produced on GFR or USG. Treatment was effective and found to reduce UPC which could suggest improved glomerular injury.


Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Nefropatias/veterinária , Leishmaniose Visceral/veterinária , Antimoniato de Meglumina/uso terapêutico , Alopurinol/administração & dosagem , Animais , Antiprotozoários/efeitos adversos , Biomarcadores , Creatinina/urina , Cães , Feminino , Taxa de Filtração Glomerular , Nefropatias/induzido quimicamente , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem
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