The aim of this study is to prospectively evaluate the barriers to care, evaluation, clinical practices, and outcomes for patients presenting with sepsis to hospitals in the Kilimanjaro Region of northern Tanzania. This will include an assessment of timing and selection of antimicrobials and administration and volume of intravenous fluids. The study also aims to characterize sepsis sub-types in the epidemiologic context of northern Tanzania using statistical clustering techniques of clinical variables and of host immune response patterns.

A prospective observational cohort study of adolescent and adult patients with sepsis presenting to hospitals in the Kilimanjaro Region, Tanzania. Participants ≥10 years of age with suspected infection and the presence of two of the following will be enrolled: (1) tympanic temperature > 38°C or < 36°C, (2) heart rate > 90 beats/minute, (3) respiratory rate > 20 breaths/minute. Participants will be observed in the Emergency Department and during admission. The following data will be collected: demographics and medical history; history of present illness; laboratory and microbiological workup; antimicrobial selection and timing; intravenous fluid timing and volume. Vital status will be determined at 7 days, hospital discharge, and 28 days post-presentation. An enrollment of up to 1250 patients with sepsis is expected over a two-year period.

This study is expected to produce additional descriptive data of sepsis epidemiology and current practice in sSA. The data will yield important insights regarding key care practices for sepsis, including antimicrobial and intravenous fluid management. Outcomes of patients with sepsis will be described, including an assessment for correlations between current care practices and mortality.

Characterization of potential sepsis sub-types will be undertaken in two domains: 1) clinical characterization via a robust battery of routine clinical laboratories (chemistry, hematology, coagulation studies), vital signs, routine clinical signs and anthropometry; 2) host immune response characterization by analysis of mRNA transcriptome expression in RNA-stabilized whole blood samples. The goal of the sub-type characterization is to identity discrete and clinically relevant sepsis phenotypes, and in doing so eventually help optimize evaluation and management of sepsis specific to the populations and health systems in sub-Saharan Africa. Detailed etiologic investigations will also take place, including blood culture, blood parasite smears, and viral respiratory testing of nasopharyngeal samples; for patients living with HIV, additional evaluations will include serum cryptococcal antigen, urine lipoarabinomannan assay (TB-LAM) and MycoFLytic blood culture. Collectively, the data collected in this observational cohort study will contribute to further developing sepsis management bundles better suited to settings sub-Saharan Africa.

Inclusion Criteria:

Persons ≥ 10 years of age presenting to hospital suspected to have an infection and meeting two of the following vital signs criteria:

• tympanic >38°C or < 36°C
• a heart rate > 90 beats per minute
• a respiratory rate of > 20 breaths per minute

Exclusion Criteria:

• patient with a language barrier
• pregnant female
• a refugee
• a prisoner

Adolescent and adult patients with sepsis presenting to emergency department or outpatient department at hospitals in Kilimanjaro Region, northern Tanzania.

Individual-level participant data will be de-identified and locator/identifying variables will be removed prior to sharing. Data availability will follow US National Institutes of Health guidelines for genomic data sharing, and it will include uploading annotated gene expression data files to the Gene Expression Omnibus system at the National Center for Biotechnology Information. Any sharing will also comply with regulations of the National Institute for Medical Research in Tanzania, including compliance with data transfer agreements between Kilimanjaro Christian Medical Centre and Duke University.

Gene expression data will become available at time of submission of the first manuscript that describes any such data. Additional data will be available per publisher or US National Institutes of Health policies or by written request to the Principal Investigators, provided that the sharing is compliant with the data sharing policies of the Tanzanian National Institute for Medical Research. Once available, there are no anticipated restrictions on the duration of availability.

For data uploaded to the Gene Expression Omnibus, access will be designated per the policies of the US National Center for Biotechnology Information. For data uploaded in compliance with publishers, access will be designated per the policies of the publisher. Data can also be shared upon written request to the Principal Investigators and only shared once appropriate data sharing procedures have taken place in accordance with the policies of the Tanzanian National Institute for Medical Research.