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Tuberculosis (TB) education seeks to increase patient knowledge about TB, while TB counselling seeks to offer tailored advice and support for medication adherence. While universally recommended, little is known about how to provide effective, efficient, patient-centred TB education and counselling (TEC) in low-income, high HIV-TB burden settings. We sought to characterise stakeholder perceptions of TEC in a public, primary care facility in Kampala, Uganda, by conducting focus group discussions with health workers and TB patients in the TB and HIV clinics. Participants valued TEC but reported that high-quality TEC is rarely provided, because of a lack of time, space, staff, planning, and prioritisation given to TEC. To improve TEC, they recommended adopting practices that have proven effective in the HIV clinic, including better specifying educational content, and employing peer educators focused on TEC. Patients and health workers suggested that TEC should not only improve TB patient knowledge and adherence, but should also empower and assist all those undergoing evaluation for TB, whether confirmed or not, to educate their households and communities about TB. Community-engaged research with patients and front-line providers identified opportunities to streamline and standardise the delivery of TEC using a patient-centred, peer-educator model.

BackgroundMany implementation efforts experience interruptions, especially in settings with developing health systems. Approaches for evaluating interruptions are needed to inform targeted re-implementation strategies.MethodsThis study took place in two public health centers with tuberculosis (TB) units in Uganda that previously implemented diabetes mellitus (DM) screening in 2017. In 2019, we conducted interviews with clinic staff to determine current DM practices. We mapped themes identified in the interviews to a Social Ecological Model with three levels: outer setting, inner setting, and individuals.ResultsWe conducted nine interviews with clinic staff. Respondents explained that DM screening ceased due to disruptions in the supply chain for glucose test strips. This outer setting interruption had cascading effects on the inner setting and individuals. The lack of screening supplies limited the staff’s opportunities to perform DM screening within the inner setting level, which was associated with diminished self-efficacy within the individual level. However, culture, compatibility and individual beliefs about DM screening sustained throughout the interruption.ConclusionsWe identified factors that diminished and sustained within and between ecological levels during a program interruption. Using this approach, other programs facing interruptions can identify factors and cascading effects of the interruption to target them for re-implementation.

BackgroundCommunities of Practice (CoPs) are a low-cost strategy for health workers to share and create knowledge through social interactions to improve the delivery of high-quality care. However, there remain critical gaps in understanding the behavioral mechanisms through which CoPs can facilitate community health worker’s (CHWs) performance. Therefore, we carried out a qualitative study of a CoP to identify the behavior change techniques (BCTs) and intervention functions that improved CHWs’ performance.MethodsWe organized CHWs from two tuberculosis (TB) clinics in Kampala, Uganda into a CoP from February to August 2018. We conducted interviews with CoP members to understand their perceptions of how the CoP influenced delivery of TB contact investigation. Using an abductive approach, we first applied inductive codes characterizing CHWs’ perceptions of how the CoP activities affected their delivery of contact investigation. We then systematically mapped these codes into their functional categories using the BCT Taxonomy and Behavior Change Wheel framework. We triangulated all interview findings with detailed field notes.ResultsAll eight members of the CoP agreed to participate in the interviews. CHWs identified five CoP activities as improving the quality of their work: (1) individual review of feedback reports, (2) collaborative improvement meetings, (3) real-time communications among members, (4) didactic education sessions, and (5) clinic-wide staff meetings. These activities represented nine different BCTs and five distinct intervention functions. Taken together, CoP meetings enabled members to foster social support, problem solving, and knowledge sharing. The CoP enabled CHWs to identify barriers they face in the field and develop solutions. The CoP was motivating, strengthened their social and professional identities within and outside of the group, and improved their self-efficacy.ConclusionsWe identified several behavioral mechanisms through which CoPs may improve CHW performance. Future studies should evaluate the importance of these mechanisms in mediating the effects of CoPs on program effectiveness.

In this paper, degradation mechanisms of optical materials, used in the light emitting diode (LED)-based products, are reviewed. The LED lighting is one of the fastest technology shifts in human history. Lighting accounts for almost 20% of the global electrical energy use, inferring that replacement of traditional lighting sources with LEDs with higher efficiencies will have major positive implications for the global energy consumption. Organic optical materials are key components in LEDs in the sense that they control the functionality of the device and they have decisive effects on the durability and reliability of LEDs. This paper aims at describing the influences of chemical structure and service conditions on the degradation mechanisms of organic optical materials in LEDs which lead to the lumen depreciation, discolouration, and colour shift of the LED light output. The contributions of different degradation mechanisms of optical and package materials in LED-based products to the lumen depreciation and colour shift are methodically reviewed.

INTRODUCTION: SARS-CoV-2 has been associated with high rates of severe hypoxemic respiratory failure. Severe COVID-19 is characterized by rapid development of acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. ARDS is considered a heterogeneous disorder and the presence of a uniform inciting agent with SARS-CoV-2 allows us to investigate subphenotypes of ARDS. We hypothesized that subphenotypes based on early lung compliance in patients with COVID-ARDS may be associated with disease outcomes including mortality. We sought to test this hypothesis in patients with COVID-ARDS. METHODS: Patients in the Yale New Haven Health System from 3/15/2020 to 5/14/2020 were included if they had a positive SARS-CoV-2 test and required intubation. After exclusion for missing data or transfer from satellite facilities, 140 of patients were included for analysis. Clinical, demographic, ventilator, and laboratory parameters were abstracted from the EMR. To identify ARDS subphenotypes, we implemented unsupervised clustering using a partitioning around medoids (PAM) algorithm on average compliance over the three days following intubation. Clustering was also performed on the NHLBI ALVEOLI cohort for use as comparator. RESULTS: Patients received a median of 6.2 cc/kg of IBW on day 1 and 6.2 on day 3. Plateau pressure was less than 30cm H2O in 81% patients and driving pressure was less than 15 in 69% of patients. Median lung compliances were day 1: 30.4 mL/cm H2O [23.0-36.1];day 2: 28.7 mL/cm H2O [21.6-36.8];and day 3: 29.7 mL/cm H2O [23.2-37.6]. By Berlin criteria, 21% of patients had mild ARDS, 46% moderate, and 26% were severe. 61% of patients were proned. Using PAM, three distinct clusters based on compliance were identified (low [LC], medium [MC], and high [HC]). Median day 1 compliance in HC group was 38.0 mL/cm H2O [33.1-44.2], 29.3 [25.2-32.3] in MC, and 19.5 mL/cm H2O [16.7-22.8] in LC. Compared to the HC group, there were no differences in PEEP, day 1 P/F ratio or tidal volume, and ventilatory ratio. HC group had higher P/F ratio day 3, lower tidal volume day 3, and lower driving pressures. There were no differences in biomarkers, comorbidities, vasopressors, paralytics, or sedatives between groups. However, Kaplan-Meier plot demonstrated higher mortality in the HC group. Cox regression model demonstrated persistence of higher mortality in the HC compared to MC group. These differences were not present in the ALVEOLI cohort. CONCLUSION: In COVID-ARDS, a subphenotype characterized by early high compliance was associated with higher mortality when compared to non-COVIDARDS patients.

IntroductionHIV status awareness is important for household contacts of patients with tuberculosis (TB). Home HIV testing during TB contact investigation increases HIV status awareness. Social interactions during home visits may influence perceived stigma and uptake of HIV testing. We designed an intervention to normalise and facilitate uptake of home HIV testing with five components: guided selection of first tester; prosocial invitation scripts; opt-out framing; optional sharing of decisions to test; and masking of decisions not to test.Methods and analysisWe will evaluate the intervention effect in a household-randomised controlled trial. The primary aim is to assess whether contacts offered HIV testing using the norming strategy will accept HIV testing more often than those offered testing using standard strategies. Approximately 198 households will be enrolled through three public health facilities in Kampala, Uganda. Households will be randomised to receive the norming or standard strategy and visited by a community health worker (CHW) assigned to that strategy. Eligible contacts ≥15 years will be offered optional, free, home HIV testing. The primary outcome, proportion of contacts accepting HIV testing, will be assessed by CHWs and analysed using an intention-to-treat approach. Secondary outcomes will be changes in perceived HIV stigma, changes in perceived TB stigma, effects of perceived HIV stigma on HIV test uptake, effects of perceived TB stigma on HIV test uptake and proportions of first-invited contacts who accept HIV testing. Results will inform new, scalable strategies for delivering HIV testing.Ethics and disseminationThis study was approved by the Yale Human Investigation Committee (2000024852), Makerere University School of Public Health Institutional Review Board (661) and Uganda National Council on Science and Technology (HS2567). All participants, including patients and their household contacts, will provide verbal informed consent. Results will be submitted to a peer-reviewed journal and disseminated to national stakeholders, including policy-makers and representatives of affected communities.Trial registration numberClinicalTrials.gov Identifier: NCT05124665.

OBJECTIVE: To assess the quality of routine childhood tuberculosis (TB) evaluation in Kampala, Uganda. SETTING AND DESIGN: This was a cross-sectional study of children aged

Setting: Seven public sector tuberculosis (TB) units and surrounding communities in Kampala, Uganda. Objective: To evaluate the influence of household-level socio-economic characteristics on completion of TB evaluation during household contact investigation. Design: A cross-sectional study nested within the control arm of a randomized, controlled trial evaluating home-based sputum collection and short messaging service communications. We used generalized estimating equations to estimate the association between completion of TB evaluation and socio-economic determinants. Results: Of 116 household contacts referred to clinics for TB evaluation, 32 (28%) completed evaluation. Completing evaluation was strongly clustered by household. Controlling for individual symptoms, contacts from households earning below-median income (adjusted risk ratio [aRR] 0.28, 95%CI 0.09-0.88, P = 0.029) and contacts from households in which the head of household had no more than primary-level education (aRR 0.40, 95%CI 0.18-0.89, P = 0.025) were significantly less likely to complete evaluation for TB. Conclusion: Socio-economic factors such as low income and education increase the risk that household contacts of TB patients will experience barriers to completing TB evaluation themselves. Further research is needed to identify specific mechanisms by which these underlying social determinants modify the capability and motivation of contacts to complete contact investigation.

Author(s): Shete, PB; Nalugwa, T; Farr, K; Ojok, C; Nantale, M; Howlett, P; Haguma, P; Ochom, E; Mugabe, F; Joloba, M; Chaisson, LH; Dowdy, DW; Moore, D; Davis, JL; Katamba, A; Cattamanchi, A | Abstract: ObjectiveTo assess the feasibility of a streamlined strategy for improving tuberculosis (TB) diagnostic evaluation and treatment initiation among patients with presumed TB.DesignSingle-arm interventional pilot study at five primary care health centers of a streamlined, SIngle-saMPLE (SIMPLE) TB diagnostic evaluation strategy: 1) examination of two smear results from a single spot sputum specimen using light-emitting diode fluorescence microscopy, and 2) daily transportation of smear-negative sputum samples to Xpert® MTB/RIF testing sites.ResultsOf 1212 adults who underwent sputum testing for TB, 99.6% had two smears examined from the spot sputum specimen. Sputum was transported for Xpert testing within 1 clinic day for 83% (907/1091) of the smear-negative patients. Of 157 (13%) patients with bacteriologically positive TB, 116 (74%) were identified using sputum smear microscopy and 41 (26%) using Xpert testing of smear-negative samples. Anti-tuberculosis treatment was initiated in 142 (90%) patients with bacteriologically positive TB, with a median time to treatment of 1 day for smear-positive patients and 6 days for smear-negative, Xpert-positive patients.ConclusionThe SIMPLE TB strategy led to successful incorporation of Xpert testing and rapid treatment initiation in the majority of patients with bacteriologically confirmed TB in a resource-limited setting.

IntroductionLower 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.MethodsThis 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.ResultsOf 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 120/min (aOR = 1.82, 95% CI: 1.37 to 2.43; P < 0.0001), oxygen saturation 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.

Setting Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings. Objective To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda. Design We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case. Results The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests. Conclusion Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes.

BACKGROUND: Little information exists about mobile phone usage or preferences for tuberculosis (TB) related health communications in Uganda. METHODS: We surveyed household contacts of TB patients in urban Kampala, Uganda, and clinic patients in rural central Uganda. Questions addressed mobile phone access, usage, and preferences for TB-related communications. We collected qualitative data about messaging preferences. RESULTS: We enrolled 145 contacts and 203 clinic attendees. Most contacts (58%) and clinic attendees (75%) owned a mobile phone, while 42% of contacts and 10% of clinic attendees shared one; 94% of contacts and clinic attendees knew how to receive a short messaging service (SMS) message, but only 59% of contacts aged 45 years (vs. 96% of contacts aged

Setting: Four in-patient health facilities in western Uganda. Objective: To determine the impact of an innovative multi-modal quality improvement program on human immunodeficiency virus (HIV) status assessment and the impact of HIV status on severe illness conditions and mortality. Design: This was a staggered, pre-post quasi-experimental study designed to assess a multi-modal intervention (collaborative improvement meetings, audit and feedback, clinical mentoring) for improving quality of care following formal training in the management of severe illness in low-income settings. Results: From August 2014 to May 2015, 5759 patients were hospitalized, of whom 2451 (42.6%) had their HIV status assessed; 395 (16.1%) were HIV-infected. HIV-infected patients were significantly more likely to meet criteria for shock (27.5% vs. 15.1%, risk ratio [RR] 1.8, 95% confidence interval [CI] 1.7-1.9, P < 0.001) and severe respiratory distress (6.7% vs. 4.3%, RR 1.5, 95%CI 1.2-2.0, P < 0.001), and were significantly more likely to die in hospital (12.0% vs. 2.9%, RR 4.1, 95%CI 3.2-5.4, P < 0.001). There was no evidence of improved HIV status assessment during the intervention period (36.5% vs. 44.8%, +8.3%, 95%CI -8.3 to 24.8, P = 0.33). Conclusions: Hospitalized HIV-infected patients in western Uganda are at high risk for severe illness and death. Novel quality improvement strategies are needed to enhance hospital-based HIV testing in high-burden settings.

SETTING Latent tuberculous infection (LTBI) remains a significant source of new active tuberculosis cases. Recent guidelines encourage primary care physicians to prescribe LTBI treatment; however, there have been no investigations into the impact on treatment completion. OBJECTIVE To estimate LTBI treatment initiation and completion rates by primary care physicians. DESIGN A historical cohort study was conducted with Quebec residents dispensed isoniazid (INH) between 1 January 1998 and 31 December 2005. Information was obtained from administrative health insurance data. Regression modeling was used to estimate the association of completion rates with prescribing physician specialty, after adjustment for initial health status and other patient characteristics. RESULTS A total of 14,753 people were dispensed INH for LTBI treatment. Primary care physicians initiated 3863 (26%) treatments. This proportion decreased from 28.7% in 1998 to 21.1% in 2005. Patients initiated on treatment by primary care physicians were less likely to complete treatment (OR 0.79, 95%CI 0.72-0.86). Only 5977 (40.5%) patients completed treatment; the average treatment duration of the primary care physician group was 11 days less (P < 0.0001). CONCLUSION Primary care physicians initiated a substantial number of LTBI treatments, but less than half of patients completed treatment regardless of the physician specialty. Primary care physicians should be supported to enhance treatment completion.

Author(s): Walter, Nicholas D; Dolganov, Gregory M; Garcia, Benjamin J; Worodria, William; Andama, Alfred; Musisi, Emmanuel; Ayakaka, Irene; Van, Tran T; Voskuil, Martin I; de Jong, Bouke C; Davidson, Rebecca M; Fingerlin, Tasha E; Kechris, Katerina; Palmer, Claire; Nahid, Payam; Daley, Charles L; Geraci, Mark; Huang, Laurence; Cattamanchi, Adithya; Strong, Michael; Schoolnik, Gary K; Davis, John Lucian | Abstract: BackgroundTreatment 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.MethodsM. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis.ResultsWithin 4 days, bacterial mRNA abundance declined g98%, indicating rapid killing. Thereafter, the rate of decline slowed g94%, 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.ConclusionsTranscriptional 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.

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1β, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8 weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study.

Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings.To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda.We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case.The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests.Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes.

RationaleIn 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.MethodsWe 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.ResultsAmong 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).ConclusionsEmpiric 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.

BackgroundDespite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care.ObjectiveTo review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support.DiscussionCurrent national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps.ConclusionIt is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

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

The prevalence and clinical course of pulmonary cryptococcosis in Sub-Saharan Africa are not well described.Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between September 2007 and July 2008 with coughor=2 weeks were enrolled. Patients with negative sputum smears for acid-fast bacilli were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii, and fungi. Patients were followed 2 and 6 months after hospital discharge.Of 407 patients enrolled, 132 (32%) underwent bronchoscopy. Of 132 BAL fungal cultures, 15 (11%) grew Cryptococcus neoformans. None of the patients were suspected to have pulmonary cryptococcosis on admission. The median CD4 count among those with pulmonary cryptococcosis was 23 cells per microliter (interquartile range = 7-51). Of 13 patients who completed 6-month follow-up, 4 died and 9 were improved, including 5 who had started antiretroviral therapy but had not received antifungal medication.Pulmonary cryptococcosis is common in HIV-infected tuberculosis suspects in Uganda. Early initiation of antiretroviral therapy in those with isolated pulmonary infection may improve outcomes, even without antifungal therapy. This finding suggests that some HIV-infected patients with C. neoformans isolated from respiratory samples may have colonization or localized infection.

Background: Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996–2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. Methods: A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. Results: In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference −5.4%, 95% CI −21% to 11%, p = 0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with Pneumocystis pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, p = 0.043), after controlling for Pneumocystis pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. Conclusions: Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.

Background: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis , although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii . Methods: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing. Results: 68% (117/172) of all patients were colonised with Pneumocystis . No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count ⩽50 cells/μl (unadjusted OR 2.4, 95% CI 1.09 to 5.48; p = 0.031) and using PCP prophylaxis (unadjusted OR 0.55, 95% CI 0.29 to 1.07; p = 0.077) were associated with Pneumocystis colonisation, although the latter association may have been due to chance. After adjustment for CD4+ T cell count, use of PCP prophylaxis was associated with a decreased odds of colonisation (adjusted OR 0.45, 95% CI 0.21 to 0.98; p = 0.045). 11 patients who were colonised were subsequently readmitted for evaluation of a second episode of pneumonia; three were found to be colonised again, but none had PCP. Conclusions: The majority of hospitalised HIV infected patients with non-PCP pneumonia are colonised with Pneumocystis . Failure to use co-trimoxazole prophylaxis and severe immunosuppression are associated with an increase in the odds of colonisation. Pneumocystis colonisation among hospitalised patients does not commonly lead to PCP.

BackgroundImplementation of new tuberculosis (TB) diagnostic strategies in resource-constrained settings is challenging. We measured the impact of solid and liquid mycobacterial cultures on treatment practices for patients undergoing TB evaluation in Kampala, Uganda.MethodsWe enrolled consecutive smear-negative, human immunodeficiency virus positive adults with cough of ⩾2 weeks from September 2009 to April 2010. Laboratory technicians performed mycobacterial cultures on solid and liquid media. We compared empiric treatment decisions with solid and liquid culture in terms of diagnostic yield and time to results, and assessed impact on patient management.ResultsOf 200 patients enrolled, 26 (13%) had culture-confirmed TB: 22 (85%) on solid culture alone, 2 (8%) on liquid culture alone, and 2 (8%) on both solid and liquid culture. Thirty-four patients received empiric anti-tuberculosis treatment, but only 10 (29%) were culture-positive. Median time to a positive result on solid culture was 92 days (interquartile range [IQR] 69-148) compared to 106 days (IQR 66-157) for liquid culture. No patients initiated treatment following a positive result on liquid culture.ConclusionThe introduction of mycobacterial culture did not influence care for patients undergoing evaluation for TB in Kampala, Uganda. Attention to contextual factors surrounding implementation is needed to ensure the effective introduction of new testing strategies in low-income countries.

Infection with Strongyloides stercoralis is typically asymptomatic in immunocompetent hosts, despite chronic infection. In contrast, immunocompromised hosts such as solid organ transplant recipients are at risk for hyperinfection syndrome and/or disseminated disease, frequently resulting in fatal outcomes. Infection in these recipients may result from reactivation of latent infection or infection through transmission from an infected donor. We describe the Centers for Disease Control and Prevention's experience with seven clusters of donor-derived infection from 2009 to 2013. Six of the seven (86%) donors were born in Latin America; donor screening was not performed prior to organ transplantation in any of these investigations. Eleven of the 20 (55%) organ recipients were symptomatic, two of whom died from complications of strongyloidiasis. We also describe the New York Organ Donor Network (NYODN) experience with targeted donor screening from 2010 to 2013. Of the 233 consented potential donors tested, 10 tested positive for Strongyloides antibody; and 18 organs were transplanted. The majority (86%) of the donors were born in Central or South America. Fourteen recipients received prophylaxis after transplantation; no recipients developed strongyloidiasis. The NYODN experience provides evidence that when targeted donor screening is performed prior to transplantation, donor-derived infection can be averted in recipients.

Background Studies of the quality of tuberculosis (TB) diagnostic evaluation of patients in high burden countries have generally shown poor adherence to international or national guidelines. Health worker perspectives on barriers to improving TB diagnostic evaluation are critical for developing clinic-level interventions to improve guideline implementation. Methods We conducted structured, in-depth interviews with staff at six district-level health centers in Uganda to elicit their perceptions regarding barriers to TB evaluation. Interviews were transcribed, coded with a standardized framework, and analyzed to identify emergent themes. We used thematic analysis to develop a logic model depicting health system and contextual barriers to recommended TB evaluation practices. To identify possible clinic-level interventions to improve TB evaluation, we categorized findings into predisposing, enabling, and reinforcing factors as described by the PRECEDE model, focusing on potentially modifiable behaviors at the clinic-level. Results We interviewed 22 health center staff between February 2010 and November 2011. Participants identified key health system barriers hindering TB evaluation, including: stock-outs of drugs/supplies, inadequate space and infrastructure, lack of training, high workload, low staff motivation, and poor coordination of health center services. Contextual barrier challenges to TB evaluation were also reported, including the time and costs borne by patients to seek and complete TB evaluation, poor health literacy, and stigma against patients with TB. These contextual barriers interacted with health system barriers to contribute to sub-standard TB evaluation. Examples of intervention strategies that could address these barriers and are related to PRECEDE model components include: assigned mentors/peer coaching for new staff (targets predisposing factor of low motivation and need for support to conduct job duties); facilitated workshops to implement same day microscopy (targets enabling factor of patient barriers to completing TB evaluation), and recognition/incentives for good TB screening practices (targets low motivation and self-efficacy). Conclusions Our findings suggest that health system and contextual barriers work together to impede TB diagnosis at health centers and, if not addressed, could hinder TB case detection efforts. Qualitative research that improves understanding of the barriers facing TB providers is critical to developing targeted interventions to improve TB care. Electronic supplementary material The online version of this article (doi:10.1186/s12913-014-0668-0) contains supplementary material, which is available to authorized users.

Author(s): Andama, Alfred O; den Boon, Saskia; Meya, David; Cattamanchi, Adithya; Worodria, William; Davis, J Lucian; Walter, Nicholas D; Yoo, Samuel D; Kalema, Nelson; Haller, Barbara; Huang, Laurence; International HIV-Associated Opportunistic Pneumonias (IHOP) Study | Abstract: BackgroundCryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa.ObjectivesTo determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ≥2 weeks and suspected tuberculosis (TB) and also to determine if antigenemia is associated with an increased mortality.MethodsBetween September 2009 and September 2010, we enrolled consecutive HIV-seropositive adults hospitalized at Mulago Hospital with cough ≥2 weeks and suspected TB. Banked serum was tested for cryptococcal antigen. We compared demographic and clinical characteristics, and 2-month mortality in patients with and without cryptococcal antigenemia.ResultsOf 563 HIV-seropositive patients, 32 (5.7%) were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg-positive patients had a lower median CD4 count compared with CrAg-negative patients (25 vs. 55 cells/μL, P = 0.02), and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A positive CrAg test was not associated with increased mortality during the 2-month follow-up period (hazard ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for CD4 count and antiretroviral therapy use at enrollment and/or follow-up.ConclusionsOccult cryptococcal antigenemia occurs commonly among hospitalized HIV-seropositive patients with suspected TB. CrAg testing should be considered in hospitalized HIV-seropositive patients with CD4 count l50 cells/μL, coupled with longer follow-up to evaluate the diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal antigenemia.

TUBERCULOSIS (TB) is a major cause of morbidity and mortality for women globally, with 3.2 million incident cases and at least 320 000 deaths reported to the World Health Organization (WHO) in 2010. Although TB represents the third leading cause of death among women aged 15–44 years, women account for just 36% of TB cases reported worldwide.1,2 Social and biological factors may account for part of this difference in incidence,3,4 but the potential contribution of sex disparities in health care delivery requires further study. Most studies examining gender and TB case detection in high-burden countries have focused on social and economic barriers that women face in accessing health care services, as evidenced by lower rates of self-referral to health clinics and longer delays between the onset of symptoms and the decision to seek care.5–7 However, sex differences in TB case detection may also result from disparities in the quality of TB evaluation provided to men and women after they present to health centers. Although the Stop TB Strategy emphasizes equitable and universal access to care,8 few studies have systematically assessed sex disparities in TB services provided in routine primary health settings in high-burden countries.9,10 To our knowledge, none have been conducted in sub-Saharan Africa, the region with the world’s lowest case detection rates. We previously reported substantial increases in case detection associated with improved adherence to evidence-based TB suspect evaluation practices recommended by the International Standards for Tuberculosis Care (ISTC)11 at primary health care clinics in rural Uganda.12 The ISTC, an evidence-based set of recommendations developed by the Tuberculosis Coalition for Technical Assistance in partnership with many national and international partners, describes the accepted standard of care worldwide for managing patients who are suspected of having or have TB. With respect to TB suspect evaluation, the ISTC states that: All persons with otherwise unexplained productive cough lasting 2–3 weeks or more should be evaluated for tuberculosis (Standard 1), All patients . . . suspected of having pulmonary tuberculosis should have at least two sputum specimens submitted for microscopic examination (Standard 2), and All patients [testing positive for TB] . . . should receive an internationally accepted first-line treatment regimen (Standard 8). In the present study, we extend our analysis to assess the influence of patient sex on the level of ISTC adherence in TB suspect evaluation to identify where in the diagnostic process sex disparities, if present, might be occurring.

Current labelling for the use of ceftiofur crystalline free acid (CCFA) in horses states that 2 i.m. doses must be administered 4 days apart to provide 10 days of therapeutic coverage. A 10 day treatment regimen is not sufficient for the long-term treatment of horses with severe lung consolidation or pleuropneumonia. There are currently no data to guide an appropriate dosing interval when a longer treatment regimen is warranted.To determine steady-state plasma and pulmonary epithelial lining fluid (PELF) concentrations of desfuroylceftiofur acetamide (DCA) after weekly i.m. administration of CCFA to adult horses.Experimental study.Seven adult horses received i.m. CCFA at a dose of 6.6 mg/kg bwt on Day 0, Day 4 and every 7 days thereafter for 3 additional doses. Concentrations of DCA in plasma and PELF were measured at various time intervals.After weekly i.m. administration, the mean (± s.d.) steady-state peak DCA concentration in plasma (2.87 ± 1.50 μg/ml) was significantly higher than that in PELF (0.84 ± 0.53 μg/ml). Mean terminal half-lives in plasma (77.5 ± 17.5 h) and PELF (92.8 ± 59.0 h) were not significantly different. Concentrations of DCA in plasma and PELF remained in the therapeutic range for the entire dosing interval.After the initial 2-dose regimen 4 days apart, weekly i.m. administration of CCFA was well tolerated and resulted in plasma and PELF DCA concentrations above the minimal inhibitory concentration that inhibits growth of at least 90% of common lower respiratory tract pathogens of horses.Weekly administration of CCFA would appear appropriate when a treatment regimen longer than 10 days is warranted based on clinical signs and disease severity.

Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes. © 2012 Taylor et al.

Objective: We describe chest radiograph (CXR) findings in a population with a high prevalence of human immunodeficiency virus (HIV) and tuberculosis (TB) in order to identify radiological features associated with TB; to compare CXR features between HIV-seronegative and HIV-seropositive patients with TB; and to correlate CXR findings with CD4 T-cell count. Methods: Consecutive adult patients admitted to a national referral hospital with a cough of duration of 2 weeks or longer underwent diagnostic evaluation for TB and other pneumonias, including sputum examination and mycobacterial culture, bronchoscopy and CXR. Two radiologists blindly reviewed CXRs using a standardised interpretation form. Results: Smear or culture-positive TB was diagnosed in 214 of 403 (53%) patients. Median CD4+ T-cell count was 50 cells mm-3[interquartile range (IQR) 14-150]. TB patients were less likely than non-TB patients to have a normal CXR (12% vs 20%, p=0.04), and more likely than non-TB patients to have a diffuse pattern of opacities (75% vs 60%, p=0.003), reticulonodular opacities (45% vs 12%, p

The GaSb/InAs materials system, with two species of both cations and anions, permits the construction of heterostructures with either InSb- or GaAs-like interfaces. As a result, this system provides an opportunity to explore the limits of interfacial control that can be achieved by vapor phase growth techniques. We have characterized a series of superlattices (SLs) prepared with both types of interfaces by X-ray diffraction, Raman spectroscopy, transmission electron microscopy and photoconductivity. The large differences in bond lengths, electronic properties and vibrational properties of InSb and GaAs interfaces allow these techniques to be sensitive probes of interfacial structure. By carefully measuring and minimizing the group V cross-contamination in the SL layers, we are able to unambiguously demonstrate the growth of SLs with almost pure InSb-like or GaAs-like interfaces.

We report the observation of spin-resolved cyclotron resonance of a 2DEG in an InAs quantum well. The data show that the g -factor of a 2DEG has a smaller energy dependence than that of bulk electrons. The reduction of the spin-splitting in a 2DEG can be accounted for by a calculation which includes the nonparabolicity of the band structure.