Community-Wide Universal HIV Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

Effect of intermittently scanned continuous glucose monitoring in people with diabetes with a psychosocial indication for initiation.

AIM: To understand the effect of intermittently scanned continuous glucose monitoring (isCGM) in people with diabetes with a 'psychosocial' indication for access. METHODS: The study utilized baseline and follow-up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes in the UK. Diabetes-related distress (DRD) was assessed using the two-item diabetes-related distress scale (DDS). Participants were categorized into two groups: high DRD (DDS score ≥ 3) and lower DRD (DDS score < 3). The t-test was used to assess the difference in the pre- and post-isCGM continuous variables. RESULTS: The study consisted of 17 036 people with diabetes, with 1314 (7%) using isCGM for 'psychosocial' reasons. Follow-up data were available for 327 participants, 322 (99%) of whom had type 1 diabetes with a median diabetes duration of 15 years; 75% (n = 241) had high levels of DRD. With the initiation of isCGM, after a mean follow-up period of 6.9 months, there was a significant reduction in DDS score; 4 at baseline versus 2.5 at follow-up (P < .001). The prevalence of high DRD reduced from 76% to 38% at follow-up (50% reduction in DRD, P < .001). There was also a significant reduction in HbA1c (78.5 mmol/mol [9.3%] at baseline vs. 66.5 mmol/mol [8.2%] at follow-up; P < .001). This group also experienced an 87% reduction in hospital admissions because of hyperglycaemia/diabetic ketoacidosis (P < .001). CONCLUSION: People with diabetes who had isCGM initiated for a psychosocial indication had high levels of DRD and HbA1c, which improved with the use of isCGM.

Clinical features of type 1 diabetes in older adults and the impact of intermittently scanned continuous glucose monitoring: An Association of British Clinical Diabetologists (ABCD) study.

AIMS: To evaluate the clinical features and impact of flash glucose monitoring in older adults with type 1 diabetes (T1D) across age groups defined as young-old, middle-old, and old-old. MATERIALS AND METHODS: Clinicians were invited to submit anonymized intermittently scanned continuous glucose monitoring (isCGM) user data to a secure web-based tool within the National Health Service secure network. We collected baseline data before isCGM initiation, such as demographics, glycated haemoglobin (HbA1c) values from the previous 12 months, Gold scores and Diabetes Distress Scale (DDS2) scores. For analysis, people with diabetes were classified as young-old (65-75 years), middle-old (>75-85 years) and old-old (>85 years). We compared baseline clinical characteristics across the age categories using a t test. All the analyses were performed in R 4.1.2. RESULTS: The study involved 1171 people with diabetes in the young-old group, 374 in the middle-old group, and 47 in the old-old group. There were no significant differences in baseline HbA1c and DDS2 scores among the young-old, middle-old, and old-old age groups. However, Gold score increased with age (3.20 [±1.91] in the young-old vs. 3.46 [±1.94] in the middle-old vs. 4.05 [±2.28] in the old-old group; p < 0.0001). This study showed reduced uptake of insulin pumps (p = 0.005) and structured education (Dose Adjustment For Normal Eating [DAFNE] course; p = 0.007) in the middle-old and old-old populations compared to the young-old population with T1D. With median isCGM use of 7 months, there was a significant improvement in HbA1c in the young-old (p < 0.001) and old-old groups, but not in the middle-old group. Diabetes-related distress score (measured by the DDS2) improved in all three age groups (p < 0.001) and Gold score improved (p < 0.001) in the young-old and old-old populations but not in the middle-old population. There was also a significant improvement in resource utilization across the three age categories following the use of is CGM. CONCLUSION: This study demonstrated significant differences in hypoglycaemia awareness and insulin pump use across the older age groups of adults with T1D. The implementation of isCGM demonstrated significant improvements in HbA1c, diabetes-related distress, hypoglycaemia unawareness, and resource utilization in older adults with T1D.

The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities.

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.).

Community-wide Prevalence of Malaria Parasitemia in HIV-Infected and Uninfected Populations in a High-Transmission Setting in Uganda.

BACKGROUND: Malaria control strategies depend on identifying individuals with parasitemia, who may be asymptomatic but retain the ability to transmit disease. Population-level survey data on parasitemia are limited and traditionally exclude adults and human immunodeficiency virus (HIV)-infected individuals. METHODS: We performed a cross-sectional survey of residents aged 18 months to 94 years in Nankoma, Uganda. Blood specimens were collected using the dried blood spot technique from 9629 residents (87.6%), and samples from a subset of 4131 were tested for malaria parasites, using loop-mediated isothermal amplification. Population-level prevalence was estimated using a weighted proportion, and predictors of parasitemia were identified using a multivariate Poisson regression model. RESULTS: The community prevalence of parasitemia was 83.8% (95% confidence interval [CI], 82.9%-84.6%). Parasite prevalence was highest among children aged 5-14 years (94.7%) and lowest among adults (61.9%). In analysis that controlled for age, HIV-infected individuals with an undetectable viral load had a lower risk of parasitemia, compared with HIV-uninfected individuals (adjusted relative risk, 0.16; 95% CI, .10-.27; P < .001). CONCLUSIONS: In a rural Ugandan community, 2 years after distribution of long-lasting insecticide-treated bed nets, the prevalence of malaria parasitemia was high across all ages, peaking in school-aged children. Persons with well-controlled HIV infection had a lower risk of parasitemia, presumably reflecting access to HIV care.

Men "missing" from population-based HIV testing: insights from qualitative research.

Men's uptake of HIV testing is critical to the success of "test and treat" strategies in generalized epidemics. This study sought to identify cultural factors and community processes that influence men's HIV testing uptake in the baseline year of an ongoing test-and-treat trial among 334,479 persons in eastern Africa (SEARCH, NCT#01864603). Data were collected using participant observation at mobile community health campaigns (CHCs) (n = 28); focus group discussions (n = 8 groups) with CHC participants; and in-depth interviews with care providers (n = 50), leaders (n = 32), and members (n = 112) of eight communities in Kenya and Uganda. An 8-person research team defined analytical codes and iteratively refined them during data collection using grounded theoretical approaches, and textual data were coded using Atlas.ti software. Structural and cultural barriers, including men's mobility and gender norms valorizing risk-taking and discouraging health-seeking behavior, were observed, and contributed to men's lower participation in HIV testing relative to women. Men's labor opportunities often require extended absences from households: during planting season, men guarded fields from monkeys from dawn until nightfall; lake fishermen traveled long distances and circulated between beaches. Men often tested "by proxy", believing their wives' HIV test results to be their status. Debates about HIV risks were vigorous, with many men questioning "traditional" masculine gender norms that enhanced risks. The promise of antiretroviral therapy (ART) to prolong health was a motivating factor for many men to participate in testing. Flexibility in operating hours of HIV testing including late evening and weekend times along with multiple convenient locations that moved were cited as facilitating factors enhancing male participating in HIV testing. Mobile testing reduced but did not eliminate barriers to men's participation in a large-scale "test & treat" effort. However, transformations in gender norms related to HIV testing and care-seeking are underway in eastern Africa and should be supported.

Expectations about future health and longevity in Kenyan and Ugandan communities receiving a universal test-and-treat intervention in the SEARCH trial.

Expectations about future health and longevity are important determinants of individuals' decisions to invest in physical and human capital. Few population-level studies have measured subjective expectations and examined how they are affected by scale-up of antiretroviral therapy (ART). We assessed these expectations in communities receiving annual HIV testing and universal ART. Longitudinal data on expectations were collected at baseline and one year later in 16 intervention communities participating in the Sustainable East Africa Research in Community Health (SEARCH) trial of the test and treat strategy in Kenya and Uganda (NCT01864603). A random sample of households with and without an HIV-positive adult was selected after baseline HIV testing. Individuals' expectations about survival to 50, 60, 70, and 80 years of age, as well as future health status and economic well-being, were measured using a Likert scale. Primary outcomes were binary variables indicating participants who reported being very likely or almost certain to survive to advanced ages. Logistic regression analyses were used to examine trends in expectations as well as associations with HIV status and viral load for HIV-positive individuals. Data were obtained from 3126 adults at baseline and 3977 adults in year 1, with 2926 adults participating in both waves. HIV-negative adults were more likely to have favorable expectations about survival to 60 years than HIV-positive adults with detectable viral load (adjusted odds ratio [AOR] 1.87, 95% CI 1.53-2.30), as were HIV-positive adults with undetectable viral load (AOR 1.41, 95% CI 1.13-1.77). Favorable expectations about survival to 60 years were more likely for all groups in year 1 compared to baseline (AOR 1.53, 95% CI 1.31-1.77). These findings are consistent with the hypothesis that universal ART leads to improved population-level expectations about future health and well-being. Future research from the SEARCH trial will help determine whether these changes are causally driven by the provision of universal ART.

"How can I tell?" Consequences of HIV status disclosure among couples in eastern African communities in the context of an ongoing HIV "test-and-treat" trial.

People living with HIV/AIDS anticipate HIV-related stigma and fear disclosure to intimate partners. Yet, disclosure is critical to reducing HIV transmission and improving care engagement. This qualitative study characterized HIV disclosure experiences and normative beliefs among couples in communities participating in an HIV test-and-treat trial in Kenya and Uganda (Sustainable East Africa Research in Community Health, NCT#01864603). In-depth interviews were conducted with care providers (n = 50), leaders (n = 32) and members (n = 112) of eight communities. Data were analyzed using grounded theoretical approaches and Atlas.ti software. Findings confirmed gender differences in barriers to disclosure: while both men and women feared blame and accusation, women also feared violence and abandonment ("I did not tell my husband because [what if] I tell him and he abandons me at the last moment when I am in labor?"). Positive consequences included partner support for increased care-seeking and adherence ("My husband keeps on reminding me 'have you taken those drugs?'") Yet negative consequences included partnership dissolution, blame, and reports of violence ("some men beat their wives just because of that [bringing HIV medications home]"). Among HIV-infected individuals in discordant relationships, men more often reported supportive spouses ("we normally share [HIV-risk-reduction strategies] since I have been infected and she is HIV negative"), than did women ("my husband refused to use condoms and even threatened to marry another wife"). Care providers lent support for HIV-positive women who wanted to engage partners in testing but feared negative consequences: "They engaged the two of us in a session and asked him if we could all test." Findings demonstrate differing experiences and support needs of women and men living with HIV in eastern Africa, with HIV-positive women in discordant couples particularly vulnerable to negative consequences of disclosure. Efforts to strengthen capacity in health systems for gender-sensitive clinician- or counselor-assisted disclosure should be accelerated within test-and-treat efforts.

Advancements in the management of obesity: a review of current evidence and emerging therapies.

INTRODUCTION: Obesity is the modern world's current epidemic, with substantial health and economic impact. This study aimed to provide a narrative overview of the past, currently available, and future treatment options that offer therapeutic and preventive advantages for obesity management. AREAS COVERED: Historically, rimonabant, and lorcaserin, were approved and used for managing non-syndromic obesity. Currently, orlistat, naltrexone/bupropion, glucagon-like peptide-1 receptor agonist (GLP-1 RA), and a few promising therapeutic agents are under investigation, including retatrutide, cagrilintide and orforglipron, which show promising weight reduction effects. We have developed a search string of the Medical Subject Headings (MeSH), including the terms GLP-1 RAs, obesity, and weight loss. This string was then used to perform a systematic literature search in the database including PubMed, EMBASE, MEDLINE, and Scopus up to January 31st, 2024. EXPERT OPINION: Managing obesity often requires medical interventions, particularly in cases of severe obesity or obesity-related comorbidities. Thus, it is important to approach obesity management holistically, considering individual needs and circumstances. In our opinion, consulting with healthcare professionals is crucial to developing a personalized plan that addresses both weight loss and overall health improvement.

Tools for mass screening of G6PD deficiency: validation of the WST8/1-methoxy-PMS enzymatic assay in Uganda.

BACKGROUND: The distribution of the enzymopathy glucose-6-phosphate dehydrogenase (G6PD) deficiency is linked to areas of high malaria endemicity due to its association with protection from disease. G6PD deficiency is also identified as the cause of severe haemolysis following administration of the anti-malarial drug primaquine and further use of this drug will likely require identification of G6PD deficiency on a population level. Current conventional methods for G6PD screening have various disadvantages for field use. METHODS: The WST8/1-methoxy PMS method, recently adapted for field use, was validated using a gold standard enzymatic assay (R&D Diagnostics Ltd ®) in a study involving 235 children under five years of age, who were recruited by random selection from a cohort study in Tororo, Uganda. Blood spots were collected by finger-prick onto filter paper at routine visits, and G6PD activity was determined by both tests. Performance of the WST8/1-methoxy PMS test under various temperature, light, and storage conditions was evaluated. RESULTS: The WST8/1-methoxy PMS assay was found to have 72% sensitivity and 98% specificity when compared to the commercial enzymatic assay and the AUC was 0.904, suggesting good agreement. Misclassifications were at borderline values of G6PD activity between mild and normal levels, or related to outlier haemoglobin values (<8.0 gHb/dl or >14 gHb/dl) associated with ongoing anaemia or recent haemolytic crises. Although severe G6PD deficiency was not found in the area, the test enabled identification of low G6PD activity. The assay was found to be highly robust for field use; showing less light sensitivity, good performance over a wide temperature range, and good capacity for medium-to-long term storage. CONCLUSIONS: The WST8/1-methoxy PMS assay was comparable to the currently used standard enzymatic test, and offers advantages in terms of cost, storage, portability and use in resource-limited settings. Such features make this test a potential key tool for deployment in the field for point of care assessment prior to primaquine administration in malaria-endemic areas. As with other G6PD tests, outlier haemoglobin levels may confound G6PD level estimation.

Subacute thyroiditis following Mpox infection in a patient with human immunodeficiency virus.

Summary: Mpox (MPX) formerly known as monkeypox was declared a public health emergency of international concern, following an outbreak that commenced in May 2022. We report a case of subacute thyroiditis following MPX infection. To our knowledge, it is the first documented incidence of this complication in humans. A 51-year-old male, with a well-controlled human immunodeficiency virus (HIV) infection on antiretroviral therapy, was reviewed 3 weeks after a positive test for MPX. The acute skin lesions and initial systemic symptoms had resolved, but he described significant neck discomfort, fatigue, weight loss and night sweats. Blood tests showed a raised C-reactive protein, free T4 and suppressed thyroid-stimulating hormone. His thyroid antibodies were negative. He was treated initially with carbimazole and propranolol, pending exclusion of any other intercurrent infection. A chest radiograph was normal; blood cultures and a combined nose and throat swab for respiratory virus PCR testing were negative. Following this, he commenced a 2-week course of prednisolone; his symptoms resolved completely within 24 h of starting. He subsequently developed hypothyroidism, which was treated with levothyroxine. The clinical features, abnormal thyroid function, raised CRP and negative thyroid antibodies 3 weeks post-MPX positive test was consistent with viral subacute thyroiditis. This case demonstrates that, as described following other viral infections, MPX can cause subacute thyroiditis, which follows a similar course to the classic form of subacute thyroiditis. Clinicians should be aware of this potential endocrine complication when attending to patients with MPX. Learning points: Subacute thyroiditis can present following mpox virus infection. Its course is similar to the classic form of subacute thyroiditis and steroids are effective. It is important to exclude other concurrent infections prior to starting steroids, especially for patients who are immunosuppressed or in other high-risk groups.

Coexisting Prolactin-Secreting Macroadenoma, Hypopituitarism and Type 1 Diabetes Mellitus in a Young Adult Male Patient.

The association between type 1 diabetes mellitus (DM) and pituitary prolactinoma is rarely reported in the literature. Herein we present a 23-year-old male patient with co-existing type 1 DM, pituitary macro-prolactinoma and panhypopituitarism secondary to mass effect. The patient presented with generalised symptoms including fatigability, cold hands, decreased insulin requirement secondary to frequent hypoglycaemic episodes two weeks following the diagnosis of type 1 DM. Initial blood workup showed evidence of possible secondary hypothyroidism. The full pituitary profile screen showed profound anterior hypopituitarism with a prolactin level of 67,168 miu/L (normal range 86-324 miu/L). Pituitary MRI showed macroadenoma, 37mm in size, with a suprasellar cystic extension but no chiasmal compression. It was treated medically with cabergoline and a repeat pituitary MRI after eight weeks of initiating treatment showed a 4-mm reduction in the size of the adenoma, and prolactin level decreased to 6,794 miu/L. The case was discussed at the Neurosurgical MDT and the outcome was to continue to monitor while on cabergoline. This case report is the second in the literature, which documented the association between type 1 DM and pituitary prolactinoma in adolescents. These patients might not present with the classical clinical features of hyperprolactinemia, and instead, they present with frequent hypoglycaemia and decreased insulin requirement due to secondary adrenal insufficiency as a consequence of the mass effect of the prolactinoma. Furthermore, non-specific symptoms, such as generalised tiredness and fatiguability, despite reasonable blood sugar control, in young patients with type 1 DM should trigger screening for all anterior pituitary hormones to exclude hypopituitarism.

Dimensions of HIV-related stigma in rural communities in Kenya and Uganda at the start of a large HIV 'test and treat' trial.

HIV-related stigma is a frequently cited barrier to HIV testing and care engagement. A nuanced understanding of HIV-related stigma is critical for developing stigma-reduction interventions to optimize HIV-related outcomes. This qualitative study documented HIV-related stigma across eight communities in east Africa during the baseline year of a large HIV test-and-treat trial (SEARCH, NCT: 01864603), prior to implementation of widespread community HIV testing campaigns and efforts to link individuals with HIV to care and treatment. Findings revealed experiences of enacted, internalized and anticipated stigma that were highly gendered, and more pronounced in communities with lower HIV prevalence; women, overwhelmingly, both held and were targets of stigmatizing attitudes about HIV. Past experiences with enacted stigma included acts of segregation, verbal discrimination, physical violence, humiliation and rejection. Narratives among women, in particular, revealed acute internalized stigma including feelings of worthlessness, shame, embarrassment, and these resulted in anxiety and depression, including suicidality among a small number of women. Anticipated stigma included fears of marital dissolution, verbal and physical abuse, gossip and public ridicule. Anticipated stigma was especially salient for women who held internalized stigma and who had experienced enacted stigma from their partners. Anticipated stigma led to care avoidance, care-seeking at remote facilities, and hiding of HIV medications. Interventions aimed at reducing individual and community-level forms of stigma may be needed to improve the lives of PLHIV and fully realize the promise of test-and-treat strategies.

The age-specific burden and household and school-based predictors of child and adolescent tuberculosis infection in rural Uganda.

BACKGROUND: The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection. METHODS: From 2015-2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5-11 years old) and adolescents (12-19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors. RESULTS: The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9-10.4) in children and 16.7% (95% CI:14.0-19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7-16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8-7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0-2.9) fold higher odds of TB infection than those who attended school in the community. CONCLUSION: Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

BACKGROUND: Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. METHODS: A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. FINDINGS: There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 [95% CI: 0.56, 1.17] p = 0.24). Most children (76.0%) tested positive by reference mRDT, but many were not prescribed AL (22.5% intervention versus 25.9% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3% invention vs 42.4% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. CONCLUSIONS: The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management.

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

BACKGROUND: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa. METHODS: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged ≥15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603. FINDINGS: Between April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90·3%), of whom 132 030 (48·2%) were adults. Of these, 117 711 (89·2%) had their HIV status established, of whom 11 964 (10·2%) were HIV positive. Of these, we measured viral load in 8828 (73·8%) people. Viral suppression occurred in 3427 (81·6%) of 4202 HIV-positive adults on ART and 4490 (50·9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48·2%) of 1827 people in west Uganda, 516 (45·0%) of 1147 in east Uganda, and 3093 (52·8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2·9%) of 16 874 couples were serodiscordant: in 287 (58·3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14·0%], viral load was >100 000 copies per mL). In Kenya, 859 (10·0%) of 8616 couples were serodiscordant: in 445 (53·0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL). INTERPRETATION: Before the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions. FUNDING: National Institute of Allergy and Infectious Diseases (National Institutes of Health) and the President's Emergency Plan for AIDS Relief.

Increased adolescent HIV testing with a hybrid mobile strategy in Uganda and Kenya.

OBJECTIVE: We sought to increase adolescent HIV testing across rural communities in east Africa and identify predictors of undiagnosed HIV. DESIGN: Hybrid mobile testing. METHODS: We enumerated 116 326 adolescents (10-24 years) in 32 communities of Uganda and Kenya ( SEARCH: NCT01864603): 98 694 (85%) reported stable (≥6 months of prior year) residence. In each community we performed hybrid testing: 2-week multidisease community health campaign that included HIV testing, followed by home-based testing of community health campaign nonparticipants. We measured adolescent HIV testing coverage and prevalence, and determined predictors of newly diagnosed HIV among HIV-infected adolescents using multivariable logistic regression. RESULTS: A total of 86 421 (88%) stable adolescents tested for HIV; coverage was 86, 90, and 88% in early (10-14), mid (15-17), and late (18-24) adolescents, respectively. Self-reported prior testing was 9, 26, and 55% in early, mid, and late adolescents tested, respectively. HIV prevalence among adolescents tested was 1.6 and 0.6% in Ugandan women and men, and 7.1 and 1.5% in Kenyan women and men, respectively. Prevalence increased in mid-adolescence for women and late adolescence for men. Among HIV-infected adolescents, 58% reported newly diagnosed HIV. In multivariate analysis of HIV-infected adolescents, predictors of newly diagnosed HIV included male sex [odds ratio (OR) = 1.97 (95% confidence interval (CI): 1.42-2.73)], Ugandan residence [OR = 2.63 (95% CI: 2.08-3.31)], and single status [OR = 1.62 (95% CI: 1.23-2.14) vs. married)]. CONCLUSIONS: The SEARCH hybrid strategy tested 88% of stable adolescents for HIV, a substantial increase over the 28% reporting prior testing. The majority (57%) of HIV-infected adolescents were new diagnoses. Mobile HIV testing for adults should be leveraged to reach adolescents for HIV treatment and prevention.