Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population

Pfizer Initiative in International Health, Division of Intramural Research, NIAID/NIHBackground: Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality. Methodology/Results: Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, Management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm3 (IQR, 16–131 cells/mm3). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250–1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacterium patients (OR 1.83, 95% CI = 1.01–3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19–327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia. Conclusion: Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings

Performance of two commercial immunochromatographic assays for rapid detection of antibodies specific to human immunodeficieny virus types 1 and 2 in serum and urine samples in a rural community-based research setting (Rakai, Uganda)

Rapid detection of human immunodeficiency virus (HIV) antibodies is of great importance in developing and developed countries to diagnose HIV infections quickly and at low cost. In this study, two new immunochromatographic rapid tests for the detection of HIV antibodies (Aware HIV-1/2 BSP and Aware HIV-1/2 U; Calypte Biomedical Corporation) were evaluated in rural Africa to determine the tests’ performance and comparability to commercially available conventional enzyme immunoassay (EIA) and Western blot (WB) tests. This prospective study was conducted from March 2005 through May 2005 using serum and urine from respondents in the Rakai Community Cohort Survey. Nine hundred sixty-three serum samples were tested with the Aware blood rapid assay (Aware-BSP) and compared to two independent EIAs for HIV plus confirmatory Calypte WB for any positive EIAs. The sensitivity of Aware-BSP was 98.2%, and the specificity was 99.8%. Nine hundred forty-two urine samples were run using the Aware urine assay (Aware-U) and linked to blood sample results for analysis. The sensitivity of Aware-U was 88.7% and specificity was 99.9% compared to blood EIAs confirmed by WB analysis. These results support the adoption of the Aware-BSP rapid test as an alternative to EIA and WB assays for the diagnosis of HIV in resource-limited settings. However, the low sensitivity of the Aware-U assay with its potential for falsely negative HIV results makes the urine assay less satisfactory

The Safety of Adult Male Circumcision in HIV-Infected and Uninfected Men in Rakai, Uganda

Ron Gray and colleagues report on complications of circumcision in HIV-infected and HIV-uninfected men from two related trials in Uganda, finding increased risk with intercourse before wound healing

Assessment of Pathogenic Contamination and Antimicrobial Activity of Selected Herbal Medicinal Remedies in Mbarara City, South Western Uganda

Abstract Background: Herbal formulations in Mbarara have been used in the treatment and management of several disease conditions extensively overtime due to low cost compared to empirical synthetic medicine, however evidenced that they can be contaminated with dangerous pathogenic organisms which are all tailored to handling practices, storage, and other environmental conditions thus, the need to further asses these herbs for safety to the consumers.Materials and methods: Forty-five (45) liquid herbal formulations for the treatment and management of communicable infections were purchased on the open market. All Samples were cultured on plate count agar for colony counts and then subcultured on different laboratory media and then analyzed for antimicrobial activity using the agar diffusion method.Results: Out of the 45 herbal formulations, 32(71.1 %) were contaminated while 13 (28.9 %) were not. Out of the organisms isolated from individual formulations, 19 (59.4 %) had Bacillus subtillis and S. aureus, 4(12.5%) had C. freundi and Proteus mirabilis, 2(6.3%), C.divergens, 1(3.1 %) Rhodotorula, 5(15.6%) Aspergillus spp, had E. cloace. 1 (3.1%) had Klebsiella spp. Of these, 29(87.9%) had contaminants within acceptable limits of less than 103CFU/mL, while 12(36.4%) beyond 103 CFU/m. Out of the 45 formulations, not even one could qualify for pharmaceutical use, all MICs all were &gt;1000mcg/mL64.4%) were active while 16(35.6%) had no activity.Conclusion: Herbal formulations in Mbarara are contaminated with various microbes and have very limited antimicrobial activity, herbalists therefore should be trained on good harvesting, safe handling, storage, and good manufacturing practices of these medicinal raw materials and their products, responsible authorities should enact policies and regulations to guide the herbalists and protect the public from adverse effects of consuming these unverified herbal medicinal remedies.</jats:p

Limitations of Rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study

Objective To evaluate the limitations of rapid tests for HIV-1. Design Diagnostic test accuracy study. Setting Rural Rakai, Uganda. Participants 1517 males aged 15-49 screened for trials of circumcision for HIV prevention. Main outcome measures Sensitivity, specificity, negative predictive values, and positive predictive values of an algorithm using three rapid tests for HIV, compared with the results of enzyme immunoassay and western blotting as the optimal methods. Results Rapid test results were evaluated by enzyme immunoassay and western blotting. Sensitivity was 97.7%. Among 639 samples where the strength of positive bands was coded if the sample showed positivity for HIV, the algorithm had low specificity (94.1%) and a low positive predictive value (74.0%). Exclusion of 37 samples (5.8%) with a weak positive band improved the specificity (99.6%) and positive predictive value (97.7%). Conclusion Weak positive bands on rapid tests for HIV should be confirmed by enzyme immunoassay and western blotting before disclosing the diagnosis. Programmes using rapid tests routinely should use standard serological assays for quality control

Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population.

BACKGROUND:Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality. METHODOLOGY/RESULTS:Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm(3) (IQR, 16-131 cells/mm(3)). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250-1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01-3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19-327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia. CONCLUSION:Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings

Flow diagram for study eligibility and follow-up to 30 days post-discharge.

<p>Flow diagram for study eligibility and follow-up to 30 days post-discharge.</p

Multivariate analysis of clinical predictors for post-discharge mortality.

<p>* Per 10-unit increase.</p

Univariate and multivariate analysis for admission laboratory predictors of in-hospital mortality at Mulago Hospital.

<p>* Model is adjusted for covariates found to be significant predictors of in-hospital mortality (i.e., unmarried marital status, decreased admission KPS, and RR>30 breaths/min) in a multivariate analysis for the general Mulago Hospital model (data not shown).</p><p>n.s. = not significant.</p