Diagnostic Prediction Model for Tuberculous Meningitis: An Individual Participant Data Meta-Analysis.

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

Difficulties reported by HIV-infected patients using antiretroviral therapy in Brazil.

OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment. INTRODUCTION: Patients perceptions about their treatment are a determinant factor for improved adherence and a better quality of life. METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis. RESULTS: Among 406 patients initiating treatment, 350 (86.2%) and 209 (51.5%) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4% and 37.3% on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm3) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit. CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.

Fulminant encephalitis associated with a vaccine strain of rubella virus.

Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

Valor diagnóstico da nested PCR em tempo real em pacientes com meningite tuberculosa / Diagnostic value of the nested real time PCR patients with tuberculous meningitis

Introdução: A meningite tuberculosa (MTB) é a forma mais grave e fatal de tuberculose. O diagnóstico oportuno e o tratamento adequado e precoce são os principais fatores associados com o bom prognóstico. Os métodos utilizados na prática médica diária - achados clínicos, exames de imagem e análise de líquido cefalorraquidiano (LCR) - têm baixa acurácia. A pesquisa do DNA do Mycobacterium tuberculosis no LCR através da reação em cadeia da polimerase (PCR, do inglês polimerase chain reaction) com a metodologia nested é promissora, especialmente quando associada à praticidade da amplificação do DNA em tempo real. Objetivo: Avaliar o valor diagnóstico da nested PCR em tempo real (nRT-PCR, do inglês nested real-time PCR) na investigação de pacientes com MTB. Métodos: Estudo observacional realizado em duas fases: uma prospectiva e outra retrospectiva. Na fase prospectiva, foram incluídos pacientes com suspeita de MTB internados no Instituto de Infectologia Emílio Ribas (IIER). Informações clínicas, laboratoriais e radiológicas foram coletadas, assim como amostra de LCR de todos os pacientes. A partir de critérios internacionais padronizados, os pacientes foram categorizados como "MTB Definitiva", "MTB Provável", "MTB Possível" e "Não MTB". A nRT-PCR, utilizando o gene alvo mpt64, foi realizada em todas as amostras de LCR no Laboratório de Meningites Bacterianas do Instituto Adolfo Lutz. Sensibilidade, especificidade e intervalos de confiança (IC 95%) da nRT-PCR foram calculados com base no padrão-ouro (cultura positiva para M. tuberculosis ou isolamento de BAAR no sistema nervoso central) e nos pacientes com outros diagnósticos estabelecidos (Não MTB). Também foi calculada a proporção de pacientes com a nRT-PCR positiva em cada categoria clínica. Na fase retrospectiva, foi realizada uma revisão de prontuários de pacientes que tiveram a nRT-PCR solicitada no IIER e no Centro de Referência e Treinamento em DST/AIDS. Os mesmos procedimentos...

Background: Tuberculous meningitis (TBM) is the most serious and lethal presentation of tuberculosis. Timely diagnosis and appropriated treatment are the main factors associated with good outcome. Methods used in the daily medical practice - clinical, radiological and cerebrospinal fluid (CSF) findings - have low accuracy. Search for Mycobacterium tuberculosis DNA in the CSF by polymerase chain reaction (PCR) using the nested methodology is promising, especially when combined with the practical approach of the real time DNA amplification. Objective: To evaluate the diagnostic value of a nested real-time PCR (nRT-PCR) in the investigation of patients with TBM. Methods: A two-phase observational study was carried out: prospective and retrospective. In the prospective phase, patients with suspected TBM hospitalized at "Instituto de Infectologia Emílio Ribas" (IIER) were included. Clinical, laboratory and radiological data were collected, as well as CSF samples of all patients. According to international standard criteria, patients were categorized as "TBM Definite", "TBM Probable", "TBM Possible" and "Not TBM". The nRT-PCR, using the mpt64 gene, was performed on all CSF sample in the Laboratory of Bacterial Meningitis, Adolfo Lutz Institute. Sensitivity, specificity and confidence intervals (95% CI) of the nRT-PCR were calculated based on the gold standard (culture positive for M. tuberculosis or AFB isolation on the central nervous system) and on patients with other established diagnoses ("Not TBM"). The proportion of patients with a positive nRT-PCR in each clinical category was also calculated. In the retrospective phase, medical chart review was performed in those patients who had the nRT-PCR requested in IIER and in the "Centro de Referência e Treinamento em DST/AIDS". The same diagnostic categorization and calculations of sensitivity and specificity were adopted. Results: 102 patients were included in the prospective phase, 92 of them...

Difficulties reported by hiv-infected patients using antiretroviral therapy in brazil

OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment. INTRODUCTION: Patients’ perceptions about their treatment are a determinant factor for improved adherence and a better quality of life. METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis. RESULTS: Among 406 patients initiating treatment, 350 (86.2 percent) and 209 (51.5 percent) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4 percent and 37.3 percent on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm³) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit. CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.