Tuberculosis (TB) is a major unrecognized cause of deadly sepsis among people with HIV in Africa, a sweeping new study reveals. Beginning treatment for TB immediately – even before sepsis patients are diagnosed with TB – could save countless lives, the researchers say.
The ATLAS study, conducted over five years at hospitals in Tanzania and Uganda, has found that more than half of the hundreds of patients enrolled in the study had TB and that immediate treatment increased their chances of survival significantly.
The first-of-its kind study was conducted by researchers at the University of Virginia School of Medicine, Tulane School of Medicine, University of Minnesota and their collaborators in Africa, including leading HIV and tuberculosis physician-scientists Stellah Mpagama from Tanzania’s Kibong’oto Infectious Diseases Hospital and Conrad Muzoora from Uganda’s Mbarara University of Science and Technology.
“In life-threatening sepsis in other parts of the world, a germ causing infection is either not found or is commonly caused by bacteria from urinary tract infections or pneumonia,” said UVA Health researcher Scott Heysell, MD, MPH, who co-led the study. “Instead, we found a treatable form of infection in the majority of people that could be targeted immediately when they presented to care.”
That would enhance the treatment patients receive, improve outcomes and, ultimately, save lives.
“In light of the 30-50% mortality associated with sepsis, our findings suggest that clinicians who work in African settings where HIV and TB are common should probably immediately provide TB treatment to patients who present to hospital with sepsis,” said UVA’s Christopher C. Moore, MD, co-lead investigator. “Given Africa’s disproportionate burden of global sepsis, implementation of this early treatment strategy could result in a substantial reduction in sepsis-related mortality across the region.”
Stopping Deadly Sepsis
Sepsis is dangerous full-body inflammation that can take hold when a person’s immune response spirals out of control in response to an infection, potentially causing organ failure and death. It is the leading cause of death worldwide, and people living with HIV are particularly vulnerable.
The ATLAS study was launched to shed light on the causes of sepsis among people living with HIV in Africa and to find better ways to treat it. After evaluating more than 400 patients with sepsis, the study found that the predominant – and often unrecognized – cause was tuberculosis. More than half of participants in the randomized trial ultimately were found to be suffering from TB.
Further, the researchers found that the highest survival rate was among the patients who received immediate treatment for TB, regardless of whether they had been formally diagnosed. Patients who did not receive TB treatment until their diagnosis had been confirmed, on the other hand, were more likely to die.
This partly reflects the difficulty of confirming a TB diagnosis in Eastern Africa, as the condition can be detectable only with sophisticated blood tests that are often unavailable or delayed, the researchers say. Further, “many of these patients have multiple infections at the same time, which makes their care more challenging,” Mpagama noted.
Current treatment guidelines generally call for TB treatment to be initiated only after a confirmed diagnosis or if the patient has not improved after receiving standard antimicrobial therapy for three to five days. But beginning TB treatment immediately, even without a diagnosis, could save many lives every year, the researchers say.
“This study has the potential to provide a blueprint for evidence-based antimicrobial approach for sepsis therapy in TB-endemic areas,” said Tulane researcher Eva Otoupalova, MD. “My hope is that this work will help lower the extremely high mortality of patients with TB-sepsis.”
Recent funding from the National Institutes of Health is allowing the researchers to continue their work in Uganda and Tanzania. They are launching a new trial to determine whether hydrocortisone to reduce inflammation and/or immediate treatment of TB and other bacterial pathogens will improve survival in patients with HIV-related sepsis.
About the Findings
The researchers have published their findings in a pair of papers in the scientific journals Lancet Infectious Diseases and eClinicalMedicine. The articles are open access, meaning they are free to read.
The ATLAS study was conducted by a team of more than 30 doctors, nurses, pharmacists, study coordinators and statisticians.
