RESUMO
BACKGROUND: Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity. METHODS: In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28 days after treatment with the standard chloroquine and 14-day primaquine (0.25 mg/kg/day) regimen. RESULTS: Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion. CONCLUSIONS: The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.
Assuntos
Antimaláricos , Deficiência de Glucosefosfato Desidrogenase , Malária Vivax , Feminino , Humanos , Masculino , Primaquina/efeitos adversos , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Hemólise , Antimaláricos/efeitos adversos , Prevalência , Glucosefosfato Desidrogenase/uso terapêutico , Hemoglobinas , Plasmodium vivaxRESUMO
BACKGROUND: A prophylactic antimalarial drug that is both effective for protection and improves compliance is in high demand. METHODS: We conducted a randomized, placebo-controlled, double-blinded phase 3 trial to evaluate the 1:1 fixed-dose combination of naphthoquine-azithromycin (NQAZ) for safety and protection against Plasmodium infections in villages along the China-Myanmar border. A total of 631 residents, 5-65 years of age, were randomized into the drug group (n = 319) and the placebo group (n = 312) to receive NZAQ and placebo, respectively, as a single-dose monthly treatment. Follow-ups were conducted weekly to monitor for adverse events and malaria infections. RESULTS: Of the 531 subjects completing the trial, there were 46 and 3 blood smear-positive Plasmodium infections in the placebo and treatment groups, respectively. For the intent-to-treat analysis, the single-dose monthly NQAZ treatment had 93.62% protective efficacy (95% confidence interval [CI]: 91.72%-95.52%). For the per-protocol analysis, NQAZ treatment provided a 93.04% protective efficacy (95% CI: 90.98%-95.1%). Three smear-positive cases in the NQAZ group were all due to acute falciparum malaria. In comparison, NQAZ treatment provided 100% protection against the relapsing malaria Plasmodium vivax and Plasmodium ovale. The treatment group had 5.6% of participants experiencing transient elevation of liver aminotransferases compared with 2.2% in the placebo group (P > .05). CONCLUSIONS: Monthly prophylaxis with NQAZ tablets was well tolerated and highly effective for preventing Plasmodium infections. It may prove useful for eliminating P. vivax in areas with a high prevalence of glucose-6-phosphate dehydrogenase deficiency in the population. CLINICAL TRIALS REGISTRATION: ChiCTR1800020140.
Assuntos
Antimaláricos , Malária Falciparum , Malária Vivax , Malária , 1-Naftilamina/análogos & derivados , Adolescente , Adulto , Idoso , Aminoquinolinas , Antimaláricos/efeitos adversos , Sudeste Asiático , Azitromicina/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Malária/tratamento farmacológico , Malária/prevenção & controle , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Malária Vivax/prevenção & controle , Pessoa de Meia-Idade , Adulto JovemRESUMO
Models of care for people living with HIV (PLWH) have varied over time due to long term survival, development of HIV-associated non-AIDS conditions, and HIV specific primary care guidelines that differ from those of the general population. The objectives of this study are to assess how often infectious disease (ID) physicians provide primary care for PLWH, assess their practice patterns and barriers in the provision of primary care. We used a 6-item survey electronically distributed to ID physician members of Emerging Infections Network (EIN). Of the 1248 active EIN members, 644 (52%) responded to the survey. Among the 644 respondents, 431 (67%) treated PLWH. Of these 431 responders, 326 (75%) acted as their primary care physicians. Responders who reported always/mostly performing a screening assessment as recommended per guidelines were: (1) Screening specific to HIV (tuberculosis 95%, genital chlamydia/gonorrhoea 77%, hepatitis C 67%, extra genital chlamydia/gonorrhoea 47%, baseline anal PAP smear for women 36% and men 34%); (2) Primary care related screening (fasting lipids 95%, colonoscopy 95%, mammogram 90%, cervical PAP smears 88%, depression 57%, osteoporosis in postmenopausal women 55% and men >50 yrs 33%). Respondents who worked in university hospitals, had <5 years of ID experience, and those who cared for more PLWH were most likely to provide primary care to all or most of their patients. Common barriers reported include: refusal by patient (72%), non-adherence to HIV medications (43%), other health priorities (44%), time constraints during clinic visit (43%) and financial/insurance limitations (40%). Most ID physicians act as primary care providers for their HIV infected patients especially if they are recent ID graduates and work in university hospitals. Current screening rates are suboptimal. Interventions to increase screening practices and to decrease barriers are urgently needed to address the needs of the aging HIV population in the United States.
Assuntos
Infecções por HIV/tratamento farmacológico , Infectologia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/prevenção & controle , Colonoscopia/estatística & dados numéricos , Continuidade da Assistência ao Paciente , Depressão/diagnóstico , Depressão/prevenção & controle , Dislipidemias/diagnóstico , Dislipidemias/prevenção & controle , Feminino , Gonorreia/diagnóstico , Gonorreia/prevenção & controle , Humanos , Masculino , Mamografia/estatística & dados numéricos , Programas de Rastreamento/normas , Adesão à Medicação , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/prevenção & controle , Teste de Papanicolaou , Atenção Primária à Saúde/normas , Inquéritos e Questionários , Fatores de Tempo , Recusa do Paciente ao Tratamento , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Estados Unidos , Esfregaço Vaginal/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVES: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). METHODS: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). RESULTS: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues. CONCLUSION: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. TRIAL REGISTRATION: NCT04334148.
Assuntos
COVID-19 , Profilaxia Pré-Exposição , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Hidroxicloroquina/efeitos adversos , Tratamento Farmacológico da COVID-19 , Pessoal de Saúde , Resultado do TratamentoRESUMO
Levamisole is a veterinary anti-helminthic used to treat several autoimmune conditions but also commonly utilized as an additive in cocaine distribution. Toxicity resulting in agranulocytosis and cutaneous necrosis in association with cocaine use is an infrequently described phenomenon of an emerging problem. Although levamisole is found extensively in the cocaine supply of the United States, relatively few cases of necrotic skin lesions associated with intranasal use have been reported. The skin necrosis secondary to levamisole toxicity is characterized by variable findings on biopsy, ranging from leukocytoclastic vasculitis to occlusive vasculopathy. The following case describes a 54-year-old male who developed fever, agranulocytosis, p-ANCA autoantibodies and extensive skin necrosis following heavy intranasal cocaine use. Necrosis of greater than 50% of the patient's total body surface area resulted and was followed by thorough wound debridement.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Levamisol/efeitos adversos , Neutropenia/induzido quimicamente , Pele/efeitos dos fármacos , Agranulocitose/induzido quimicamente , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Cocaína/química , Cocaína/normas , Contaminação de Medicamentos , Febre/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Pele/patologia , Estados UnidosRESUMO
The pulmonary effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), are well documented; however, more evidence is needed to understand its effect on multiple organ systems. We present the case of a 69-year-old male with dyspnea for two weeks and bilateral conjunctivitis who tested positive for SARS-CoV-2. He was found to be hypoxic, requiring supplemental oxygen. On hospital day two, he complained of worsening left eye pain with the development of a left lower eyelid ulcer. He underwent a CT of facial bones, which showed findings consistent with pre-septal cellulitis and abscess. Samples from bilateral conjunctival secretions and left lower eyelid ulcer tested positive for herpes simplex virus-1 (HSV-1), and negative for SARS-CoV-2. He received supportive care, antibiotics, and famciclovir with almost complete resolution of his ocular complaints. This case illustrates an atypical COVID-19 presentation and raises concern as to how this virus modulates the immune system, allowing for concurrent viral infections.
RESUMO
Pancytopenia and neutropenia due to coronavirus disease 2019 (COVID-19) are rare. Here we report a case of neutropenia as a sequela of COVID-19 with concern for bone marrow infiltration. The patient was successfully treated with granulocyte colony-stimulating factor.
RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19-related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance. METHODS: This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA's Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (nâ =â 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (nâ =â 200). The primary outcome was a composite of 29-day COVID-19-related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events. RESULTS: Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14-.38]; Pâ <â .001). The mortality rate was 0% in the mAb group compared with 3.5% in the control group (Pâ =â .02). Only 2 patients receiving mAb experienced a serious adverse event requiring treatment. CONCLUSIONS: Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.
RESUMO
A 54-year-old Caucasian woman presented with corneal ulcer of the right eye of 4 weeks duration after scratching her cornea while removing her contact lens and artificial eye lashes. Her visual acuity was 20/32 (left eye) and finger counting (right eye). She had a 3x3 mm epithelial defect with underlying corneal oedema and hypopyon. Right eye cultures grew Paecilomyces species. Topical and systemic antifungal agents were initiated. Due to the sight-threatening disease, the patient underwent surgical intervention with intrastromal injection of amphotericin B and a large conjunctival flap covering 75% of the right eye corneal ulcer. After 3 months of therapy, she had near-complete resolution of the corneal ulcer. Unfortunately, recurrence of the corneal ulcer occurred within 3 weeks of cessation of therapy, prompting reinitiation of ophthalmic and systemic antifungal agents. The patient was advised to continue therapy for 6 months with regular follow-up.
Assuntos
Anfotericina B/administração & dosagem , Úlcera da Córnea/tratamento farmacológico , Ceratite/patologia , Micoses/microbiologia , Paecilomyces/isolamento & purificação , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Edema da Córnea/patologia , Úlcera da Córnea/microbiologia , Úlcera da Córnea/patologia , Infecções Oculares Fúngicas/complicações , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/cirurgia , Feminino , Humanos , Injeções Intraoculares , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Ceratite/cirurgia , Pessoa de Meia-Idade , Micoses/complicações , Micoses/diagnóstico , Recidiva , Retalhos Cirúrgicos , Resultado do Tratamento , Acuidade VisualRESUMO
We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grew Cryptococcus neoformans on fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.
Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Criptococose , Cryptococcus neoformans/isolamento & purificação , Fluconazol/administração & dosagem , Doenças Pulmonares Intersticiais , Pulmão , Lúpus Eritematoso Sistêmico , Antifúngicos/administração & dosagem , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/microbiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVES: To study rates and predictors of hepatitis C virus (HCV) cure among human immunodeficiency virus (HIV)/HCV-coinfected patients, and then to evaluate the effect of attendance at clinic visits on HCV cure. METHODS: Retrospective cohort study of adult HIV/HCV-coinfected patients who initiated and completed treatment for HCV with direct-acting antivirals (DAAs) between January 1, 2014, and June 30, 2015. RESULTS: Eighty-four participants reported completing treatment. The median age was 58 years (interquartile ratio, 50-66); 88% were male and 50% were black. One-third were cirrhotic and half were HCV-treatment-experienced. The most commonly used regimen was sofosbuvir/ledipasvir (40%) followed by simeprevir/sofosbuvir (30%). Cure was achieved in 83.3%, 11.9% relapsed, and 2.3% experienced virological breakthrough. Two patients (2.3%) did not complete treatment based on pill counts and follow-up visit documentation. In multivariable analysis, cure was associated with attendance at follow-up clinic visits (odds ratio [OR], 9.0; 95% CI, 2.91-163) and with use of an integrase-based HIV regimen versus other non-integrase regimens, such as non-nucleoside analogues or protease inhibitors (OR, 6.22; 95% CI 1.81-141). Age, race, genotype, presence of cirrhosis, prior HCV treatment, HCV regimen, and pre-treatment CD4 counts were not associated with cure. CONCLUSIONS: Real-world HCV cure rates with DAAs in HCV/HIV coinfection are lower than those seen in clinical trials. Cure is associated with attendance at follow-up clinic visits and with use of an integrase-based HIV regimen. Future studies should evaluate best antiretroviral regimens, predictors of attendance at follow-up visits, impact of different monitoring protocols on medication adherence, and interventions to ensure adequate models of HIV/HCV care.