Search

BackgroundAntiretroviral therapy (ART) assures major gains in health outcomes among people living with HIV, however, this benefit may not be realized by all due to care interruptions. Mobile populations comprise a subgroup that is likely to have sub-optimal care engagement, resulting in discontinuation of ART. We sought to evaluate the barriers to care engagement among highly mobile individuals living with HIV and explore options aimed at improving engagement in care for this group.MethodsQualitative in-depth interviews were conducted in 2020 among a purposive sample of twelve persons living with HIV and eight health care providers in western Kenya, within a mixed methods study of mobility in communities participating in the SEARCH trial (NCT01864603). We explored the barriers to care engagement among mobile individuals living with HIV and explored different options aimed at enhancing care engagement. These included options such as a coded card containing treatment details, alternative drug packaging to conceal drug identity, longer refills to cover travel period, wrist bands with data storage capability to enable data transfer and "warm handoff" by providers to new clinics upon transfer. Data were inductively analyzed to understand the barriers and acceptability of potential interventions to address them.ResultsStigma and lack of disclosure, rigid work schedules, and unpredictability of travel were major barriers to care engagement for highly mobile individuals living with HIV. Additionally, lack of flexibility in clinic schedules and poor provider attitude were identified as health-system-associated barriers to care engagement. Options that enhance flexibility, convenience and access to care were viewed as the most effective means of addressing the barriers to care by both patients and providers. The most preferred option was a coded card with treatment details followed by alternative drug packaging to conceal drug identity due to stigma and longer refills to cover travel periods.ConclusionHighly mobile individuals living with HIV desire responsive, flexible, convenient and patient-centered care delivery models to enhance care engagement. They embraced simple health delivery improvements such as coded cards, alternative drug packaging and longer refills to address challenges of mobility.

BackgroundAdditional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya.MethodsIn a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report.ResultsOf 704 seroconverters, 63% were women. Young (15-24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%).ConclusionIn the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates.

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.

BackgroundThe 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.MethodsFrom 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.ResultsThe 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.ConclusionChildren 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.

BackgroundHypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]-although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions.MethodsWe sought to evaluate the consistency of HTN program delivery within the SEARCH study (NCT01864603) among 95,000 adults in 32 rural communities in Uganda and Kenya from 2013-2016. To achieve this objective, we designed and performed a fidelity evaluation of the step-by-step process (cascade) of HTN care within SEARCH, calculating rates of HTN screening, linkage to care, and follow-up care. We evaluated SEARCH's assessment of each participant's HTN status against measured blood pressure and HTN history.FindingsSEARCH completed blood pressure screens on 91% of participants. SEARCH HTN screening was 91% sensitive and over 99% specific for HTN relative to measured blood pressure and patient history. 92% of participants screened HTN+ received clinic appointments, and 42% of persons with HTN linked to subsequent care. At follow-up, 82% of SEARCH clinic participants received blood pressure checks; 75% received medication appropriate for their blood pressure; 66% remained in care; and 46% had normal blood pressure at their most recent visit.ConclusionThe SEARCH study's consistency in delivering screening and treatment services for HTN was generally high, but SEARCH could improve effectiveness in linking patients to care and achieving HTN control. Its model for implementing population-scale HTN testing and care through an existing HIV test-and-treat program-and protocol for evaluating the intervention's stepwise fidelity and care outcomes-may be adapted, strengthened, and scaled up for use across multiple resource-limited settings.

BackgroundChronic kidney disease (CKD) may be common among individuals living in sub-Saharan Africa due to the confluence of CKD risk factors and genetic predisposition.MethodsWe ascertained the prevalence of CKD and its risk factors among a sample of 3,686 participants of a population-based HIV trial in rural Uganda and Kenya. Prevalent CKD was defined as a serum creatinine-based estimated glomerular filtration rate

BackgroundPrevious research indicates clinical outcomes among HIV-infected men in sub-Saharan Africa are sub-optimal. The SEARCH test and treat trial (NCT01864603) intervention included antiretroviral care delivery designed to address known barriers to HIV-care among men by decreasing clinic visit frequency and providing flexible, patient-centered care with retention support. We sought to understand facilitators and barriers to retention in care in this universal treatment setting through quantitative and qualitative data analysis.MethodsWe used a convergent mixed methods study design to evaluate retention in HIV care among adults (age > = 15) during the first year of the SEARCH (NCT01864603) test and treat trial. Cox proportional hazards regression was used to evaluate predictors of retention in care. Longitudinal qualitative data from n = 190 in-depth interviews with HIV-positive individuals and health care providers were analyzed to identify facilitators and barriers to HIV care engagement.ResultsThere were 1,863 men and 3,820 women who linked to care following baseline testing. Retention in care was 89.7% (95% CI 87.0-91.8%) among men and 89.0% (86.8-90.9%) among women at one year. In both men and women older age was associated with higher rates of retention in care at one year. Additionally, among men higher CD4+ at ART initiation and decreased time between testing and ART initiation was associated with higher rates of retention. Maintaining physical health, a patient-centered treatment environment, supportive partnerships, few negative consequences to disclosure, and the ability to seek care in facilities outside of their community of residence were found to promote retention in care.ConclusionsFeatures of the ART delivery system in the SEARCH intervention and social and structural advantages emerged as facilitators to retention in HIV care among men. Messaging around the health benefits of early ART start, decreasing logistical barriers to HIV care, support of flexible treatment environments, and accelerated linkage to care, are important to men's success in ART treatment programs. Men already benefit from increased social support following disclosure of their HIV-status. Future efforts to shift gender norms towards greater equity are a potential strategy to support high levels of engagement in care for both men and women.

BackgroundAntiretroviral therapy (ART) assures major gains in health outcomes among people living with HIV, however, this benefit may not be realized by all due to care interruptions. Mobile populations comprise a subgroup that is likely to have sub-optimal care engagement, resulting in discontinuation of ART. We sought to evaluate the barriers to care engagement among highly mobile individuals living with HIV and explore options aimed at improving engagement in care for this group.MethodsQualitative in-depth interviews were conducted in 2020 among a purposive sample of twelve persons living with HIV and eight health care providers in western Kenya, within a mixed methods study of mobility in communities participating in the SEARCH trial (NCT01864603). We explored the barriers to care engagement among mobile individuals living with HIV and explored different options aimed at enhancing care engagement. These included options such as a coded card containing treatment details, alternative drug packaging to conceal drug identity, longer refills to cover travel period, wrist bands with data storage capability to enable data transfer and "warm handoff" by providers to new clinics upon transfer. Data were inductively analyzed to understand the barriers and acceptability of potential interventions to address them.ResultsStigma and lack of disclosure, rigid work schedules, and unpredictability of travel were major barriers to care engagement for highly mobile individuals living with HIV. Additionally, lack of flexibility in clinic schedules and poor provider attitude were identified as health-system-associated barriers to care engagement. Options that enhance flexibility, convenience and access to care were viewed as the most effective means of addressing the barriers to care by both patients and providers. The most preferred option was a coded card with treatment details followed by alternative drug packaging to conceal drug identity due to stigma and longer refills to cover travel periods.ConclusionHighly mobile individuals living with HIV desire responsive, flexible, convenient and patient-centered care delivery models to enhance care engagement. They embraced simple health delivery improvements such as coded cards, alternative drug packaging and longer refills to address challenges of mobility.

IntroductionIncomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission.MethodsFrom 2012-2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases.ResultsOf 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (p

BackgroundCountry decisions to scale-up "test and treat" approaches for HIV depend on consideration of both the health and economic consequences of such investments. Evidence about economic impacts of expanded antiretroviral therapy (ART) provision is particularly relevant for decisions regarding foreign assistance levels for HIV/AIDS programs. We used baseline data from the Sustainable East Africa Research in Community Health (SEARCH) cluster randomized controlled trial in Kenya and Uganda to examine the association between HIV status, CD4+ T-cell counts, viral suppression, and multiple indicators of economic well-being.Methods and findingsSocio-economic surveys were conducted in households with HIV-positive and HIV-negative adults sampled after a census of 32 communities participating in the SEARCH trial (NCT01864603). Data were obtained for 11,500 individuals from 5,884 households in study communities. Participants were stratified based on their own HIV status as well as CD4 counts and viral suppression status if they were HIV-positive. HIV-negative participants residing in households with no HIV-positive adults were considered separately from HIV-negative participants residing in households with ≥1 HIV-positive adult. Generalized estimating equation models were used to examine the relationship between HIV status, CD4 counts, ART, viral suppression, and outcomes of employment, self-reported illness, lost time from usual activities due to illness, healthcare utilization, health expenditures, and hospitalizations. In all models, HIV-negative participants in households with no HIV-positive persons were the reference group. There was no significant difference in the probability of being employed between HIV-positive participants with CD4>500 and the reference group of HIV-negative participants residing in households with no HIV-positive adults (marginal effect, ME, 1.49 percentage points; 95% confidence interval, CI, -1.09, 4.08). However, HIV-positive participants with CD4 351-500 were less likely to be employed than the reference group (ME -4.50, 95% CI -7.99, -1.01), as were HIV-positive participants with CD4 ≤350 (ME -7.41, 95% CI -10.96, -3.85). Similarly, there was no significant difference in employment likelihood between HIV-negative participants who resided in households with a CD4>500 HIV-positive person and the reference group (ME -1.78, 95% CI -5.16, 1.59). HIV-negative participants residing with an HIV-positive person with CD4 351-500, however, were less likely to be employed than the reference group (ME -7.03, 95% CI -11.49, -2.57), as were people residing with a household member with CD4 ≤350 (ME -6.28, 95% CI -10.76, -1.80). HIV-positive participants in all CD4 categories were more likely to have lost time from usual activities due to illness and have incurred healthcare expenditures. Those with CD4>500 had better economic outcomes than those with CD4 351-500, even among those not virally suppressed (p = 0.004) and not on ART (p = 0.01).ConclusionsData from a large population-representative sample of households in east Africa showed a strong association between the health of HIV-positive persons and economic outcomes. The findings suggest there may be economic benefits associated with maintaining high CD4 counts, both for HIV-positive persons and their HIV-negative household members. The association of high CD4 counts with improved outcomes is consistent with the hypothesis that early ART initiation can avert declines in employment and other economic outcomes. Prospective longitudinal evaluation is needed to assess the causal impact of early ART initiation on economic functioning of households.

BackgroundDespite substantial progress, gaps in the HIV care cascade remain large: globally, while about 36.7 million people were living with HIV in 2015, 11.9 million of these individuals did not know their HIV status, 12.7 million were in need of antiretroviral therapy (ART) and 13.0 million were not virally suppressed. We sought to deepen understanding of the barriers to care engagement at three critical steps of the care cascade proposed to make greatest impact for attaining the UNAIDS 90-90-90 targets aimed at shutting down the HIV epidemic.MethodsAnalyses were conducted among HIV-infected adults in rural East Africa. Qualitative data were collected using in-depth interviews among 63 individuals participating in an ongoing test-and treat trial (NCT01864683) in its baseline year (July 2013-June 2014). Audio recordings were transcribed, translated into English, and coded using Atlas.ti software. Data were analyzed using a thematic framework for explaining barriers to care engagement that drew upon both theory and prior empirical research in similar settings.ResultsMultiple barriers to engagement in care were observed. HIV-related stigma across dimensions of anticipated, internalized and enacted stigma manifested in denial and fears of disclosure, and influenced lapses in care engagement across multiple steps in the cascade. Poverty (lack of food and transport), lack of social support, work interference, prior negative experiences with health services, drug side effects, and treatment fatigue also negatively affected ART adherence and viral suppression. Gender differences were observed, with work interference and denial disproportionately affecting men compared to women.ConclusionMultiple barriers to HIV care engagement still pervade rural sub-Saharan settings threatening the realization of the UNAIDS 90-90-90 targets. To control the epidemic, efforts need to be accelerated to combat stigma. Patient economic empowerment, innovative drug formulations, as well as more patient-responsive health systems, may help overcome barriers to engagement in care.

BackgroundAdditional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya.MethodsIn a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report.ResultsOf 704 seroconverters, 63% were women. Young (15-24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%).ConclusionIn the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates.

Hepcidin is a peptide hormone that targets the iron exporter ferroportin, thereby limiting iron entry into the bloodstream. It is generated in hepatocytes mainly in response to increased body iron stores or inflammatory cues. Iron stimulates expression of bone morphogenetic protein 6 (BMP6) from liver sinusoidal endothelial cells, which in turn binds to BMP receptors on hepatocytes and induces the SMAD signaling cascade for transcriptional activation of the hepcidin-encoding HAMP mRNA. SMAD signaling is also essential for inflammatory HAMP mRNA induction by the IL-6/STAT3 pathway. Herein, we utilized human Huh7 hepatoma cells and primary murine hepatocytes to assess the effects of iron perturbations on signaling to hepcidin. Iron chelation appeared to slightly impair signaling to hepcidin. Subsequent iron supplementation not only failed to reverse these effects, but drastically reduced basal HAMP mRNA and inhibited HAMP mRNA induction by BMP6 and/or IL-6. Thus, treatment of cells with excess iron inhibited basal and BMP6-mediated SMAD5 phosphorylation and induction of HAMP, ID1 and SMAD7 mRNAs in a dose-dependent manner. Iron also inhibited IL-6-mediated STAT3 phosphorylation and induction of HAMP and SOCS3 mRNAs. These responses were accompanied by induction of GCLC and HMOX1 mRNAs, known markers of oxidative stress. We conclude that hepatocellular iron overload suppresses hepcidin by inhibiting the SMAD and STAT3 signaling pathways downstream of their respective ligands.

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.

ObjectiveMaternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda.DesignProspective cohort.MethodsHIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.ResultsMean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining

BackgroundThe 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.MethodsFrom 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.ResultsThe 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.ConclusionChildren 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.

BackgroundHypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]-although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions.MethodsWe sought to evaluate the consistency of HTN program delivery within the SEARCH study (NCT01864603) among 95,000 adults in 32 rural communities in Uganda and Kenya from 2013-2016. To achieve this objective, we designed and performed a fidelity evaluation of the step-by-step process (cascade) of HTN care within SEARCH, calculating rates of HTN screening, linkage to care, and follow-up care. We evaluated SEARCH's assessment of each participant's HTN status against measured blood pressure and HTN history.FindingsSEARCH completed blood pressure screens on 91% of participants. SEARCH HTN screening was 91% sensitive and over 99% specific for HTN relative to measured blood pressure and patient history. 92% of participants screened HTN+ received clinic appointments, and 42% of persons with HTN linked to subsequent care. At follow-up, 82% of SEARCH clinic participants received blood pressure checks; 75% received medication appropriate for their blood pressure; 66% remained in care; and 46% had normal blood pressure at their most recent visit.ConclusionThe SEARCH study's consistency in delivering screening and treatment services for HTN was generally high, but SEARCH could improve effectiveness in linking patients to care and achieving HTN control. Its model for implementing population-scale HTN testing and care through an existing HIV test-and-treat program-and protocol for evaluating the intervention's stepwise fidelity and care outcomes-may be adapted, strengthened, and scaled up for use across multiple resource-limited settings.

BackgroundChronic kidney disease (CKD) may be common among individuals living in sub-Saharan Africa due to the confluence of CKD risk factors and genetic predisposition.MethodsWe ascertained the prevalence of CKD and its risk factors among a sample of 3,686 participants of a population-based HIV trial in rural Uganda and Kenya. Prevalent CKD was defined as a serum creatinine-based estimated glomerular filtration rate ResultsThe estimated CKD prevalence was 6.8% (95% CI 5.7-8.1%) overall and varied by region, being 12.5% (10.1-15.4%) in eastern Uganda, 3.9% (2.2-6.8%) in southwestern Uganda and 3.7% (2.7-5.1%) in western Kenya. Risk factors associated with greater CKD prevalence included age ≥60 years (adjusted prevalence ratio [aPR] 3.5 [95% CI 1.9-6.5] compared with age 18-29 years), HIV infection (aPR 1.6 [1.1-2.2]), and residence in eastern Uganda (aPR 3.9 [2.6-5.9]). However, two-thirds of individuals with CKD did not have HIV, diabetes, or hypertension as risk factors. Furthermore, we noted many individuals who did not have proteinuria had dipstick positive leukocyturia or hematuria.ConclusionThe prevalence of CKD is appreciable in rural East Africa and there are considerable regional differences. Conventional risk factors appear to only explain a minority of cases, and leukocyturia and hematuria were common, highlighting the need for further research into understanding the nature of CKD in sub-Saharan Africa.

BackgroundBoth HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.MethodologyThis prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.ResultsExpression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.ConclusionTB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts>350 cells/mm3.

Hepatic iron overload, a hallmark of hereditary hemochromatosis, triggers progressive liver disease. There is also increasing evidence for a pathogenic role of iron in non-alcoholic fatty liver disease (NAFLD), which may progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular cancer. Mouse models of hereditary hemochromatosis and NAFLD can be used to explore potential interactions between iron and lipid metabolic pathways. Hfe-/- mice, a model of moderate iron overload, were reported to develop early liver fibrosis in response to a high fat diet. However, this was not the case with Hjv-/- mice, a model of severe iron overload. These data raised the possibility that the Hfe gene may protect against liver injury independently of its iron regulatory function. Herein, we addressed this hypothesis in a comparative study utilizing wild type, Hfe-/-, Hjv-/- and double Hfe-/-Hjv-/- mice. The animals, all in C57BL/6J background, were fed with high fat diets for 14 weeks and developed hepatic steatosis, associated with iron overload. Hfe co-ablation did not sensitize steatotic Hjv-deficient mice to liver injury. Moreover, we did not observe any signs of liver inflammation or fibrosis even in single steatotic Hfe-/- mice. Ultrastructural studies revealed a reduced lipid and glycogen content in Hjv-/- hepatocytes, indicative of a metabolic defect. Interestingly, glycogen levels were restored in double Hfe-/-Hjv-/- mice, which is consistent with a metabolic function of Hfe. We conclude that hepatocellular iron excess does not aggravate diet-induced steatosis to steatohepatitis or early liver fibrosis in mouse models of hereditary hemochromatosis, irrespectively of the presence or lack of Hfe.

Hepcidin is an iron regulatory peptide hormone that is secreted from hepatocytes and inhibits iron efflux from tissues to plasma. Under inflammatory conditions, hepcidin is transcriptionally induced by IL-6/STAT3 signaling and promotes hypoferremia, an innate immune response to infection. If this pathway remains unresolved, chronic overexpression of hepcidin contributes to the anemia of inflammation, a common medical condition. Previous work showed that carbon monoxide (CO) releasing drugs (CORMs) can attenuate inflammatory induction of hepcidin. Because CO is physiologically generated during heme degradation by heme oxygenase 1 (HO-1), an IL-6-inducible enzyme with anti-inflammatory properties, we hypothesized that hepatocellular HO-1 may operate as a physiological feedback regulator of hepcidin that resolves inflammatory signaling. To address this, we generated and analyzed hepatocyte-specific HO-1 knockout (Hmox1Alb-Cre) mice. We show that these animals mount appropriate hepcidin-mediated hypoferremic response to LPS-induced inflammation, with kinetics similar to those of control Hmox1fl/fl mice. Likewise, primary hepatocytes from Hmox1Alb-Cre and Hmox1fl/fl mice exhibit similar degree and kinetics of hepcidin induction following IL-6 treatment. We conclude that hepatocellular HO-1 has no physiological function on hepcidin regulation by the inflammatory pathway.

BackgroundPrevious research indicates clinical outcomes among HIV-infected men in sub-Saharan Africa are sub-optimal. The SEARCH test and treat trial (NCT01864603) intervention included antiretroviral care delivery designed to address known barriers to HIV-care among men by decreasing clinic visit frequency and providing flexible, patient-centered care with retention support. We sought to understand facilitators and barriers to retention in care in this universal treatment setting through quantitative and qualitative data analysis.MethodsWe used a convergent mixed methods study design to evaluate retention in HIV care among adults (age > = 15) during the first year of the SEARCH (NCT01864603) test and treat trial. Cox proportional hazards regression was used to evaluate predictors of retention in care. Longitudinal qualitative data from n = 190 in-depth interviews with HIV-positive individuals and health care providers were analyzed to identify facilitators and barriers to HIV care engagement.ResultsThere were 1,863 men and 3,820 women who linked to care following baseline testing. Retention in care was 89.7% (95% CI 87.0-91.8%) among men and 89.0% (86.8-90.9%) among women at one year. In both men and women older age was associated with higher rates of retention in care at one year. Additionally, among men higher CD4+ at ART initiation and decreased time between testing and ART initiation was associated with higher rates of retention. Maintaining physical health, a patient-centered treatment environment, supportive partnerships, few negative consequences to disclosure, and the ability to seek care in facilities outside of their community of residence were found to promote retention in care.ConclusionsFeatures of the ART delivery system in the SEARCH intervention and social and structural advantages emerged as facilitators to retention in HIV care among men. Messaging around the health benefits of early ART start, decreasing logistical barriers to HIV care, support of flexible treatment environments, and accelerated linkage to care, are important to men's success in ART treatment programs. Men already benefit from increased social support following disclosure of their HIV-status. Future efforts to shift gender norms towards greater equity are a potential strategy to support high levels of engagement in care for both men and women.

INTRODUCTION:Incomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission. METHODS:From 2012-2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases. RESULTS:Of 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (p

BACKGROUND:Country decisions to scale-up "test and treat" approaches for HIV depend on consideration of both the health and economic consequences of such investments. Evidence about economic impacts of expanded antiretroviral therapy (ART) provision is particularly relevant for decisions regarding foreign assistance levels for HIV/AIDS programs. We used baseline data from the Sustainable East Africa Research in Community Health (SEARCH) cluster randomized controlled trial in Kenya and Uganda to examine the association between HIV status, CD4+ T-cell counts, viral suppression, and multiple indicators of economic well-being. METHODS AND FINDINGS:Socio-economic surveys were conducted in households with HIV-positive and HIV-negative adults sampled after a census of 32 communities participating in the SEARCH trial (NCT01864603). Data were obtained for 11,500 individuals from 5,884 households in study communities. Participants were stratified based on their own HIV status as well as CD4 counts and viral suppression status if they were HIV-positive. HIV-negative participants residing in households with no HIV-positive adults were considered separately from HIV-negative participants residing in households with ≥1 HIV-positive adult. Generalized estimating equation models were used to examine the relationship between HIV status, CD4 counts, ART, viral suppression, and outcomes of employment, self-reported illness, lost time from usual activities due to illness, healthcare utilization, health expenditures, and hospitalizations. In all models, HIV-negative participants in households with no HIV-positive persons were the reference group. There was no significant difference in the probability of being employed between HIV-positive participants with CD4>500 and the reference group of HIV-negative participants residing in households with no HIV-positive adults (marginal effect, ME, 1.49 percentage points; 95% confidence interval, CI, -1.09, 4.08). However, HIV-positive participants with CD4 351-500 were less likely to be employed than the reference group (ME -4.50, 95% CI -7.99, -1.01), as were HIV-positive participants with CD4 ≤350 (ME -7.41, 95% CI -10.96, -3.85). Similarly, there was no significant difference in employment likelihood between HIV-negative participants who resided in households with a CD4>500 HIV-positive person and the reference group (ME -1.78, 95% CI -5.16, 1.59). HIV-negative participants residing with an HIV-positive person with CD4 351-500, however, were less likely to be employed than the reference group (ME -7.03, 95% CI -11.49, -2.57), as were people residing with a household member with CD4 ≤350 (ME -6.28, 95% CI -10.76, -1.80). HIV-positive participants in all CD4 categories were more likely to have lost time from usual activities due to illness and have incurred healthcare expenditures. Those with CD4>500 had better economic outcomes than those with CD4 351-500, even among those not virally suppressed (p = 0.004) and not on ART (p = 0.01). CONCLUSIONS:Data from a large population-representative sample of households in east Africa showed a strong association between the health of HIV-positive persons and economic outcomes. The findings suggest there may be economic benefits associated with maintaining high CD4 counts, both for HIV-positive persons and their HIV-negative household members. The association of high CD4 counts with improved outcomes is consistent with the hypothesis that early ART initiation can avert declines in employment and other economic outcomes. Prospective longitudinal evaluation is needed to assess the causal impact of early ART initiation on economic functioning of households.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition for which there are currently no medical therapies other than supportive care involving the application of mechanical ventilation. However, mechanical ventilation itself can worsen ARDS by damaging the alveolocapillary barrier in the lungs. This allows plasma-derived fluid and proteins to leak into the airspaces of the lung where they interfere with the functioning of pulmonary surfactant, which increases the stresses of mechanical ventilation and worsens lung injury. Once such ventilator-induced lung injury (VILI) is underway, managing ARDS and saving the patient becomes increasingly problematic. Maintaining an intact alveolar barrier thus represents a crucial management goal, but the biophysical processes that perforate this barrier remain incompletely understood. To study the dynamics of barrier perforation, we subjected initially normal mice to an injurious ventilation regimen that imposed both volutrauma (overdistension injury) and atelectrauma (injury from repetitive reopening of closed airspaces) on the lung, and observed the rate at which macromolecules of various sizes leaked into the airspaces as a function of the degree of overall injury. Computational modeling applied to our findings suggests that perforations in the alveolocapillary barrier appear and progress according to a rich-get-richer mechanism in which the likelihood of a perforation getting larger increases with the size of the perforation. We suggest that atelectrauma causes the perforations after which volutrauma expands them. This mechanism explains why atelectrauma appears to be essential to the initiation of VILI in a normal lung, and why atelectrauma and volutrauma then act synergistically once VILI is underway.

BACKGROUND:Despite substantial progress, gaps in the HIV care cascade remain large: globally, while about 36.7 million people were living with HIV in 2015, 11.9 million of these individuals did not know their HIV status, 12.7 million were in need of antiretroviral therapy (ART) and 13.0 million were not virally suppressed. We sought to deepen understanding of the barriers to care engagement at three critical steps of the care cascade proposed to make greatest impact for attaining the UNAIDS 90-90-90 targets aimed at shutting down the HIV epidemic. METHODS:Analyses were conducted among HIV-infected adults in rural East Africa. Qualitative data were collected using in-depth interviews among 63 individuals participating in an ongoing test-and treat trial (NCT01864683) in its baseline year (July 2013-June 2014). Audio recordings were transcribed, translated into English, and coded using Atlas.ti software. Data were analyzed using a thematic framework for explaining barriers to care engagement that drew upon both theory and prior empirical research in similar settings. RESULTS:Multiple barriers to engagement in care were observed. HIV-related stigma across dimensions of anticipated, internalized and enacted stigma manifested in denial and fears of disclosure, and influenced lapses in care engagement across multiple steps in the cascade. Poverty (lack of food and transport), lack of social support, work interference, prior negative experiences with health services, drug side effects, and treatment fatigue also negatively affected ART adherence and viral suppression. Gender differences were observed, with work interference and denial disproportionately affecting men compared to women. CONCLUSION:Multiple barriers to HIV care engagement still pervade rural sub-Saharan settings threatening the realization of the UNAIDS 90-90-90 targets. To control the epidemic, efforts need to be accelerated to combat stigma. Patient economic empowerment, innovative drug formulations, as well as more patient-responsive health systems, may help overcome barriers to engagement in care.

Many individuals at risk of streptococcal infection respond poorly to the pneumococcal polysaccharide vaccine Pneumovax 23. Identification of actionable pathways able to enhance Pneumovax responsiveness is highly relevant. We investigated the contribution of the extracellular adenosine pathway regulated by the ecto-nucleotidase CD73 in Pneumovax-induced antibody responses. Using gene-targeted mice, we demonstrated that CD73-or A2a adenosine receptor deficiency significantly delayed isotype switching. Nevertheless, CD73- or A2aR- deficient adult mice ultimately produced antigen-specific IgG3 and controlled Streptococcus pneumoniae infection as efficiently as wild type (WT) mice. Compared to adults, young WT mice failed to control S. pneumoniae infection after vaccination and this was associated with lower levels of CD73 on innate B cells. We hypothesized that pharmacological activation of A2a receptor may improve Pneumovax 23 immunization in young WT mice. Remarkably, administration of the A2a adenosine receptor agonist CGS 21680 significantly increased IgG3 responses and significantly enhanced survival after S. pneumoniae challenge. Our study thus suggests that pharmacological activation of the A2a adenosine receptor could improve the efficacy of Pneumovax 23 vaccination in individuals at risk of streptococcal infection.

This study aims to understand the influence of the ethical and legal issues on cloud computing adoption in the field of genomics research. To do so, we adapted Diffusion of Innovation (DoI) theory to enable understanding of how key stakeholders manage the various ethical and legal issues they encounter when adopting cloud computing. Twenty semi-structured interviews were conducted with genomics researchers, patient advocates and cloud service providers. Thematic analysis generated five major themes: 1) Getting comfortable with cloud computing; 2) Weighing the advantages and the risks of cloud computing; 3) Reconciling cloud computing with data privacy; 4) Maintaining trust and 5) Anticipating the cloud by creating the conditions for cloud adoption. Our analysis highlights the tendency among genomics researchers to gradually adopt cloud technology. Efforts made by cloud service providers to promote cloud computing adoption are confronted by researchers' perpetual cost and security concerns, along with a lack of familiarity with the technology. Further underlying those fears are researchers' legal responsibility with respect to the data that is stored on the cloud. Alternative consent mechanisms aimed at increasing patients' control over the use of their data also provide a means to circumvent various institutional and jurisdictional hurdles that restrict access by creating siloed databases. However, the risk of creating new, cloud-based silos may run counter to the goal in genomics research to increase data sharing on a global scale.

Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse.To describe the current practices and quality of TB evaluation for children with cough ≥2 weeks' duration presenting to community health centers in Uganda.Cross-sectional analysis of children (

The high burden of undiagnosed HIV in sub-Saharan Africa is a major obstacle for HIV prevention and treatment. Multi-disease, community health campaigns (CHCs) offering HIV testing are a successful approach to rapidly increase HIV testing rates and identify undiagnosed HIV. However, a greater understanding of population-level uptake is needed to maximize effectiveness of this approach.After community sensitization and a census, a five-day campaign was performed in May 2012 in a rural Ugandan community. The census enumerated all residents, capturing demographics, household location, and fingerprint biometrics. The CHC included point-of-care screening for HIV, malaria, TB, hypertension and diabetes. Residents who attended vs. did not attend the CHC were compared to determine predictors of participation.Over 12 days, 18 census workers enumerated 6,343 residents. 501 additional residents were identified at the campaign, for a total community population of 6,844. 4,323 (63%) residents and 556 non-residents attended the campaign. HIV tests were performed in 4,795/4,879 (98.3%) participants; 1,836 (38%) reported no prior HIV testing. Of 2674 adults tested, 257 (10%) were HIV-infected; 125/257 (49%) reported newly diagnosed HIV. In unadjusted analyses, adult resident campaign non-participation was associated with male sex (62% male vs. 67% female participation, p = 0.003), younger median age (27 years in non-participants vs. 32 in participants; p

The impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs.A5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser.Illumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda.Prospective cohort.HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis.Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining

Phenotypic bacitracin resistance has been reported in Clostridium perfringens. However, the genes responsible for the resistance have not yet been characterized. Ninety-nine C. perfringens isolates recovered from broilers and turkeys were tested for phenotypic bacitracin resistance. Bacitracin MIC(90) (>256 µg/ml) was identical for both turkey and chicken isolates; whereas MIC(50) was higher in turkey isolates (6 µg/ml) than in chicken isolates (3 µg/ml). Twenty-four of the 99 isolates showed high-level bacitracin resistance (MIC breakpoint >256 µg/ml) and the genes encoding for this resistance were characterized in C. perfringens c1261_A strain using primer walking. Sequence analysis and percentages of amino acid identity revealed putative genes encoding for both an ABC transporter and an overproduced undecaprenol kinase in C. perfringens c1261_A strain. These two mechanisms were shown to be both encoded by the putative bcrABD operon under the control of a regulatory gene, bcrR. Efflux pump inhibitor thioridazine was shown to increase significantly the susceptibility of strain c1261_A to bacitracin. Upstream and downstream from the bcr cluster was an IS1216-like element, which may play a role in the dissemination of this resistance determinant. Pulsed-field gel electrophoresis with prior double digestion with I-CeuI/MluI enzymes followed by hybridization analyses revealed that the bacitracin resistance genes bcrABDR were located on the chromosome. Semi-quantitative RT-PCR demonstrated that this gene cluster is expressed under bacitracin stress. Microarray analysis revealed the presence of these genes in all bacitracin resistant strains. This study reports the discovery of genes encoding for a putative ABC transporter and an overproduced undecaprenol kinase associated with high-level bacitracin resistance in C. perfringens isolates from turkeys and broiler chickens.

The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish.A five-day, multi-disease campaign, offering diagnostic, preventive, treatment and referral services, was performed in May 2011. Services included point-of-care screening for HIV, malaria, TB, hypertension and diabetes. Finger-prick diagnostics eliminated the need for phlebotomy. HIV-infected adults met clinic staff and peer counselors on-site; those with CD4 ≤ 100/µL underwent intensive counseling and rapid referral for antiretroviral therapy (ART). Community participation, case-finding yield, and linkage to care three months post-campaign were analyzed.Of 6,300 residents, 2,323/3,150 (74%) adults and 2,020/3,150 (69%) children participated. An estimated 95% and 52% of adult female and male residents participated respectively. Adult HIV prevalence was 7.8%, with 46% of HIV-infected adults newly diagnosed. Thirty-nine percent of new HIV diagnoses linked to care. In a pilot subgroup with CD4 ≤ 100, 83% linked and started ART within 10 days. Malaria was identified in 10% of children, and hypertension and diabetes in 28% and 3.5% of adults screened, respectively. Sixty-five percent of hypertensives and 23% of diabetics were new diagnoses, of which 43% and 61% linked to care, respectively. Screening identified suspected TB in 87% of HIV-infected and 19% of HIV-uninfected adults; 52% percent of HIV-uninfected TB suspects linked to care.In an integrated campaign engaging 74% of adult residents, we identified a high burden of undiagnosed HIV, hypertension and diabetes. Improving male attendance and optimizing linkage to care require new approaches. The campaign demonstrates the feasibility of integrating hypertension, diabetes and communicable diseases into HIV initiatives.

Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB.Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period.TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts>350 cells/mm3.

In the US, an unacceptably high percentage of pregnant women do not undergo prenatal HIV testing. Previous studies have found increased uptake of prenatal HIV testing with abbreviated pre-test counseling, however little is known about patient decision making, testing satisfaction and knowledge in this setting.A randomized-controlled, non-inferiority trial was conducted from October 2006 through February 2008 at San Francisco General Hospital (SFGH), the public teaching hospital of the City and County of San Francisco. A total of 278 English- and Spanish-speaking pregnant women were randomized to receive either abbreviated or standard nurse-performed HIV test counseling at the initial prenatal visit. Patient decision making experience was compared between abbreviated versus standard HIV counseling strategies among a sample of low-income, urban, ethnically diverse prenatal patients. The primary outcome was the decisional conflict score (DCS) using O'Connor low-literacy scale and secondary outcomes included satisfaction with test decision, basic HIV knowledge and HIV testing uptake. We conducted an intention-to-treat analysis of 278 women--134 (48.2%) in the abbreviated arm (AA) and 144 (51.8%) in the standard arm (SA). There was no significant difference in the proportion of women with low decisional conflict (71.6% in AA vs. 76.4% in SA, p = .37), and the observed mean difference between the groups of 3.88 (95% CI: -0.65, 8.41) did not exceed the non-inferiority margin. HIV testing uptake was very high (97. 8%) and did not differ significantly between the 2 groups (99.3% in AA vs. 96.5% in SA, p = .12). Likewise, there was no difference in satisfaction with testing decision (97.8% in AA vs. 99.3% in SA, p = .36). However, women in AA had significantly lower mean HIV knowledge scores (78.4%) compared to women in SA (83.7%, p