Objective In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag (‘TB LAM’) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis. Design Prospective diagnostic accuracy study. Setting Hospital and outpatient settings in Uganda and South Africa. Participants HIV-infected adults with tuberculosis symptoms and/or signs. Methods Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and two respiratory specimens for smear microscopy and mycobacterial culture. Main outcome measures For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis. Results 1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4≤100 cells/mm3. The test was specific in 559/573 (97.6%) of patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4≤100. CD4≤50 (adjusted odds ratio [AOR] 6.2, P<0.001) or 51–100 (AOR 7.1, P<0.001), mycobacteremia (AOR 6.1; P<0.01) and hospitalization (AOR 2.6, P=0.03) were independently associated with a positive TB LAM test. Conclusions In HIV-positive adults with CD4≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in less than 30 minutes and without the need for equipment or reagents.

BackgroundAntibiotic consumption is a major driver of bacterial resistance. To address the increasing burden of multi-drug resistant bacterial infections, antibiotic stewardship programmes are promoted worldwide to rationalize antibiotic prescribing and conserve remaining antibiotics. Few studies have been reported from developing countries and none from Africa that report on an intervention based approach with outcomes that include morbidity and mortality.MethodsAn antibiotic prescription chart and weekly antibiotic stewardship ward round was introduced into two medical wards of an academic teaching hospital in South Africa between January-December 2012. Electronic pharmacy records were used to collect the volume and cost of antibiotics used, the patient database was analysed to determine inpatient mortality and 30-day re-admission rates, and laboratory records to determine use of infection-related tests. Outcomes were compared to a control period, January-December 2011.ResultsDuring the intervention period, 475.8 defined daily doses were prescribed per 1000 inpatient days compared to 592.0 defined daily doses/1000 inpatient days during the control period. This represents a 19.6% decrease in volume with a cost reduction of 35% of the pharmacy’s antibiotic budget. There was a concomitant increase in laboratory tests driven by requests for procalcitonin. There was no difference in inpatient mortality or 30-day readmission rate during the control and intervention periods.ConclusionsIntroduction of antibiotic stewardship ward rounds and a dedicated prescription chart in a developing country setting can achieve reduction in antibiotic consumption without harm to patients. Increased laboratory costs should be anticipated when introducing an antibiotic stewardship program.

The polymyxin antibiotic colistin is an antibiotic of last resort for the treatment of extensively drug-resistant Gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae. The State of the World's Antibiotics report in 2015 highlighted South Africa (SA)'s increasing incidence of these 'superbugs' (3.2% of Klebsiella pneumoniae reported from SA were carbapenemase producers), and in doing so, underscored SA's increasing reliance on colistin as a last line of defence. Colistin resistance effectively renders such increasingly common infections untreatable.

Introduction intussusception in South African (SA) children is often severe. A proportion of cases require management at quaternary hospitals which are a scare resource in SA. A geospatial investigation of severe paediatric intussusception (SPI) in the KwaZulu-Natal (KZN) province of SA would assist with identifying regions which should be targeted for preventative interventions. This could reduce resource utilisation for this condition at quaternary hospitals. The objective of this study was to determine the geospatial distribution of SPI in KZN. Methods this was a retrospective analysis of data for patients with SPI who were admitted to a quaternary hospital in KZN over an 11-year period. Data related to patient demographics, duration of hospitalization, surgical intervention, inpatient mortality and residential postal code were extracted from the electronic hospital admissions system. Each residential postal code was linked to a corresponding KZN district municipality. Descriptive statistical methods were used to determine the distribution of various characteristics in the study sample. Semi-quantitative geospatial analysis was used to determine the distribution of patients with SPI in each KZN district municipality. Results the study sample consisted of 182 patients with SPI. Most patients were <1 year old (83.5%), male (51.1%) and black African (87.9%). All patients underwent surgical intervention. Inpatient mortality was 2.7%. The majority of patients in the study sample resided in the eThekwini and King Cetshwayo district municipalities (51.1% and 14.8%, respectively). Conclusion preventative interventions for SPI should be considered for rollout in the eThekwini and King Cetshwayo district municipalities of KZN, SA.

NCT01392911.

BackgroundWorkers in clinical microbiology laboratories are exposed to a variety of pathogenic microorganisms. Salmonella species is among the most commonly reported bacterial causes of laboratory-acquired infections. We report on three cases of laboratory-acquired Salmonella enterica serotype Typhi (Salmonella Typhi) infection which occurred over the period 2012 to 2016 in South Africa.MethodsLaboratory investigation included phenotypic and genotypic characterization of isolates. Phenotypic analysis included standard microbiological identification techniques, serotyping and antimicrobial susceptibility testing. Genotypic analysis included the molecular subtyping methodologies of pulsed-field gel electrophoresis analysis, multilocus sequence typing and whole-genome sequencing (WGS); with WGS data analysis including phylogenetic analysis based upon comparison of single nucleotide polymorphism profiles of isolates.ResultsAll cases of laboratory-acquired infection were most likely the result of lapses in good laboratory practice and laboratory safety. The following critical issues were highlighted. There was misdiagnosis and misreporting of Salmonella Typhi as nontyphoidal Salmonella by a diagnostic laboratory, with associated public health implications. We highlight issues concerning the importance of accurate fluoroquinolone susceptibility testing and interpretation of results according to updated guidelines. We describe potential shortcomings of a single disk susceptibility screening test for fluoroquinolone susceptibility and suggest that confirmatory minimum inhibitory concentration testing should always be performed in cases of invasive Salmonella infections. These antimicrobial susceptibility testing issues resulted in inappropriate ciprofloxacin therapy which may have been responsible for failure in clearance of pathogen from patients. Salmonella Typhi capsular polysaccharide vaccine was not protective in one case, possibly secondarily to a faulty vaccine.ConclusionsMolecular subtyping of isolates proved effective to investigate the genetic relatedness of isolates. Molecular subtyping data interpreted together with epidemiological data allowed us to pinpoint the most likely sources for our cases of laboratory-acquired infection.

Setting Inpatient hospitals in South Africa and Uganda Objective To evaluate the cost-effectiveness of a lateral flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in HIV-infected adults (CD4+ T-cell counts<100 cells/μL) with symptoms of active TB. Design Decision-analytic cost-utility model with the primary outcome being the incremental cost-effectiveness ratio (ICER), expressed in 2010 US dollars per disability-adjusted life year (DALY) averted, from the perspective of a public-sector TB control program. Results and Conclusion For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate TB treatments and averted 224 DALYs. Estimated cost-utility was $353 per DALY averted (95% uncertainty range: $192–$1161) in South Africa and $86 per DALY averted (95% uncertainty range: $49–$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost-utility was most sensitive to assay specificity, cost of TB treatment, life expectancy after TB cure, and cohort TB prevalence but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per-capita gross domestic product in South Africa ($7275) and Uganda ($509).

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