Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda: a cross-sectional study.

Background: Cryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm(3) or less in Mulago Hospital, Kampala, Uganda.

Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care.

Cryptococcal meningitis is a leading cause of death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of symptoms, and those who are asymptomatic but CRAG positive have a high risk of subsequent cryptococcal meningitis and mortality. A new CRAG point of care immunochromatographic test is available that is remarkably easy to administer without laboratory infrastructure or expertise and has excellent sensitivity and specificity.

Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis.

Objective: Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda.

Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study.

Background: Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.

Methods And Findings: We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS.

Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-saharan Africa.

Objective: HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression.

Methods: In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4/μL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.

Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome.

Background: Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20%-40% of ART-naive persons with AIDS and prior CM. Pathogenesis is unknown.

Methods: We compared initial cerebrospinal fluid (CSF) cultures, inflammatory markers, and cytokine profiles in ART-naive patients with AIDS who did or did not subsequently develop IRIS after starting ART.

Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings.

Background: Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Subclinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with subclinical cryptococcosis and the efficacy of preemptive fluconazole therapy.

Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance.

Background: Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS.

Materials And Methods: Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008.

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.

Treatment of severe sepsis with artemether-lumefantrine is associated with decreased mortality in Ugandan patients without malaria.

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.

Development and evaluation of a clinical algorithm to monitor patients on antiretrovirals in resource-limited settings using adherence, clinical and CD4 cell count criteria.

Background: Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings.

Methods: A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression.

Biomarkers of HIV Immune Reconstitution Inflammatory Syndrome.

Dysregulation of the immune system drives HIV pathogenesis. As we develop new ways to treat HIV and AIDS, we encounter new clinical ramifications of our treatment on regulatory components of the immune system. HIV-associated Immune Reconstitution Inflammatory Syndrome (IRIS) occurs after initiation of anti-retroviral therapy (ART) with inappropriate and dysbalanced restoration of the immune system resulting in pathologic inflammatory reactions with significant morbidity.

Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy.

Background: Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa.

Methods: Two prospective, observational cohorts enrolled human immunodeficiency virus (HIV)-infected, antiretroviral-naive persons with CM in Kampala, Uganda. The first cohort was enrolled in 2001-2002 (n = 92), prior to the availability of highly active antiretroviral therapy (HAART), and the second was enrolled in 2006-2007 (n = 44), when HAART was available.

Evaluation of filter paper transfer of whole-blood and plasma samples for quantifying HIV RNA in subjects on antiretroviral therapy in Uganda.

Background: Most HIV-infected subjects on antiretroviral therapy (ART) in resource-limited settings do not undergo virologic monitoring. There is an urgent need for cheap, accessible HIV RNA assays for early diagnosis of virologic failure. We investigated filter paper transfer (FPT) of whole blood and plasma as an alternative to standard plasma-based assays for virologic monitoring in Uganda.

Point-of-care lactate testing predicts mortality of severe sepsis in a predominantly HIV type 1-infected patient population in Uganda.

Background: Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis.

Methods: A prospective observational study enrolled 253 patients at a national referral hospital in Uganda.

Functional adrenal insufficiency among critically ill patients with human immunodeficiency virus in a resource-limited setting.

Background: Functional adrenal insufficiency (FAI) is associated with increased mortality and is defined as subnormal cortisol production during acute severe illness.

Methods: After screening 200 adult patients admitted in the medical emergency unit of Mulago Hospital, Kampala, Uganda, 113 critically ill HIV-infected adults not receiving corticosteroids were enrolled after obtaining informed consent to determine the prevalence and factors associated with FAI.

Results: Functional adrenal insufficiency, defined in this study as morning total serum cortisol level of View Article and Find Full Text PDF

The TB pandemic: an old problem seeking new solutions.

Tuberculosis (TB) continues to kill more than 2 million people globally each year. Annual TB case notification rates have risen up to fourfold since the mid-1980s, with the highest rate of 1000/100,000 around Cape Town, South Africa. There is an urgent need for novel diagnostic methods and preventive vaccines to control this epidemic.

Diagnosis and treatment of malaria.

Despite accurate diagnostic tests over-diagnosis and presumptive treatment are common practice

A renal aspergilloma--an unusual presentation of aspergillosis in an HIV patient.

Background: Aspergillosis is a fungal infection occasionally found in immunosuppressed patients. The recommended management of patients with renal aspergilloma remains unclear.

Methods: An HIV patient presented with flank pain and an abdominal mass.