Evaluating the Quality of Tuberculosis Contact Investigation in Cali, Colombia: A Retrospective Cohort Study.

Tuberculosis (TB) contact investigation facilitates earlier TB diagnosis and initiation of preventive therapy, but little data exist about the quality of its implementation. We conducted a retrospective cohort study to evaluate processes of TB contact investigation for index TB patients diagnosed in Cali, Colombia, in 2017, including dropout at each stage and overall yield. We constructed multivariable models to identify predictors of completing 1) the baseline household visit and 2) a follow-up clinic visit for TB evaluation among referred contacts. Sixty-eight percent (759/1,120) of registered TB patients were eligible for contact investigation; 77% (582/759) received a household visit. Odds of completing a household visit were significantly lower among men (adjusted odds ratio [aOR]: 0.6; 95% CI: 0.4-0.9; P = 0.009) and patients living in Cali's western zone (aOR: 0.5; 95% CI: 0.3-0.8; P = 0.008). Among 1880 screened contacts, 31% (n = 582) met the criteria for clinic referral, 47% (n = 271) completed a clinic visit, and 85% (231/271) completed testing. After adjusting for clustering by index patient, odds of completing referral were higher among contacts with cough (aOR: 22; 95% CI: 7.1-66; P < 0.001) and contacts living in the western zone (aOR: 4.1; 95% CI: 1.2-15; P = 0.03). The cumulative probability of a symptomatic contact from an eligible household completing TB evaluation was only 28%. The yield of active TB patients among contacts was only 0.3% (5/1880). Only 16% (17/103) of children aged < 5 years and none of the eight persons living with HIV, reported preventive therapy initiation. Routine monitoring of process indicators may facilitate quality improvement to close gaps in contact tracing and increase yield.

Feasibility, Acceptability, and Adoption of Digital Fingerprinting During Contact Investigation for Tuberculosis in Kampala, Uganda: A Parallel-Convergent Mixed-Methods Analysis.

BACKGROUND: In resource-constrained settings, challenges with unique patient identification may limit continuity of care, monitoring and evaluation, and data integrity. Biometrics offers an appealing but understudied potential solution. OBJECTIVE: The objective of this mixed-methods study was to understand the feasibility, acceptability, and adoption of digital fingerprinting for patient identification in a study of household tuberculosis contact investigation in Kampala, Uganda. METHODS: Digital fingerprinting was performed using multispectral fingerprint scanners. We tested associations between demographic, clinical, and temporal characteristics and failure to capture a digital fingerprint. We used generalized estimating equations and a robust covariance estimator to account for clustering. In addition, we evaluated the clustering of outcomes by household and community health workers (CHWs) by calculating intraclass correlation coefficients (ICCs). To understand the determinants of intended and actual use of fingerprinting technology, we conducted 15 in-depth interviews with CHWs and applied a widely used conceptual framework, the Technology Acceptance Model 2 (TAM2). RESULTS: Digital fingerprints were captured for 75.5% (694/919) of participants, with extensive clustering by household (ICC=.99) arising from software (108/179, 60.3%) and hardware (65/179, 36.3%) failures. Clinical and demographic characteristics were not markedly associated with fingerprint capture. CHWs successfully fingerprinted all contacts in 70.1% (213/304) of households, with modest clustering of outcomes by CHWs (ICC=.18). The proportion of households in which all members were successfully fingerprinted declined over time (ρ=.30, P<.001). In interviews, CHWs reported that fingerprinting failures lowered their perceptions of the quality of the technology, threatened their social image as competent health workers, and made the technology more difficult to use. CONCLUSIONS: We found that digital fingerprinting was feasible and acceptable for individual identification, but problems implementing the hardware and software lead to a high failure rate. Although CHWs found fingerprinting to be acceptable in principle, their intention to use the technology was tempered by perceptions that it was inconsistent and of questionable value. TAM2 provided a valuable framework for understanding the motivations behind CHWs' intentions to use the technology. We emphasize the need for routine process evaluation of biometrics and other digital technologies in resource-constrained settings to assess implementation effectiveness and guide improvement of delivery.

Predictors of Mortality Among Hospitalized Patients With Lower Respiratory Tract Infections in a High HIV Burden Setting.

INTRODUCTION: Lower respiratory tract infections (LRTIs) are a leading cause of mortality in sub-Saharan Africa. Triaging identifies patients at high risk of death, but laboratory tests proposed for use in severity-of-illness scores are not readily available, limiting their clinical use. Our objective was to determine whether baseline characteristics in hospitalized participants with LRTI predicted increased risk of death. METHODS: This was a secondary analysis from the Mulago Inpatient Non-invasive Diagnosis-International HIV-associated Opportunistic Pneumonias (MIND-IHOP) cohort of adults hospitalized with LRTI who underwent standardized investigations and treatment. The primary outcome was all-cause mortality at 2 months. Predictors of mortality were determined using multiple logistic regression. RESULTS: Of 1887 hospitalized participants with LRTI, 372 (19.7%) died. The median participant age was 34.3 years (interquartile range, 28.0-43.3 years), 978 (51.8%) were men, and 1192 (63.2%) were HIV-positive with median CD4 counts of 81 cells/µL (interquartile range, 21-226 cells/µL). Seven hundred eleven (37.7%) participants had a microbiologically confirmed diagnosis. Temperature <35.5°C [adjusted odds ratio (aOR) = 1.77, 95% confidence intervals (CI): 1.20 to 2.60; P = 0.004], heart rate >120/min (aOR = 1.82, 95% CI: 1.37 to 2.43; P < 0.0001), oxygen saturation <90% (aOR = 2.74, 95% CI: 1.97 to 3.81; P < 0.0001), being bed-bound (aOR = 1.88, 95% CI: 1.47 to 2.41; P < 0.0001), and being HIV-positive (aOR = 1.49, 95% CI: 1.14 to 1.94; P = 0.003) were independently associated with mortality at 2 months. CONCLUSIONS: Having temperature <35.5°C, heart rate >120/min, hypoxia, being HIV-positive, and bed-bound independently predicts mortality in participants hospitalized with LRTI. These readily available characteristics could be used to triage patients with LRTI in low-income settings. Providing adequate oxygen, adequate intravenous fluids, and early antiretroviral therapy (in people living with HIV/AIDS) may be life-saving in hospitalized patients with LRTI.

Empiric TB Treatment of Severely Ill Patients With HIV and Presumed Pulmonary TB Improves Survival.

RATIONALE: In 2007, World Health Organization (WHO) issued emergency recommendations on empiric treatment of sputum acid-fast bacillus smear-negative patients with possible tuberculosis (TB) in HIV-prevalent areas, and called for operational research to evaluate their effectiveness. We sought to determine if early, empiric TB treatment of possible TB patients with abnormal chest radiography or severe illness as suggested by the 2007 WHO guidelines, is associated with improved survival. METHODS: We prospectively enrolled consecutive HIV-seropositive inpatients at Mulago Hospital in Kampala, Uganda, from 2007 to 2011 with cough for ≥2 weeks. We retrospectively examined the effect of empiric TB treatment before discharge on 8-week survival among those with and without a WHO-defined "danger sign," including fever >39°C, tachycardia >120 beats per minute, or tachypnea >30 breaths per minute. We modeled the interaction between empiric TB treatment and danger signs, and their combined effect on 8-week survival, and adjusted for relevant covariates. RESULTS: Among 631 sputum smear-negative patients, 322 (51%) had danger signs. Cumulative 8-week survival of patients with danger signs was significantly higher with empiric TB treatment (80%) than without treatment (64%, P < 0.001). After adjusting for duration of cough and concurrent hypoxemia, patients with danger signs who received empiric TB treatment had a 44% reduction in 8-week mortality (risk ratio 0.56, 95% confidence interval: 0.34-0.91, P = 0.020). CONCLUSIONS: Empiric TB treatment of HIV-seropositive, smear-negative, presumed pulmonary TB patients with 1 or more danger signs is associated with improved 8-week survival. Enhanced implementation of the 2007 WHO empiric treatment recommendations should be encouraged whenever and wherever rapid and highly sensitive diagnostic tests for TB are unavailable.

Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis.

BACKGROUND: Treatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli. METHODS: M. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis. RESULTS: Within 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories-including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days. CONCLUSIONS: Transcriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens.