Hemorrhage May Be ‘Infrequent’ Feature in Latest Ebola Outbreak

In a departure from past Ebola outbreaks, roughly 90% of the patients testing positive for Bundibugyo virus disease (BVD) had no hemorrhagic signs or bleeding at presentation, according to a preliminary report.

In fact, the bleeding rate among the laboratory confirmed cases in the study was no higher than in patients with suspected BVD who tested negative (10.4% vs 10.3%), reported Placide Mbala-Kingebeni, PhD, of the National Institute of Biomedical Research in Kinshasa, Democratic Republic of Congo, and colleagues.

“Hemorrhagic signs were infrequent” at presentation, they wrote in the New England Journal of Medicine.

Previous outbreaks of BVD “have reported substantially higher rates of hemorrhage than in this cohort,” according to the research team, though they cautioned that the lower rate “could be due to differences in reporting practices.”

Unexplained bleeding is present in roughly 40% of Ebola cases, according to the CDC. In one study specific to BVD involving a 2007 outbreak, researchers reported that 54% of laboratory-confirmed cases had some kind of bleeding.

BVD’s early symptoms such as fever, muscle pain, and headache aren’t specific to the disease, complicating detection and differential diagnosis without laboratory confirmation.

In the current outbreak, patients with a confirmed case were more likely than those testing negative to present with fever (74.3% vs 64.9%) and gastrointestinal and systemic signs, including vomiting (66.7% vs 50.8%), diarrhea (67.4% vs 49.6%), anorexia or loss of appetite (39.5% vs 17.2%), and abdominal pain (37.3% vs 16.3%).

BVD-positive patients were also more likely to have difficulty breathing (34.1% vs 10.9%) and swallowing (32.8% vs 10.7%). Sex and age had little impact on symptom profiles, according to the researchers.

“Signs and symptoms highly predictive of confirmed disease might be used to help prioritize access to scarce diagnostics or support more targeted isolation and cohorting practices for infection prevention and control,” Mbala-Kingebeni and colleagues wrote.

“These early data from the current BVD outbreak suggest a clinical syndrome largely compatible with that of other Filoviruses, enabling clinical and public health responses to be tailored to this expected disease course,” they added.

As of June 23, the World Health Organization (WHO) has reported 1,138 confirmed BVD cases and 293 deaths, for a case fatality ratio of 26%. The vast majority are in Congo, with some in neighboring Uganda. The case fatality ratios in the two prior BVD outbreaks (2007 in Uganda and 2012 in Congo) were 30% and 50%.

WHO officials have warned that the current outbreak’s potentially lower mortality rate and milder symptoms than other Ebola outbreaks could make it tougher to control and could potentially prolong the epidemic.

One concern flagged by Mbala-Kingebeni and colleagues was the week-long delay between when a patient developed symptoms and their sample was taken for collection observed in the study.

“If this delay at least partially reflects delays from symptom onset to presentation at a health facility, stronger advocacy for earlier presentation is needed to improve survival and to limit viral shedding in communities,” they wrote.

Their analysis examined 2,351 recorded BVD cases in a database from May 3 and June 8, ultimately including 505 with laboratory-confirmed BVD and 635 with suspected disease but who tested negative.

Among those two groups, 18.8% of the positive patients and 10.2% of the negative patients died by the June 8 data cutoff. Given the limited data on final outcomes and unknown denominators, however, those findings can’t be interpreted as the BVD outbreak’s case fatality rate, cautioned Mbala-Kingebeni and colleagues.

Among a subset of the positive patients, those who died had lower cycle-thresholds (Ct) values — pointing to higher viral loads — than the survivors (median Ct value: 24.4 vs 28.7).