SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019-2022.

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.

The Mirasol Evaluation of Reduction in Infections Trial (MERIT): study protocol for a randomized controlled clinical trial.

BACKGROUND: Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). METHODS: MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. DISCUSSION: Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. TRIAL REGISTRATION: Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669 . Registered on 9 November 2018.

Primary care provider notions on instituting community-based geriatric support in Uganda.

BACKGROUND: Understanding of the most economical and sustainable models of providing geriatric care to Africa's rising ageing population is critical. In Uganda, the number of old adults (60 years and above) continues to rise against absence of policies and guidelines, and models for providing care to this critical population. Our study explored public primary health care provider views on how best community-based geriatric support (CBGS) could be instituted as an adaptable model for delivering geriatric care in Uganda's resource-limited primary public health care settings. METHODS: We interviewed 20 key informants from four districts of Bukomansimbi, Kalungu, Rakai, and Lwengo in Southern Central Uganda. Respondents were leads (in-charges) of public primary health units that had spent at least 6 months at the fore said facilities. All interviews were audio-recorded, transcribed verbatim, and analysed based on Hsieh and Shannon's approach to conventional manifest content analysis. RESULTS: During analysis, four themes emerged: 1) Structures to leverage for CBGS, 2) How to promote CBGS, 3) Who should be involved in CBGS, and 4) What activities need to be leveraged to advance CBGS? The majority of the respondents viewed using the existing village health team and local leadership structures as key to the successful institutionalization of CBGS; leveraging community education and sensitization using radio, television, and engaging health workers, family relatives, and neighbors. Health outreach activities were mentioned as one of the avenues that could be leveraged to provide CBGS. CONCLUSION: Provider notions pointed to CBGS as a viable model for instituting geriatric care in Uganda's public primary healthcare system. However, this requires policymakers to leverage existing village health team and local governance structures, conduct community education and sensitization about CBGS, and bring onboard health workers, family relatives, and neighbors.

Predictors of failure on second-line antiretroviral therapy with protease inhibitor mutations in Uganda.

INTRODUCTION: Failure on second-line antiretroviral therapy (ART) with protease inhibitor (PI) mutations (VF-M) is on the rise. However, there is a paucity of information on the factors associated with this observation in low-income countries. Knowledge of underlying factors is critical if we are to minimize the number of PLHIV switched to costly third-line ART. Our study investigated the factors associated with VF-M. METHODS: We conducted a matched case-control analysis of patients' records kept at the Joint Clinical Research Center, starting from January 2008 to May 2018. We matched records of patients who failed the second-line ART with major PI mutations (cases) with records of patients who were virologically suppressed (controls) by a ratio of 1:3. Data analysis was conducted using STATA Version 14. Categorical variables were compared with the outcomes failure on second-line ART with PI mutations using the Chi-square and Fisher's exact tests where appropriate. Conditional logistic regression for paired data was used to assess the association between the outcome and exposure variables, employing the backward model building procedure. RESULTS: Of the 340 reviewed patients' records, 53% were women, and 6.2% had previous tuberculosis treatment. Males (aOR = 2.58, [CI 1.42-4.69]), and patients concurrently on tuberculosis treatment while on second-line ART (aOR = 5.65, [CI 1.76-18.09]) had higher odds of VF-M. ART initiation between 2001 and 2015 had lower odds of VF-M relative to initiation before the year 2001. CONCLUSION: Males and patients concomitantly on tuberculosis treatment while on second-line ART are at a higher risk of VF-M. HIV/AIDS response programs should give special attention to this group of people if we are to minimize the need for expensive third-line ART. We recommend more extensive, explorative studies to ascertain underlying factors.

Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17% by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29% (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.

Lopinavir/ritonavir monotherapy after 24 weeks of second-line antiretroviral therapy in Africa: a randomized controlled trial (SARA).

BACKGROUND: Boosted protease inhibitor (bPI) monotherapy (bPImono) potentially has substantial cost, safety and operational benefits. It has never been evaluated as second-line antiretroviral therapy (ART) in Africa. METHODS: After 24 weeks of lopinavir/ritonavir-containing second-line therapy, DART participants were randomized to remain on combination therapy (CT), or change to bPImono maintenance (SARA trial; ISRCTN53817258). Joint primary end points were CD4(+) T-cell changes 24 weeks later and serious adverse events (SAEs); retrospectively assayed viral load (VL) was a secondary end point. Analyses were intention-to-treat. RESULTS: A total of 192 participants were randomized to CT (n=95) or bPImono (n=97) and followed for median 60 weeks (IQR 45-84). Participants received median 4.0 years (IQR 3.5-4.4) first-line ART. Median CD4(+) T-cell count at first-line failure was 86 cells/mm(3) (47-136), increasing to 245 cells/mm(3) (173-325) after 24-week induction when 77% had VL<50 copies/ml. Overall, 44 (23%) were receiving second-line therapy with bPI and nucleoside reverse transcriptase inhibitors (NRTI) only, and 148 (77%) with bPI plus non-NRTI (NNRTI) with or without NRTI. At 24 weeks after randomization to CT versus bPImono, mean CD4(+) T-cell increase was 42 (CT, n=85) versus 49 cells/mm(3) (bPImono, n=88; adjusted difference 13 [95% CI -15, 43], P=0.37; non-inferior compared with predetermined non-inferiority margin [-33]). Virological suppression was greater for CT versus bPImono (trend P=0.009): 77% (70/91) versus 60% (56/94) were <50 copies/ml, and 5% (5) versus 14% (13) were ≥1,000 copies/ml, respectively. A total of 0 (0%) versus 5 (5%) participants had major protease inhibitor mutations and 3 (3%) versus 0 (0%) new NNRTI/NRTI mutations were detected during follow-up. Two participants (1 CT and 1 bPImono) died >24 weeks after randomization, and 5 (2 CT and 3 bPImono) experienced SAEs (P=0.51). CONCLUSIONS: bPImono following a 24-week second-line induction was associated with similar CD4(+) T-cell response, but increased low-level viraemia, generally without protease inhibitor resistance. Longer-term trials are needed to provide definitive evidence about effectiveness in Africa.