Assuntos
Betacoronavirus , Culicidae , Malária , Animais , COVID-19 , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral , SARS-CoV-2RESUMO
BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.
Assuntos
Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Antimaláricos/uso terapêutico , Benin/epidemiologia , Agentes Comunitários de Saúde , Progressão da Doença , Gâmbia/epidemiologia , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malásia/epidemiologia , Moçambique/epidemiologia , Plasmodium falciparum/patogenicidade , Tanzânia/epidemiologia , Tempo para o Tratamento/economia , Uganda/epidemiologia , Iêmen/epidemiologia , Zâmbia/epidemiologiaRESUMO
BACKGROUND: Hypophosphatemia is common in severe infections including malaria. Previous studies suggested that serum phosphate concentrations correlate with temperature, but it is unclear whether the type of infection and other factors occurring during infection influence this association. Here relationships were investigated between serum phosphate levels, cause of fever, demographic, clinical and laboratory parameters. METHODS: Anonymized data were analysed from 633 adults with malaria or other febrile illness admitted to Northwick Park Hospital, London, UK. Univariable and multivariable generalized linear model analyses were performed to examine associations with serum phosphate levels. Interaction terms were included to investigate whether cause of fever (malaria vs other illness), malaria parasite species, or malaria severity influenced the association of other variables with phosphate. RESULTS: Hypophosphatemia was common in subjects with malaria (211/542 (39%)), and in other febrile illnesses (24/91 (26%)), however median phosphate levels did not differ significantly by diagnostic group, parasite species or severity of malaria. In all analyses, there were highly significant negative associations between serum phosphate and axillary temperature, and positive associations between serum phosphate and platelet count. There were no significant interactions between these variables and cause of fever, parasite species or severity of illness. Sodium and potassium concentrations were associated with serum phosphate in subjects with malaria and when data from all subjects was combined. CONCLUSION: Serum phosphate is consistently associated with temperature and platelet count in adults with diverse causes of fever. This may be a consequence of phosphate shifts from plasma into cells to support ATP generation for thermogenesis and platelet activation.
Assuntos
Temperatura Corporal , Malária Falciparum/metabolismo , Malária Vivax/metabolismo , Fosfatos/sangue , Adulto , Testes Diagnósticos de Rotina , Feminino , Humanos , Londres , Malária Falciparum/sangue , Malária Vivax/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Amoxicilina/uso terapêutico , Clofazimina/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/uso terapêutico , Linezolida/uso terapêutico , Modelos Logísticos , Macrolídeos/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Oxazolidinonas/uso terapêutico , Tioacetazona/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. METHODS: Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. RESULTS: A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). CONCLUSIONS: Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.
Assuntos
Pneumonectomia/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/cirurgia , Adulto , Antituberculosos/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologiaRESUMO
BACKGROUND: An increasing proportion of malaria cases diagnosed in UK residents with a history of travel to malaria endemic areas are due to Plasmodium falciparum. METHODS: In order to identify travellers at most risk of acquiring malaria a proportional hazards model was used to estimate the risk of acquiring malaria stratified by purpose of travel and age whilst adjusting for entomological inoculation rate (EIR) and duration of stay in endemic countries. RESULTS: Travellers visiting friends and relatives and business travellers were found to have significantly higher hazard of acquiring malaria (adjusted hazard ratio (HR) relative to that of holiday makers 7.4, 95% CI 6.4-8.5, p < 0. 0001 and HR 3.4, 95% CI 2.9-3.8, p < 0. 0001, respectively). All age-groups were at lower risk than children aged 0-15 years. CONCLUSIONS: These estimates of the increased risk for business travellers and those visiting friends and relatives should be used to inform programmes to improve awareness of the risks of malaria when travelling.
Assuntos
Doenças Endêmicas/estatística & dados numéricos , Malária Falciparum/etnologia , Malária Falciparum/epidemiologia , Medicina de Viagem , Adolescente , Adulto , África Subsaariana/etnologia , Idoso , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Plasmodium falciparum , Fatores de Risco , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Intervalos de Confiança , Feminino , Humanos , Masculino , Razão de Chances , Recidiva , Falha de TratamentoRESUMO
Pyrexia of unknown origin is an important clinical presentation in both paediatric and adult medicine. We present a case of pyrexia of unknown origin in a 14 year-old boy which turned out to be due to infection with Brucella melitensis, despite the patient not having left Great Britain - an officially brucellosis-free country - in six years. Repeated history-taking provided a clue to the diagnosis.
Assuntos
Brucelose/etiologia , Queijo/microbiologia , Contaminação de Alimentos , Adolescente , Brucelose/complicações , Brucelose/diagnóstico , Queijo/intoxicação , Febre/etiologia , Doenças Transmitidas por Alimentos/complicações , Doenças Transmitidas por Alimentos/diagnóstico , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
RATIONALE: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. OBJECTIVES: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. METHODS: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNgamma and IL-2 ELISpot assays and FACS. MEASUREMENTS AND MAIN RESULTS: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-gamma and IL-2 response that was durable for 52 weeks. The magnitude of IFN-gamma response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin-vaccinated individuals. Antigen 85A-specific polyfunctional CD4(+) T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. CONCLUSIONS: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas. Clinical trial registered with www.clinicaltrials.gov (NCT00456183).
Assuntos
Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Tuberculose/imunologia , Tuberculose/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teste Tuberculínico , Tuberculose/diagnóstico , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto JovemRESUMO
The majority of individuals infected with Mycobacterium tuberculosis achieve lifelong immune containment of the bacillus. What constitutes this effective host immune response is poorly understood. We compared the frequencies of gamma interferon (IFN-gamma)-secreting T cells specific for five region of difference 1 (RD1)-encoded antigens and one DosR-encoded antigen in 205 individuals either with active disease (n = 167), whose immune responses had failed to contain the bacillus, or with remotely acquired latent infection (n = 38), who had successfully achieved immune control, and a further 149 individuals with recently acquired asymptomatic infection. When subjects with an IFN-gamma enzyme-linked immunospot (ELISpot) assay response to one or more RD1-encoded antigens were analyzed, T cells from subjects with active disease recognized more pools of peptides from these antigens than T cells from subjects with nonrecent latent infection (P = 0.002). The T-cell frequencies for peptide pools were greater for subjects with active infection than for subjects with nonrecent latent infection for summed RD1 peptide pools (P Assuntos
Antígenos de Bactérias
, Proteínas de Bactérias
, Interferon gama/metabolismo
, Mycobacterium tuberculosis/imunologia
, Linfócitos T/imunologia
, Tuberculose/diagnóstico
, Tuberculose/imunologia
, Adolescente
, Adulto
, Antígenos de Bactérias/imunologia
, Proteínas de Bactérias/imunologia
, Criança
, Feminino
, Humanos
, Técnicas Imunoenzimáticas/métodos
, Masculino
, Pessoa de Meia-Idade
, Adulto Jovem
RESUMO
BACKGROUND: Over a 16-year period, we conducted a clinical study of malaria acquired worldwide in adults from malaria-nonendemic countries, to determine risk factors for severe Plasmodium falciparum malaria. METHODS: All patients with confirmed malaria who were managed by our unit from 1991 to 2006 were prospectively evaluated. Factors predicting disease severity according to (1) strict World Health Organization (WHO) criteria, (2) a composite measure of unfavorable outcome, and (3) length of hospital stay were identified by logistic and linear regression analyses. RESULTS: We evaluated 676 episodes of malaria, 482 (71%) due to P. falciparum and 194 (29%) due to nonfalciparum parasites. Black patients had a significantly reduced risk of developing WHO-defined severe falciparum malaria, with Asian patients having odds of severe falciparum malaria that were 8.05-fold (95% confidence interval [CI], 2.93-22.1-fold) higher and white patients having odds that were 8.20-fold (95% CI, 2.94-22.9-fold) higher. Black patients also had a reduced risk of an unfavorable outcome and of a prolonged stay in the hospital, compared with the risks for white or Asian patients. Of 6 patients with falciparum malaria who died, none were black. In univariate analysis, patients with parasitemias of >or= 2% had odds of severe falciparum malaria 12-fold higher than those of patients with parasitemias of <2% (73% vs. 19%). Patients with a history of previous clinical malaria, regardless of ethnicity, had a significantly reduced risk of WHO-defined severe falciparum malaria (odds ratio, 0.35 [95% CI, 0.15-0.80]). CONCLUSIONS: The findings of this study demonstrate that ethnicity and parasitemia are important independent risk factors for severe falciparum malaria in adults from malaria-nonendemic countries and that a history of previous clinical malaria significantly reduces the risk of WHO-defined severe falciparum malaria.
Assuntos
Malária Falciparum/patologia , Malária Falciparum/fisiopatologia , Plasmodium falciparum/isolamento & purificação , Índice de Gravidade de Doença , Adulto , Animais , Feminino , Humanos , Tempo de Internação , Malária Falciparum/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Parasitemia , Plasmodium/isolamento & purificação , Estudos Prospectivos , Grupos Raciais , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: India, China and Russia account for more than 62% of multidrug resistant tuberculosis (MDRTB) globally. Within India, locations like urban metropolitan Mumbai with its burgeoning population and high incidence of TB are suspected to be a focus for MDRTB. However apart from sporadic surveys at watched sites in the country, there has been no systematic attempt by the Revised National Tuberculosis Control Programme (RNTCP) of India to determine the extent of MDRTB in Mumbai that could feed into national estimates. Drug susceptibility testing (DST) is not routinely performed as a part of programme policy and public health laboratory infrastructure, is limited and poorly equipped to cope with large scale testing. METHODS: From April 2004 to January 2007 we determined the extent of drug resistance in 724 {493 newly diagnosed, previously untreated and 231 first line treatment failures (sputum-smear positive at the fifth month after commencement of therapy)} cases of pulmonary tuberculosis drawn from the RNTCP in four suboptimally performing municipal wards of Mumbai. The observations were obtained using a modified radiorespirometric Buddemeyer assay and validated by the Swedish Institute for Infectious Disease Control, Stockholm, a supranational reference laboratory. Data was analyzed utilizing SPSS 10.0 and Epi Info 2002. RESULTS: This study undertaken for the first time in RNTCP outpatients in Mumbai reveals a high proportion of MDRTB strains in both previously untreated (24%) and treatment-failure cases (41%). Amongst new cases, resistance to 3 or 4 drug combinations (amplified drug resistance) including isoniazid (H) and rifampicin (R), was greater (20%) than resistance to H and R alone (4%) at any point in time during the study. The trend for monoresistance was similar in both groups remaining highest to H and lowest to R. External quality control revealed good agreement for H and R resistance (k = 0.77 and 0.76 respectively). CONCLUSION: Levels of MDRTB are much higher in both previously untreated and first line treatment-failure cases in the selected wards in Mumbai than those projected by national estimates. The finding of amplified drug resistance suggests the presence of a well entrenched MDRTB scenario. This study suggests that a wider set of surveillance sites are needed to obtain a more realistic view of the true MDRTB rates throughout the country. This would assist in the planning of an adequate response to the diagnosis and care of MDRTB.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Fatores de Risco , Escarro/microbiologia , Falha de Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , População Urbana , Adulto JovemRESUMO
BACKGROUND: The role of new T-cell-based blood tests for tuberculosis in the diagnosis of active tuberculosis is unclear. OBJECTIVE: To compare the performance of 2 interferon-gamma assays and tuberculin skin testing in adults with suspected tuberculosis. DESIGN: Prospective study conducted in routine practice. SETTING: 2 urban hospitals in the United Kingdom. PATIENTS: 389 adults, predominantly of South Asian and black ethnicity, with moderate to high clinical suspicion of active tuberculosis. INTERVENTION: Tuberculin skin testing, the enzyme-linked immunospot assay (ELISpot) incorporating early secretory antigenic target-6 and culture filtrate protein-10 (standard ELISpot), and ELISpot incorporating a novel antigen, Rv3879c (ELISpot(PLUS)) were performed during diagnostic assessment by independent persons who were blinded to results of the other test. MEASUREMENTS: Sensitivity, specificity, predictive values, and likelihood ratios. RESULTS: 194 patients had a final diagnosis of active tuberculosis, of which 79% were culture-confirmed. Sensitivity for culture confirmed and highly probable tuberculosis was 89% (95% CI, 84% to 93%) with ELISpot(PLUS), 85% (CI, 79% to 90%) with standard ELISpot, 79% (CI, 72% to 85%) with 15-mm threshold tuberculin skin testing, and 83% (CI, 77% to 89%) with stratified thresholds of 15 and 10 mm in vaccinated and unvaccinated patients, respectively. The ELISpot(PLUS) assay was more sensitive than tuberculin skin testing with 15-mm cutoff points (P = 0.01) but not with stratified cutoff points (P = 0.10). The ELISpot(PLUS) assay had 4% higher diagnostic sensitivity than standard ELISpot (P = 0.02). Combined sensitivity of ELISpot(PLUS) and tuberculin skin testing was 99% (CI, 95% to 100%), conferring a negative likelihood ratio of 0.02 (CI, 0 to 0.06) when both test results were negative. LIMITATIONS: Local standards for tuberculin skin testing differed from others used internationally. The study sample included few immunosuppressed patients. CONCLUSION: The ELISpot(PLUS) assay is more sensitive than standard ELISpot and, when used in combination with tuberculin skin testing, enables rapid exclusion of active infection in patients with moderate to high pretest probability of tuberculosis.
Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Interferon gama/sangue , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Teste TuberculínicoRESUMO
A cluster of 6 cases of Plasmodium falciparum malaria occurred in a UK airport among 30 travelers returning to the United States from East Africa. Molecular genotyping analysis indicated that all had been exposed to different parasites. The travelers' use of chemoprophylaxis was poor; their perception of risk was limited.
Assuntos
Malária Falciparum/epidemiologia , Adulto , Antimaláricos/uso terapêutico , Análise por Conglomerados , Surtos de Doenças , Humanos , Quênia/epidemiologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Viagem , Uganda/epidemiologia , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Fixed-dose combination antimalarial drugs have played an increasingly important role in the treatment and chemoprophylaxis of falciparum malaria since the worldwide failure of monotherapy with chloroquine. Atovaquone-proguanil is one such combination drug used both for prophylaxis in travellers, and for treatment of acute malaria cases in European hospitals and clinics. METHODS: A series of eight atovaquone-proguanil treatment failures and two prophylaxis breakthroughs from four UK hospitals from 2004-2008 were analysed for evidence of mutations in the pfcyt-b gene, previously found to be associated with failure of the atovaquone component. RESULTS: Parasites carrying pfcyt-b mutations were found in five falciparum malaria patients with recrudescent parasitaemia occurring weeks after apparently successful treatment of a primary infection with atovaquone-proguanil. Four of these cases carried parasites with the Tyr268Cys mutation in pfcyt-b, previously reported in two French patients with malaria. In contrast, mutations in pfcyt-b were not found in three patients treated with atovaquone-proguanil who exhibited delayed clearance of the primary infection, nor in two returning travellers with malaria who had used the combination for prophylaxis. Using current and previously published data, mean time to recrudescence of parasites carrying pfcytb codon 268 mutations was estimated as 28.0 days after treatment (95% C.I. 23.0 - 33.0 days), whereas treatment failures without codon 268 mutations received rescue treatment an average of 4.71 days after initial AP treatment (95% C.I. 1.76 - 7.67 days). CONCLUSION: Genetically-determined parasite resistance to atovaquone is associated with delayed recrudescence of resistant parasites three weeks or more after initial clearance of parasitaemia by atovaquone/proguanil therapy. The 268-Cys allele of pfcyt-b may have been overlooked in previous studies of atovaquone-proguanil treatment failure as it is not detected by current RFLP methods.
Assuntos
Antimaláricos/uso terapêutico , Atovaquona/uso terapêutico , Citocromos b/genética , Malária Falciparum/genética , Parasitemia/genética , Plasmodium falciparum/genética , Proguanil/uso terapêutico , Adulto , Animais , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Atovaquona/administração & dosagem , Atovaquona/efeitos adversos , Pré-Escolar , DNA de Protozoário/genética , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Mutação , Parasitemia/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/isolamento & purificação , Reação em Cadeia da Polimerase , Proguanil/administração & dosagem , Proguanil/efeitos adversos , Recidiva , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared. METHODS: The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage. RESULTS: The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy. CONCLUSIONS: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.
Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Lavagem Broncoalveolar , Lavagem Gástrica , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Técnicas de Diagnóstico do Sistema Respiratório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologiaRESUMO
Individuals possessing red cells negative for the Duffy blood group antigen are said to possess absolute resistance to infection by the malarial parasite Plasmodium vivax. Now in this issue of Transactions, initial evidence is presented from the Brazilian Amazon to suggest that P. vivax is being transmitted amongst Duffy-negative individuals. This supports data from East Africa where the same phenomenon has been observed. Thus the emerging picture is that P. vivax in both South America and in Africa is now evolving pathways other than Duffy to enter red cells.
Assuntos
Sistema do Grupo Sanguíneo Duffy/genética , Malária/imunologia , Plasmodium vivax/imunologia , Animais , Antígenos de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Duffy/imunologia , Humanos , Malária/transmissãoRESUMO
We present a case of Kikuchi's disease causing meningitis associated with fever and treated successfully with corticosteroids alone. This is considered to be rare but provides an instructive example of how the diagnosis may be confused with that of tuberculous meningitis and highlights the importance of histopathological analysis.
Assuntos
Linfadenite Histiocítica Necrosante/complicações , Meningite/diagnóstico , Meningite/etiologia , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Humanos , Linfonodos/patologia , Prednisolona/uso terapêuticoRESUMO
Presence of early secretory antigenic target-6 (ESAT-6)-specific, interferon- gamma -secreting T cells in blood accurately marks tuberculosis infection. In tuberculous pleural effusions from 10 patients with tuberculosis, these cells were concentrated a mean of 15-fold (standard deviation, +/-6-fold), relative to their level in peripheral blood (P=.014), and displayed rapid effector function. Such cells were absent in 8 control patients with nontuberculous pleural disease. The recruitment of ESAT-6-specific T cells to inflamed tuberculous tissue demonstrates their function in vivo and suggests a novel way to diagnose tuberculous pleuritis.