Challenges and Fears of Adolescents and Young Adults Living with HIV Facing Transition to Adult HIV Care.

Adolescents and young adults living with perinatally-acquired HIV (AYLPHIV) have poor outcomes along each step of the HIV care continuum due to challenges in seeking care and advocating for themselves. The transition from paediatric to adult HIV care is a particularly high-risk period for AYLPHIV in rural Uganda. We conducted in-depth interviews with AYLPHIV (n = 30), caregivers (n = 10), and healthcare providers (n = 10) to understand challenges facing AYLPHIV during the transition from paediatric to adult HIV care. Themes were identified by thematic content analysis. Transition-related challenges and fears included difficulty navigating the adult HIV clinic; loss of informational support; long wait times at the adult HIV clinic; lack of privacy, and fear of HIV status disclosure and stigma; and loss of support from caregivers, and health care providers. Before transitioning to adult HIV care, AYLPHIV should be adequately prepared and given appropriate information to help them navigate adult HIV care.

Intrapersonal predictors of internalized stigma among school going adolescents living with HIV in southwestern Uganda.

We assessed the association between internalized HIV stigma, resilience, health locus of control, coping self-efficacy and empowerment among adolescents living with HIV in Uganda. We conducted a cross-sectional study between August and October 2020 among 173 adolescents aged 13-18 years attending Mbarara Regional Referral Hospital's HIV clinic. We used linear regression to determine the association between HIV stigma and intrapersonal factors adjusting for sociodemographic characteristics. The median age of the participants was 16 (IQR 3) years. There was a negative correlation between HIV stigma and resilience (ß= -0.03, p < 0.001), internal health locus of control (ß= -0.095, p < 0.001) and coping self-efficacy (ß= -0.02, p < 0.001), while empowerment was positively correlated (ß = 0.07, p < 0.001) with HIV stigma. After adjusting for the intrapersonal factors (resilience, health locus of control, coping self-efficacy and empowerment) and socio-demographic characteristics (education level and boarding school), only internal health locus of control (ß=-0.044, p = 0.016) and coping self-efficacy (ß=-0.015, p < 0.001) remained significantly correlated with HIV stigma. The findings suggest that interventions focusing on intrapersonal factors such as internal locus of control, empowerment and resilience may contribute towards reduction of HIV stigma among adolescents in boarding schools.

Interventions to Increase HIV Testing Uptake in Global Settings.

PURPOSE OF REVIEW: HIV testing is the critical first step to direct people living with HIV (PLWH) to treatment. However, progress is still being made towards the UNAIDS benchmark of 95% of PLWH knowing their status by 2030. Here, we discuss recent interventions to improve HIV testing uptake in global settings. RECENT FINDINGS: Successful facility-based HIV testing interventions involve couples and index testing, partner notification, and offering of incentives. Community-based interventions such as home-based self-testing, mobile outreach, and hybrid approaches have improved HIV testing in low-resource settings and among priority populations. Partnerships with trusted community leaders have also increased testing among populations disproportionally impacted by HIV. Recent HIV testing interventions span a breadth of facility- and community-based approaches. Continued research is needed to engage men in sub-Saharan Africa, people who inject drugs, and people who avoid biomedical care. Interventions should consider supporting linkage to care for newly diagnosed PLWH.

Xpert MTB/RIF diagnosis of childhood tuberculosis from sputum and stool samples in a high TB-HIV-prevalent setting.

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.

Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda.

Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.

A qualitative analysis of self-management needs of adolescents and young adults living with perinatally acquired HIV in rural, southwestern Uganda.

The number of adolescents living with HIV remains high in sub-Saharan Africa with poorer HIV treatment outcomes among adolescents and young adults compared to individuals in other age groups. For adolescents and young adults living with perinatally acquired HIV (AYLPHIV), the transition from pediatric to adult HIV care is a particularly high-risk period. We conducted a qualitative study to understand self-management needs of AYLPHIV in rural, southwestern Uganda as they prepare to transition to adult HIV care in order to inform relevant interventions that can enable AYLPHIV acquire the necessary skills to manage their illness as they age into adulthood. We conducted 60 in-depth interviews with AYLPHIV (n = 30), caregivers (n = 20) and health care providers (n = 10) from the HIV clinic at Mbarara Regional Referral Hospital. We used an interview guide that focused on perceptions about transition to adult HIV care, challenges with transitioning, navigating HIV care, and self-management needs for AYLPHIV (from the perspectives of AYLPHIV, their caregivers, and health care providers). We used thematic analysis to identify themes related to AYLPHIV's self-management skills. We identified several self-management needs that we grouped under two major themes; social support and empowerment for AYLPHIV to assume responsibility for their own health and to navigate adult HIV care independently. The sub-themes under social support were information support, instrumental support, and emotional support as the sub themes while sub-themes under empowerment included self-advocacy skills, interpersonal skills, self-care skills, and disclosure skills. Taken together, these findings indicate that AYLPHIV need to be supported and empowered to maximize their chances of successfully transitioning to adult HIV care. Support comes from peers and caregivers. AYLPHIV require knowledge about their HIV status and empowerment with different skills including: self-advocacy skills, interpersonal skills, self-care skills, and HIV status disclosure skills, in order to assume responsibilities related to independent HIV care.

Traditional healer support to improve HIV viral suppression in rural Uganda (Omuyambi): study protocol for a cluster randomized hybrid effectiveness-implementation trial.

BACKGROUND: Rural African people living with HIV face significant challenges in entering and remaining in HIV care. In rural Uganda, for example, there is a threefold higher prevalence of HIV compared to the national average and lower engagement throughout the HIV continuum of care. There is an urgent need for appropriate interventions to improve entry and retention in HIV care for rural Ugandans with HIV. Though many adults living with HIV in rural areas prioritize seeking care services from traditional healers over formal clinical services, healers have not been integrated into HIV care programs. The Omuyambi trial is investigating the effectiveness of psychosocial support delivered by traditional healers as an adjunct to standard HIV care versus standard clinic-based HIV care alone. Additionally, we are evaluating the implementation process and outcomes, following the Consolidated Framework for Implementation Research. METHODS: This cluster randomized hybrid type 1 effectiveness-implementation trial will be conducted among 44 traditional healers in two districts of southwestern Uganda. Healers were randomized 1:1 into study arms, where healers in the intervention arm will provide 12 months of psychosocial support to adults with unsuppressed HIV viral loads receiving care at their practices. A total of 650 adults with unsuppressed HIV viral loads will be recruited from healer clusters in the Mbarara and Rwampara districts. The primary study outcome is HIV viral load measured at 12 months after enrollment, which will be analyzed by intention-to-treat. Secondary clinical outcome measures include (re)initiation of HIV care, antiretroviral therapy adherence, and retention in care. The implementation outcomes of adoption, fidelity, appropriateness, and acceptability will be evaluated through key informant interviews and structured surveys at baseline, 3, 9, 12, and 24 months. Sustainability will be measured through HIV viral load measurements at 24 months following enrollment. DISCUSSION: The Omuyambi trial is evaluating an approach that could improve HIV outcomes by incorporating previously overlooked community lay supporters into the HIV cascade of care. These findings could provide effectiveness and implementation evidence to guide the development of policies and programs aimed at improving HIV outcomes in rural Uganda and other countries where healers play an essential role in community health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05943548. Registered on July 5, 2023. The current protocol version is 4.0 (September 29, 2023).

Adaption and pilot testing of a lay HIV supporter program for traditional healers: a mixed methods study in rural Uganda.

BACKGROUND: Half of people living with HIV (PLWH) in sub-Saharan Africa default from care within two years. In Uganda, and across sub-Saharan Africa, traditional healers (TH) are ubiquitous and often serve as the first line of health care. We hypothesized that with lay support training, TH could support relinkage to HIV care and ART adherence among rural Ugandan PLWH who have defaulted from HIV care. METHODS: Following the ADAPT-ITT framework, we adapted an evidence-based layperson HIV support program from South Africa for delivery by Ugandan TH. The ADAPT-ITT framework consists of (1) Assessment of needs; (2) Deciding which evidence-based interventions to adapt; (3) Adaptation of interventions; (4) Production of drafted adapted interventions; (5) Topical expert feedback; (6) Integration of expert feedback; (7) Training personnel; and (8) Testing the adapted intervention. The Testing phase was completed via a pilot mixed methods prospective cohort study. The study population included 12 TH practicing in Mbarara Township and 20 adult PLWH with suboptimal ART adherence (CASE adherence index score < 10) who received care from a participating TH and who resided in Mbarara Township. Primary outcome was re-linkage to HIV care within 14 days. Secondary outcomes were ART re-initiation, ART adherence, retention in care after 9 months, and implementation measures. Qualitative interviews were conducted with all participants. RESULTS: Data from the Assessment phase indicated that logistical challenges played an important role in disengagement from care among PLWH who receive care from TH, notably geographical distance to clinics and transportation costs. Additionally, HIV-related stigma and lack of social support were identified as barriers to entering and remaining in HIV care. Two core elements of the intervention were identified during the Production phase: (1) TH facilitating rapid re-linkage to HIV care and (2) TH provision of psychosocial support. In the pilot study phase, baseline median CASE adherence score was 3; only 5% of PLWH were adherent to ART via 4-day recall. The TH-delivered support achieved 100% linkage and ART initiation within 14 days, 95% ART adherence, and 100% of PLWH were retained in HIV care after 9 months. CONCLUSIONS: The ADAPT-ITT framework successfully guided the adaption of a community health worker-delivered intervention for delivery by TH. TH successfully facilitated re-linkage to HIV care, support ART adherence, and retention in care for PLWH when trained as part of a lay support person program. Future studies are needed to evaluate scale-up and long-term impact.

Electronic Antiretroviral Therapy Adherence Monitors and Associated Interventions Improve Adolescent-Caregiver Relationships and Self-Efficacy Among Adolescents and Young Adults with HIV in Uganda.

Many adolescents and young adults with HIV (AYWH) struggle with antiretroviral therapy (ART) adherence and experience poorer outcomes than adults. Relevant factors include forgetfulness and poor self-efficacy related to their evolving neurobiology. We qualitatively explored experiences of AYWH-caregivers dyads using real-time ART adherence monitors and associated reminder functions in the home setting. As part of an implementation science-oriented study, AYWH used the Wisepill adherence monitor for 3 months. AYWH could also opt for short message service (SMS) self-reminders, a self-selected social supporter for delayed or missed doses, or an alarm reminder. We conducted in-depth interviews with randomly selected AYWH-caregiver dyads regarding their experience using the monitor. Qualitative data were analyzed using inductive content analysis. We completed 15 AYWH-caregiver dyad interviews. Of the AYWH, 67% were female, mean age was 16 years, 56% lived with their biological mother, and 86% were virologically suppressed. AYWH and their caregivers generally found the adherence monitors acceptable, though some had privacy concerns. AYWH felt the monitors helped them take charge of their medication, largely through the real-time alarm and SMS reminders; this took the burden of adherence reminders away from the caregivers, improving strained AYWH-caregiver relationships. Two adolescents reported rebound poor adherence after monitor withdrawal. ART adherence monitors and associated tools were largely acceptable to AYWH and their caregivers in home settings. The intervention helped improve AYWH self-efficacy and alleviated burden from some AYWH-caregiver relationships. Rebound poor adherence suggests the need for on-going support and/or other means to achieve intrinsic mechanisms for sustained adherence. Clinical Trial Registration number: NCT03825952.

Bacterial meningitis among children under the age of 2 years in a high human immunodeficiency virus prevalence area after Haemophilus influenzae type b vaccine introduction.

AIM: The aim of this study was to describe bacterial causes of meningitis among children < 2 years in a high human immunodeficiency virus (HIV) prevalence area after introduction of routine Haemophilus influenzae type b vaccination. METHODS: Data collected between April 2003 and December 2008 were extracted from a surveillance database and medical records of children < 2 years admitted in Mbarara Hospital, Uganda with suspected bacterial meningitis. HIV infection was confirmed using rapid tests and polymerase chain reaction and bacterial meningitis by using cerebrospinal fluid culture. RESULTS: Between April 2003 and December 2008, 1464 children under 5 years were admitted with suspected bacterial meningitis of which 1235 (84.4%) had cerebrospinal fluid collected; 894 (72.4%) of these samples were from children < 2 years. Of the 894 samples, 64 (7.2%) grew an organism including Streptococcus pneumoniae (26; 41%), Salmonella species (20; 31%), H. influenzae (6; 9%) and coliforms (7; 11%), and five (8%) grew contaminants that are all coagulase negative Staphylococcus. Of the 894 children, 468 (52.3%) were tested for HIV; 16.7% were positive. Fifty-one children had a pathogenic isolate and a treatment outcome, and 23 (45%) died; 13 (56.6%) deaths were due to S. pneumoniae, eight (34.8%) were due to Salmonella spp., one (4.3%) was due to H. influenzae and one (4.3%) was due to coliforms. HIV infection was associated with a threefold increase in mortality, increased likelihood of a bacterial isolate and decreased likelihood of malaria parasitaemia. CONCLUSION: Following H. influenzae type b vaccine introduction, S. pneumoniae and Salmonella spp. are the major causes of bacterial meningitis among children < 2 years in Uganda. Pneumococcal conjugate vaccines and reduction in mother to child transmission of HIV could reduce the observed mortality.

Perspectives About Transition Readiness Among Adolescents and Young People Living With Perinatally Acquired HIV in Rural, Southwestern Uganda: A Qualitative Study.

ABSTRACT: Despite the availability of antiretroviral therapy, treatment outcomes are worse among adolescents and young adults living with perinatally acquired HIV (AYLPHIV). These disparities are magnified during the transition from pediatric to adult-based HIV care. We conducted in-depth interviews with AYLPHIV aged 15-24 years ( n = 30), their caregivers ( n = 10), and health care providers ( n = 10). All participants provided written assent and/or informed consent to enroll. Thematic content analysis was used to identify and analyze themes relevant to transition readiness. We grouped perspectives on transition readiness into 4 themes: preparation for transition, communication between stakeholders, social support, and timing of transition. AYLPHIV in sub-Saharan Africa who are facing a transition to adult HIV care should be equipped with relevant information about their illness, self-advocacy skills, and support from caregivers and health care providers to remain engaged in HIV care.

How informal healthcare providers improve uptake of HIV testing: qualitative results from a randomized controlled trial.

OBJECTIVE: Uganda is HIV-endemic with a prevalence of 5.7%. Lack of epidemic control has been attributed to low engagement with HIV testing. Collaborating with informal healthcare providers, such as traditional healers, has been proposed as a strategy to increase testing uptake. We explored acceptability and implementation of an HIV testing program where traditional healers delivered point-of-care testing and counseling to adults of unknown serostatus (clinicaltrials.gov NCT#03718871). METHODS: This study was conducted in rural, southwestern Uganda. We interviewed participating traditional healers ( N  = 17) and a purposive sample of trial participants ( N  = 107). Healers were practicing within 10 km of Mbarara township, and 18+ years old. Participants were 18+ years old; sexually active; had received care from participating healers; self-reported not receiving an HIV test in prior 12 months; and not previously diagnosed with HIV infection. Interviews explored perceptions of a healer-delivered HIV testing model and were analyzed following a content-analysis approach. RESULTS: Most participants were female individuals ( N  = 68, 55%). Healer-delivered HIV testing overcame structural barriers, such as underlying poverty and rural locations that limited use, as transportation was costly and often prohibitive. Additionally, healers were located in villages and communities, which made services more accessible compared with facility-based testing. Participants also considered healers trustworthy and 'confidential'. These qualities explain some preference for healer-delivered HIV testing, in contrast to 'stigmatizing' biomedical settings. CONCLUSION: Traditional healer-delivered HIV testing was considered more confidential and easily accessible compared with clinic-based testing. Offering services through traditional healers may improve uptake of HIV testing services in rural, medically pluralistic communities.

Traditional healer-delivered point-of-care HIV testing versus referral to clinical facilities for adults of unknown serostatus in rural Uganda: a mixed-methods, cluster-randomised trial.

BACKGROUND: HIV counselling and testing are essential to control the HIV epidemic. However, HIV testing uptake is low in sub-Saharan Africa, where many people use informal health-care resources such as traditional healers. We hypothesised that uptake of HIV tests would increase if provided by traditional healers. We aimed to determine the effectiveness of traditional healers delivering HIV testing at point of care compared with referral to local clinics for HIV testing in rural southwestern Uganda. METHODS: We did a mixed-methods study that included a cluster-randomised trial followed by individual qualitative interviews among a sample of participants in Mbarara, Uganda. Traditional healers aged 18 years or older who were located within 8 km of the Mbarara District HIV clinic, were identified in the 2018 population-level census of traditional healers in Mbarara District, and delivered care to at least seven clients per week were randomly assigned (1:1) as clusters to an intervention or a control group. Healers screened their clients for eligibility, and research assistants confirmed eligibility and enrolled clients who were aged 18 years or older, were receiving care from a participating healer, were sexually active (ever had intercourse), self-reported not having received an HIV test in the previous 12 months (and therefore considered to be of unknown serostatus), and had not previously been diagnosed with HIV infection. Intervention group healers provided counselling and offered point-of-care HIV tests to adult clients. Control group healers provided referral for HIV testing at nearby clinics. The primary outcome was the individual receipt of an HIV test within 90 days of study enrolment. Safety and adverse events were recorded and defined on the basis of prespecified criteria. This study is registered with ClinicalTrials.gov, NCT03718871. FINDINGS: Between Aug 2, 2019, and Feb 7, 2020, 17 traditional healers were randomly assigned as clusters (nine to intervention and eight to control), with 500 clients of unknown HIV serostatus enrolled (250 per group). In the intervention group, 250 clients (100%) received an HIV test compared with 57 (23%) in the control group, a 77% (95% CI 73-82) increase in testing uptake, after adjusting for the effect of clustering (p<0·0001). Ten (4%) of 250 clients in the intervention group tested HIV positive, seven of whom self-reported linkage to HIV care. No new HIV cases were identified in the control group. Qualitative interviews revealed that HIV testing delivered by traditional healers was highly acceptable among both providers and clients. No safety or adverse events were reported. INTERPRETATION: Delivery of point-of-care HIV tests by traditional healers to adults of unknown serostatus significantly increased rates of HIV testing in rural Uganda. Given the ubiquity of healers in Africa, this approach holds promise as a new pathway to provide community-based HIV testing, and could have a dramatic effect on uptake of HIV testing in sub-Saharan Africa. FUNDING: US National Institute of Mental Health, National Institutes of Health.

Childhood trauma, major depressive disorder, suicidality, and the modifying role of social support among adolescents living with HIV in rural Uganda.

BACKGROUND: Childhood trauma is associated with mental health problems among adolescents living with HIV (ALHIV) in sub-Saharan Africa, but little is known about potential moderating factors. METHODS: We enrolled 224 ALHIV aged 13-17 years and collected information on childhood trauma, major depressive disorder, and suicidality. We used modified multivariable Poisson regression to estimate the association between the mental health outcome variables and childhood trauma, and to assess for effect modification by social support. RESULTS: Major depressive disorder had a statistically significant association with emotional abuse (adjusted relative risk [ARR] 2.57; 95% CI 1.31-5.04; P=0.006) and physical abuse (ARR 2.16; 95% CI 1.19-3.89; P=0.01). The estimated association between any abuse and major depressive disorder was statistically significant among those with a low level of social support (ARR 4.30; 95% CI 1.64-11.25; P=0.003) but not among those with a high level of social support (ARR 1.30; 95% CI 0.57-2.98; P=0.52). Suicidality also had a statistically significant association with emotional abuse (ARR 2.03; 95% CI 1.05-3.920; P=0.03) and physical abuse (ARR 3.17; 95% CI 1.60-6.25.; P=0.001), but no differences by social support were noted. LIMITATIONS: Corporal punishment is used widely in schools and homes as a form of discipline in Uganda; this cultural practice could have biased reporting about physical abuse. CONCLUSIONS: Childhood trauma is associated with poor mental health among ALHIV, but its effects may be moderated by social support. More research is needed to develop social support interventions for ALHIV with adverse childhood experiences for improved mental health outcomes.

Challenges in using mobile phones for collection of antiretroviral therapy adherence data in a resource-limited setting.

Frequent antiretroviral therapy adherence monitoring could detect incomplete adherence before viral rebound develops and thus potentially prevent treatment failure. Mobile phone technologies make frequent, brief adherence interviews possible in resource-limited settings; however, feasibility and acceptability are unknown. Interactive voice response (IVR) and short message service (SMS) text messaging were used to collect adherence data from 19 caregivers of HIV-infected children in Uganda. IVR calls or SMS quantifying missed doses were sent in the local language once weekly for 3-4 weeks. Qualitative interviews were conducted to assess participant impressions of the technologies. Participant interest and participation rates were high; however, weekly completion rates for adherence queries were low (0-33%), most commonly due to misunderstanding of personal identification numbers. Despite near ubiquity of mobile phone technology in resource-limited settings, individual level collection of healthcare data presents challenges. Further research is needed for effective training and incentive methods.

Surveillance for Streptococcus pneumoniae meningitis in children aged <5 years: implications for immunization in Uganda.

Affordable pneumococcal conjugate vaccines will soon become available to developing countries through the Global Alliance for Vaccines and Immunization. Data on Streptococcus pneumoniae meningitis epidemiology in Uganda will assist decision makers in determining the best national vaccine policy. We reviewed acute bacterial meningitis surveillance data for children aged <5 years from 3 sentinel surveillance sites in 3 Ugandan districts collected from 2001 through 2006. Serotype and antibiotic-resistance testing were performed on pneumococcal isolates collected from 2005 through 2006 from the Kampala district in the tropical central region of Uganda. Minimum pneumococcal meningitis incidence estimates were calculated for a portion of the Kampala district and all of the Gulu district, where case ascertainment was more complete. At the 3 sites, 14,388 probable acute bacterial meningitis cases were observed. The most common cause identified was S. pneumoniae (n = 331; 35% of all confirmed cases), which had an overall case fatality ratio of 19%. Yearly pneumococcal meningitis incidence was 3-20 cases per 100,000 population in Kampala versus 28-42 cases per 100,000 population in Gulu. The most commonly identified serotypes were 6A/6B (40%); 43% of isolates were serotypes that are in the available 7-valent pneumococcal conjugate vaccine and 70% are in the proposed 13-valent pneumococcal vaccine. Twenty-five isolates (83%) had intermediate resistance to penicillin but none were fully resistant. Pneumococcal meningitis is common and severe in Uganda, indicating a role for the pneumococcal conjugate vaccine.

Action for child survival: elimination of Haemophilus influenzae type b meningitis in Uganda.

OBJECTIVE: To guide immunization policy, we determined the public health benefit of introducing Haemophilus influenzae type b (Hib) vaccine in Uganda and estimated the vaccine effectiveness. METHODS: Surveillance data for acute bacterial meningitis among children aged 0-59 months were reviewed from three hospital sentinel sites, for July 2001 to June 2007, to determine the incidence of Hib meningitis, the effectiveness of Hib vaccine with a case-control design, and the number of vaccine-preventable cases and deaths of Hib disease in Uganda. FINDINGS: Of the 13 978 children from 17 districts with suspected bacterial meningitis, 269 had confirmed Hib meningitis, declining from 69 patients in the prevaccine year (2001-2002) to three in 2006-2007. Hib meningitis incidence dropped from 88 cases per 100,000 children aged < 5 years in the year before vaccine introduction to 13 within 4 years, and to near zero in the fifth year. Vaccine effectiveness for 2 or more doses was 93% (95% confidence interval, CI: 69-99) against confirmed Hib meningitis and 53% (95% CI: 11-68) against purulent meningitis of unknown cause. In Uganda, Hib vaccine prevents an estimated 28 000 cases of pneumonia and meningitis, 5000 deaths and 1000 severe meningitis sequelae each year. CONCLUSION: Infant immunization with Hib vaccine has virtually eliminated Hib meningitis in Uganda within 5 years. Ensuring long-term benefits of Hib vaccine urgently requires sustainable vaccine financing, high-quality ongoing surveillance, and a health sector able to deliver a robust immunization programme.

Outcome of Children With Presumptive Tuberculosis in Mbarara, Rural Uganda.

BACKGROUND: Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality. METHODS: A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model. RESULTS: Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination. CONCLUSIONS: The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.

Rapid Serological Tests Ineffectively Screen for HIV Exposure in HIV-Positive Infants.

BACKGROUND: Data on the performance and utility of rapid serological tests in infants to determine HIV exposure are unclear and in some instances contradictory. This study sought to understand the performance of rapid serological tests in high HIV burden, high Option B+ coverage settings to be used as an HIV exposure screening tool. METHODS: A total of 3600 infants up to 24 months of age at 4 regional hospitals in Uganda were systematically enrolled and tested simultaneously using both HIV rapid serological and nucleic acid-based tests. RESULTS: Only 58 of the 94 HIV-positive infants who received both rapid serological and nucleic acid-based tests were positive with the rapid serological test (sensitivity: 61.7%; 95% confidence interval: 51.1 to 71.5). Using rapid serological tests to screen infants for exposure to HIV and follow-up nucleic acid-based testing would have missed 38.3% (36 of 94) of HIV-positive infants. Finally, several HIV-positive infants who were negative by rapid serological test presented to well-child entry points and were considered healthy. All 3 HIV-positive infants presenting to outreach and immunization were negative by rapid serological testing and 73% (8 of 11) presenting to outpatient. CONCLUSIONS: These data suggest that the use of rapid serological tests may have inadequate performance as an indicator of exposure and potential HIV infection among infants presenting at both well-child (immunization and community outreach) and sick-infant (nutrition and inpatient) entry points. To improve the identification of HIV-positive infants, nucleic acid-based testing should instead be considered in infants aged younger than 18 months.

Where have all the children gone? High HIV prevalence in infants attending nutrition and inpatient entry points.

INTRODUCTION: Despite notable progress towards PMTCT, only 50% of HIV-exposed infants in sub-Saharan Africa were tested within the first 2 months of life and only 30% of HIV-infected infants are on antiretroviral treatment. This study assessed HIV prevalence in infants and children receiving care at various service entry points in primary healthcare facilities in Uganda. METHODS: A total of 3600 infants up to 24 months of age were systematically enrolled and tested at four regional hospitals across Uganda. Six hundred infants were included and tested from six facility entry points: PMTCT, immunization, inpatient, nutrition, outpatient and community outreach services. FINDINGS: The traditional EID entry point, PMTCT, had a prevalence of 3.8%, representing 19.6% of the total HIV-positive infants identified in the study. Fifty percent of the 117 identified HIV-positive infants were found in the nutrition wards, which had a prevalence of 9.8% (p < 0.001 compared to PMTCT). Inpatient wards had a prevalence of 3.5% and yielded 17.9% of the HIV-positive infants identified. Infants tested at immunization wards and through outreach services identified 0.8% and 1.7% of the HIV-positive infants respectively, and had a prevalence of less than 0.3%. CONCLUSIONS: Expanding routine early infant diagnosis screening beyond the traditional PMTCT setting to nutrition and inpatient entry points will increase the identification of HIV-infected infants. Careful reflection for appropriate testing strategies, such as maternal re-testing to identify new HIV infections and HIV-exposed infants in need of follow-up testing and care, at immunization and outreach services should be considered given the expectedly low prevalence rates. These findings may help HIV care programmes significantly expand testing to improve access to early infant diagnosis and paediatric treatment.