In the midst of the ongoing Ebola outbreak in the Democratic Republic of the Congo, and in the absence of antiviral medications for the disease, the World Health Organization (WHO) has issued updated guidelines for the clinical management of filovirus disease, according to a press release from the organization. The new guidelines apply to all types of Ebola and Marburg viruses including the Bundibugyo (the culprit in the current Congo outbreak), Sudan, and Tai Forest viruses.

The guidelines feature evidence-based recommendations with a focus on supportive care to improve outcomes. Key recommendations include the use of clinical laboratory tests for patient monitoring in order to promptly identify problems such as hypoglycemia and metabolic disruptions. The guidelines also advise oral and intravenous (IV) rehydration; early, targeted use of IV fluids and vasoactive medications for treating shock; and appropriate use of antibiotics to manage bacterial sepsis or other co-occurring bacterial infections in filovirus disease patients.

In addition, the guidelines include conditional recommendations against the use of tranexamic acid to manage hemorrhage in most patients with filovirus disease, with the exception of individuals with filovirus who are experiencing postpartum hemorrhage.

Finally, structured follow-up care is strongly recommended for patients who survive filovirus disease, with a moderate certainty of evidence, according to the guidelines.

The new guidelines were designed to help health workers who are on the ground caring for patients and to inform planning by health facility administrators and health policymakers, according to the WHO.

Clinical and Logistical Challenges

Given the lack of an Ebola-specific antiviral medication, the management of patients with Ebola remains supportive at this time, said Thomas M. Kerkering, MD, infectious diseases specialist and professor of medicine at Virginia Tech Carilion School of Medicine, Roanoke, Virginia.

“It is important for WHO to outline this supportive clinical management and the degree of evidence behind the recommendations; we are dealing with resource-poor situations, and these guidelines take that into account,” said Kerkering.

Key points in the new guidelines include the management of patients with oral rehydration solutions, Kerkering said. “If intravenous fluids are needed, they point out that a peripheral IV is usually sufficient,” he noted. If blood pressure support is needed, the guidelines state that norepinephrine is the preferred agent to use, he added. Kerkering also highlighted the updated recommendations for when to use and not use tranexamic acid to control excessive bleeding.

The biggest challenge in implementing the updated guidelines will be the availability of supplies, followed by dissemination of the guidelines to frontline health workers, Kerkering said.

The current outbreak results from the Bundibugyo species of Ebolavirus, which is distinct from the more common Ebola Zaire and for which there is no proven or licensed vaccine or monoclonal antibody treatment to prevent or treat the disease, said Michele Barry, MD, professor of medicine and tropical diseases at Stanford University, Palo Alto, California.

The WHO guidelines on infection prevention and control released in May and on clinical case management in June collectively emphasize early case detection, contact tracing, rapid isolation, early supportive care, community engagement, and experimental vaccine evaluation, said Barry.

The updated guidelines have a much stronger emphasis than previous guidelines on aggressive supportive care, Barry said. “The new guidance provides clearer recommendations for mild versus severe disease and also includes recommendations for pediatric patients and neonates, pregnant women, and survivors with persistent complications,” she said. Older Ebola guidance focused mainly on acute care; by contrast, “the new recommendations build on what we have learned from Ebola Zaire outbreaks, which demonstrated viral persistence, for example, in eyes or semen, along with the mental health sequelae of having had Ebola,” Barry explained.

A significant challenge in managing the current outbreak is contact tracing and isolation in an area of conflict, said Barry. “Violence and mistrust, as well as attacks on healthcare facilities, are major barriers. Food shortages in the region are also complicating contact tracing and isolation efforts as people migrate looking for food and thus leaving isolation,” she added. “In addition, US medical volunteers are challenged by the threat of potential quarantine in Kenya or the inability to enter the US during their quarantine period,” she said.

Research Gaps

Looking ahead, collecting data on current patients to determine the efficacy of these guidelines would be imperative, Kerkering noted.

“Prevention of future outbreaks will be difficult and will depend upon early recognition of an Ebola case before spread can take hold,” he said. “For example, if a patient presents with fever, nausea, and vomiting, the most common and most likely diagnosis in these settings is going to be malaria, and the patient will be given malaria medication and sent back into the community,” he explained. Therefore, a rapid, easily implemented diagnostic test for Ebola would be most welcome, Kerkering added.

Vaccine experimentation and monoclonal antibody trials are needed, and some data from such studies are starting to emerge, said Barry. A pan-filovirus vaccine that protects against all Ebola and Marburg species would be ideal, she said.

Kerkering and Barry reported having no relevant disclosures.