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.

Iron deficiency in whole blood donors in a resource-poor setting: A cross-sectional study in Uganda.

BACKGROUND AND OBJECTIVE: Blood donation is known to result in iron deficiency (ID), with a higher prevalence in females. There is little published data on the frequency of ID among blood donors in resource-poor settings. We determined the prevalence of ID in blood donors in Uganda. METHODS: We conducted a descriptive cross-sectional study at the Uganda Blood Transfusion Service, Kampala from December 2021 to February 2022. A sample of 500 whole blood donors was enrolled. The evaluation included demographic characteristics, donation history, nutritional history, complete blood count, and serum ferritin. The primary outcome was the proportion of donors with serum ferritin <15 µg/L. RESULTS: The median (IQR) serum ferritin was 25 (12-47) µg/L and 89 (52-133) µg/L among female and male donors respectively. The prevalence of iron deficiency (serum ferritin <15 µg/L) among donating individuals was 11.5% (8.7-14.9), while among low haemoglobin deferrals, 61.5% (50.9-71.1). The prevalence was high among females [33.0% (27.9-38.6)] compared with males [2.5% (1.0-5.8)], but even higher among females younger than 24 years [35.4% (29.2-42.1)]. Factors associated with ID (adjusted odds ratio, 95% Cl, and significance) were; female donors (15.81, 5.17, 48.28, p < 0.001) and a high RDW (6.89, 2.99, 15.90, p < 0.001). We found a moderate correlation between serum ferritin and RDW (r = -0.419 and -0.487 for males and females respectively). CONCLUSION: Iron deficiency is common among blood donors in Uganda, affecting mostly young female donors. Considerations to adopt evidence-based strategies to prevent and manage ID among blood donors-such as serum ferritin monitoring and iron supplementation are highly recommended.

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.

Efficacy of convalescent plasma for treatment of COVID-19 in Uganda.

RATIONALE: Convalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. OBJECTIVE: In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. MEASUREMENTS: Patients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalised and randomised to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR-negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety. MAIN RESULTS: A total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5-62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4-8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4-11) vs 4 (IQR=4-6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5-7) vs 7 (IQR=5-10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476). CONCLUSION: In this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration number NCT04542941.

Hepatitis C in Uganda: Identification of infected blood donors for micro-elimination.

BACKGROUND: The drive to eliminate viral hepatitis by 2030 is underway. However, locally generated data on active infection is required to focus such efforts. We performed a regionally-inclusive survey to determine prevalence of active HCV, genotypes and related factors among Ugandan blood donors. METHODS: Participants from regional blood banks and blood collection centers were surveyed for information on demographic, clinical and lifestyle factors. Blood was assayed for HCV infection, HCV genotypes and subtypes. Logistic regression was performed to determine factors associated with active HCV infection. RESULTS: Of 1243 participants, 1041 (83.7%) were male, average age (SD), 27.7 (9.8). Prevalence of active HCV infection was 7.8% and we identified 3 genotypes. Median age (adj. OR (95% CI) = 1.03 (1.01-1.06), p-value = 0.040)), Northern region of birth versus Central or Eastern (adj. OR (95% CI) = 10.25 (2.65-39.68), p-value = 0.001)), Northern residence, versus Central or Eastern (adj. OR (95% CI) = 0.23 (0.08-0.65), p-value = 0.006)), and being married (versus single/divorced) adj. OR 2.49(1.3-4.79), p-value = 0.006 were associated with active HCV infection. CONCLUSION: Targeted interventions in at-risk populations coupled with linkage to care and treatment will help achieve the WHO elimination goals in this setting.

Improving blood transfusion safety in resource-poor countries: a case study of using leucocyte reduced blood in Uganda.

BACKGROUND: The majority of blood transfusion safety strategies recommended by the WHO for resource-poor countries focus mainly on reducing the risk of transfusion-transmitted infections (TTIs). Other technologies such as leucocyte reduction may represent complementary strategies for improving transfusion safety. OBJECTIVE: To evaluate the role of using leucocyte reduced blood in a resource-poor country. METHODS: Pre-storage leucocyte reduced (LR) red blood cells (RBCs) were specially prepared for the Tissue Oxygenation by Transfusion in severe Anaemia and Lactic acidosis (TOTAL) study, at the Uganda Blood Transfusion Services from February 2013 through May 2015. Quality control tests were performed to evaluate the procedure, and the incremental cost of an LR-RBC unit was estimated. RESULTS: A total of 608 RBCs units were leucocyte reduced. Quality control tests were performed on 55 random RBCs units. The median (IQR) residual leucocyte count was 4 (0·5-10) WBC/uL, equivalent to 1·8x106 WBC per unit. The estimated incremental unit cost of leucocyte reduction was $37 USD per LR RBC unit. CONCLUSION: Leucocyte reduction of blood in a resource-poor country is doable although relatively costly. As such, its value in resource-poor countries should be weighed against other transfusion safety propositions.

Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub-Saharan Africa.

BACKGROUND AND OBJECTIVES: Paediatric blood transfusion for severe anaemia in hospitals in sub-Saharan Africa remains common. Yet, reports describing the haematological quality of donor blood or storage duration in routine practice are very limited. Both factors are likely to affect transfusion outcomes. MATERIALS AND METHODS: We undertook three audits examining the distribution of pack types, haematological quality and storage duration of donor blood used in a paediatric clinical trial of blood at four hospitals in Africa (Uganda and Malawi). RESULTS: The overall distribution of whole blood, packed cells (plasma-reduced by centrifugation) and red cell concentrates (RCC) (plasma-reduced by gravity-dependent sedimentation) used in a randomised trial was 40·7% (N = 1215), 22·4% (N = 669) and 36·8% (N = 1099), respectively. The first audit found similar median haematocrits of 57·0% (50·0,74·0), 64·0% (52·0,72·5; P = 0·238 vs. whole blood) and 56·0% (48·0,67·0; P = 0·462) in whole blood, RCC and packed cells, respectively, which resulted from unclear pack labelling by blood transfusion services (BTS). Re-training of the BTS, hospital blood banks and clinical teams led to, in subsequent audits, significant differences in median haematocrit and haemoglobins across the three pack types and values within expected ranges. Median storage duration time was 12 days (IQR: 6, 19) with 18·2% (537/2964) over 21 days in storage. Initially, 9 (2·8%) packs were issued past the recommended duration of storage, dropping to 0·3% (N = 7) in the third audit post-training. CONCLUSION: The study highlights the importance of close interactions and education between BTS and clinical services and the importance of haemovigilance to ensure safe transfusion practice.

B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.

BACKGROUND: Prior studies have suggested that transfusion of stored red blood cells (RBCs) with increased levels of cell-free hemoglobin might reduce the bioavailability of recipient nitric oxide (NO) and cause myocardial strain. METHODS: Ugandan children (ages 6-60 months) with severe anemia and lactic acidosis were randomly assigned to receive RBCs stored 1-10 days versus 25-35 days. B-type natriuretic peptide (BNP), vital signs, renal function test results, and plasma hemoglobin were measured. Most children had either malaria or sickle cell disease and were thus at risk for reduced NO bioavailability. RESULTS: Seventy patients received RBCs stored 1-10 days, and 77 received RBCs stored 25-35 days. The median (interquartile range) cell-free hemoglobin was nearly 3 times higher in longer-storage RBCs (26.4 [15.5-43.4] µmol/L) than in shorter-storage RBCs (10.8 [7.8-18.6] µmol/L), P < .0001. Median (interquartile range) BNP 2 hours posttransfusion was 156 (59-650) pg/mL (shorter storage) versus 158 (59-425) pg/mL (longer storage), P = .76. BNP values 22 hours posttransfusion were 110 (46-337) pg/mL (shorter storage) versus 96 (49-310) pg/mL (longer storage), P = .76. Changes in BNP within individuals from pretransfusion to 2 hours (or 22 hours) posttransfusion were not significantly different between the study groups. BNP change following transfusion did not correlate with the concentration of cell-free hemoglobin in the RBC supernatant. Blood pressure, blood urea nitrogen, creatinine, and change in plasma hemoglobin were not significantly different in the 2 groups. CONCLUSION: In a randomized trial among children at risk for reduced NO bioavailability, we found that BNP, blood pressure, creatinine, and plasma hemoglobin were not higher in patients receiving RBCs stored for 25-35 versus 1-10 days.

Cerebral Oximetry in Ugandan Children With Severe Anemia: Clinical Categories and Response to Transfusion.

IMPORTANCE: Severe anemia, defined as a hemoglobin level of less than 5.0 g/dL, affects millions of children worldwide. The brain has a high basal demand for oxygen and is especially vulnerable to hypoxemia. Previous studies have documented neurocognitive impairment in children with severe anemia. Data on cerebral tissue oxygenation in children with severe anemia and their response to blood transfusion are limited. OBJECTIVE: To measure hemoglobin saturation in cerebral tissue (cerebral tissue oxygen saturation [tSo2]) before, during, and after blood transfusion in a cohort of children presenting to hospital with severe anemia. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, observational cohort study conducted from February 2013 through May 2015 and analyzed in July 2015 at a university hospital pediatric acute care facility in Kampala, Uganda, of 128 children, ages 6 to 60 months who were enrolled in a larger clinical trial, with a presenting hemoglobin level of less than 5.0 g/dL and a blood lactate level greater than 5mM. Most children had either malaria or sickle cell disease. EXPOSURES: Red blood cell (RBC) transfusion given as 10 mL/kg over 120 minutes. MAIN OUTCOMES AND MEASURES: Clinical and laboratory characteristics of children with pretransfusion cerebral tSo2 levels less than 65%, 65% to 75%, and greater than 75%. Change in cerebral tSo2 as a result of transfusion. RESULTS: Of 128 children included in the study, oximetry results in 8 cases were excluded owing to motion artifacts; thus, 120 were included in this analysis. Cerebral tSo2 values prior to transfusion ranged from 34% to 87% (median, 72%; interquartile range [IQR], 65%-76%). Eighty-one children (67%) demonstrated an initial cerebral tSo2 level (≤75%) corresponding to an oxygen extraction ratio greater than 0.36. Patients with sickle cell disease (n = 17) and malaria (n = 15) contributed in nearly equal numbers to the subgroup with an initial cerebral tSo2 (<65%). The level of consciousness, hemoglobin concentration, blood lactate level, and thigh muscle tSo2 level were poor predictors of cerebral oxygen saturation. Following RBC transfusion, the median (IQR) cerebral tSo2 level increased to 78% (73%-82%) (P < .001), but 21% of children failed to achieve a tSo2 level greater than 75%. CONCLUSIONS AND RELEVANCE: Severe anemia in children is frequently associated with low cerebral oxygenation levels as measured by near-infrared spectroscopy. Hemoglobin level and lactate concentration did not predict low cerebral tSo2 levels. Cerebral tSo2 levels increase with RBC transfusion with different patterns of response. More studies are needed to evaluate the use of noninvasive cerebral tissue oximetry in the care of children with severe anemia.

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia: The TOTAL Randomized Clinical Trial.

IMPORTANCE: Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. OBJECTIVE: To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. DESIGN, SETTING, AND PARTICIPANTS: Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. INTERVENTIONS: Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n = 145) vs 1 to 10 days (shorter-storage group; n = 145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. RESULTS: In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ∞], P < .001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups. CONCLUSIONS AND RELEVANCE: Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01586923.

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial.

BACKGROUND: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted. METHODS/DESIGN: TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness. DISCUSSION: If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.

Transfusion Medicine in Sub-Saharan Africa: Conference Summary.

In November 2014, a 3-day conference devoted to transfusion medicine in sub-Saharan Africa was held in Kampala, Uganda. Faculty from academic institutions in Uganda provided a broad overview of issues pertinent to transfusion medicine in Africa. The conference consisted of lectures, demonstrations, and discussions followed by 5 small group workshops held at the Uganda Blood Transfusion Service Laboratories, the Ugandan Cancer Institute, and the Mulago National Referral Hospital. Highlighted topics included the challenges posed by increasing clinical demands for blood, the need for better patient identification at the time of transfusion, inadequate application of the antiglobulin reagent during pretransfusion testing, concern regarding proper recognition and evaluation of transfusion reactions, the expanded role for nurse leadership as a means to improve patient outcomes, and the need for an epidemiologic map of blood usage in Africa. Specialty areas of focus included the potential for broader application of transcranial Doppler and hydroxyurea therapy in sickle cell disease, African-specific guidelines for transfusion support of cancer patients, the challenges of transfusion support in trauma, and the importance of African-centered clinical research in pediatric and obstetric transfusion medicine. The course concluded by summarizing the benefits derived from an organized quality program that extended from the donor to the recipient. As an educational tool, the slide-audio presentation of the lectures will be made freely available at the International Society of Blood Transfusion Academy Web site: http://www.isbtweb.org/academy/.