Serum Procalcitonin Levels in Children with Clinical Syndromes for Targeting Antibiotic Use at an Emergency Department of a Kenyan Hospital.

Serum procalcitonin (PCT) was measured in 228 children aged 1 month to 15 years at an emergency department of a hospital located in an area without local malaria transmission in children with suspected infections; 21% (49) children had a clinical syndrome for suspected bacterial infections (Syndrome+ve). In children with Syndrome+ve criteria, 27/49 (55.1%) had PCT ≥0.5 µg/l but only 59/179 (32.9%) of those Syndrome-ve had abnormal PCT, χ2 = 8.0, p = 0.005; positive likelihood ratio = 2.0 [95% confidence interval (CI) 1.2-3.3]; negative likelihood ratio = 0.8 (95% CI 0.7-1.0). In patients with pneumonia, 9/15 (60%) with severe pneumonia had PCT ≥0.5 µg/l compared to 11/21 (52.4%) with non-severe pneumonia, χ2 = 0.2, p = 0.65. Children with clinical signs of pneumonia or clinical signs suggestive of bacterial infections fulfilling clinical syndromic definitions for suspected bacterial infections commonly have elevated PCT level. PCT levels are associated with disease severity and antibiotic trials guided by PCT levels may be needed where cultures are not available.

Mortality risk over time after early fluid resuscitation in African children.

BACKGROUND: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear. METHODS: In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20-40 ml/kg 5% albumin or 0.9% saline over 1-2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other). RESULTS: Two thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death. CONCLUSIONS: The increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resulted from slower decrease in mortality risk over the ensuing 4 days. Thus, administration of modest bolus volumes appeared to prevent mortality risk declining at the same rate that it would have done without a bolus, rather than harm associated with bolus resulting from a concurrent increased risk of death peri-bolus administration. TRIAL REGISTRATION: ISRCTN69856593. Date of registration 15 December 2008.

Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa.

BACKGROUND: Hyperlactataemia (HL) is a biomarker of disease severity that predicts mortality in patients with sepsis and malaria. Lactate clearance (LC) during resuscitation has been shown to be a prognostic factor of survival in critically ill adults, but little data exist for African children living in malaria-endemic areas. METHODS: In a secondary data analysis of severely ill febrile children included in the Fluid Expansion as Supportive Therapy (FEAST) resuscitation trial, we assessed the association between lactate levels at admission and LC at 8 h with all-cause mortality at 72 h (d72). LC was defined as a relative lactate decline ≥ 40% and/or lactate normalisation (lactate < 2.5 mmol/L). RESULTS: Of 3170 children in the FEAST trial, including 1719 children (57%) with Plasmodium falciparum malaria, 3008 (95%) had a baseline lactate measurement, 2127 (71%) had HL (lactate ≥ 2.5 mmol/L), and 1179 (39%) had severe HL (≥ 5 mmol/L). Within 72 h, 309 children (10.3%) died, of whom 284 (92%) had baseline HL. After adjustment for potential confounders, severe HL was strongly associated with mortality (Odds Ratio (OR) 6.96; 95% CI 3.52, 13.76, p < 0.001). This association was not modified by malaria status, despite children with malaria having a higher baseline lactate (median 4.6 mmol/L vs 3 mmol/L; p < 0.001) and a lower mortality rate (OR = 0.42; p < 0.001) compared to non-malarial cases. Sensitivity and specificity analysis identified a higher lactate on admission cut-off value predictive of d72 for children with malaria (5.2 mmol/L) than for those with other febrile illnesses (3.4 mmol/L). At 8 h, 2748/3008 survivors (91%) had a lactate measured, 1906 (63%) of whom had HL on admission, of whom 1014 (53%) fulfilled pre-defined LC criteria. After adjustment for confounders, LC independently predicted survival after 8 h (OR 0.24; 95% CI 0.14, 0.42; p < 0.001). Absence of LC (< 10%) at 8 h was strongly associated with death at 72 h (OR 4.62; 95% CI 2.7, 8.0; p < 0.001). CONCLUSIONS: Independently of the underlying diagnosis, HL is a strong risk factor for death at 72 h in children admitted with severe febrile illnesses in Africa. Children able to clear lactate within 8 h had an improved chance of survival. These findings prompt the more widespread use of lactate and LC to identify children with severe disease and monitor response to treatment. TRIAL REGISTRATION: ISRCTN69856593 Registered 21 January 2009.

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.

Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness.

BACKGROUND: Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group. METHODS: We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion. RESULTS: Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL). Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda. 1,387/3,082 (45%) children were transfused (81% within 8 hours). Adherence to WHO transfusion guidelines was poor. Among severely anaemic children who were not transfused, 52% (54/103) died within 8 hours, and 90% of these deaths occurred within 2.5 hours of randomisation. By 24 hours, 128/1,002 (13%) severely anaemic children had died, compared to 36/501 (7%) and 71/843 (8%) of those with moderate and mild anaemia, respectively. Among children without severe hypotension who were randomised to receive fluid boluses of 0.9% saline or albumin, mortality was increased (10.6% and 10.5%, respectively) compared to controls (7.2%), regardless of admission Hb level. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6 to 13% at the four Ugandan centres. Adverse reactions to blood were rare (0.4%). CONCLUSIONS: Severe anaemia complicates one third of childhood admissions with serious febrile illness to hospitals in East Africa, and is associated with increased mortality. A high proportion of deaths occurred within 2.5 hours of admission, emphasizing the need for rapid recognition and prompt blood transfusion. Adherence to current WHO transfusion guidelines was poor. The high rates of re-transfusion suggest that 20 mL/kg whole blood or 10 mL/kg packed cells may undertreat a significant proportion of anaemic children. Future evaluation of the impact of a larger volume of transfused blood and optimum transfusion management of children with Hb of <6 g/dL is warranted.

Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score.

BACKGROUND: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. METHODS: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. RESULTS: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. CONCLUSIONS: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.

Mortality after fluid bolus in African children with severe infection.

BACKGROUND: The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established. METHODS: We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. RESULTS: The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. CONCLUSIONS: Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.).

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.

Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria.

OBJECTIVES: A previous meta-analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution compared to other resuscitation fluids. Human albumin solution is expensive and not readily available in Africa. We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids, Dextran 70 and hydroxyethyl starch, to inform future trial design. DESIGN: An open-label randomized, controlled, phase II safety and efficacy trial. SETTING: High-dependency unit, Kilifi District Hospital, Kenya. PATIENTS: Children aged >6 months with severe falciparum malaria and acidosis (base deficit >8 mmol). INTERVENTIONS: Boluses (20-40 mL/kg) of 6% Dextran 70 and 6% hydroxyethyl starch (130/0.4). MEASUREMENTS AND MAIN RESULTS: Primary end point: resolution of shock over 8 hrs. Secondary end points include resolution of acidosis, in-hospital mortality, and adverse events (allergic reactions, pulmonary edema, and neurologic sequelae). A total of 79 children were enrolled: 39 received Dextran 70 and 40 received hydroxyethyl starch. No significant difference was observed in Dextran 70 and hydroxyethyl starch groups for shock resolution at 8 hrs: 23/37 (62%) and 25/39 (64%), respectively (p = .99). Acidosis resolution and respiratory distress were marginally superior in the hydroxyethyl starch group: 3/39 (8%) remained acidotic at 8 hrs versus 10/37 (27%) in the Dextran 70 arm (p = .05). There were four deaths (5%): two per arm, including three deaths in the coma subgroup (3/39, 8%). No other new adverse event was reported. CONCLUSIONS: Correction of shock by volume expansion with either Dextran 70 or hydroxyethyl starch in children with severe malaria acidosis is safe with low mortality, including the highest risk cases admitted in coma. Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria.

Phase II trial of isotonic fluid resuscitation in Kenyan children with severe malnutrition and hypovolaemia.

BACKGROUND: Children with severe malnutrition who develop shock have a high mortality. Contrary to contemporaneous paediatric practice, current guidelines recommend use of low dose hypotonic fluid resuscitation (half-strength Darrows/5% dextrose (HSD/5D). We evaluated the safety and efficacy of this guideline compared to resuscitation with a standard isotonic solution. METHODS: A Phase II randomised controlled, safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock (non-diarrhoeal shock). Eligible children were randomised to HSD/5D or Ringer's Lactate (RL). A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours (as recommended by guidelines) while those randomised to RL received 10 ml/kg aliquots half hourly (maximum 40 ml/kg). Primary endpoint was resolution of shock at 8 and 24 hours. Secondary outcomes included resolution of acidosis, adverse events and mortality. RESULTS: 61 children were enrolled: 41 had shock and severe dehydrating diarrhoea, 20 had presumptive septic shock; 69% had decompensated shock. By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 (68%) and RL14/25 (52%), p = 0.39. Oliguria was more prevalent at 8 hours in the HSD/5D group, 9/22 (41%), compared to RL-3/25 (12%), p = 0.02. Mortality was high, HSD/5D-15/26(58%) and RL 13/29(45%); p = 0.42. Most deaths occurred within 48 hours of admission. Neither pulmonary oedema nor cardiogenic failure was detected. CONCLUSIONS: Outcome was universally poor characterised by persistence of shock, oliguria and high case fatality. Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy. Although isotonic fluid resuscitation did not result in cardiogenic heart failure, as previously feared, we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock. The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock, defining rate and volumes required to inform future guidelines. TRIAL REGISTRATION: The trial is registered as ISCRTN: 61146418.

Estimating hospital catchments from in-patient admission records: a spatial statistical approach applied to malaria.

Admission records are seldom used in sub-Saharan Africa to delineate hospital catchments for the spatial description of hospitalised disease events. We set out to investigate spatial hospital accessibility for severe malarial anaemia (SMA) and cerebral malaria (CM). Malaria admissions for children between 1 month and 14 years old were identified from prospective clinical surveillance data recorded routinely at four referral hospitals covering two complete years between December 2015 to November 2016 and November 2017 to October 2018. These were linked to census enumeration areas (EAs) with an age-structured population. A novel mathematical-statistical framework that included EAs with zero observations was used to predict hospital catchment for malaria admissions adjusting for spatial distance. From 5766 malaria admissions, 5486 (95.14%) were linked to specific EA address, of which 272 (5%) were classified as cerebral malaria while 1001 (10%) were severe malaria anaemia. Further, results suggest a marked geographic catchment of malaria admission around the four sentinel hospitals although the extent varied. The relative rate-ratio of hospitalisation was highest at <1-hour travel time for SMA and CM although this was lower outside the predicted hospital catchments. Delineation of catchments is important for planning emergency care delivery and in the use of hospital data to define epidemiological disease burdens. Further hospital and community-based studies on treatment-seeking pathways to hospitals for severe disease would improve our understanding of catchments.

Survival and haematological recovery of children with severe malaria transfused in accordance to WHO guidelines in Kilifi, Kenya.

BACKGROUND: Severe anaemia requiring emergency blood transfusion is a common complication of malaria in children. To ensure access for urgent blood transfusion, the World Health Organization has developed clear guidelines with haemoglobin thresholds prevent unwarranted transfusion,. Few studies have reported outcome and haematological recovery of children with severe malaria where transfusion practice complies with WHO recommendations. METHODS: A prospective observational study of survivors of severe and complicated malaria transfused in accordance with WHO guidelines. Children were invited for review at one month post-discharge. Non-attendees were traced in the community to ascertain survival. RESULTS: Outcome was assessed in 213 survivors. Those transfused were younger, had a higher base deficit, mean lactate levels and a higher prevalence of respiratory distress. As expected mean admission haemoglobin (Hb) was significantly lower amongst transfused [5.0 g/dL SD: 1.9] compared to non-transfused children [8.3 g/dL SD: 1.7] (p < 0.001). At discharge mean Hb was similar 6.4 g/dL [SD: 1.5] and 6.8 g/dL [SD: 1.6] respectively (p = 0.08), most children remained moderately to severely anaemic. At one month follow up 166 children (78%) returned, in whom we found no differences in mean Hb between the transfused (10.2 g/dL [SD: 1.7]) and non-transfused (10.0 g/dL [SD: 1.3]) survivors (p = 0.25). The major factors affecting haematological recovery were young age (<24 months) and concomitant malaria parasitaemia; Hb being 8.8 g/dL [SD: 1.5] in parasitaemic individuals compared with 10.5 g/dL [SD: 1.3] in those without (p < 0.001). CONCLUSION: This data supports the policy of rational use of blood transfusion, as proposed in the WHO guidelines, for children with anaemia in areas where access to emergency transfusion is not guaranteed. We have provided empirical data indicating that transfusion does not influence superior recovery in haemoglobin concentrations and therefore cannot be justified on this basis alone. This may help resolve the disparity between international policy and current clinical practice. Effective anti-malarial treatment at discharge may prevent reoccurrence of anaemia.

Spleen volume and clinical disease manifestations of severe Plasmodium falciparum malaria in African children.

BACKGROUND: Plasmodium falciparum malaria is common in African children. Severe disease manifestations include severe malarial anemia (SMA) and cerebral malaria (CM). In vitro studies suggest that splenic sequestration is associated with SMA and protective against CM. We sought to characterize the relationship between ultrasonographically derived spleen volume (SV), clinical manifestations and outcome. METHODS: We conducted a prospective observational study of severe malaria and SV in children aged 3 months to 12 years in Eastern Uganda. An SV normogram was generated from 186 healthy controls and adjusted for total body surface area (TBSA). Children with severe P. falciparum malaria were classified according to disease phenotype, and SV z-scores were compared for cases and controls to assess the degree of spleen enlargement. RESULTS: One hundred and four children with severe malaria, median age 19.2 months, were enrolled; 54 were classified as having SMA and 15 with CM. Mortality was 27% in the CM group vs 1.9% in the SMA group. TBSA-adjusted SV z-scores were lower in children with CM compared to SMA (1.98 [95% CI 1.38-2.57] vs 2.73 [95% CI 2.41-3.04]; p=0.028). Mean SV z-scores were lower in children who died (1.20 [95% CI 0.14-2.25]) compared to survivors (2.58 [95% CI 2.35-2.81]); p=0.004. CONCLUSIONS: SV is lower in CM compared to SMA. Severe malaria with no increase in SV z-score may be associated with mortality.