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.

Malaria parasitemia among blood donors in Uganda.

BACKGROUND: Malaria remains a leading transfusion associated infectious risk in endemic areas. However, the prevalence of malaria parasitemia has not been well characterized in blood donor populations. This study sought to determine the prevalence of Plasmodium in red blood cell (RBC) and whole blood (WB) units after the rainy season in Uganda. METHODS AND MATERIALS: Between May and July 2018, blood was collected from the sample diversion pouch of 1000 WB donors in Kampala and Jinja, Uganda. The RBC pellet from ethylenediamine tetraacetic acid (EDTA) anticoagulated blood was stored at -80°C until testing. DNA was extracted and nested PCR was used to screen samples at the genus level for Plasmodium, with positive samples further tested for species identification. RESULTS: Malaria parasitemia among asymptomatic, eligible blood donors in two regions of Uganda was 15.4%; 87.7% (135/154) of infections were with P. falciparum, while P. malariae and P. ovale were also detected. There were 4.3% of blood donors who had mixed infection with multiple species. Older donors (>30 years vs. 17-19 years; aPR = 0.31 [95% CI = 0.17-0.58]), females (aPR = 0.60 [95% CI = 0.42-0.87]), repeat donors (aPR = 0.44 [95% CI = 0.27-0.72]) and those donating near the capital city of Kampala versus rural Jinja region (aPR = 0.49 [95% CI = 0.34-0.69]) had a lower prevalence of malaria parasitemia. CONCLUSIONS: A high proportion of asymptomatic blood donors residing in a malaria endemic region demonstrate evidence of parasitemia at time of donation. Further research is needed to quantify the risk and associated burden of transfusion-transmitted malaria (TTM) in order to inform strategies to prevent TTM.

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.

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.

A Model for Estimating the Burden of Disease of Transfusion-Transmitted Infection.

Objectives: Blood transfusion is an important mode of infectious disease transmission in low- and middle-income countries (LMICs). This study describes a model to determine the prevalence of transfusion-transmitted infections (TTIs) and the associated burden of disease. Methods: A five-step model was developed to determine the TTI-related burden of disease measured by disability-adjusted life years (DALYs). Uganda was selected as the study country. Results: Approximately 298,266 units of blood were transfused in Uganda in 2019, yielding an estimated TTI incidence of 6,858 new TTIs (2.3% of transfused units) and prevalence of 19,141 TTIs (6.4% of transfused units). The total burden of disease is 2,903 DALYs, consisting of approximately 2,590 years of life lost (YLLs), and 313 years lived with disability (YLDs). Conclusion: The incidence and prevalence of TTIs and the associated burden of disease can be calculated on a local and national level. The model can be applied by health ministries to estimate the impact of TTIs in order to develop blood safety strategies to reduce the burden of disease.

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.

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.