Mortality Among Children Aged <5 Years Living with HIV Who Are Receiving Antiretroviral Treatment - U.S. President's Emergency Plan for AIDS Relief, 28 Supported Countries and Regions, October 2020-September 2022.

Globally, children aged <5 years, including those living with HIV who are not receiving antiretroviral treatment (ART), experience disproportionately high mortality. Global mortality among children living with HIV aged <5 years receiving ART is not well described. This report compares mortality and related clinical measures among infants aged <1 year and children aged 1-4 years living with HIV with those among older persons aged 5-14, 15-49, and ≥50 years living with HIV receiving ART services at all clinical sites supported by the U.S. President's Emergency Plan for AIDS Relief. During October 2020-September 2022, an average of 11,980 infants aged <1 year and 105,510 children aged 1-4 years were receiving ART each quarter; among these infants and children receiving ART, 586 (4.9%) and 2,684 (2.5%), respectively, were reported to have died annually. These proportions of infants and children who died ranged from four to nine times higher in infants aged <1 year, and two to five times higher in children aged 1-4 years, than the proportions of older persons aged ≥5 years receiving ART. Compared with persons aged ≥5 years living with HIV, the proportions of children aged <5 years living with HIV who experienced interruptions in treatment were also higher, and the proportions who had a documented HIV viral load result or a suppressed viral load were lower. Prioritizing and optimizing HIV and general health services for children aged <5 years living with HIV receiving ART, including those recommended in the WHO STOP AIDS Package, might help address these disproportionately poorer outcomes.

Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Scale-Up of HIV Antiretroviral Therapy and Estimation of Averted Infections and HIV-Related Deaths - Uganda, 2004-2022.

On January 28, 2003, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest commitment by any nation to address a single disease in history, was announced.* In April 2004, the first person in the world to receive PEPFAR-supported antiretroviral therapy (ART) was a man aged 34 years in Uganda. Effective ART reduces morbidity and mortality among persons with HIV infection (1) and prevents both mother-to-child transmission (MTCT) (2) and sexual transmission once viral load is suppressed to undetectable levels (<200 viral copies/mL) (3). By September 2022, more than 1.3 million persons with HIV infection in Uganda were receiving PEPFAR-supported ART, an increase of approximately 5,000% from September 2004. As indicators of the ART program's effectiveness, a proxy MTCT rate decreased 77%, from 6.4% in 2010 to 1.5% in 2022, and the viral load suppression rate (<1,000 viral copies/mL) increased 3%, from 91% in 2016 to 94% in September 2022. During 2004-2022, ART scale-up helped avert nearly 500,000 HIV infections, including more than 230,000 infections among HIV-exposed infants, and approximately 600,000 HIV-related deaths. Going forward, efforts will focus on identifying all persons with HIV infection and rapidly linking them to effective ART. PEPFAR remains committed to continued strong partnership with the Government of Uganda, civil society, and other development partners toward sustainable solutions aligned with the Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track strategy to ending the global AIDS epidemic by 2030† and safeguarding impact achieved in the long term.

Risk factors for mortality among patients diagnosed with multi-drug resistant tuberculosis in Uganda- a case-control study.

BACKGROUND: The World Health Organization (WHO) End TB strategy aims to reduce mortality due to tuberculosis (TB) to less than 5% by 2035. However, mortality due to multidrug-resistant tuberculosis (MDR-TB) remains particularly high. Globally, almost 20% of patients started on MDR-TB treatment die during the course of treatment every year. We set out to examine the risk factors for mortality among a cohort of patients diagnosed with MDR-TB in Uganda. METHODS: We conducted a case-control study nested within the national MDR-TB cohort. We defined cases as patients who died from any cause during the course of MDR-TB treatment. We selected two controls for each case from patients alive and on MDR-TB treatment at the time that the death occurred (incidence-density sampling). We matched the cases and controls on health facility at which they were receiving care. We performed conditional logistic regression to identify the risk factors for mortality. RESULTS: Data from 198 patients (66 cases and 132 controls) started on MDR-TB treatment from January 1 to December 31, 2016, was analyzed for this study. Cases were similar to controls in age/sex distribution, occupation and history of TB treatment. However, cases were more likely to be HIV infected while controls were more likely to have attained secondary level education. On multivariate regression analysis, co-infection with HIV (aOR 1.9, 95% CI [1.1-4.92] p = 0.05); non-adherence to MDR-TB treatment (aOR 1.92, 95% CI [1.02-4.83] p = 0.04); age over 50 years (aOR 3.04, 95% CI [1.13-8.20] p = 0.03); and having no education (aOR 3.61, 95% CI [1.1-10.4] p = 0.03) were associated with MDR-TB mortality. CONCLUSION: To mitigate MDR-TB mortality, attention must be paid to provision of social support particularly for older persons on MDR-TB treatment. In addition, interventions that support treatment adherence and promote early detection and management of TB among HIV infected persons should also be emphasized.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study.

INTRODUCTION: Systematic screening for TB among patients presenting to care and among high risk populations is recommended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches implemented by a large urban TB project in central Uganda. METHODS: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (numbers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and community TB registers. RESULTS: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). CONCLUSION: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study

Introduction: Systematic screening for TB among patients presenting to care and among high risk populations is recom- mended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches imple- mented by a large urban TB project in central Uganda. Methods: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (num- bers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and com- munity TB registers. Results: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). Conclusion: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years

Households experiencing catastrophic costs due to tuberculosis in Uganda: magnitude and cost drivers.

BACKGROUND: Tuberculosis (TB) patients in Uganda incur large costs related to the illness, and while seeking and receiving health care. Such costs create access and adherence barriers which affect health outcomes and increase transmission of disease. The study ascertained the proportion of Ugandan TB affected households incurring catastrophic costs and the main cost drivers. METHODS: A cross-sectional survey with retrospective data collection and projections was conducted in 2017. A total of 1178 drug resistant (DR) TB (44) and drug sensitive (DS) TB patients (1134), 2 weeks into intensive or continuation phase of treatment were consecutively enrolled across 67 randomly selected TB treatment facilities. RESULTS: Of the 1178 respondents, 62.7% were male, 44.7% were aged 15-34 years and 55.5% were HIV positive. For each TB episode, patients on average incurred costs of USD 396 for a DS-TB episode and USD 3722 for a Multi drug resistant tuberculosis (MDR TB) episode. Up to 48.5% of households borrowed, used savings or sold assets to defray these costs. More than half (53.1%) of TB affected households experienced TB-related costs above 20% of their annual household expenditure, with the main cost drivers being non-medical expenditure such as travel, nutritional supplements and food. CONCLUSION: Despite free health care in public health facilities, over half of Ugandan TB affected households experience catastrophic costs. Roll out of social protection interventions like TB assistance programs, insurance schemes, and enforcement of legislation related to social protection through multi-sectoral action plans with central NTP involvement would palliate these costs.

Improving TB case notification in northern Uganda: evidence of a quality improvement-guided active case finding intervention.

BACKGROUND: Strategies to identify and treat undiagnosed prevalent cases that have not sought diagnostic services on their own, are necessary to treat TB in patients earlier and interrupt transmission. Late presentation for medical services of symptomatic patients require special efforts to detect early and notify TB in high risk populations. An intervention that combined quality improvement with facility-led active case finding (QI-ACF) was implemented in 10 districts of Northern Uganda with the highest TB burden to improve case notification among populations at highest risk of TB. METHODS: Using QI-ACF intervention approach in 48 facilities, we; 1) targeted key vulnerable populations, 2) engaged district and facility teams in TB systems strengthening, 3) conducted systematic screening and diagnosis in vulnerable groups (people living with HIV, fishing communities, and prisoners), and 4) trained health workers on national x-ray diagnosis guidelines for smear-negative patients. Facility-led QI-ACF meant that health care providers identified the target population, mobilized and massively screened suspects, and addressed gaps in documentation. Chest X-ray diagnosis was promoted for smear-negative TB among those suspects whose sputum examination was negative. The effect of the intervention on case notification was then assessed separately over the post intervention period. RESULTS: Over all TB case notification in the intervention districts increased from 171 to 223 per 100,000 population between the baseline months of October-December 2016 and end line month of April-June 2017. TB patient contacts had the majority of TB positive cases identified during active case finding (40, 6.1%). Fishing communities had the highest TB positivity rate at 6.8%. Prisoners accounted for the lowest number of TB positive cases at 34 (2.3%). CONCLUSION: Targeting should be applied at all levels of TB intervention to improve yield: targeting districts and facilities with the lowest rates of case notification and targeting index patient contacts, HIV clients, and fishing communities. Screening tools are useful to guide health workers to identify presumptive cases. Efforts to improve availability of x-ray for TB diagnosis contributed to almost half of the new cases identified. Having all HIV patients who were eligible for viral load provide sputum for TB screening proved easy to implement.

Response to anti-tuberculosis treatment by people over age 60 in Kampala, Uganda.

While old age is a known risk factor for developing active tuberculosis (TB), studies on TB in the population aged 60 years and older (considered elderly in this study) are few, especially in the developing world. Results of the TB prevalence survey in Uganda found high TB prevalence (570/100,000) in people over 65. We focused on treatment outcomes in the elderly to understand this epidemic better. We conducted a retrospective analysis of data from TB facility registers in Kampala City for the period 2014-2015. We analyzed the 2014-15 cohort with respect to age, sex, disease class, patients' human immunodeficiency virus (HIV) and directly observed therapy (DOT) status, type of facility, and treatment outcomes and compared findings in the elderly (≥60) and younger (<60) age groups. Of 15,429 records, 3.3% (514/15,429) were for elderly patients. The treatment success rate (TSR) among elderly TB patients (68.3%) was lower than that of the non-elderly (80.9%) and the overall TSR 80.5%, (12,417/15,429) in Kampala. Although the elderly were less likely to test positive for HIV than the young (AOR 0.39; 95% CI 0.33-0.48, p<0.001), they had a two-fold higher risk of unfavorable treatment outcomes (AOR 2.14; CI 1.84-2.72, p<0.001) and were more likely to die while on treatment (AOR 1.86; CI 1.27-2.73; p = 0.001). However, there was no statistically significantly difference between treatment outcomes among HIV-positive and HIV-negative elderly TB patients. Compared to the younger TB patients, elderly TB patients have markedly poorer treatment outcomes, although TB/HIV co-infection rates in this age group are lower.

Evaluation of Automated Molecular Testing Rollout for Tuberculosis Diagnosis Using Routinely Collected Surveillance Data - Uganda, 2012-2015.

In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted.