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Bacterial bloodstream infections rival malaria as a common cause of illness and death in sub-Saharan Africa, according to an analysis from more than 58,000 hospitalized patients across a dozen countries conducted by Duke University researchers.

But clinicians with limited resources may treat these patients for malaria, not bacterial infection.

“Clinicians in resource-limited settings face a diagnostic and therapeutic challenge when confronted with a patient who has a fever, especially when the patient does not show evidence of malaria and has no symptoms that easily indicate the source of infection,” said Elizabeth A. Reddy, fellow in the Division of Infectious Diseases and International Health at Duke University Medical Center and lead author of the study.

“Bacterial bloodstream infection is one of the most important considerations for a patient with fever, but its role may be under-appreciated or under-emphasized in some areas in Africa," Reddy said. "This can result in persistent attempts to treat malaria even in the absence of evidence that the illness is caused by malaria.”

The study, published in The Lancet Infectious Diseases, includes an analysis of 22 studies over a 22-year period that used blood cultures to identify non-malaria bloodstream infections among adults and children admitted to hospitals in 12 African countries.

“The fact that only 22 articles were included out of the 10,000 we reviewed is one potential indication of the degree to which the overall importance of non-malaria bloodstream infection may be under-recognized in many circles,” said Reddy.  “However, these 22 studies yielded data for an impressive 58,296 hospitalized patients representing  all major regions of Africa, allowing us to provide a ‘big picture’ of this phenomenon.”

Bacterial or fungal bloodstream infections were identified among 13.4 percent of patients with fever and 7.4 percent of patients admitted to the hospital regardless of fever history.  In other words, nearly one in 13 hospitalized patients across Africa may have a non-malaria bloodstream infection.  This is important because researchers cite other studies in which many patients were initially treated for malaria, and later found to have a bacterial bloodstream infection.

Malaria has been the primary focus of work on fever-related illness in sub-Saharan Africa for decades because of its high prevalence and relatively simple laboratory diagnosis, while “laboratory capacity to diagnose non-malaria causes of fever has been limited,” said co-author John Crump, an associate professor of medicine and site director at the Duke-Kilimanjaro Christian Medical Centre (KCMC), which is supported by the Duke Global Health Institute.

The research team also found bacterial bloodstream infections have a substantial impact on mortality, and are often associated with HIV/AIDS. Data collected from 13 of the 22 studies revealed an 18.1 percent in-hospital mortality rate among patients with bloodstream infections. Researchers were also able to document that HIV infection, affecting roughly 23 million people in Africa, is associated with increased prevalence of bacterial and fungal bloodstream infections.

Researchers say health outcomes in Africa may be improved by scaling-up laboratory facilities to allow for accurate diagnosis and directed treatment of patients with bloodstream infections, as well as to inform local policy on likely prevalence, pathogens, and antimicrobial susceptibility patterns.

“We are in a position to alter the trajectory of health outcomes and antimicrobial resistance in Africa> by emphasizing preventive measures and improving laboratories’ ability to make correct diagnoses,” said Reddy. “Bacterial bloodstream infection is a cause of preventable morbidity and mortality, and we hope that raising awareness of its importance will make a difference by directing local treatment practices, prioritizing the availability and uptake of vaccines, and promoting the development of high quality laboratory diagnostics.”

The study is part of a large ongoing program on fever-related illness through the Duke-KCMC collaboration in Moshi, Tanzania. The research team also includes Andrea Shaw, a pediatrics resident.  Fever-related illness research at the site is supported by funding from the US National Institutes of Health International Studies on AIDS Associated Co-infections program (ISAAC), and the Bill & Melinda Gates Foundation.