The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.

BACKGROUND: Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. METHODS: We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. FINDINGS: Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). INTERPRETATION: Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.

Household wealth and HIV incidence over time, rural Uganda, 1994-2018.

OBJECTIVE: To examine the relationship between household wealth and HIV incidence in rural Uganda over time from 1994 to 2018. In research conducted early in the epidemic, greater wealth (i.e. higher socioeconomic status, SES) was associated with higher HIV prevalence in sub-Saharan Africa (SSA); this relationship reversed in some settings in later years. DESIGN: Analysis of associations over time in a population-based open cohort of persons 15-49 years from 17 survey-rounds in 28 continuously followed communities of the Rakai Community Cohort Study (RCCS). METHODS: The RCCS sample averaged 8622 individuals and 5387 households per round. Principal components analysis was used to create a nine-item asset-based measure of household wealth. Poisson regression with generalized estimating equation (GEE) and exchangeable correlation structure was used to estimate HIV incidence rate ratios (IRRs) by SES quartile, survey-round, sex, and age group. RESULTS: From 1994 to 2018, SES rose considerably, and HIV incidence declined from 1.45 to 0.40 per 100 person-years (IRR = 0.39, 95% CI = 0.32--0.47, P < 0.001). HIV incidence was similar by SES category in the initial survey intervals (1994-1997); however, higher SES groups showed greater declines in HIV incidence over time. Multivariable analyses showed significant associations between HIV incidence and SES (IRR = 0.55 for highest compared with lowest quartile, 95% CI = 0.45--0.66, P < 0.001) controlling for time, sex, and age group. CONCLUSION: Beyond the early years of the RCCS, higher SES was associated with lower HIV incidence and SES gradients widened over time. The poor, like other key populations, should be targeted for HIV prevention, including treatment as prevention.

Phenotypic characteristics and asthma severity in an East African cohort of adults and adolescents with asthma: findings from the African severe asthma project.

RATIONALE: The relationship between clinical and biomarker characteristics of asthma and its severity in Africa is not well known. METHODS: Using the Expert Panel Report 3, we assessed for asthma severity and its relationship with key phenotypic characteristics in Uganda, Kenya and Ethiopia. The characteristics included adult onset asthma, family history of asthma, exposures (smoking and biomass), comorbidities (HIV, hypertension, obesity, tuberculosis (TB), rhinosinusitis, gastro-oesophageal disease (GERD) and biomarkers (fractional exhaled nitric oxide (FeNO), skin prick test (SPT) and blood eosinophils). We compared these characteristics on the basis of severity and fitted a multivariable logistic regression model to assess the independent association of these characteristics with asthma severity. RESULTS: A total of 1671 patients were enrolled, 70.7% women, with median age of 40 years. The prevalence of intermittent, mild persistent, moderate persistent and severe persistent asthma was 2.9%, 19.9%, 42.6% and 34.6%, respectively. Only 14% were on inhaled corticosteroids (ICS). Patients with severe persistent asthma had a higher rate of adult onset asthma, smoking, HIV, history of TB, FeNO and absolute eosinophil count but lower rates of GERD, rhinosinusitis and SPT positivity. In the multivariate model, Ethiopian site and a history of GERD remained associated with asthma severity. DISCUSSION: The majority of patients in this cohort presented with moderate to severe persistent asthma and the use of ICS was very low. Improving access to ICS and other inhaled therapies could greatly reduce asthma morbidity in Africa.

Population-level adult mortality following the expansion of antiretroviral therapy in Rakai, Uganda.

There are limited data on the impact of antiretroviral therapy (ART) on population-level adult mortality in sub-Saharan Africa. We analysed data for 2000-14 from the Rakai Community Cohort Study (RCCS) in Uganda, where free ART was scaled up after 2004. Using non-parametric and parametric (Weibull) survival analysis, we estimated trends in average person-years lived between exact ages 15 and 50, per capita life-years lost to HIV, and the mortality hazards of people living with HIV (PLHIV). Between 2000 and 2014, average adult life-years lived before age 50 increased significantly, from 26.4 to 33.5 years for all women and from 28.6 to 33.8 years for all men. As of 2014, life-years lost to HIV had declined significantly, to 1.3 years among women and 0.4 years among men. Following the roll-out of ART, mortality reductions among PLHIV were initially larger in women than men, but this is no longer the case.

HIV Prevention Efforts and Incidence of HIV in Uganda.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Uptake and correlates of cervical cancer screening among HIV-infected women attending HIV care in Uganda.

BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at high risk of cervical cancer. OBJECTIVE: This study assessed uptake and correlates of cervical screening among HIV-infected women in care in Uganda. METHODS: A nationally representative cross-sectional survey of HIV-infected women in care was conducted from August to November 2016. Structured interviews were conducted with 5198 women aged 15-49 years, from 245 HIV clinics. Knowledge and uptake of cervical screening and human papillomavirus (HPV) vaccination were determined. Correlates of cervical screening were assessed with modified Poisson regression to obtain prevalence ratios (PRs) using Stata version 12.0. RESULTS: Overall, 94.0% (n = 4858) had ever heard of cervical screening and 66% (n = 3732) knew a screening site. However, 47.4% (n = 2302) did not know the schedule for screening and 50% (n = 2409) did not know the symptoms of cervical cancer. One-third (33.7%; n = 1719) rated their risk of cervical cancer as low. Uptake of screening was 30.3% (n = 1561). Women who had never been screened cited lack of information (29.6%; n = 1059) and no time (25.5%; n = 913) as the main reasons. Increased likelihood of screening was associated with receipt of HIV care at a level II health center [adj. PR 1.89, 95% confidence interval (CI) 1.29-2.76] and private facilities (adj. PR 1.68, 95% CI 1.16-3.21), knowledge of cervical screening (adj. PR 2.19, 95% CI 1.78-2.70), where to go for screening (adj. PR 6.47, 95% CI 3.69-11.36), and low perception of risk (adj. PR 1.52, 95% CI 1.14-2.03). HPV vaccination was 2%. CONCLUSIONS: Cervical screening and HPV vaccination uptake were very low among HIV-infected women in care in Uganda. Improved knowledge of cervical screening schedules and sites, and addressing fears and risk perception may increase uptake of cervical screening in this vulnerable population.

Effect of a participatory multisectoral maternal and newborn intervention on maternal health service utilization and newborn care practices: a quasi-experimental study in three rural Ugandan districts.

BACKGROUND: The MANIFEST study in eastern Uganda employed a participatory multisectoral approach to reduce barriers to access to maternal and newborn care services. OBJECTIVES: This study analyses the effect of the intervention on the utilization of maternal and newborn services and care practices. METHODS: The quasi-experimental pre- and post-comparison design had two main components: community mobilization and empowerment, and health provider capacity building. The primary outcomes were utilization of antenatal care (ANC), delivery and postnatal care, and newborn care practices. Baseline (n = 2237) and endline (n = 1946) data were collected from women of reproductive age. The  data was analysed using difference in differences (DiD) analysis and  logistic regression. RESULTS: The DiD results revealed an 8% difference in early ANC attendance (p < 0.01) and facility delivery (p < 0.01). Facility delivery increased from 66% to 73% in the intervention area, but remained unchanged in the comparison area (64% vs 63%, p < 0.01). The DiD results also demonstrated a 20% difference in clean cord care (p < 0.001) and an 8% difference in delayed bathing (p < 0.001). The intervention elements that predicted facility delivery were attending ANC four times [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.17-1.74] and saving for maternal health (aOR 2.11, 95% CI 1.39-3.21). Facility delivery and village health team (VHT) home visits were key predictors for clean cord care and skin-to-skin care. CONCLUSIONS: The multisectoral approach had positive effects on early ANC attendance, facility deliveries and newborn care practices. Community resources such as VHTs and savings are crucial to maternal and newborn outcomes and should be supported. VHT-led health education should incorporate practical measures that enable families to save and access transport services to enhance adequate preparation for birth.

Maternal and neonatal implementation for equitable systems. A study design paper.

BACKGROUND: Evidence on effective ways of improving maternal and neonatal health outcomes is widely available. The challenge that most low-income countries grapple with is implementation at scale and sustainability. OBJECTIVES: The study aimed at improving access to quality maternal and neonatal health services in a sustainable manner by using a participatory action research approach. METHODS:  The  study consisted of a quasi-experimental design, with a participatory action research approach to implementation in three rural districts (Pallisa, Kibuku and Kamuli) in Eastern Uganda. The intervention had two main components; namely, community empowerment for comprehensive birth preparedness, and health provider and management capacity-building. We collected data using both quantitative and qualitative methods using household and facility-level structured surveys, record reviews, key informant interviews and focus group discussions. We purposively selected the participants for the qualitative data collection, while for the surveys we interviewed all eligible participants in the sampled households and health facilities. Descriptive statistics were used to describe the data, while the difference in difference analysis was used to measure the effect of the intervention. Qualitative data were analysed using thematic analysis. CONCLUSIONS: This study was implemented to generate evidence on how to increase access to quality maternal and newborn health services in a sustainable manner using a multisectoral participatory  approach.

Facilitators and barriers to uptake and adherence to lifelong antiretroviral therapy among HIV infected pregnant women in Uganda: a qualitative study.

BACKGROUND: In 2012, Uganda started implementing lifelong antiretroviral therapy (ART) for prevention of mother to child transmission (PMTCT) in line with the WHO 2012 guidelines. This study explored experiences of HIV infected pregnant and breastfeeding women regarding barriers and facilitators to uptake and adherence to lifelong ART. METHODS: This was a cross-sectional qualitative study conducted in three districts (Masaka, Mityana and Luwero) in Uganda, between February and May 2014. We conducted in-depth interviews with 57 pregnant and breastfeeding women receiving care in six health facilities, who had been on lifelong ART for at least 6 months. Data analysis was done using a content thematic approach with Atlas-ti software. RESULTS: Initiation of lifelong ART was done the same day the mother tested HIV positive. Several women felt the counselling was inadequate and had reservations about taking ART for life. The main motivation to initiate and adhere to ART was the desire to have an HIV-free baby. Adherence was a challenge, ranging from not taking the drugs at the right time, to completely missing doses and clinic appointments. Support from their male partners and peer family support groups enhanced good adherence. Fear to disclose HIV status to partners, drug related factors (side effects and the big size of the tablet), and HIV stigma were major barriers to ART initiation and adherence. Transition from antenatal care to HIV chronic care clinics was a challenge due to fear of stigma and discrimination. CONCLUSIONS: In order to maximize the benefits of lifelong ART, adequate preparation of women before ART initiation and on-going support through family support groups and male partner engagement are critical, particularly after birth and cessation of breastfeeding.

Maternal Influences on Access to and Use of Infant ARVs and HIV Health Services in Uganda.

Vertical transmission of HIV is responsible for about 14 % of new HIV cases reported each year in sub-Saharan Africa. Barriers that prevent women from accessing and using antiretroviral medications (ARVs) for themselves and their infants perpetuate the epidemic. To identify influences on access to and use of infant HIV health services, specifically nevirapine administration, we conducted a mixed methods study among HIV-positive women in Uganda. This included a cross-sectional survey (n = 384) and focus group discussions (n = 6, 5-9 participants each). Of the 384 women, 80 % gave nevirapine to their infants within 72 h of birth. Factors independently associated with nevirapine administration were lack of maternal adherence to ARVs (AOR 3.55, 95 % CI 1.36-9.26) and attending a support group (AOR 2.50, 95 % CI 1.06-5.83). Non-health facility births were inversely related to nevirapine use (AOR 0.02, 95 % CI 0.003-0.09). Focus group discussions identified four themes impacting access and use: attending a support group, health care worker attitudes, lack of partner support, and poor health messaging regarding ARVs. Improving health care worker messaging regarding ARVs and providing women with needed support to access and use infant ARV prophylaxis is critical to overcoming access barriers. Eliminating these barriers may prevent numerous HIV infections each year saving the lives of many HIV-exposed infants.

Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda.

BACKGROUND: The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but findings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women. METHODS: In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15-49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984. FINDINGS: Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09-4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49-26·3; p=0·012). INTERPRETATION: Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa. FUNDING: Bill and Melinda Gates Foundation, Doris Duke Charitable Foundation, US National Institutes of Health, and Fogarty International Center.

Safety of medical male circumcision in human immunodeficiency virus-infected men in Rakai, Uganda.

OBJECTIVE: To assess the safety of medical male circumcision (MMC) among human immunodeficiency virus (HIV)-infected men with CD4 levels <350 cells/mm(3), CD4 counts ≥ 350 cells/mm(3), and HIV-negative men. METHODS: Two hundred forty-two HIV-infected men and a sample of 262 HIV-negative consenting men aged 12 years or older who requested free MMC were enrolled in a prospective study. Blood for HIV testing and a CD4 count were collected before surgery. During weekly follow-up over 6 weeks, data were collected on wound healing and adverse events (AEs) by examination, and resumption of sex and condom use ascertained by interview. Surgery-related AEs were characterized by type, severity, management, and resolution. Chi-square and Fisher's exact tests were used to test for differences in AE proportions. RESULTS: Overall, only 2 of the 453 men experienced moderate AEs, a rate of 0.44 per 100 surgeries. No AE occurred among HIV-negative men, whereas the AE rate among HIV-infected men with CD4 counts ≥ 350 cells/mm(3) was 0.79 per 100 surgeries, and among men with CD4 counts <350 cells/mm(3) the rate was 1.19 per 100 surgeries (P = .214). AE rates were comparable for all characteristics (P >.05). CONCLUSION: HIV-positive men can be safely included in MMC roll out programs without necessitating presurgery CD4 counts determination.

Poor immunological recovery among severely immunosuppressed antiretroviral therapy-naïve Ugandans.

INTRODUCTION: CD4 T lymphocytes remain the surrogate measure for monitoring HIV progress in resource-limited settings. The absolute CD4 cell counts form the basis for antiretroviral therapy (ART) initiation and monitoring among HIV-infected adults. However, the rate of CD4 cell change differs among patients, and the factors responsible are inadequately documented. OBJECTIVE: This study investigated the relationship between HIV severity and ART outcomes among ART-naïve Ugandans, with the primary outcome of complete immunological recovery among patients of different baseline CD4 counts. METHODS: Patients' records at two HIV/ART sites - the Joint Clinic Research Centre (JCRC) in the Kampala region and Mbarara Hospital in Western Uganda - were reviewed. Records of 426 patients - 68.3% female and 63.2% from JCRC - who initiated ART between 2002 and 2007 were included. HIV severity was based on baseline CD4 cell counts, with low counts considered as severe immunosuppression, while attaining 418 CD4 cells/µL signified complete immunological recovery. Incidence rates of complete immunological recovery were calculated for, and compared between baseline CD4 cell categories: <50 with ≥50, <100 with ≥100, <200 with ≥200, and ≥200 with ≥250 cells/µL. RESULTS: The incidence of complete immunological recovery was 158 during 791.9 person-years of observation, and patients with baseline CD4 ≥ 200 cells/µL reached the end point of immunological recovery 1.89 times faster than the patients with baseline CD4 < 200 cells/µL. CD4 cell change also differed by time, sex, and site, with a faster increase observed during the first year of treatment. CD4 cell increase was faster among females, and among patients from Mbarara. CONCLUSION: Initiating ART at an advanced HIV stage was the main reason for poor immunological recovery among Ugandans. Earlier ART initiation might lead to better immunological responses.

High prevalence of malaria parasitemia and anemia among hospitalized children in Rakai, Uganda.

BACKGROUND: There is a paucity of data on malaria among hospitalized children in malaria endemic areas. We determined the prevalence, presentation and treatment outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda. METHODS: Children under five years hospitalized in Kalisizo hospital or Bikira health center in Rakai district, Uganda between May 2011 and May 2012 were enrolled and followed-up until discharge, death or referral. Data were collected on social-demographic characteristics, current and past illnesses and clinical signs and symptoms. Blood smears, hemoglobin (Hgb) levels and HIV testing were performed from finger/heel prick blood. The associations between malaria infection and other factors were estimated using log-binomial regression to estimate adjusted prevalence risk ratios (aPRR) and 95% confidence intervals (CIs), controlling for clustering at health facilities. RESULTS: 2471 children were enrolled. The most common medical presentations were fever (96.2%), cough (61.7%), vomiting (44.2%), diarrhea (20.8%), and seizures (16.0%). The prevalence of malaria parasitemia was 54.6%. Children with malaria were more likely to present with a history of fever (aPRR 2.23; CI 1.18-4.24) and seizures (aPRR 1.12; CI 1.09-1.16). Confirmed malaria was significantly lower among girls than boys (aPRR 0.92; CI 0.91-0.93), HIV infected children (aPRR 0.60 CI 0.52-0.71), and children with diarrhea (aPRR 0.76; CI 0.65-0.90). The overall prevalence of anemia (Hgb<10 g/dl) was 56.3% and severe anemia (Hgb<6 g/dL) was 17.8%. Among children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received blood transfusion. Malaria associated mortality was 0.6%. CONCLUSION: There was a high prevalence of malaria parasitemia and anemia among inpatient children under five years. Malaria prevention is a priority in this population.

Effects of hormonal contraceptive use on HIV acquisition and transmission among HIV-discordant couples.

BACKGROUND: The risk of HIV associated with hormonal contraceptives is controversial. We assessed hormonal contraceptive use and HIV incidence in HIV-discordant couples in Rakai, Uganda. METHODS: HIV-discordant couples were retrospectively identified from a cohort between 1999 and 2009. Hormonal contraception included oral contraception, depomedroxyprogesterone acetate (DMPA), and implants (Norplant). Poisson regression estimated adjusted incidence rate ratios (adjIRRs) associated with hormonal contraceptive methods. A case-control subanalysis estimated odds ratios (ORs) of HIV associated with hormonal contraceptive, adjusted for viral load and age. RESULTS: We identified 190 male HIV-positive/female HIV-negative (M+F-) and 159 male HIV- negative/female HIV-positive (M-F+) couples not using antiretroviral therapy or condoms. Female HIV incidence was 5.8/100 person-years (py) among nonhormonal contraceptive users, 12.0/100 py among oral contraceptive users [adjIRR 2.65, 95% confidence interval (CI) 0.82-8.60], 4.5 among Norplant users (adjIRR: 0.89, 95% CI 0.11-7.10), and 7.5/100 py among DMPA users (adjIRR 1.42, 95% CI 0.60-3.36). Male HIV incidence was 7.4/100 py during nonhormonal contraceptive use, 16.5/100 py during female oral contraceptive use (adjIRR 2.52, 95% CI 0.49-12.95), and 4.9/100 py with DMPA use (adjIRR 0.57, 95% CI 0.19-1.70). The number of female seroconverters was three among oral contraceptive users, one among Norplant users, and seven among DMPA users. Male seroconverters were two during female oral contraceptive use, none with Norplant use, and three with DMPA use. In a nested case-control analysis after adjustment for HIV viral load, the adjOR associated with oral contraceptive use was 1.59 (95% CI 0.32-97.85) for M+F- and 2.11 (95% CI 0.18-25.26) for M-F+ couples. For DMPA use, the adjOR was 1.44 (95% CI 0.46-4.51) for M+F- and 1.40 (95% CI 0.30-6.49) for M-F+ couples. CONCLUSION: We did not observe significant risk of HIV acquisition or transmission with oral contraceptives or DMPA use in HIV discordant couples, but several point estimates were above 1.0 and statistical power was limited.

Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial.

BACKGROUND: Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda. METHODS: We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300-400 cells per µL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per µL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log(10) viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov, number NCT00405821. FINDINGS: 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58-0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50,000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43-0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50,000 copies per mL (0·90, 0·54-1·5; p=0·688). No safety issues related to aciclovir treatment were identified. INTERPRETATION: Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50,000 copies per mL or more before initiation of antiretroviral treatment. FUNDING: National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA).

Increasing access to institutional deliveries using demand and supply side incentives: early results from a quasi-experimental study.

BACKGROUND: Geographical inaccessibility, lack of transport, and financial burdens are some of the demand side constraints to maternal health services in Uganda, while supply side problems include poor quality services related to unmotivated health workers and inadequate supplies. Most public health interventions in Uganda have addressed only selected supply side issues, and universities have focused their efforts on providing maternal services at tertiary hospitals. To demonstrate how reforms at Makerere University College of Health Sciences (MakCHS) can lead to making systemic changes that can improve maternal health services, a demand and supply side strategy was developed by working with local communities and national stakeholders. METHODS: This quasi-experimental trial is conducted in two districts in Eastern Uganda. The supply side component includes health worker refresher training and additions of minimal drugs and supplies, whereas the demand side component involves vouchers given to pregnant women for motorcycle transport and the payment to service providers for antenatal, delivery, and postnatal care. The trial is ongoing, but early analysis from routine health information systems on the number of services used is presented. RESULTS: Motorcyclists in the community organized themselves to accept vouchers in exchange for transport for antenatal care, deliveries and postnatal care, and have become actively involved in ensuring that women obtain care. Increases in antenatal, delivery, and postnatal care were demonstrated, with the number of safe deliveries in the intervention area immediately jumping from <200 deliveries/month to over 500 deliveries/month in the intervention arm. Voucher revenues have been used to obtain needed supplies to improve quality and to pay health workers, ensuring their availability at a time when workloads are increasing. CONCLUSIONS: Transport and service vouchers appear to be a viable strategy for rapidly increasing maternal care. MakCHS can design strategies together with stakeholders using a learning-by-doing approach to take advantage of community resources.

Effect of changing antiretroviral treatment eligibility criteria on patient load in Kampala, Uganda.

In many resource-poor countries, CD4 count thresholds of eligibility for antiretroviral treatment (ART) were initially low (<200 cells/mm(3)) but are now being increased to improve patient survival and to reduce HIV transmission. There are few quantitative data on the effect of such increases on the demand for ART. The objective of this study was to measure HIV prevalence and the proportion of HIV-positives eligible for antiretroviral therapy at different CD4 cut-off levels among users of public health care services in Kampala, Uganda. We recruited 1200 adults from three primary care clinics in Kampala, including equal numbers of family planning (FP) clients, pregnant women, adult patients with any complaint, and persons seeking HIV counseling and testing. All participants were screened for HIV and those positive had a CD4 count done. HIV prevalence in all patients was 16.9% (203/1200). ART eligibility based on CD4 counts significantly increased from 36% at a 200 cells/mm(3) cut-off to 44% at 250 cells and to 57% at 350 cells cut-off (p for χ(2) trend<0.001). We concluded that changing cut-off levels to higher CD4 counts will significantly increase patient load in Kampala's primary care clinics, but a phased implementation should minimize negative effects on quality of care.

HIV-1 subtypes and differences in heterosexual HIV transmission among HIV-discordant couples in Rakai, Uganda.

OBJECTIVE: To determine whether heterosexual transmission of HIV differs according to HIV-1 subtype. DESIGN: A retrospective observational cohort. METHODS: HIV-1 subtype effects on heterosexual HIV-1 transmission were determined among 268 HIV-discordant couples retrospectively identified from a population cohort in Rakai, Uganda. HIV-1 subtype (gag and gp41 sequencing and multiregion hybridization assay) and viral loads (reverse transcriptase PCR) were determined. Adjusted incidence rate ratios (adj IRR) of HIV transmission by subtype were estimated by multivariable Poisson regression adjusting for characteristics of index HIV-positive and HIV-negative partners. RESULTS: Adjusting for index HIV-positive partners' age, viral load, stage of disease, genital ulcer disease, and HIV-negative partners' genital ulcer disease and nonuse of condoms, subtype A viruses were associated with a higher rate of transmission than subtype D [adj.IRR 1.98, 95% confidence interval (CI) 1.17-3.34], but no differences in transmission were observed between recombinant viruses and subtype D (aIRR 1.53, P = 0.25). Index-positive partners' age less than 30 years (adj.IRR 3.44, 95% CI 1.75-6.78) and viral load (adj.IRR 2.37, 95% CI 1.75-3.21), and index-negative partners' genital ulcer disease (adj.IRR 1.71, 95% CI 1.08-2.70) and nonuse of condoms (adj.IRR 1.94, 95% CI 1.15-3.28) were significant determinants of HIV transmission. CONCLUSION: In Rakai, Uganda, subtype A viruses have a significantly higher rate of heterosexual transmission than subtype D viruses. Differential subtype transmission efficiency may be important for HIV vaccine evaluation and could contribute to subtype-specific HIV epidemics in sub-Saharan Africa.