Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.

OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell's C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test. RESULTS: The cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001). CONCLUSIONS: Among the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.

Cohort profile: a migratory cohort study of US Marines who train in Australia.

PURPOSE: In 2012, US Marines and Sailors began annual deployments to Australia to participate in joint training exercises with the Australian Defence Force and other partners in the region. During their training, US service members are exposed to a variety of infectious disease threats not normally encountered by American citizens. This paper describes a cohort of US Marines and Sailors enrolled during five rotations to Australia between 2016 and 2020. PARTICIPANTS: Study participation is strictly voluntary. Group informational sessions are held prior to deployment to describe the study structure and goals, as well as the infectious disease threats that participants may encounter while in Australia. All participants provided written informed consent. Consented participants complete a pre-deployment questionnaire to collect data including basic demographic information, military occupational specialty, travel history, family history, basic health status and personal habits such as alcohol consumption. Blood is collected for serum, plasma and peripheral blood mononuclear cells (PBMC) processing. Data and specimen collection is repeated up to three times: before, during and after deployment. FINDINGS TO DATE: From the five rotations that comprised the 2016-2020 Marine Rotational Force-Darwin, we enrolled 1289 volunteers. Enrolments during this period were overwhelmingly white male under the age of 24 years. Most of the enrollees were junior enlisted and non-commissioned officers, with a smaller number of staff non-commissioned officers and commissioned officers, and minimal warrant officers. Over half of the enrollees had occupational specialty designations for infantry. FUTURE PLANS: In the future, we will screen samples for serological evidence of infection with Burkholderia pseudomallei, Coxiella burnetii, Ross River virus, SARS-CoV-2 and other operationally relevant pathogens endemic in Australia. Antigenic stimulation assays will be performed on PBMCs collected from seropositive individuals to characterise the immune response to these infections in this healthy American population.

Next-generation Diagnostics for Melioidosis: Evaluation of a Prototype i-STAT Cartridge to Detect Burkholderia pseudomallei Biomarkers.

BACKGROUND: Infection with the gram-negative bacterium Burkholderia pseudomallei can result in melioidosis, a life-threatening disease that can be difficult to diagnose. Culture remains the gold standard for diagnosis but requires laboratory resources not available in many endemic regions. A lateral flow immunoassay has shown promise for POC diagnostics but suffers from low sensitivity when used on blood samples. PCR also has low sensitivity on blood, attributed to the low bacterial numbers in blood observed in melioidosis patients, even when bacteraemic. METHODS: A prototype i-STAT cartridge was developed to utilize the monoclonal antibody specific for the capsule of pathogenic Burkholderia species employed on the LFI. The resulting POC assay was evaluated on 414 clinical specimens from Darwin, Australia and Cambodia. RESULTS: The i-STAT assay accurately distinguished Australian blood culture positive melioidosis patients from Australian patients hospitalized with other infections (AUC = 0.91, 95% CI 0.817 - 1.0). We derived an assay cutoff with 76% sensitivity and 94% specificity that correctly classified 88% (n = 74) of the Australian patients. Interestingly, only 46% (6/13) of the culture-positive melioidosis patients in Cambodia were classified correctly. Of great importance however, the assay detected capsule from blood samples for 32% of blood culture negative melioidosis patients in both cohorts and previously undiagnosed melioidosis patients in Cambodia. In addition the assay showed high sensitivity and specificity for urine, pus and sputum. CONCLUSIONS: Diagnostic tools that are not dependent upon the growth kinetics or the levels of bacteremia of B. pseudomallei represent the next-generation of diagnostics and must be pursued further.