Bacterial Genotyping of Central Nervous System Tuberculosis in South Africa: Heterogenic Mycobacterium tuberculosis Infection and Predominance of Lineage 4.

Tuberculous meningitis (TBM), the most severe extrapulmonary manifestation of tuberculosis, is caused by the pathogen Mycobacterium tuberculosis The M. tuberculosis complex includes seven lineages, all described to harbor a unique geographical dissemination pattern and clinical presentation. In this study, we set out to determine whether a certain M. tuberculosis lineage demonstrated tropism to cause TBM in patients from Cape Town, South Africa. DNA was extracted from formalin-fixed paraffin-embedded central nervous system (CNS) tissue from a unique neuropathological cohort of 83 TBM patients, collected between 1975 and 2012. M. tuberculosis lineages 1, 2, 3, and 4 were determined using an allele-specific PCR and Sanger sequencing. Of the 83 patient specimens tested, bacterial characterization could be performed on 46 specimens (55%). M. tuberculosis lineage 4 was present in 26 patient specimens (56%), and non-lineage 4 was identified in 10 cases (22%). Moreover, genomic heterogeneity was detected in the CNS specimens of 7 adults and 3 children. We could show that infection of the CNS is not restricted to a single M. tuberculosis lineage and that even young children with rapid progression of disease can harbor more than one M. tuberculosis lineage in the CNS.

Cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis.

SETTING: Cape Town, South Africa, 2014. OBJECTIVE: To assess the societal costs and cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis. DESIGN: This was an economic evaluation from a societal perspective using probabilistic analysis. Health care, informal care, lost productivity costs and costs in other sectors, health-related quality of life (HRQoL) and family impact were assessed during interviews with care givers, children, medical staff and management. RESULTS: Societal costs for home-based treatment were USD3857, and USD28 043 for in-hospital treatment. Home-based vs. in-hospital treatment HRQoL scores were 90.9% vs. 84.5%, while family impact scores were 94.8% vs. 73.1%. The point estimate of the incremental cost-effectiveness ratio indicated that improving HRQoL and family impact by 1% was associated with a saving of respectively USD3726 and USD1140 for home-based vs. in-hospital treatment. The probability that home-based treatment was less expensive and more effective than in-hospital treatment was 96.3% for HRQoL and 100% for family impact. CONCLUSION: Societal costs of home-based treatment were lower than for in-hospital treatment. Children treated at home had a better HRQoL and family impact scores. Home-based treatment was a cost-effective alternative to in-hospital treatment of drug-susceptible tuberculous meningitis.

Lipoarabinomannan enzyme-linked immunosorbent assay for early diagnosis of childhood tuberculous meningitis.

SETTING: Tuberculous meningitis (TBM) is a severe complication of tuberculosis (TB) predominantly affecting young children. Early initiation of treatment is important to prevent morbidity and mortality associated with TBM, emphasising the importance of early diagnosis. Among the most promising new methods for diagnosing TB are antigen-detection assays based on the detection of lipoarabinomannan (LAM). OBJECTIVE: To evaluate the diagnostic value of a commercial, antigen-capture enzyme-linked immunosorbent assay (ELISA) test based on the detection of LAM in urine for the early diagnosis of TBM in children. METHOD: A cross-sectional study in which urine samples from paediatric patients with suspected TBM attending the Tygerberg Children's Hospital, Cape Town, South Africa, were tested for LAM. RESULTS: Complete data were available for 50 of 56 patients with suspected TBM. TBM was diagnosed in 21 (42%) patients and excluded in 29 (58%). The LAM ELISA had a sensitivity of 4.8% and a specificity of 93.1%. Serial measurements in the first 2 weeks after treatment initiation did not improve test performance. CONCLUSION: We have shown that urinary LAM detection was of little value for the diagnosis of TBM in a cohort of paediatric patients with suspected TBM.

Instruments to assess physical activity in patients with osteoarthritis of the hip or knee: a systematic review of measurement properties.

OBJECTIVE: There is no consensus on the best approach for measuring physical activity in patients with osteoarthritis (OA) of the hip or knee. The aims of this study were (1) to identify all physical activity measures that have been validated in patients with OA of the hip or knee and to systematically review their measurement properties, and (2) to give recommendations on which instrument is most suitable for what purpose. DESIGN: A search was performed in PubMed, Embase, and Sportdiscus (complete databases until November 10, 2010). Three reviewers independently evaluated the quality of the included studies, using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Subsequently, the reviewers independently evaluated the quality of the included physical activity instruments, using the recently developed QAPAQ checklist for appraising the qualitative attributes and measurement properties of physical activity questionnaires. RESULTS: Nine studies were included, in which 12 measurement instruments were evaluated: five single-item rating scales, six multi-item questionnaires, and one pedometer. In general, the methodological quality of the studies was poor to moderate. Only the Lower-Extremity Activity Scale (LEAS) and the pedometer received positive ratings for content validity. The LEAS and Baecke questionnaire received positive ratings for reliability. The University of California at Los Angeles (UCLA), the Tegner score, and the LEAS received positive ratings for construct validity. The Daily Activity Questionnaire (DAQ) received a positive rating for criterion validity. Responsiveness was not evaluated for any of the included instruments. CONCLUSION: For monitoring physical activity levels of populations the UCLA or LEAS seem most useful. For studies measuring physical activity as a risk factor for developing OA or as a protective factor against functional decline there is not enough evidence for any instrument to conclude that it has adequate measurement properties. For follow-up studies on wear in joint replacement patients we recommend to use accelerometers. However, more validation studies of adequate quality are needed for all included instruments.