Henry Ddungu

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.

Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov).

Pain among ambulatory HIV/AIDS patients: multicenter study of prevalence, intensity, associated factors, and effect.

UNLABELLED This study aimed to determine the prevalence, intensity, associated factors, and effect of pain among ambulatory HIV/AIDS patients. Three-hundred two adult ambulatory HIV/AIDS patients were consecutively recruited from HIV/AIDS outpatient clinics at 2 teaching hospitals in Uganda. The presence and intensity of pain were self-reported using the Brief Pain Inventory (BPI); symptom data were collected using the Memorial Symptom Assessment Scale (MSAS-SF); and quality of life (QOL) was assessed using the Medical Outcome Scale-HIV. Forty-seven percent reported pain in the 7 days prior to the survey and pain was a symptom at the time of diagnosis for 68%. On the 0 to 10 numeric scale, 53% reported mild pain (1-4 rating), 20% reported moderate pain (5-6 rating) while 27% reported severe pain (7-10 rating). Gender was not associated with pain intensity, but reduced functional performance, increasing number of symptoms, advanced HIV disease , physical symptom distress (MSAS-SF), and number of health comorbidities were significantly associated with pain intensity (P < .04). Increasing pain intensity was associated with greater functional ability impairment (BPI functional interference index) and poorer QOL. Pain is a common symptom among ambulatory HIV/AIDS patients and has a debilitating effect on QOL. There is a significant unmet need for pain relief in the population. PERSPECTIVE This article discusses the characteristics and effect of pain on function and QOL in East African patients. It also contributes information on characteristics of HIV/AIDS adult patients in the East Africa demonstrating the aspects in which pain is similar across different cultures.

Digital clubbing in tuberculosis--relationship to HIV infection, extent of disease and hypoalbuminemia.

BackgroundDigital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed.MethodsA cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done.ResultsTwo hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB.ConclusionClubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia.

Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.

Blood utilization at a national referral hospital in sub-Saharan Africa

A safe and adequate supply of blood is critical to improving health care systems in sub‐Saharan Africa, where little is known about the current use of blood. The aim of this study was to comprehensively describe the use of blood at a tertiary care hospital to inform future efforts to strengthen blood programs in resource‐limited settings.

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.

Prevalence and morphological types of anaemia and hookworm infestation in the medical emergency ward, Mulago Hospital, Uganda

INTRODUCTION Anaemia is common worldwide, although the burden is highest in developing countries where nutrient deficiencies and chronic infections are prevalent. OBJECTIVE To determine the prevalence and morphological types of anaemia and assess the hookworm burden among patients in the medical emergency ward at Mulago national referral hospital, Uganda. METHODS In a cross-sectional descriptive study 395 patients were recruited by systematic random sampling and their socio-demographic characteristics and clinical details collected. A complete blood count and peripheral film examination were done and stool examined for hookworm ova. STATISTICAL ANALYSIS Data were processed using Epi-Info version 6 and Stata version 9. The chi-square test was used for categorical variables and Students t-test for non-categorical variables. Multiple logistic regression was used to determine factors predictive of anaemia. RESULTS Of the patients 255 (64.6%) had anaemia. The prevalence was higher among males (65.8%) than females (63.7%). Fatigue (odds ratio (OR) 2.1, confidence interval (CI) 1.37 - 3.24), dizziness (OR 1.64, CI 1.07 - 2.44), previous blood transfusion (OR 2.83, CI 1.32 - 6.06), lymphadenopathy (OR 2.99, CI 1.34 - 6.66) and splenomegaly (OR 5.22, CI 1.78 - 15.28) were significantly associated with anaemia. Splenomegaly, low body mass index (BMI) (<19) and being HIV positive were independently associated with anaemia. The commonest type of anaemia was hypochromic microcytic (34.1%). Only 10.6% of anaemic patients had hookworm infestation. CONCLUSIONS In our study the prevalence of anaemia (64.6%) was very high. Splenomegaly, HIV infection and low BMI were independently associated with anaemia. The commonest type of anaemia was microcytic hypochromic (34.1%). There was a low prevalence of hookworm infestation.

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/.

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] &mgr;mol/L) than in shorter‐storage RBCs (10.8 [7.8‐18.6] &mgr;mol/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.