The Immune Response during Sepsis in a Tropical setting; The impact of co-infection with HIV or malaria.

Bacterial sepsis is a major cause of death in Africa. Recent evidence indicates that African patients with culture confirmed bloodstream infection are frequently co-infected with either HIV or malaria. Knowledge on the impact of these co-infections on the immune response during bacterial sepsis is highly limited. Therefore we will perform a prospective observational study to determine the impact of co-infection with HIV or malaria on the immune response during bacterial sepsis and its influence on clinical outcome. At the same time, we will identify micro-organisms causing sepsis and their antimicrobial resistance patterns. Patients will be recruited in the Albert Schweitzer hospital in Lambaréne, Gabon. We expect to enroll 2500 patients with symptoms indicating sepsis, of which an estimated 250 will have positive blood cultures. Cohorts (N = 50 per cohort) will be constituted consisting of patients with culture confirmed bacterial sepsis with or without co-infection with HIV or malaria, and afebrile controls without bacterial infection and with or without chronic HIV or malaria. In whole blood, plasma and purified blood cell populations, pro-inflammatory and anti-inflammatory markers known to be important in sepsis pathogenesis will be measured. In addition, gene expression profiles of purified cells will be compared using whole genome microarrays to discover new genes or pathways involved in sepsis pathogenesis.

Co-infection with either HIV or malaria may have a major impact on the immune response during bacterial sepsis. Current knowledge on the pathogenesis of sepsis indicates an unbalanced response to infection characterized by both excessive pro-inflammatory responses and immune suppression. This disturbance is expected to be even more profound in the presence of HIV/malaria co-infection, at least in part due to hyper-responsiveness of PRRs triggering innate immunity.

Blood culture results: Maximum timepoint 7 days after admission.

Admission related mortality: Maximum timepoint 3 weeks after admission.

Sepsis related organ failure: Monitoring during admission.

Systemic markers of inflammation: Day 0, 2, 6 and 30.

Cell specific markers of inflammation: Day 2.

All cause mortality: 6 months.

Venous blood draw.