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BackgroundA timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. ObjectiveThe Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. MethodsThe PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. ResultsA pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. ConclusionsThe findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment. Trial RegistrationClinicalTrials.gov NCT03900091; https://clinicaltrials.gov/ct2/show/NCT03900091 International Registered Report Identifier (IRRID)DERR1-10.2196/21430

BACKGROUND: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. METHODS: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. RESULTS: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). CONCLUSIONS: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.

BackgroundPostdischarge death in children is increasingly being recognized as a major contributor to overall child mortality. The PAediatric Risk Assessment (PARA) app is an mHealth tool developed to aid health care workers in resource-limited settings such as Sub-Saharan Africa to identify pediatric patients at high risk of both in-hospital and postdischarge mortality. The intended users of the PARA app are health care workers (ie, nurses, doctors, and clinical officers) with varying levels of education and technological exposure, making testing of this clinical tool critical to successful implementation. ObjectiveOur aim was to summarize the usability evaluation of the PARA app among target users, which consists of assessing the ease of use, functionality, and navigation of the interfaces and then iteratively improving the design of this clinical tool. MethodsHealth care workers (N=30) were recruited to participate at Mbarara Regional Referral Hospital and Holy Innocents Children’s Hospital in Mbarara, Southwestern Uganda. This usability study was conducted in two phases to allow for iterative improvement and testing of the interfaces. The PARA app was evaluated using quantitative and qualitative measures, which were compared between Phases 1 and 2 of the study. Participants were given two patient scenarios that listed hypothetical information (ie, demographic, social, and clinical data) to be entered into the app and to determine the patient’s risk of in-hospital and postdischarge mortality. Time-to-completion and user errors were recorded for each participant while using the app. A modified computer system usability questionnaire was utilized at the end of each session to elicit user satisfaction with the PARA app and obtain suggestions for future improvements. ResultsThe average time to complete the PARA app decreased by 30% from Phase 1 to Phase 2, following user feedback and modifications. Participants spent the longest amount of time on the oxygen saturation interface, but modifications following Phase 1 cut this time by half. The average time-to-completion (during Phase 2) for doctors/medical students was 3 minutes 56 seconds. All participants agreed they would use the PARA app if available at their health facility. Given a high PARA risk score, participants suggested several interventions that would be appropriate for the sociocultural context in southwestern Uganda, which involved strengthening discharge and referral procedures within the current health care system. ConclusionsThrough feedback and modifications made during this usability study, the PARA app was developed into a user-friendly app, encompassing user expectations and culturally intuitive interfaces for users with a range of technological exposure. Doctors and medical students had shorter task completion times, though all participants reported the usefulness of this tool to improve postdischarge outcomes.

The association between sexual violence and depression is well known, but the temporal aspects of the association have not been well established. We analyzed data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed every 3 months for a median of 1.8 years of follow-up. The method of generalized estimating equations (GEE) was used to model the marginal expectation of depression symptom severity (Hopkins Symptom Checklist for Depression), mental health-related quality of life (MOS-HIV Mental Health Summary), and heavy drinking (Alcohol Use Disorders Identification Test) as a function of self-reported forced-sex victimization in the 3 months prior to interview. Estimates were adjusted for variables known to confound the association between victimization and mental health status. To assess any potential reciprocal relationships, we reversed the temporal ordering of the exposures and outcomes and refitted similar GEE models. In multivariable analyses, victimization was associated with greater depression symptom severity (b = 0.17; 95% CI = [0.02, 0.33]) and lower mental health-related quality of life (b = -5.65; 95% CI = [-9.34, -1.96]), as well as increased risks for probable depression (adjusted relative risk [ARR] = 1.58; 95% CI = [1.01, 2.49) and heavy drinking (ARR = 3.99; 95% CI = [1.84, 8.63]). We did not find strong evidence of a reciprocal relationship. Our findings suggest that forced sex is associated with adverse mental health outcomes among HIV-positive women in rural Uganda. Given the substantial mental health-related impacts of victimization, effective health sector responses are needed.

BackgroundCross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.PurposeThe purpose of this study is to examine the bidirectional relationship between social support and HIV stigma.MethodsWe collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma.ResultsLagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations.ConclusionsInterventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.

IntroductionFood insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes.DesignLongitudinal cohort study.MethodsParticipants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence 400 copies/ml); and low CD4 T-cell count (

BackgroundHIV is highly stigmatized, compromising both treatment and prevention in resource-limited settings.PurposeWe sought to study the relationship between internalized HIV-related stigma and serostatus disclosure and to determine the extent to which this association varies with the degree of social distance.MethodsWe fit multivariable Poisson regression models, with cluster-correlated robust estimates of variance, to data from 259 persons with HIV enrolled in an ongoing cohort study in rural Uganda.ResultsPersons with more internalized stigma were less likely to disclose their seropositivity. The magnitude of association increased with social distance such that the largest association was observed for public disclosures and the smallest association was observed for disclosures to sexual partners.ConclusionsAmong persons with HIV in rural Uganda, internalized stigma was negatively associated with serostatus disclosure. The inhibiting effect of stigma was greatest for the most socially distant ties.

Program implementers and qualitative researchers have described how increasing availability of HIV antiretroviral therapy (ART) is associated with improvements in psychosocial health and internalized stigma. To determine whether, and through what channels, ART reduces internalized stigma, we analyzed data from 262 HIV-infected, treatment-naïve persons in rural Uganda followed from ART initiation over a median of 3.4 years. We fitted Poisson regression models with cluster-correlated robust estimates of variance, specifying internalized stigma as the dependent variable, adjusting for time on treatment as well as socio-demographic, clinical, and psychosocial variables. Over time on treatment, internalized stigma declined steadily, with the largest decline observed during the first 2 years of treatment. This trend remained statistically significant after multivariable adjustment (χ(2) = 28.3; P = 0.03), and appeared to be driven by ART-induced improvements in HIV symptom burden, physical and psychological wellbeing, and depression symptom severity.

ObjectiveTo investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status.DesignThe Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda.MethodsParticipants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics.ResultsTwo hundred twenty-eight ART-naive participants were followed for up to 3 years, and 41% were severely food insecure at baseline. The mean food insecurity score progressively declined (test for linear trend P < 0.0001), beginning with the second quarter (b = -1.6; 95% confidence interval: -2.7 to -0.45) and ending with the final quarter (b = -6.4; 95% confidence interval: -10.3 to -2.5). PHS and nutritional status improved in a linear fashion over study follow-up (P < 0.001). Inclusion of PHS in the regression model attenuated the relationship between ART duration and food security.ConclusionsAmong HIV-infected individuals in Uganda, food insecurity decreased and nutritional status and PHS improved over time after initiation of ART. Changes in food insecurity were partially explained by improvements in PHS. These data support early initiation of ART in resource-poor settings before decline in functional status to prevent worsening food insecurity and its detrimental effects on HIV treatment outcomes.

BackgroundDepression is associated with increased HIV transmission risk, increased morbidity, and higher risk of HIV-related death among HIV-infected women. Low sexual relationship power also contributes to HIV risk, but there is limited understanding of how it relates to mental health among HIV-infected women.MethodsParticipants were 270 HIV-infected women from the Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of individuals initiating antiretroviral therapy (ART) in Mbarara, Uganda. Our primary predictor was baseline sexual relationship power as measured by the Sexual Relationship Power Scale (SRPS). The primary outcome was depression severity, measured with the Hopkins Symptom Checklist (HSCL), and a secondary outcome was a functional scale for mental health status (MHS). Adjusted models controlled for socio-demographic factors, CD4 count, alcohol and tobacco use, baseline WHO stage 4 disease, social support, and duration of ART.ResultsThe mean HSCL score was 1.34 and 23.7% of participants had HSCL scores consistent with probable depression (HSCL>1.75). Compared to participants with low SRPS scores, individuals with both moderate (coefficient b = -0.21; 95%CI, -0.36 to -0.07) and high power (b = -0.21; 95%CI, -0.36 to -0.06) reported decreased depressive symptomology. High SRPS scores halved the likelihood of women meeting criteria for probable depression (adjusted odds ratio = 0.44; 95%CI, 0.20 to 0.93). In lagged models, low SRPS predicted subsequent depression severity, but depression did not predict subsequent changes in SPRS. Results were similar for MHS, with lagged models showing SRPS predicts subsequent mental health, but not visa versa. Both Decision-Making Dominance and Relationship Control subscales of SRPS were associated with depression symptom severity.ConclusionsHIV-infected women with high sexual relationship power had lower depression and higher mental health status than women with low power. Interventions to improve equity in decision-making and control within dyadic partnerships are critical to prevent HIV transmission and to optimize mental health of HIV-infected women.