Severe malaria due to Plasmodium falciparum causes more than 800,000 deaths every year. Primary therapy with quinine or artesunate is generally effective in controlling P. falciparum parasitemia, but mortality from cerebral malaria and other forms of severe malaria remains unacceptably high. Longterm cognitive impairment is also common in children with cerebral malaria. Of the numerous adjunctive therapies for cerebral malaria and severe malaria studied over the past five decades, only one (albumin) was associated with a reduction in mortality. In this article, we review past and ongoing studies of adjunctive therapy, and examine the evidence of efficacy for newer therapies, including inhibitors of cytoadherence (e.g., levamisole), immune modulators (e.g., rosiglitazone), agents that increase nitric oxide levels (e.g., arginine) and neuroprotective agents (e.g., erythropoietin).
Background: Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia Objective: We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital. Methods: One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) < 2.6mmol/l) which was expressed as relative risk (RR). Efficacy of the dextrose infusion was computed using 1-RR. Results: From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09-0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63-0.90). Conclusion: Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital.(ClinicalTrials.gov Identifier: NCT01688674)
Objective: To evaluate the effect of Highly Active Anti-Retroviral Therapy (HAART) and cotrimoxazole prophylaxis usage (CTX) on incidence of morbidity within the first year of HAART-eligibility.Methods: Between July 1999 and April 2006, we collected information on morbidity from an open cohort of HAARTeligible patients (according to WHO criteria). We compared morbidity among patients initiating HAART to morbidity before the stepwise introduction of HAART and CTX. We used available patients on HAART to select randomly a historical group of HAART-naïve but eligible patients who had proportionally the same WHO stage and sex distribution. Patients aged 16 years or older, visited the study team 6-monthly and when ill. Patients' demographics, WHO stage, HAART status, CTX, any new morbidity event (disease, drug-related and recurrent), haemoglobin and CD4 counts were collected from the beginning of follow up to the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of CTX by Mantel-Haenszel methods and adjusted for the effect of other confounders by negative binomial regression.Results: 219 HAART patients (median age 37 years; 73% women; 85% CTX; median Hb 11.7 g/dl and median CD4 131 cells/ul) experienced 94 events. They contributed 127 Person-Years of Observations (PYOs). 616 HAART-naïve patients (median age 33 years; 70% women; 33% CTX; median Hb 11.2 g/dl and median CD4 131 cells/ml) experienced 862 events. They contributed 474 PYOs. The overall morbidity among HAART patients during their first year of treatment was 78% lower (HR = 0.22, 95% CI: 0.15-0.31) than the overall incidence among HAART-naïve patients in unadjusted analysis. CTX also had a protective effect against morbidity (adjusted HR = 0.55, 95% CI: 0.38-0.79).Conclusions: Morbidity reduced significantly within the first year of initiating HAART in this setting. CTX had additional significant protection against morbidity.Background: A proportion of individuals who start highly active antiretroviral therapy (HAART) fail to achieve adequate CD4 cell reconstitution. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV clinic in Uganda, where patients initiate HAART with severe immunodeficiency.Methods: We analyzed data from a prospective research cohort of 559 patients initiating HAART between 04/04-04/05 at the Infectious Diseases Institute, Kampala. We defined SO-CD4 as either of a) <50 CD4 cells/l increase after 6 months of HAART, b) <100 cells/l increase after 12 months and c) <200 cells/l after 24 months. We assessed the cumulative risk of adverse clinical events [death and recurrent or new acquired immunodeficiency syndrome (AIDS)-defining illness] by Kaplan-Meier analysis.Results: Of 559 patients initiating HAART, 386 (69%) were female, with a median age of 38 years (IQR 33-34), and CD4 count of 98 cells/l (IQR 21-163); 283 (51%) had a CD4 count <100 cells. 414 (74%) started D4T ...
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