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

Cryptosporidiosis among People Living with HIV/AIDS on Highly Active Anti-Retroviral Therapy (HAART) at Mukono Church of Uganda Hospital, Uganda

This study was carried out to estimate the prevalence of cryptosporidiosis among People living with HIV (PLWH) on Highly active antiretroviral therapy (HAART)and relate the prevalence to possession of pets and the immune status of the individual attending ART at Mukono church of Uganda hospital. A cross sectional study was carried out among 232 people living with HIV between June and July, 2014. Interview with questionnaires and document reviews were used to collect data. Stool samples were obtained from each patient and processed using formal-ether concentration method, stained by modified Ziehl-Neelsen staining method and parasites were examined by direct microscopy. Univariate and multivariate analysis were carried out. Level of significancewas set at p-value of 0.05. A total of 232 patients participated in the study. The mean age was 36.0

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

BACKGROUND: Severe anemia (SA, 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

Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda [version 2; peer review: 3 approved]

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

Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda [version 1; referees: 2 approved, 1 approved with reservations]

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; calorimetric 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 assessed by the admitting nurse as having severe (164; 51.0%), moderate (99; 30.7%) or mild (57; 17.7%) 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

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

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.

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 nonsequentially 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

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: ISRCTN6985659

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. Keywords: Severe anaemia, Readmissio