Transfusion Volume for Children with Severe Anemia in Africa.

BACKGROUND: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. METHODS: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality. RESULTS: A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. CONCLUSIONS: Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

BACKGROUND: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. METHODS: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. RESULTS: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. CONCLUSIONS: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

A predictive algorithm for identifying children with sickle cell anemia among children admitted to hospital with severe anemia in Africa.

Sickle cell anemia (SCA) is common in sub-Saharan Africa where approximately 1% of births are affected. Severe anemia is a common cause for hospital admission within the region yet few studies have investigated the contribution made by SCA. The Transfusion and Treatment of severe anemia in African Children Trial (ISRCTN84086586) investigated various treatment strategies in 3983 children admitted with severe anemia (hemoglobin < 6.0 g/dl) based on two severity strata to four hospitals in Africa (three Uganda and one Malawi). Children with known-SCA were excluded from the uncomplicated stratum and capped at 25% in the complicated stratum. All participants were genotyped for SCA at trial completion. SCA was rare in Malawi (six patients overall), so here we focus on the participants recruited in Uganda. We present baseline characteristics by SCA status and propose an algorithm for identifying children with unknown-SCA. Overall, 430 (12%) and 608 (17%) of the 3483 Ugandan participants had known- or unknown-SCA, respectively. Children with SCA were less likely to be malaria-positive and more likely to have an affected sibling, have gross splenomegaly, or to have received a previous blood transfusion. Most outcomes, including mortality and readmission, were better in children with either known or unknown-SCA than non-SCA children. A simple algorithm based on seven admission criteria detected 73% of all children with unknown-SCA with a number needed to test to identify one new SCA case of only two. Our proposed algorithm offers an efficient and cost-effective approach to identifying children with unknown-SCA among all children admitted with severe anemia to African hospitals where screening is not widely available.

A Clinical and Physiological Prospective Observational Study on the Management of Pediatric Shock in the Post-Fluid Expansion as Supportive Therapy Trial Era.

OBJECTIVES: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy. DESIGN: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints. SETTING: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019. PATIENTS: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion. INTERVENTIONS: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers. MEASUREMENT AND MAIN RESULTS: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 µg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome. CONCLUSIONS: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data.

BACKGROUND: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. METHODS: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. RESULTS: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63-3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19-1.74), p < 0.001); history of transfusion (1.48(1.13-1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21-1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47-0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47-0.76), p < 0.001); younger-age (1.07 (1.03-1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46-0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23-2.44) and 1.46(1.18-1.82) respectively compared to no splenomegaly. Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria. CONCLUSIONS: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important. TRIAL REGISTRATION: ISRCTN ISRCTN84086586 .

The clinical spectrum of severe childhood malaria in Eastern Uganda.

BACKGROUND: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. METHODS: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months-12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma. RESULTS: A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16-1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72-7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39-9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29-4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia. CONCLUSIONS: Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.

Assessment of Myocardial Function and Injury by Echocardiography and Cardiac Biomarkers in African Children With Severe Plasmodium falciparum Malaria.

OBJECTIVES: Perturbed hemodynamic function complicates severe malaria. The Fluid Expansion as Supportive Therapy trial demonstrated that fluid resuscitation, involving children with severe malaria, was associated with increased mortality, primarily due to cardiovascular collapse, suggesting that myocardial dysfunction may have a role. The aim of this study was to characterize cardiac function in children with severe malaria. DESIGN: A prospective observational study with clinical, laboratory, and echocardiographic data collected at presentation (T0) and 24 hours (T1) in children with severe malaria. Cardiac index and ejection fraction were calculated at T0 and T1. Cardiac troponin I and brain natriuretic peptide were measured at T0. We compared clinical and echocardiographic variables in children with and without severe malarial anemia (hemoglobin < 5 mg/dL) at T0 and T1. SETTING: Mbale Regional Referral Hospital. PATIENTS: Children 3 months to 12 years old with severe falciparum malaria. INTERVENTIONS: Usual care. MEASUREMENTS AND MAIN RESULTS: We enrolled 104 children, median age 23.3 months, including 61 children with severe malarial anemia. Cardiac troponin I levels were elevated (> 0.1 ng/mL) in n equals to 50, (48%), and median brain natriuretic peptide was within normal range (69.1 pg/mL; interquartile range, 48.4-90.8). At T0, median Cardiac index was significantly higher in the severe malarial anemia versus nonsevere malarial anemia group (6.89 vs 5.28 L/min/m) (p = 0.001), which normalized in both groups at T1 (5.60 vs 5.13 L/min/m) (p = 0.452). Cardiac index negatively correlated with hemoglobin, r equals to -0.380 (p < 0.001). Four patients (3.8%) had evidence of depressed cardiac systolic function (ejection fraction < 45%). Overall, six children died, none developed pulmonary edema, biventricular failure, or required diuretic treatment. CONCLUSIONS: Elevation of cardiac index, due to increased stroke volume, in severe malaria is a physiologic response to circulatory compromise and correlates with anemia. Following whole blood transfusion and antimalarial therapy, cardiac index in severe malarial anemia returns to normal. The majority (> 96%) of children with severe malaria have preserved myocardial systolic function. Although there is evidence for myocardial injury (elevated cardiac troponin I), this does not correlate with cardiac dysfunction.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

BACKGROUND: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). METHODS: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. RESULTS: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. CONCLUSIONS: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.

BACKGROUND: Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes. METHODS: We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range (IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival. RESULTS: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload. CONCLUSION: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted. TRIAL REGISTRATION: ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.

An intricate vagina penetrating injury with a 22 cm cassava stick in situ for 6 months: a case report.

BACKGROUND: Trauma remains one of the major causes of morbidity and mortality and a threat to attainment of sustainable development goal 11. Genital urinary trauma is reported in about 10% of patients presenting with trauma worldwide, and in about 6.6% of patients in Sub-Saharan Africa. If not careful enough, one may miss the foreign body in the vagina and this may be associated with morbidity, and although  rare, mortality. CASE PRESENTATION: We report a case of a 7-year-old Black Ugandan that had suffered vagina trauma 6 months prior to presentation at our facility and presented with chronic vagina pus discharge for 6 months. Prior examinations had failed to recognize the foreign body and so did the two abdominal pelvic ultrasound scans. During examination under anesthesia, we were able to locate the cassava stick that had caused penetrating vagina injury and we were able to dislodge it. It was a blunt cassava stick with length of 22 cm and diameter of 2 cm. Although it had gone through the peritoneal cavity, we did not do a laparotomy. CONCLUSION: This case emphasizes the need for a thorough vaginal exam including the need to do it under anesthesia with good lighting even when ultrasound scan findings are normal. It presents an opportunity for one to manage penetrating peritoneal injury without a laparotomy in highly selected cases. Gynecologists should be keen as well to rule out child molestation.

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

BACKGROUND: Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. METHODS: Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. RESULTS: Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. CONCLUSIONS: Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. TRIAL REGISTRATION: ISRCTN69856593.

Endotoxaemia is common in children with Plasmodium falciparum malaria.

BACKGROUND: Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. METHODS: We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. RESULTS: Endotoxaemia (endotoxin activity ≥0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGFß (Spearman rho: TNFα: r=-0.122, p=0.121; IL6: r=-0.330, p<0.0001; IL10: r=-0.461, p<0.0001; TGFß: r=-0.173, p<0.027). CONCLUSIONS: Endotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.

Bacterial colonization, species diversity and antimicrobial susceptibility patterns of indwelling urinary catheters from postpartum mothers attending a Tertiary Hospital in Eastern Uganda.

BACKGROUND: Postpartum urinary Catheter-Related Infections (CRIs) are a significant cause of maternal sepsis. Several studies done have reported the presence of mixed populations of bacteria with a significant increase in Extended-Spectrum Beta-Lactamase (ESBL) Enterobacteriaceae spps, Methicillin-Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant (MDR) bacteria in urine and blood cultures of catheterized patients despite the use of prophylactic antibiotics. This study aimed at determining the bacterial species diversity and susceptibility patterns of indwelling urinary catheters from postpartum mothers attending Mbale Regional Referral Hospital (MRRH). METHODS: A cross-sectional study employing quantitative and qualitative was carried out in MRRH among postpartum mothers with urinary catheters and their care-takers. The purposive non-random sampling strategy was used to collect data using an interviewer-administered questionnaire for the quantitative data collection and in-depth interviews for qualitative data collection. All the data collection tools used were developed, pretested and validated. At the point of de-catheterization, Catheter tips from enrolled participants were cut about 2-3cm below the balloon aseptically into test-tube containing peptone water, sonication technique employed, and incubation done 24hours then cultured to ensure phenotypic identification. An antibiotic sensitivity test was performed using the disc diffusion method following Clinical and Laboratory Standards Institute (CLSI) guidelines. Quantitative data collected was entered in Microsoft Excel and then exported to STATA14 for statistical analysis. Thematic analysis was used to analyse and organise qualitative data by an inductive coding method using Nvivo 12 software. RESULTS: In this study, 208 postpartum mothers participated, the majority of whom were caesarean section mothers of age range 20-24 years and 17 care-takers with a median age of 32 years. The prevalence of catheter tips bacterial colonisation was 98% despite 88.5% of the participants being on broad-spectrum antibiotics. The average duration of catheterisation was 2 days. All bacteria isolates were potential uro-pathogens with a mean occurrence of 2 bacteria species in each urinary catheter tip. The rates of MDR to commonly used antibiotics were high. The urinary catheter size of greater than F14 and duration of catheterization greater than 2 days were significantly associated with the number of bacterial species isolated from each sample. The maintenance care and knowledge of care-urinary catheter care among the care-takers was found sub-optimal. CONCLUSION: There was a high prevalence of catheter colonisation with bacterial spps diversity averaging 2 spps per sample despite use of broad spectrum antibiotics. The MDR rates were high, which calls for routine culture and sensitivity. Health workers practicing obstetric medicine need to pay attention to catheter sizes during catheterisation and its duration. Health education should be part of antenatal and postnatal care education.

KANGAROO MOTHER CARE: A QUALITATIVE STUDY ON THE PRACTICE AND EXPERIENCES OF MOTHERS OF PRETERM NEONATES IN A TERTIARY TEACHING HOSPITAL IN EASTERN UGANDA.

Introduction: Globally, neonatal deaths continues to be a challenge especially to to attainment of sustainable development goal 3. About 4 million neonatal deaths per year, with 99% of the deaths occurring in low and middle resource countries, 75% of these occurring in the first week of life. Prematurity remains an indirect leading cause of mortality and morbidity. Uganda's progress on the improvement of perinatal morbidity and mortality has largely stagnated at 27 deaths per 1,000 live births from the year 2006. One of the cost-effective readily available interventions that would curtail perinatal mortality is kangaroo mother care(KMC)- a low tech four decades old intervention. However challenges about its implementation persist on in Uganda despite intensified implementation and roll-out startegies in 2010. This study, the first of its kind to the best of our knowledge in eastern Uganda sought to find the facilitators and barriers of KMC. Materials and methods: This was a qualitative study using in-depth interviews(IDI) carried out at a tertiary university teaching hospital. Twenty IDIs were carried out among mothers/caretakers using the phenomena theory. After each IDI, each transcript was analyzed by two researchers working independently using NVIVO software version 11 plus (QSR International, Burlington, Massachusetts) and themes and subthemes developed. Results: Majority of mothers/caretakers, were adolescents and young adults and primiparous at 55%. The major facilitators to KMC were supportive staff that facilitated positive attitude, ability to substitute provider and family support.The major barriers were lack of family support, lack of male involvement, maternal stress and poor health and multiple gender roles, infrastructural challenges, and misconceptions associated with preterm births such as early sexual intercourse and lack of herbal medicine use. Conclusion: More facility leadership involvement and engagement of mothers during antenatal, community and promotion of male involvement in sexual and reproductive health matters will improve uptake of KMC. This can be spearheadded by sexual and reproductive health, and neonatal and child health care service providers.

Live Experiences of Adolescent Mothers Attending Mbale Regional Referral Hospital: A Phenomenological Study.

BACKGROUND: Adolescence is a period of transition from childhood to adulthood, and is a critical stage in ones' development. It is characterized by immense opportunities and risks. By 2016, 16% of the world's population was of adolescents, with 82% residing in developing countries. About 12 million births were in 15-19 year olds. Sub-Saharan Africa, particularly East Africa, has high adolescent pregnancy rates, as high as 35.8% in eastern Uganda. Maternal mortality ratio (MMR) attributable to 15-19 years olds is significant with 17.1% of Uganda's MMR 336/100.000 live births being in this age group. Whereas research is awash with contributing factors to such pregnancies, little is known about lived experiences during early motherhood. This study reports the lived experiences of adolescent mothers attending Mbale Hospital. MATERIALS AND METHODS: A phenomenological study design was used in which adolescent mothers that were attending Young Child Clinic were identified from the register and simple random sampling was used to select participants. We called these mothers by way of phone numbers and asked them to come for focus group discussions that were limited to 9 mothers per group and lasting about 45 minutes-1 hour. Ethical approval was sought and informed written consent obtained from participants. At every focus group discussion, the data which had largely been taken in local languages was transcribed and translated verbatim into English. RESULTS: The research revealed that adolescent mothers go through hard times especially with the changes of pregnancy and fear of unknown during intrapartum and immediate postpartum period and are largely treated negatively by family and other community members in addition to experiencing extreme hardships during parenting. However, these early mothers' stress is alleviated by the joy of seeing their own babies. CONCLUSION: Adolescent motherhood presents a high risk group and efforts to support them during antenatal care with special adolescent ANC clinics and continuous counseling together with their household should be emphasized to optimize outcome not only during pregnancy but also thereafter. Involving these mothers in technical courses to equip them with skills that can foster self-employment and providing support to enable them pursue further education should be explored.

Malaria preventive practices and delivery outcomes: A cross-sectional study of parturient women in a tertiary hospital in Eastern Uganda.

BACKGROUND: Uganda ranks third in the number of deaths attributable to malaria and has some of the highest recorded malaria transmission rates in the general population. Malaria in Pregnancy is associated with detrimental effects for the mother and unborn baby and these effects seem to have long term effects and consequences on the life of the baby. Despite the preventive measures put in place by the World Health Organization in antenatal care, the burden of malaria in pregnancy is still high. We determined the use of malaria preventive strategies during pregnancy and the presence of plasmodium infection, anemia, and low birth weight babies at delivery among parturient women at Mbale regional referral hospital in eastern Uganda. METHODS: A cross-sectional study was conducted among 210 women delivering at MRRH between July 2017 and January 2018. Information on demographics, antenatal care, and prevention practices was collected using an interviewer-administered questionnaire. Maternal venous blood and cord blood samples were screened for Plasmodium infection by both microscopy of Giemsa-stained blood films and Plasmodium falciparum rapid diagnostic test (pf. HPR2 mRDT). Polymerase Chain Reaction (PCR) was done on cord blood. The presence of anemia was determined by the use of an automated hemoglobin analyzer. Data were analyzed using descriptive and analytical statistics. RESULTS: Of the 210 women, 3 (1.4%) and 19(9.1%) tested positive for malaria by using Giemsa stained blood smear microscopy and malaria rapid diagnosticMRDT tests respectively. PCR detected 4(%) of Plasmodium in cord blood. Twenty-nine percent of the women had anaemia and 11 (5.2%) had low birth weight babies. Only 23.3% of the women received at least three doses of IPTp-SP and 57.9% reported sleeping under an Insecticide Treated Net the night before the survey. The women who reported sleeping under a mosquito net the previous night (OR 0.67, 95% CI: 0.24-1.86) and those who reported taking fansidar as a directly observed therapy (OR 0.31, 95% CI: 0.04-2.39) appeared to have few chances of getting plasmodium infection though the findings were not statistically significant. CONCLUSION: The effective use of malaria preventive strategies (IPT-SP and Insecticide Treated Nets) was generally low. Most of the women took less than three doses of SP and there was no strict adherence to the recommended directly observed therapy. The prevalence of Plasmodium infection during pregnancy was low though maternal anaemia and low birth weight were relatively high.

Prevalence, Indications, and Community Perceptions of Caesarean Section Delivery in Ngora District, Eastern Uganda: Mixed Method Study.

BACKGROUND: Uganda has a high maternal mortality ratio (MMR) of 336/100,000 live births. Caesarean section is fundamental in achieving equity and equality in emergency obstetric care services. Despite it being a lifesaving intervention, it is associated with risks. There has been a surge in caesarean section rates in some areas, yet others remain underserved. Studies have shown that rates exceeding 15% do not improve maternal and neonatal morbidity and mortality. Our study aimed at determining the prevalence, indications, and community perceptions of caesarean section delivery in Eastern Uganda. METHODS AND MATERIALS: It was both health facility and commuity based cross-sectional descriptive study in Ngora district, Eastern Uganda. Mixed methods of data collection were employed in which quantitative data were collected by retrospectively reviewing all charts of all the mothers that had delivered at the two comprehensive emergency obstetric care service facilities between April 2018 and March 2019. Qualitative data were collected by focus group discussions till point of saturation. Data were entered into EpiData (version 3.1) and analyzed using SPSS software (version 24). Qualitative data analysis was done by transcribing and translating into English verbatim and then analyzed into themes and subthemes with the help of NVIVO 12. RESULTS: Of the total 2573 deliveries, 14% (357/2573) were by CS. The major single indications were obstructed labour 17.9%, fetal distress 15.3%, big baby 11.6%, and cephalopelvic disproportion (CPD) 11%. Although appreciated as lifesaving for young mothers, those with diseases and recurrent intrauterine fetal demise, others considered CS a curse, marriage-breaker, misfortune, money-maker and a sign of incompetent health workers, and being for the lazy women and the rich civil servants. The rise was also attributed to intramuscular injections and contraceptive use. Overall, vaginal delivery was the preferred route. CONCLUSION: Several misconceptions that could hinder access to CS were found which calls for more counseling and male involvement. Although facility based, the rate is higher than the desired 5-15%. It is higher than the projected increase of 36% by 2021. It highlights the need for male involvement during counseling and consent for CS and concerted efforts to demystify community misconceptions about women that undergo CS. These misconceptions may be a hindrance to access to CS.

Asymptomatic bacteriuria among pregnant women attending antenatal care at Mbale Hospital, Eastern Uganda.

BACKGROUND: Asymptomatic bacteriuria in pregnancy (ASBP) is associated with adverse pregnancy outcomes such as pyelonephritis, preterm or low birth weight delivery if untreated. The aim of this study was to determine the prevalence of asymptomatic bacteriuria, the isolated bacterial agents, and their antibiotic sensitivity patterns in pregnant women attending antenatal care at Mbale Hospital. METHODS: This was a cross sectional study in which 587 pregnant women with no symptoms and signs of urinary tract infection were recruited from January to March 2019. Mid-stream clean catch urine samples were collected from the women using sterile containers. The urine samples were cultured using standard laboratory methods. The bacterial colonies were identified and antibiotic sensitivity was done using disc diffusion method. Chi squared tests and logistic regression were done to identify factors associated with asymptomatic bacteriuria. A p value < 0.05 was considered statistically significant. RESULTS: Out of the 587 pregnant women, 22 (3.75%) tested positive for asymptomatic bacteriuria. Women aged 20-24 years were less likely to have ASBP when compared to women aged less than 20 years (AOR = 0.14, 95%CI 0.02-0.95, P = 0.004). The most common isolates in descending order were E. coli (n = 13, 46.4%) and S.aureus (n = 9, 32.1%). Among the gram negative isolates, the highest sensitivity was to gentamycin (82.4%) and imipenem (82.4%). The gram positive isolates were sensitive to gentamycin (90.9%) followed by imipenem (81.8%). All the isolates were resistant to sulphamethoxazole with trimethoprim (100%). Multidrug resistance was 82.4% among gram negative isolates and 72.4% among the gram positive isolates. CONCLUSION: There was high resistance to the most commonly used antibiotics. There is need to do urine culture and sensitivity from women with ASBP so as to reduce the associated complications.

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial.

BACKGROUND: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes. METHODS: Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete. FINDINGS: From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79-1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86-1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84-1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89-1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions). INTERPRETATION: Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa. FUNDING: Medical Research Council and Department for International Development.

Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda.

Background: Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supply. Methods: We conducted a prospective descriptive study of hospitalized children aged 2 months - 12 years at Mbale and Soroti Regional Referral Hospitals, assessed to have pallor at triage by a nurse and two clinicians. Haemoglobin levels were measured using the HemoCue ® Hb 301 system (gold standard); the Haemoglobin Colour Scale; Colorimetric and Sahli's methods. We report clinical assessments of the degree of pallor, clinicians' intention to transfuse, inter-observer agreement, limits of agreement using the Bland-Altman method, and the sensitivity and specificity of each method in comparison to HemoCue ® Results: We recruited 322 children, clinically-assessed by the admitting nurse (n=314) as having severe (166; 51.6%), moderate (97; 30.1%) or mild (51; 15.8%) pallor. Agreement between the clinicians and the nurse were good: Clinician A Kappa=0.68 (0.60-0.76) and Clinician B Kappa=0.62 (0.53-0.71) respectively ( P<0.0001 for both). The nurse, clinicians A and B indicated that of 94/116 (81.0%), 83/121 (68.6%) and 93/120 (77.5%) respectively required transfusion. HemoCue ® readings indicated anaemia as mild (Hb10.0-11.9g/dl) in 8/292 (2.7%), moderate (Hb5.0-9.9g/dl) in 132/292 (45.2%) and severe (Hb<5.0g/dl) in 152/292 (52.1%). Comparing to HemoCue® the Sahli's method performed best in estimation of severe anaemia, with sensitivity 84.0% and specificity 87.9% and a Kappa score of  0.70 (0.64-0.80). Conclusions: Clinical assessment of severe pallor results has a low specificity for the diagnosis of severe anaemia. To target blood transfusion Hb measurement by either Hemocue® or Sahli's method for the cost of USD 4 or and USD 0.25 per test, respectively would be more cost-effective.