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The Etiology of Sepsis in Uganda

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, June 5, 2018

It is often the case in sepsis—the life-threatening dysregulated immune response to infection—that no inciting cause is found using traditional diagnostic testing. Even when a diagnosis is made, it is often delayed because of the time it takes for traditional microbiological techniques to yield a diagnosis. This time delay is critical, as time to effective antimicrobial therapy is a major factor in outcome. In addition to making treatment decisions extremely difficult, failing to promptly identify what is causing a possibly fatal infectious disease deprives epidemiologists of potentially crucial information. The scenario of sepsis whose etiology is unknown occurs in both resource-rich and resource-poor locations. A new study published in Clinical Infectious Diseases used sophisticated and comprehensive diagnostic technology and details causes of sepsis in Uganda.

43 Target PCR Used

The diagnostic test used by Moore and colleagues was a 43 target PCR array card that tests for various bacteria, viruses, fungi, and protozoa. A convenience sample of preserved blood specimens from 336 adult patients enrolled in a prior sepsis study conducted during 2008-09 was used. Cryptococcal antigen testing was also performed on some of the specimens.

HIV Common in Subjects; CMV Viremia Most Commonly Identified

The median age of study subjects was 34 years, and the in-hospital mortality rate was 27% in the sample. HIV infection was present in the majority of patients (84%).

A target microorganism was detected in 72% of samples. The most common microbes identified were cytomegalovirus (41%), Mycobacterium tuberculosis (21%), malaria (10%), and pneumococcus (9%). Other identified etiologies included hepatitis E, dengue, leptospirosis, cryptococcosis, brucellosis, and Q fever.

Mortality was associated with CMV viremia and M. tuberculosis bacteremia, with higher mortality rates correlated with the quantitative burden of infection.

Sensitivity of the PCR assay was compared to standard culture and was 61%, perhaps reflecting the fact that less than 2 milliliters of blood per sample could be used for this study.

Specific Diagnosis Should Be Standard of Care

While this paper’s generalizability is highly skewed, given the presence of HIV infection in the vast majority of study subjects as well as the significance of CMV viremia in the critically ill (40% of viremic patients had bacterial co-infection), it provides important evidence for the feasibility and yield of such sophisticated testing. It is also significant that, even using such tools as were employed in this study, 28% were still left without a diagnosis, which argues for using even more broadly targeted testing to achieve full capture. Such diagnostic products are increasingly becoming commercially available.

Understanding which infections are making people critically ill is an essential task that not only improves patient outcomes, antimicrobial stewardship activities, and infection control procedures but also provides crucial information that can inform pandemic preparedness and outbreak response. This activity will yield valuable information in any setting in which it is deployed and should increasingly become part of routine clinical care.

 

Reference

Moore CC, Jacob ST, Banura P, et al. Etiology of sepsis in Uganda using a quantitative PCR-based TaqMan Array Card. Clin Infect Dis 2018. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy472/5032704. Accessed June 4, 2018.