M. tuberculosis Infection Attributable to Exposure in Social Networks of Tuberculosis Cases in an Urban African Community.

Background: The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas. Methods: To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis. Results: Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure. Conclusions: This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.

Acceptability, Usefulness, and Ease of Use of an Enhanced Video Directly Observed Treatment System for Supporting Patients With Tuberculosis in Kampala, Uganda: Explanatory Qualitative Study.

BACKGROUND: In tuberculosis (TB) control, nonadherence to treatment persists as a barrier. The traditional method of ensuring adherence, that is, directly observed therapy, faces significant challenges that hinder its widespread adoption. Digital adherence technologies such as video directly observed therapy (VDOT) are emerging as promising solutions. However, as these novel technologies gain momentum, a critical gap is the lack of comprehensive studies evaluating their efficacy and the unique experiences of patients in Africa. OBJECTIVE: The aim of this study was to assess patients' experiences that affected acceptability, usefulness, and ease of use with an enhanced VDOT system during monitoring of TB treatment. METHODS: We conducted individual open-ended interviews in a cross-sectional exit qualitative study in Kampala, Uganda. Thirty participants aged 18-65 years who had completed the VDOT randomized trial were purposively selected to represent variability in sex, adherence level, and HIV status. We used a hybrid process of deductive and inductive coding to identify content related to the experience of study participation with VDOT. Codes were organized into themes and subthemes, which were used to develop overarching categories guided by constructs adapted from the modified Technology Acceptance Model for Resource-Limited Settings. We explored participants' experiences regarding the ease of use and usefulness of VDOT, thereby identifying the facilitators and barriers to its acceptability. Perceived usefulness refers to the benefits users expect from the technology, while perceived ease of use refers to how easily users navigate its various features. We adapted by shifting from assessing perceived to experienced constructs. RESULTS: The participants' mean age was 35.3 (SD 12) years. Of the 30 participants, 15 (50%) were females, 13 (43%) had low education levels, and 22 (73%) owned cellphones, of which 10 (45%) had smartphones. Nine (28%) were TB/HIV-coinfected, receiving antiretroviral therapy. Emergent subthemes for facilitators of experienced usefulness and ease of VDOT use were SMS text message reminders, technology training support to patients by health care providers, timely patient-provider communication, family social support, and financial incentives. TB/HIV-coinfected patients reported the added benefit of adherence support for their antiretroviral medication. The external barriers to VDOT's usefulness and ease of use were unstable electricity, technological malfunctions in the app, and lack of cellular network coverage in rural areas. Concerns about stigma, disease disclosure, and fear of breach in privacy and confidentiality affected the ease of VDOT use. CONCLUSIONS: Overall, participants had positive experiences with the enhanced VDOT. They found the enhanced VDOT system user-friendly, beneficial, and acceptable, particularly due to the supportive features such as SMS text message reminders, incentives, technology training by health care providers, and family support. However, it is crucial to address the barriers related to technological infrastructure as well as the privacy, confidentiality, and stigma concerns related to VDOT.

Patient satisfaction among persons living with HIV/AIDS and receiving antiretroviral therapy in urban Uganda: A factor analysis.

INTRODUCTION: Patient satisfaction is an important predictor of health outcomes among patients in HIV/AIDS treatment and care, yet it is rarely measured in routine clinic settings in most of Africa. The aims of our study were to evaluate the internal validity and reliability of the Consumer Assessment of Healthcare Providers and Systems instrument for measuring satisfaction, assess the general level of patient satisfaction, and identify the factors associated with the level of satisfaction among patients receiving antiretroviral therapy in Uganda. MATERIALS AND METHODS: We conducted a cross-sectional study of 475 HIV/AIDS-infected patients from July to August 2015 in Kampala, Uganda. Eligible participants were 18 years or older, consented to the study and receiving antiretroviral therapy and outpatient care at the selected public health clinic. This study used a modified version of the validated Consumer Assessment of Healthcare Providers and Systems (CAHPS) instrument to assess the level of satisfaction among HIV/AIDS patients receiving outpatient care. We collected data on socio-demographics, clinical variables and 18-items adapted from the CAHPS instrument rating satisfaction with aspects of health services. We conducted an exploratory factor analysis to assess the internal validity of the 18 items and multiple linear regression analysis of factors associated with patient satisfaction with care. RESULTS: Majority of the respondents were females (76.8%), and the mean age was 37 years (SD = 10). The modified CAHPS instrument had high internal consistency (Cronbach's α = 0.94) for measuring satisfaction with HIV/AIDS care. Female sex (p = 0.016), perceived providers' technical and interpersonal skills (p = 0.022), emotional health (p = 0.032), and quality of reception services (p<0.001) were significantly associated with satisfaction in this urban HIV/AIDS public clinic. CONCLUSION: The reliability of the CAHPS instrument was high for measuring satisfaction. Providers' technical and interpersonal skills, and the quality of reception services are key to achieving patient satisfaction. Health system interventions to address the gaps identified will enhance the quality of patient-centered HIV/AIDS care in the Ugandan setting.

Ethical, Legal, and Sociocultural Issues in the Use of Mobile Technologies and Call Detail Records Data for Public Health in the East African Region: Scoping Review.

BACKGROUND: The exponential scale and pace of real-time data generated from mobile phones present opportunities for new insights and challenges across multiple sectors, including health care delivery and public health research. However, little attention has been given to the new ethical, social, and legal concerns related to using these mobile technologies and the data they generate in Africa. OBJECTIVE: The objective of this scoping review was to explore the ethical and related concerns that arise from the use of data from call detail records and mobile technology interventions for public health in the context of East Africa. METHODS: We searched the PubMed database for published studies describing ethical challenges while using mobile technologies and related data in public health research between 2000 and 2020. A predefined search strategy was used as inclusion criteria with search terms such as "East Africa," "mHealth," "mobile phone data," "public health," "ethics," or "privacy." We screened studies using prespecified eligibility criteria through a two-stage process by two independent reviewers. Studies were included if they were (1) related to mobile technology use and health, (2) published in English from 2000 to 2020, (3) available in full text, and (4) conducted in the East African region. We excluded articles that (1) were conference proceedings, (2) studies presenting an abstract only, (3) systematic and literature reviews, (4) research protocols, and (5) reports of mobile technology in animal subjects. We followed the five stages of a published framework for scoping reviews recommended by Arksey and O'Malley. Data extracted included title, publication year, target population, geographic region, setting, and relevance to mobile health (mHealth) and ethics. Additionally, we used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Extension for Scoping Reviews checklist to guide the presentation of this scoping review. The rationale for focusing on the five countries in East Africa was their geographic proximity, which lends itself to similarities in technology infrastructure development. RESULTS: Of the 94 studies identified from PubMed, 33 met the review inclusion criteria for the final scoping review. The 33 articles retained in the final scoping review represent studies conducted in three out of five East African countries: 14 (42%) from Uganda, 13 (39%) from Kenya, and 5 (16%) from Tanzania. Three main categories of concerns related to the use of mHealth technologies and mobile phone data can be conceptualized as (1) ethical issues (adequate informed consent, privacy and confidentiality, data security and protection), (2) sociocultural issues, and (3) regulatory/legal issues. CONCLUSIONS: This scoping review identified major cross-cutting ethical, regulatory, and sociocultural concerns related to using data from mobile technologies in the East African region. A comprehensive framework that accounts for the critical concerns raised would be valuable for guiding the safe use of mobile technology data for public health research purposes.

Bioinformatics mentorship in a resource limited setting.

BACKGROUND: The two recent simultaneous developments of high-throughput sequencing and increased computational power have brought bioinformatics to the forefront as an important tool for effective and efficient biomedical research. Consequently, there have been multiple approaches to developing bioinformatics skills. In resource rich environments, it has been possible to develop and implement formal fully accredited graduate degree training programs in bioinformatics. In resource limited settings with a paucity of expert bioinformaticians, infrastructure and financial resources, the task has been approached by delivering short courses on bioinformatics-lasting only a few days to a couple of weeks. Alternatively, courses are offered online, usually over a period of a few months. These approaches are limited by both the lack of sustained in-person trainer-trainee interactions, which is a key part of quality mentorships and short durations which constrain the amount of learning that can be achieved. METHODS: Here, we pioneered and tested a bioinformatics training/mentorship model that effectively uses the available expertise and computational infrastructure to deliver an in-person hands-on skills training experience. This is done through a few physical lecture hours each week, guided personal coursework over the rest of the week, group discussions and continuous close mentorship and assessment of trainees over a period of 1 year. RESULTS: This model has now completed its third iteration at Makerere University and has successfully mentored trainees, who have progressed to a variety of viable career paths. CONCLUSIONS: One-year (intermediate) skills based in-person bioinformatics training and mentorships are viable, effective and particularly appropriate for resource limited settings.

Association between tuberculosis in men and social network structure in Kampala, Uganda.

BACKGROUND: Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. METHODS: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). RESULTS: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. CONCLUSIONS: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.

Stakeholders' Perceptions of Benefits of and Barriers to Using Video-Observed Treatment for Monitoring Patients With Tuberculosis in Uganda: Exploratory Qualitative Study.

BACKGROUND: Nonadherence to treatment remains a barrier to tuberculosis (TB) control. Directly observed therapy (DOT) is the standard for monitoring adherence to TB treatment worldwide, but its implementation is challenging, especially in resource-limited settings. DOT is labor-intensive and inconvenient to both patients and health care workers. Video DOT (VDOT) is a novel patient-centered alternative that uses mobile technology to observe patients taking medication remotely. However, the perceptions and acceptability of potential end users have not been evaluated in Africa. OBJECTIVE: This study explores stakeholders' acceptability of, as well as perceptions of potential benefits of and barriers to, using VDOT to inform a pilot study for monitoring patients with TB in urban Uganda. METHODS: An exploratory, qualitative, cross-sectional study with an exit survey was conducted in Kampala, Uganda, from April to May 2018. We conducted 5 focus group discussions, each comprising 6 participants. Groups included patients with TB (n=2 groups; male and female), health care providers (n=1), caregivers (n=1), and community DOT volunteer workers (n=1). The questions that captured perceived benefits and barriers were guided by domains adopted from the Technology Acceptance Model. These included perceived usefulness, ease of use, and intent to use technology. Eligible participants were aged ≥18 years and provided written informed consent. For patients with TB, we included only those who had completed at least 2 months of treatment to minimize the likelihood of infection. A purposive sample of patients, caregivers, health care providers, and community DOT workers was recruited at 4 TB clinics in Kampala. Trained interviewers conducted unstructured interviews that were audio-recorded, transcribed, and analyzed using inductive content analysis to generate emerging themes. RESULTS: The average age of participants was 34.5 (SD 10.7) years. VDOT was acceptable to most participants on a scale of 1 to 10. Of the participants, 70% (21/30) perceived it as highly acceptable, with scores ≥8, whereas 30% (9/30) scored between 5 and 7. Emergent themes on perceived benefits of VDOT were facilitation of easy adherence monitoring, timely follow-up on missed doses, patient-provider communication, and saving time and money because of minimal travel to meet in person. Perceived barriers included limited technology usability skills, inadequate cellular connectivity, internet access, availability of electricity, cost of the smartphone, and use of the internet. Some female patients raised concerns about the disruption of their domestic work routines to record videos. The impact of VDOT on privacy and confidentiality emerged as both a perceived benefit and barrier. CONCLUSIONS: VDOT was acceptable and perceived as beneficial by most study participants, despite potential technical and cost barriers. Mixed perceptions emerged about the impact of VDOT on privacy and confidentiality. Future efforts should focus on training users, ensuring adequate technical infrastructure, assuring privacy, and performing comparative cost analyses in the local context.

Community drivers of tuberculosis diagnostic delay in Kampala, Uganda: a retrospective cohort study.

BACKGROUND: Recent approaches to TB control have focused on identifying and treating active cases to halt further transmission. Patients with TB symptoms often delay to seek care, get appropriate diagnosis, and initiate effective treatment. These delays are partly influenced by whom the patients contact within their community network. We aimed to evaluate the community drivers of diagnostic delay in an urban setting in Uganda. METHODS: In this study we analyze data from a retrospective cohort of 194 TB patients in Kampala, Uganda. We characterized the patterns of contacts made by patients seeking care for TB symptoms. The main outcome of interest was total community contact delay, defined as the time patients spent seeking care before visiting a provider capable of diagnosing TB. RESULTS: Visits to health providers without access to appropriate diagnostic services accounted for 56% of contacts made by cohort members, and were significantly associated with community contact delay, as were symptoms common to other prevalent illnesses, such as bone and joint pain. CONCLUSIONS: Education programs aimed at primary care providers, as well as other community members, may benefit case identification, by informing them of rarer symptoms of TB, potential for co-infections of TB and other prevalent diseases, and the availability of diagnostic services.

Defining an intermediate category of tuberculin skin test: A mixture model analysis of two high-risk populations from Kampala, Uganda.

One principle of tuberculosis control is to prevent the development of tuberculosis disease by treating individuals with latent tuberculosis infection. The diagnosis of latent infection using the tuberculin skin test is not straightforward because of concerns about immunologic cross reactivity with the Bacille Calmette-Guerin (BCG) vaccine and environmental mycobacteria. To parse the effects of BCG vaccine and environmental mycobacteria on the tuberculin skin test, we estimated the frequency distribution of skin test results in two divisions of Kampala, Uganda, ten years apart. We then used mixture models to estimate parameters for underlying distributions and defined clinically meaningful criteria for latent infection, including an indeterminate category. Using percentiles of two underlying normal distributions, we defined two skin test readings to demarcate three ranges. Values of 10 mm or greater contained 90% of individuals with latent infection; values less than 7.2 mm contained 80% of individuals without infection. Contacts with values between 7.2 and 10 mm fell into an indeterminate zone where it was not possible to assign infection. We conclude that systematic tuberculin skin test surveys within populations at risk, combined with mixture model analysis, may be a reproducible, evidence-based approach to define meaningful criteria for latent tuberculosis infection.

Using a Mobile Health Intervention (DOT Selfie) With Transfer of Social Bundle Incentives to Increase Treatment Adherence in Tuberculosis Patients in Uganda: Protocol for a Randomized Controlled Trial.

BACKGROUND: The World Health Organization's End TB Strategy envisions a world free of tuberculosis (TB)-free of deaths, disease, and suffering due to TB-by 2035. Nonadherence reduces cure rates, prolongs infectiousness, and contributes to the emergence of multidrug-resistant TB (MDR-TB). Moreover, MDR-TB is a growing, complex, and costly problem that presents a major obstacle to TB control. Directly observed therapy (DOT) for treatment adherence monitoring is the recommended standard; however, it is challenging to implement at scale because it is labor-intensive. Mobile health interventions can facilitate remote adherence monitoring and minimize the costs and inconveniences associated with standard DOT. OBJECTIVE: The study aims to evaluate the effectiveness of using video directly observed therapy (VDOT) plus incentives to improve medication adherence in TB treatment versus usual-care DOT in an African context. METHODS: The DOT Selfie study is an open-label, randomized controlled trial (RCT) with 2 parallel groups, in which 144 adult patients with TB aged 18-65 years will be randomly assigned to receive the usual-care DOT monitoring or VDOT as the intervention. The intervention will consist of a smartphone app, a weekly internet subscription, translated text message reminders, and incentives for those who adhere. The participant will use a smartphone to record and send time-stamped encrypted videos showing their daily medication ingestion. This video component will directly substitute the need for daily face-to-face meetings between the health provider and patients. We hypothesize that the VDOT intervention will be more effective because it allows patients to swallow their pills anywhere, anytime. Moreover, patients will receive mobile-phone-based "social bundle" incentives to motivate adherence to continued daily submission of videos to the health system. The health providers will log into a secured computer system to verify treatment adherence, document missed doses, investigate the reasons for missed doses, and follow prespecified protocol measures to re-establish medication adherence. The primary endpoint is the adherence level as measured by the fraction of expected doses observed over the treatment period. The main secondary outcome will be time-to-treatment completion in both groups. RESULTS: This study was funded in 2019. Enrollment began in July and is expected to be completed by November 2020. Data collection and follow-up are expected to be completed by June 2021. Results from the analyses based on the primary endpoint are expected to be submitted for publication by December 2021. CONCLUSIONS: This random control trial will be among the first to evaluate the effectiveness of VDOT within an African setting. The results will provide robust scientific evidence on the implementation and adoption of mobile health (mHealth) tools, coupled with incentives to motivate TB medication adherence. If successful, VDOT will apply to other low-income settings and a range of chronic diseases with lifelong treatment, such as HIV/AIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04134689; http://clinicaltrials.gov/ct2/show/NCT04134689. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18029.

Excess Risk of Tuberculosis Infection Among Extra-household Contacts of Tuberculosis Cases in an African City.

BACKGROUND: Although households of tuberculosis (TB) cases represent a setting for intense transmission of Mycobacterium tuberculosis, household exposure accounts for <20% of transmission within a community. The aim of this study was to estimate excess risk of M. tuberculosis infection among household and extra-household contacts of index cases. METHODS: We performed a cross-sectional study in Kampala, Uganda, to delineate social networks of TB cases and matched controls without TB. We estimated the age-stratified prevalence difference of TB infection between case and control networks, partitioned as household and extra-household contacts. RESULTS: We enrolled 123 index cases, 124 index controls, and 2415 first-degree network contacts. The prevalence of infection was highest among household contacts of cases (61.5%), lowest among household contacts of controls (25.2%), and intermediary among extra-household TB contacts (44.9%) and extra-household control contacts (41.2%). The age-adjusted prevalence difference between extra-household contacts of cases and their controls was 5.4%. The prevalence of infection was similar among the majority of extra-household case contacts and corresponding controls (47%). CONCLUSIONS: Most first-degree social network members of TB cases do not have adequate contact with the index case to experience additional risk for infection, but appear instead to acquire infection through unrecognized exposures with infectious cases in the community.

Defining adequate contact for transmission of Mycobacterium tuberculosis in an African urban environment.

BACKGROUND: The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment. METHODS: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing. RESULTS: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named "Setting" captured 61% of the variance whereas the second, named 'Relationship' captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores. CONCLUSIONS: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.

Low Prevalence of Tuberculin Skin Test Boosting among Community Residents in Uganda.

Boosted tuberculin skin test (TST) reactions can be misclassified as new latent tuberculosis (TB) infection. To our knowledge, no study has evaluated the prevalence of TST boosting in a population-based sample in high TB burden settings. We determined the prevalence of TST boosting among urban residents in Uganda. We evaluated 99 participants with initial TST < 5 mm and repeated a skin test after 2 weeks. We found that only 2% had boosted TST reactions suggesting that most TST conversions could represent new TB infections in this high-burden setting.

Psychosocial adjustment in perinatally human immunodeficiency virus infected or exposed children - a Retrospective Cohort Study.

OBJECTIVE: To determine whether perinatal HIV infection and exposure adversely affected psychosocial adjustment (PA) between 6 and 18 years of life (i.e. during school-age and adolescence). METHODS: We enrolled 58 perinatally HIV-infected, 56 HIV-exposed uninfected and 54 unexposed controls from Kampala, Uganda. Perinatal HIV status was determined by 18 months of age using a DNA-polymerase chain-reaction test and was confirmed via HIV rapid diagnostic test at psychosocial testing when the children were 6 to 18 years old. Five indicators of PA (depressive symptoms, distress, hopelessness, positive future orientation and esteem) were measured using validated, culturally adapted and translated instruments. Multivariable linear regression analyses estimated HIV-status-related percent differences (ß) in PA indicators and corresponding 95% confidence intervals (CIs). RESULTS: During school-age and adolescence, positive outlook (ß=-3.8, 95% CI: -7.2, -0.1) and self-esteem (ß=-4.3, 95% CI: -6.7, -1.8) scores were significantly lower, whereas depressive (ß=11.4, 95% CI: 3.3, 19.5) and distress (ß=12.3, 95% CI: 5.9, 18.7) symptoms were elevated for perinatally HIV-infected, compared to unexposed controls and exposed uninfected children. Similarly, positive outlook (ß=-4.3, 95% CI: -7.3, -1.2) and self-esteem were lower for exposed controls versus HIV-unexposed children. Hopelessness was similar by perinatal HIV status. Likewise, the distress and depressive symptom levels were comparable for HIV-exposed uninfected and HIV-unexposed children. CONCLUSIONS: Perinatal HIV infection predicted higher distress and depressive symptoms, while HIV-affected status (infection/exposure) predicted low self-esteem and diminished positive outlook in the long term. However, HIV-affected status had no impact on hopelessness, suggesting that psychosocial interventions as an integral component of HIV care for infected children or primary care exposed uninfected children may improve PA and quality of life in these vulnerable groups.

Perinatal HIV Status and Executive Function During School-Age and Adolescence: A Comparative Study of Long-Term Cognitive Capacity Among Children From a High HIV Prevalence Setting.

The aim of this study was to determine whether perinatal HIV infection (PHIV), HIV-exposed uninfected (PHEU) versus HIV-unexposed (PHU) status predicted long-term executive function (EF) deficit in school-aged Ugandan children.Perinatal HIV status was determined by 18 months via DNA polymerase chain reaction test and confirmed at cognitive assessment between 6 and 18 years using HIV rapid-diagnostic test. Primary outcome is child EF measured using behavior-rating inventory of executive function questionnaire across 8 subscales summed to derive the global executive composite (GEC). EF was proxy-reported by caregivers and self-reported by children 11 years or older. Descriptive analyses by perinatal HIV status included derivation of mean, standard deviations (SD), number, and percent (%) of children with EF deficits warranting clinical vigilance. Raw scores were internally standardized by age and sex adjustment. EF scores warranting clinical vigilance were defined as ≥ mean + 1.5SD. t Tests for mean score differences by perinatal HIV status and linear-regression models were implemented in SAS version 9.4 to derive HIV status-related EF deficits (ß) and 95% confidence intervals (CIs).Proxy-reported and self-reported EF were assessed in 166 and 82 children, respectively. GEC deficit was highest for PHIV (mean = 121.9, SD = 29.9), intermediate for PHEU (mean = 107.5, SD = 26.8), and lowest for PHU (mean = 103.4, SD = 20.7; P-trend < 0.01). GEC deficit levels warranting clinical vigilance occurred in 9 (15.8%), 5 (9.3%) and 0 (0%) PHIV, PHEU, and PHU children, respectively (P-trend = 0.01). Nineteen percent (n = 32) children had deficits requiring clinical vigilance in ≥2 proxy-reported EF subscales. Of these, multisubscale deficits occurred in 35.1%, 13.0%, and 9.3% of PHIV, PHEU, and PHU respectively (P-trend = 0.001). Multivariable analyses find significantly higher GEC deficits for PHIV compared with PHU and PHEU children regardless of respondent (all P values <0.01). Proxy-reported EF performance was similar for PHEU compared with PHU; however, child self-reported GEC scores were elevated by 12.8 units (95% CI: 5.4-25.5) for PHEU compared with PHU.PHIV had long-term EF deficits compared with other groups. Furthermore, PHEU ≥11 years may have long-term EF deficits compared with PHU, but future studies are needed to clarify this relationship. Cognitive remediation interventions with emphasis on EF may translate to improvements in long-term functional survival in HIV-affected children from sub-Saharan Africa.

Four Degrees of Separation: Social Contacts and Health Providers Influence the Steps to Final Diagnosis of Active Tuberculosis Patients in Urban Uganda.

BACKGROUND: Delay in tuberculosis (TB) diagnosis adversely affects patients' outcomes and prolongs transmission in the community. The influence of social contacts on steps taken by active pulmonary TB patients to seek a diagnosis has not been well examined. METHODS: A retrospective study design was use to enroll TB patients on treatment for 3 months or less and aged ≥18 years from 3 public clinics in Kampala, Uganda, from March to July 2014. Social network analysis was used to collect information about social contacts and health providers visited by patients to measure the number of steps and time between onset of symptoms and final diagnosis of TB. RESULTS: Of 294 TB patients, 58 % were male and median age was 30 (IQR: 24-38) years. The median number of steps was 4 (IQR: 3, 7) corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs. 46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in their social network. The first step to initiate seeking care accounted for 41 % of the patients' time to diagnosis while visits to non-TB providers and TB providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 % CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 % CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis. CONCLUSIONS: There were four degrees of separation between the onset of symptoms in a TB patient and a final diagnosis. Both social and provider networks of patients influenced the diagnostic pathways. Most delays occurred in the first step which represents decisions to seek help, and through interactions with non-TB health providers. TB control programs should strengthen education and active screening in the community and in health care settings to ensure timely diagnosis of TB.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

BACKGROUND: Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. METHODS: This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. RESULTS: cART was associated with a monthly rise of 15.7 cells/µl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). CONCLUSIONS: TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART.