Sex and HIV Differences in Preserved Ratio Impaired Spirometry (PRISm) Among Ugandans Postpneumonia.

Background: Preserved ratio impaired spirometry (PRISm), defined as a normal ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (≥0.70) with low FEV1 (<80% predicted), has been associated with increased mortality in the general population. Female sex has been associated with increased odds of PRISm in people without HIV. People with HIV (PWH) are at increased risk for lung function abnormalities, but whether HIV modifies the effect of sex on PRISm development is largely unknown. Methods: Adults with and without HIV underwent baseline followed by serial spirometry after completing therapy for pneumonia, predominantly tuberculosis (TB), in Kampala, Uganda. Using generalized estimating equations adjusted for age, body mass index, smoking, biomass fuel exposure, HIV, and TB status, we compared individuals with PRISm with those with normal spirometry. These models were stratified by HIV status. Results: Of 339 baseline participants, 153 (45%) were women; 129 (38%) had HIV, of whom 53% were women. Overall, 105/339 participants (31%) had PRISm at baseline. HIV was associated with lower odds of PRISm (adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.68; P = .001). Female sex trended toward increased odds of PRISm among all participants (aOR, 1.65; 95% CI, 0.99-2.75; P = .052). The association between female sex and PRISm tended to be stronger among PWH (aOR, 3.16; 95% CI, 1.14-8.76; P = .03) than among those without HIV (aOR, 1.34; 95% CI, 0.73-2.45; P = .34); this study was underpowered to detect an HIV-sex interaction of this magnitude (P = .30). Conclusions: Among Ugandan adults who recovered from pneumonia, female sex was associated with increased odds and HIV with decreased odds of PRISm, suggesting independent sex and HIV effects on PRISm pathogenesis.

Efficacy and Impact of Peer-Led Education for Persons with Tuberculosis in Kampala, Uganda: A Pre-Post Implementation Study.

Introduction: Universal TB education and counseling (TEC) is routinely recommended for promoting knowledge and medication adherence, but the quality of delivery often varies because of inadequate clinic space, time, and health worker training. Peer-led counseling is a promising but understudied solution to these challenges. We sought to evaluate the efficacy of a peer-led TEC strategy among newly diagnosed adults initiating TB treatment in Kampala, Uganda. Methods: We conducted a longitudinal, pre-post implementation study comparing the routine, healthcare-worker-led and peer-led strategies for delivery of TEC to consecutive adult persons with TB at a large, public primary-care clinic. Trained staff administered a standardized TB knowledge survey to all persons with TB immediately following TEC. We compared TB knowledge by type of TEC received using t-tests. Results: We enrolled 161 persons with TB, 80 who received conventional TEC from health workers between June and July 2018, and 81 who received peer-led TEC between August and November 2019. The proportions of women (28% vs. 31%, p = 0.64) and persons living with HIV (36% vs 30%, p = 0.37) were similar in the pre- and post-implementation periods. Peer-led TEC was associated with a more significant increase in disease-specific (difference +21%, 95% CI +18% to + 24%, p < 0.0001) and treatment-specific TB knowledge scores (difference +14%, 95% CI + 10% to + 18%, p< 0.0001) than routine healthcare worker-delivered TEC. All TB knowledge constructs were significantly higher for those in the post-implementation period than those in the pre-implementation period. Nine participants met our threshold for adequate knowledge (score ≥ 90%) for disease-specific TB knowledge in the pre-implementation period compared to 63 (78%) in the post-implementation period (+67%, 95% CI + 55% - +78%, p < 0.001). Twenty-eight (35%) met the adequate knowledge threshold for TB treatment-specific knowledge in the pre-implementation period compared to 60 (74%) in the post-implementation period (+ 39%, 95% CI + 25 to + 53%, p < 0.0001). Finally, the proportion achieving TB treatment success (cure or completed) increased substantially from the pre-implementation period (n = 49, 68%) to the post-implementation period (n = 63, 88%), a difference of + 19% (95% CI + 6% to + 33%, p = 0.005). Conclusion: Our findings suggest that peer-led TEC is more efficacious than routine TEC at improving TB knowledge and treatment outcomes. Future studies should evaluate the implementation and effectiveness of the peer-led TEC strategy when scaled to a larger number of clinics.

The feasibility, acceptability, and preliminary impact of real-time monitors and SMS on tuberculosis medication adherence in southwestern Uganda: Findings from a mixed methods pilot randomized controlled trial.

We conducted a pilot randomized controlled trial among patients initiating treatment for drug-sensitive tuberculosis (TB). Participants received real-time electronic adherence monitors and were randomized (1:1:1) to: (i) daily SMS (reminders to TB patients and notifications to social supporters sent daily for 3 months, then triggered by late or missed dosing for 3 months); (ii) weekly SMS (reminders to TB patients and notifications to social supporters sent weekly for 3 months, then triggered by late or missed dosing for 3 months); or (iii) control (no SMS). Feasibility was mainly verified by the technical function of the intervention at Month 6. The primary outcome was percent adherence as ascertained by the real time monitor. Quantitative feasibility/acceptability data were summarized descriptively. Percentage adherence and adherence patterns were assessed and compared by linear regression models. Qualitative acceptability data was collected through interviews and analyzed using content analysis. Among 63 participants, the median age was 35 years, 75% had no regular income, and 84% were living with HIV. Feasibility was demonstrated as most of the daily [1913/2395 (80%)] and weekly [631/872 (72%)] SMS reminders to TB patients were sent successfully. Also, most of the daily [1577/2395 (66%)] and weekly [740/872 (85%)] SMS notifications to social supporters and adherence data (96%) were sent successfully. Challenges included TB status disclosure, and financial constraints. All patients perceived the intervention to be useful in reminding and motivating them to take medication. Median adherence (IQR) in the daily SMS, weekly SMS, and control arms was 96.1% (84.8, 98.0), 92.5% (80.6, 96.3), and 92.2% (56.3, 97.8), respectively; however, differences between the intervention and control arms were not statistically significant. Real-time monitoring linked to SMS was feasible and acceptable and may have improved TB medication adherence. Larger studies are needed to further assess impact on adherence and clinical outcomes. Trial registration. ClinicalTrials.gov registration number: NCT03800888. https://ichgcp.net/clinical-trials-registry/NCT03800888.

Deep learning prediction of hospital readmissions for asthma and COPD.

QUESTION: Severe asthma and COPD exacerbations requiring hospitalization are linked to increased disease morbidity and healthcare costs. We sought to identify Electronic Health Record (EHR) features of severe asthma and COPD exacerbations and evaluate the performance of four machine learning (ML) and one deep learning (DL) model in predicting readmissions using EHR data. STUDY DESIGN AND METHODS: Observational study between September 30, 2012, and December 31, 2017, of patients hospitalized with asthma and COPD exacerbations. RESULTS: This study included 5,794 patients, 1,893 with asthma and 3,901 with COPD. Patients with asthma were predominantly female (n = 1288 [68%]), 35% were Black (n = 669), and 25% (n = 479) were Hispanic. Black (44 vs. 33%, p = 0.01) and Hispanic patients (30 vs. 24%, p = 0.02) were more likely to be readmitted for asthma. Similarly, patients with COPD readmissions included a large percentage of Blacks (18 vs. 10%, p < 0.01) and Hispanics (8 vs. 5%, p < 0.01). To identify patients at high risk of readmission index hospitalization data of a subset of 2,682 patients, 777 with asthma and 1,905 with COPD, was analyzed with four ML models, and one DL model. We found that multilayer perceptron, the DL method, had the best sensitivity and specificity compared to the four ML methods implemented in the same dataset. INTERPRETATION: Multilayer perceptron, a deep learning method, had the best performance in predicting asthma and COPD readmissions, demonstrating that EHR and deep learning integration can improve high-risk patient detection.

Exploring stakeholders perspectives on TB contact investigation in Cali, Colombia: a qualitative study.

Introduction: Contact investigation is a proven intervention for tuberculosis (TB) case finding and prevention. Although widely endorsed by national public health authorities and the World Health Organization, many countries struggle to implement it effectively. The objective of the study is to describe and characterize the barriers and facilitators of TB contact investigation in Cali, Colombia from the perspective and experience of the key stakeholders involved. Methods: We collected data from group discussions during two workshop sessions with clinic and public health staff involved in TB contact investigation (June 2019 and March 2020 respectively) and semi-structured interviews with TB cases and their household contacts (July 2019 to April 2020). We undertook an inductive thematic analysis with the RADaR technique to characterize the barriers and facilitators of the TB contact investigation process. Results: The two workshops included 21 clinics and 12 public health staff. We also conducted 26 semi-structured interviews with TB cases and their household contacts. Using thematic analysis, we identified four common themes: Healthcare Operations, Essential Knowledge, Time Limitations and Competing Responsibilities, and Interpersonal Interactions. The main barriers to conducting household visits were low data quality, stigma and mistrust, safety concerns for health workers, and limited resources. The main barriers to TB uptake by contacts were competing responsibilities, low TB risk perceptions among contacts, and difficulty accessing diagnostic tests for contacts. In contrast, good communication and social skills among health workers and accurate TB knowledge facilitated successful household visits and TB test uptake, according to key stakeholders. Conclusion: This study provides a deeper understanding of TB contact investigation barriers and facilitators in a high-prevalence urban setting in a middle-income country from the perspective and experience of key stakeholders. The study shed light on the barriers that hinder household contacts engagement and TB test uptake such as issues of systemic capacity and TB knowledge. Also, highlighted facilitators such as the importance of interpersonal communication skills among health workers in the public and private sector. The insights from this study can serve as a valuable resource for public health organizations seeking to enhance their contact investigation efforts and improve TB control in similar settings.

A user-centred implementation strategy for tuberculosis contact investigation in Uganda: protocol for a stepped-wedge, cluster-randomised trial.

BACKGROUND: Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. METHODS: We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities. DISCUSSION: This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries. TRIAL REGISTRATION: The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

A user-centred implementation strategy for tuberculosis contact investigation in Uganda: Protocol for a stepped-wedge, cluster-randomised trial.

Background Tuberculosis (TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. Methods We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including 1) a TB-education booklet, 2) a contact-identification algorithm, 3) an instructional sputum-collection video, and 4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including 1) collaborative improvement meetings, 2) regular audit-and-feedback reports, and 3) a digital group-chat application designed to develop a community of practice. Sites will cross from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB (#554), the Uganda National Council for Science and Technology (#HS1720ES), and the Yale Institutional Review Board (#2000023199) approved the study with a waiver of informed consent for the main trial implementation-effectiveness outcomes. We will submit trial results for publication in a peer-reviewed journal and disseminate findings to local shareholders, including policymakers and representatives of affected communities. Discussion This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden setting using contact investigation. It will help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustain evidence-based interventions in low-and-middle-income countries. Trial registration number ClinicalTrials.gov Identifier: NCT05640648.

Sex modifies the risk of HIV-associated obstructive lung disease in Ugandans postpneumonia.

OBJECTIVES: Spirometric abnormalities are frequent, and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD. DESIGN AND METHODS: To evaluate the associations between sex and HIV with abnormal lung function, women and men with and without HIV underwent spirometric testing after completing therapy for pneumonia, including tuberculosis (TB), in Kampala, Uganda. OLD was defined as a postbronchodilator forced expiratory volume in the first second to forced vital capacity (FEV 1 /FVC) ratio less than 0.70. Associations between sex, HIV, and lung function were evaluated using multivariable regression models including sex-by-HIV interaction terms after adjusting for age, BMI, smoking status, and TB status. RESULTS: Among 348 participants, 147 (42%) were women and 135 (39%) were HIV-positive. Sixteen (11%) women and 23 men (11%) had OLD. The HIV-sex interaction was significant for obstructive lung disease ( P  = 0.04). In the adjusted stratified analysis, women with HIV had 3.44 (95% CI 1.11-12.0; P  = 0.04) increased odds of having OLD compared with men with HIV. Women without HIV did not have increased odds of having OLD compared with men without HIV. CONCLUSION: HIV appears to increase the risk of OLD to a greater degree in women than in men in an urban Ugandan setting. The mechanistic explanation for this interaction by sex remains unclear and warrants further study.

mHealth to improve implementation of TB contact investigation: a case study from Uganda.

BACKGROUND: Implementation science offers a systematic approach to adapting innovations and delivery strategies to new contexts but has yet to be widely applied in low- and middle-income countries. The Fogarty Center for Global Health Studies is sponsoring a special series, "Global Implementation Science Case Studies," to address this gap. METHODS: We developed a case study for this series describing our approach and lessons learned while conducting a prospective, multi-modal study to design, implement, and evaluate an implementation strategy for TB contact investigation in Kampala, Uganda. The study included formative, evaluative, and summative phases that allowed us to develop and test an adapted contact investigation intervention involving home-based sample collection for TB and HIV testing. We concurrently developed a multi-component mHealth implementation strategy involving fingerprint scanning, electronic decision support, and automated reporting of test results via text message. We then conducted a household-randomized, hybrid implementation-effectiveness trial comparing the adapted intervention and implementation strategy to usual care. Our assessment included nested quantitative and qualitative studies to understand the strategy's acceptability, appropriateness, feasibility, fidelity, and costs. Reflecting on this process with a multi-disciplinary team of implementing researchers and local public health partners, we provide commentary on the previously published studies and how the results influenced the adaptation of international TB contact investigation guidelines to fit the local context. RESULTS: While the trial did not show improvements in contact investigation delivery or public health outcomes, our multi-modal evaluation strategy helped us identify which elements of home-based, mHealth-facilitated contact investigation were feasible, acceptable, and appropriate and which elements reduced its fidelity and sustainability, including high costs. We identified a need for better tools for measuring implementation that are simple, quantitative, and repeatable and for greater attention to ethical issues in implementation science. CONCLUSIONS: Overall, a theory-informed, community-engaged approach to implementation offered many learnings and actionable insights for delivering TB contact investigation and using implementation science in low-income countries. Future implementation trials, especially those incorporating mHealth strategies, should apply the learnings from this case study to enhance the rigor, equity, and impact of implementation research in global health settings.

Frequency of HIV serodifferent couples within TB-affected households in a setting with a high burden of HIV-associated TB.

INTRODUCTION: Strong epidemiological links between human immunodeficiency virus (HIV) and tuberculosis (TB) may make household TB contact investigation an efficient strategy for HIV screening and finding individuals in serodifferent partnerships at risk of HIV and linking them to HIV prevention services. We aimed to compare the proportions of HIV serodifferent couples in TB-affected households and in the general population of Kampala, Uganda. METHODS: We included data from a cross-sectional trial of HIV counselling and testing (HCT) in the context of home-based TB evaluation in Kampala, Uganda in 2016-2017. After obtaining consent, community health workers visited the homes of participants with TB to screen contacts for TB and offer HCT to household members ≥ 15 years. We defined index participants and their spouses or parents as couples. Couples were classified as serodifferent if confirmed by self-reported HIV status or by HIV testing results. We used a two-sample test of proportions to compare the frequency of HIV serodifference among couples in the study to its prevalence among couples in Kampala in the 2011 Uganda AIDS Indicator Survey (UAIS). RESULTS: We included 323 index TB participants and 507 household contacts aged ≥ 18 years. Most index participants (55%) were male, while most (68%) adult contacts were female. There was ≥ 1 couple in 115/323 (35.6%) households, with most couples (98/115, 85.2%) including the index participant and spouse. The proportion of households with HIV-serodifferent couples was 18/323 (5.6%), giving a number-needed-to-screen of 18 households. The proportion of HIV serodifference among couples identified in the trial was significantly higher than among couples in the UAIS (15.7% vs. 8%, p = 0.039). The 18 serodifferent couples included 14 (77.8%) where the index participant was living with HIV and the spouse was HIV-negative, and 4 (22.2%) where the index partner was HIV-negative, while the spouse was living with HIV. CONCLUSIONS: The frequency of HIV serodifference among couples identified in TB-affected households was higher than in the general population. TB household contact investigation may be an efficient strategy for identifying people with substantial exposure to HIV and linking them to HIV prevention services.

Implementation of a Hardware-Assisted Bluetooth-Based COVID-19 Tracking Device in a High School: Mixed Methods Study.

BACKGROUND: Contact tracing is a vital public health tool used to prevent the spread of infectious diseases. However, traditional interview-format contact tracing (TCT) is labor-intensive and time-consuming and may be unsustainable for large-scale pandemics such as COVID-19. OBJECTIVE: In this study, we aimed to address the limitations of TCT. The Yale School of Engineering developed a Hardware-Assisted Bluetooth-based Infection Tracking (HABIT) device. Following the successful implementation of HABIT in a university setting, this study sought to evaluate the performance and implementation of HABIT in a high school setting using an embedded mixed methods design. METHODS: In this pilot implementation study, we first assessed the performance of HABIT using mock case simulations in which we compared contact tracing data collected from mock case interviews (TCT) versus Bluetooth devices (HABIT). For each method, we compared the number of close contacts identified and identification of unique contacts. We then conducted an embedded mixed methods evaluation of the implementation outcomes of HABIT devices using pre- and postimplementation quantitative surveys and qualitative focus group discussions with users and implementers according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. RESULTS: In total, 17 students and staff completed mock case simulations in which 161 close contact interactions were detected by interview or Bluetooth devices. We detected significant differences in the number of close contacts detected by interview versus Bluetooth devices (P<.001), with most (127/161, 78.9%) contacts being reported by interview only. However, a significant number (26/161, 16.1%; P<.001) of contacts were uniquely identified by Bluetooth devices. The interface, ease of use, coherence, and appropriateness were highly rated by both faculty and students. HABIT provided emotional security to users. However, the prototype design and technical difficulties presented barriers to the uptake and sustained use of HABIT. CONCLUSIONS: Implementation of HABIT in a high school was impeded by technical difficulties leading to decreased engagement and adherence. Nonetheless, HABIT identified a significant number of unique contacts not reported by interview, indicating that electronic technologies may augment traditional contact tracing once user preferences are accommodated and technical glitches are overcome. Participants indicated a high degree of acceptance, citing emotional reassurance and a sense of security with the device.

"I can't do it": A qualitative study exploring case and contact experiences with COVID-19 contact tracing.

BACKGROUND: Low engagement in contact tracing for COVID-19 dramatically reduces its impact, but little is known about how experiences, environments and characteristics of cases and contacts influence engagement. METHODS: We recruited a convenience sample of COVID-19 cases and contacts from the New Haven Health Department's contact tracing program for interviews about their contact tracing experiences. We analyzed transcripts thematically, organized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model, and identified candidate interventions using the linked Behavior Change Wheel Framework. RESULTS: We interviewed 21 cases and 12 contacts. Many felt physically or psychologically incapable of contact tracing participation due to symptoms or uncertainty about protocols. Environmental factors and social contacts also influenced engagement. Finally, physical symptoms, emotions and low trust in and expectations of public health authorities influenced motivation to participate. CONCLUSION: To improve contact tracing uptake, programs should respond to clients' physical and emotional needs; increase clarity of public communications; address structural and social factors that shape behaviors and opportunities; and establish and maintain trust. We identify multiple potential interventions that may help achieve these goals.

Centering Health Equity Within COVID-19 Contact Tracing: Connecticut's Community Outreach Specialist Program.

CONTEXT: The COVID-19 pandemic has disproportionately impacted vulnerable populations, including those who are non-English-speaking and those with lower socioeconomic status; yet, participation of these groups in contact tracing was initially low. Distrust of government agencies, anticipated COVID-19-related stigma, and language and cultural barriers between contact tracers and communities are common challenges. PROGRAM: The Community Outreach Specialist (COS) program was established within the Connecticut Department of Public Health (DPH) COVID-19 contact tracing program to encourage participation in contact tracing and address a need for culturally competent care and social and material support among socially vulnerable and non-English-speaking populations in 11 high-burden jurisdictions in Connecticut. IMPLEMENTATION: In partnership with state and local health departments, we recruited 25 COS workers with relevant language skills from target communities and trained them to deliver contact tracing services to vulnerable and non-English speaking populations. EVALUATION: We conducted a cross-sectional analysis using data from ContaCT, DPH's enterprise contact tracing system. Overall, the COS program enrolled 1938 cases and 492 contacts. The proportion of residents reached (ie, called and interviewed) in the COS program was higher than that in the regular contact tracing program for both cases (70% vs 57%, P < .001) and contacts (84% vs 64%, P < .001). After adjusting for client age, sex, race and ethnicity, language, and jurisdiction, we found that the COS program was associated with increased reach for contacts (odds ratio [OR] = 1.52; 95% confidence interval [95% CI], 1.17-1.99) but not for cases (OR = 0.78; 95% CI, 0.70-0.88). Rapid qualitative analysis of programmatic field notes and meeting reports provided evidence that the COS program was feasible and acceptable to clients and contributed to COVID-19 education and communication efforts. CONCLUSION: A COS program employing a client-centered, community-engaged strategy for reaching vulnerable and non-English-speaking populations was feasible and more effective at reaching contacts than standard COVID-19 contact tracing.

Feasibility and Sensitivity of Saliva GeneXpert MTB/RIF Ultra for Tuberculosis Diagnosis in Adults in Uganda.

The objective of this prospective observational study carried out at China-Uganda Friendship Hospital-Naguru in Kampala, Uganda, was to determine the performance of GeneXpert MTB/RIF Ultra (Xpert Ultra) molecular testing on saliva for active tuberculosis (TB) disease among consecutive adults undergoing TB diagnostic evaluation who were Xpert Ultra positive on sputum. We calculated sensitivity to determine TB diagnostic performance in comparison to a composite reference standard of Mycobacterium tuberculosis liquid and solid cultures on two spot sputum specimens. Xpert Ultra on a single saliva sample had a sensitivity of 90% (95% confidence interval [CI], 81 to 95%) relative to the composite sputum culture-based reference standard, similar to the composite sensitivity of 87% (95% CI, 77 to 94%) for fluorescence microscopy (FM) for acid-fast bacilli on two sputum smears. The sensitivity of salivary Xpert Ultra was 24% lower (95% CI for difference, 2 to 48%; P = 0.003) among persons living with HIV (71%; 95% CI, 44 to 90%) than among persons living without HIV (95%; 95% CI, 86 to 99%) and 46% higher (95% CI, 14 to 77%; P < 0.0001) among FM-positive (96%; 95% CI, 87 to 99%) than among FM-negative (50%; 95% CI, 19 to 81%) patients. The semiquantitative Xpert Ultra grade was systematically higher in sputum than in a paired saliva sample from the same patient. In conclusion, molecular testing of saliva for active TB diagnosis was feasible and almost as sensitive as molecular testing of sputum in a high TB burden setting. IMPORTANCE Tuberculosis is among the leading causes of morbidity and mortality worldwide, in large part because >3 million people go undiagnosed and untreated each year. Sputum has been the mainstay for TB diagnosis for over a century but can be difficult for patients to produce. In addition, the vigorous coughing required during sputum collection can lead to infection of nearby individuals and health workers. In this case-only study, applying the ultra-sensitive GeneXpert MTB/RIF Ultra molecular diagnostic assay to saliva detected 90% of culture-confirmed TB cases among 81 adults who were undergoing TB evaluation at the outpatient department of a general hospital in Uganda and tested sputum GeneXpert MTB/RIF Ultra positive. These results suggest that saliva may be a feasible and sensitive alternative to sputum for TB diagnosis, thereby meeting two key metrics proposed by the World Health Organization in its target performance profile for a nonsputum test for TB.

Assessing the quality of tuberculosis care using routine surveillance data: a process evaluation employing the Zero TB Indicator Framework in Mongolia.

OBJECTIVES: To evaluate the feasibility of the Zero TB Indicator Framework as a tool for assessing the quality of tuberculosis (TB) case-finding, treatment and prevention services in Mongolia. SETTING: Primary health centres, TB dispensaries, and surrounding communities in four districts of Mongolia. DESIGN: Three retrospective cross-sectional cohort studies, and two longitudinal studies each individually nested in one of the cohort studies. PARTICIPANTS: 15 947 community members from high TB-risk populations; 8518 patients screened for TB in primary health centres and referred to dispensaries; 857 patients with index TB and 2352 household contacts. PRIMARY AND SECONDARY OUTCOME MEASURES: 14 indicators of the quality of TB care defined by the Zero TB Indicator Framework and organised into three care cascades, evaluating community-based active case-finding, passive case-finding in health facilities and TB screening and prevention among close contacts; individual and health-system predictors of these indicators. RESULTS: The cumulative proportions of participants receiving guideline-adherent care varied widely, from 96% for community-based active case-finding, to 79% for TB preventive therapy among household contacts, to only 67% for passive case-finding in primary health centres and TB dispensaries (range: 29%-80% across districts). The odds of patients completing active TB treatment decreased substantially with increasing age (aOR: 0.76 per decade, 95% CI: 0.71 to 0.83, p<0.001) and among men (aOR: 0.56, 95% CI: 0.36 to 0.88, p=0.013). Contacts of older index patients also had lower odds of initiating and completing of TB preventive therapy (aOR: 0.60 per decade, 95% CI: 0.38 to 0.93, p=0.022). CONCLUSIONS: The Zero TB Framework provided a feasible and adaptable approach for using routine surveillance data to evaluate the quality of TB care and identify associated individual and health system factors. Future research should evaluate strategies for collecting process indicators more efficiently; gather qualitative data on explanations for low-quality care; and deploy quality improvement interventions.

Pneumonia surveillance with culture-independent metatranscriptomics in HIV-positive adults in Uganda: a cross-sectional study.

BACKGROUND: Pneumonia is a leading cause of death worldwide and is a major health-care challenge in people living with HIV. Despite this, the causes of pneumonia in this population remain poorly understood. We aimed to assess the feasibility of metatranscriptomics for epidemiological surveillance of pneumonia in patients with HIV in Uganda. METHODS: We performed a retrospective observational study in patients with HIV who were admitted to Mulago Hospital, Kampala, Uganda between Oct 1, 2009, and Dec 31, 2011. Inclusion criteria were age 18 years or older, HIV-positivity, and clinically diagnosed pneumonia. Exclusion criteria were contraindication to bronchoscopy or an existing diagnosis of tuberculosis. Bronchoalveolar lavage fluid was collected within 72 h of admission and a combination of RNA sequencing and Mycobacterium tuberculosis culture plus PCR were performed. The primary outcome was detection of an established or possible respiratory pathogen in the total study population. FINDINGS: We consecutively enrolled 217 patients during the study period. A potential microbial cause for pneumonia was identified in 211 (97%) patients. At least one microorganism of established respiratory pathogenicity was identified in 113 (52%) patients, and a microbe of possible pathogenicity was identified in an additional 98 (45%). M tuberculosis was the most commonly identified established pathogen (35 [16%] patients; in whom bacterial or viral co-infections were identified in 13 [37%]). Streptococcus mitis, although not previously reported as a cause of pneumonia in patients with HIV, was the most commonly identified bacterial organism (37 [17%] patients). Haemophilus influenzae was the most commonly identified established bacterial pathogen (20 [9%] patients). Pneumocystis jirovecii was only identified in patients with a CD4 count of less than 200 cells per mL. INTERPRETATION: We show the feasibility of using metatranscriptomics for epidemiologic surveillance of pneumonia by describing the spectrum of respiratory pathogens in adults with HIV in Uganda. Applying these methods to a contemporary cohort could enable broad assessment of changes in pneumonia aetiology following the emergence of SARS-CoV-2. FUNDING: US National Institutes of Health, Chan Zuckerberg Biohub.

Theory-Informed Design of a Tailored Strategy for Implementing Household TB Contact Investigation in Uganda.

Since 2012, the World Health Organization has recommended household contact investigation as an evidence-based intervention to find and treat individuals with active tuberculosis (TB), the most common infectious cause of death worldwide after COVID-19. Unfortunately, uptake of this recommendation has been suboptimal in low- and middle-income countries, where the majority of affected individuals reside, and little is known about how to effectively deliver this service. Therefore, we undertook a systematic process to design a novel, theory-informed implementation strategy to promote uptake of contact investigation in Uganda, using the COM-B (Capability-Opportunity-Motivation-Behavior) model and the Behavior Change Wheel (BCW) framework. We systematically engaged national, clinic-, and community-based stakeholders and collectively re-examined the results of our own formative, parallel mixed-methods studies. We identified three core behaviors within contact investigation that we wished to change, and multiple antecedents (i.e., barriers and facilitators) of those behaviors. The BCW framework helped identify multiple intervention functions targeted to these antecedents, as well as several policies that could potentially enhance the effectiveness of those interventions. Finally, we identified multiple behavior change techniques and policies that we incorporated into a multi-component implementation strategy, which we compared to usual care in a household cluster-randomized trial. We introduced some components in both arms, including those designed to facilitate initial uptake of contact investigation, with improvement relative to historical controls. Other components that we introduced to facilitate completion of TB evaluation-home-based TB-HIV evaluation and follow-up text messaging-returned negative results due to implementation failures. In summary, the Behavior Change Wheel framework provided a feasible and transparent approach to designing a theory-informed implementation strategy. Future studies should explore the use of experimental methods such as micro-randomized trials to identify the most active components of implementation strategies, as well as more creative and entrepreneurial methods such as human-centered design to better adapt the forms and fit of implementation strategies to end users.

A cost analysis of implementing mobile health facilitated tuberculosis contact investigation in a low-income setting.

INTRODUCTION: Mobile health (mHealth) applications may improve timely access to health services and improve patient-provider communication, but the upfront costs of implementation may be prohibitive, especially in resource-limited settings. METHODS: We measured the costs of developing and implementing an mHealth-facilitated, home-based strategy for tuberculosis (TB) contact investigation in Kampala, Uganda, between February 2014 and July 2017. We compared routine implementation involving community health workers (CHWs) screening and referring household contacts to clinics for TB evaluation to home-based HIV testing and sputum collection and transport with test results delivered by automated short messaging services (SMS). We carried out key informant interviews with CHWs and asked them to complete time-and-motion surveys. We estimated program costs from the perspective of the Ugandan health system, using top-down and bottom-up (components-based) approaches. We estimated total costs per contact investigated and per TB-positive contact identified in 2018 US dollars, one and five years after program implementation. RESULTS: The total top-down cost was $472,327, including $358,504 (76%) for program development and $108,584 (24%) for program implementation. This corresponded to $320-$348 per household contact investigated and $8,873-$9,652 per contact diagnosed with active TB over a 5-year period. CHW time was spent primarily evaluating household contacts who returned to the clinic for evaluation (median 30 minutes per contact investigated, interquartile range [IQR]: 30-70), collecting sputum samples (median 29 minutes, IQR: 25-30) and offering HIV testing services (median 28 minutes, IQR: 17-43). Cost estimates were sensitive to infrastructural capacity needs, program reach, and the epidemiological yield of contact investigation. CONCLUSION: Over 75% of all costs of the mHealth-facilitated TB contact investigation strategy were dedicated to establishing mHealth infrastructure and capacity. Implementing the mHealth strategy at scale and maintaining it over a longer time horizon could help decrease development costs as a proportion of total costs.

Cost-effectiveness analysis of human-centred design for global health interventions: a quantitative framework.

INTRODUCTION: Human-centred design (HCD) is a problem-solving approach that is increasingly used to develop new global health interventions. However, there is often a large initial cost associated with HCD, and global health decision-makers would benefit from an improved understanding of the cost-effectiveness of HCD, particularly the trade-offs between the up-front costs of design and the long-term costs of delivering health interventions. METHODS: We developed a quantitative framework from a health systems perspective to illustrate the conditions under which HCD-informed interventions are likely to be cost-effective, taking into consideration five elements: cost of HCD, per-client intervention cost, anticipated number of clients reached, anticipated incremental per-client health benefit (ie, disability-adjusted life years (DALYs) averted) and willingness-to-pay. We evaluated several combinations of fixed and implementation cost scenarios based on the estimated costs of an HCD-informed approach to tuberculosis (TB) contact investigation in Uganda over a 2-year period to illustrate the use of this framework. RESULTS: The cost-effectiveness of HCD-informed TB contact investigation in Uganda was estimated to vary from US$8400 (2400 clients reached, lower HCD cost estimate) to US$306 000 per DALY averted (120 clients reached, baseline HCD cost estimate). In our model, cost-effectiveness was improved further when the interventions were expected to have wider reach or higher per-client health benefits. CONCLUSION: HCD can be cost-effective when used to inform interventions that are anticipated to reach a large number of clients, or in which the cost of HCD is smaller relative to the cost of delivering the intervention itself.

Core components of a Community of Practice to improve community health worker performance: a qualitative study.

BACKGROUND: Communities of Practice (CoPs) offer an accessible strategy for healthcare workers to improve the quality of care through knowledge sharing. However, not enough is known about which components of CoPs are core to facilitating behavior change. Therefore, we carried out a qualitative study to address these important gaps in the literature on CoPs and inform planning for an interventional study of CoPs. METHODS: We organized community health workers (CHWs) from two tuberculosis (TB) clinics in Kampala, Uganda, into a CoP from February to June 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 Behavior Change Technique (BCT) Taxonomy and the Behavior Change Wheel framework. We triangulated all interview findings with detailed field notes. RESULTS: All eight members of the CoP agreed to participate in the interviews. CHWs identified five CoP activities as core to 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 incorporated nine different BCTs and five distinct intervention functions. CHWs reported that these activities provided a venue for them to share challenges, exchange knowledge, engage in group problem solving, and benefit from social support. CHWs also explained that they felt a shared sense of ownership of the CoP, which motivated them to propose and carry out innovations. CHWs described that the CoP strengthened their social and professional identities within and outside the group, and improved their self-efficacy. CONCLUSIONS: We identified the core components and several 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.