Kate Johnson

May 15, 2014

BARCELONA, Spain — Thomas Fletcher, MD, inspired a lecture hall packed with infectious disease experts by focusing on the simple things during a late-breaking session here at the 24th European Congress of Clinical Microbiology and Infectious Diseases.

Dr. Fletcher, who is from the Department of Pandemic and Epidemic Diseases at the World Health Organization, was doing Ebola virus infection case-management work in Conakry, Guinea, and had just cleared his mandatory 21 days of quarantine.

Although a therapy and vaccine for the highly contagious and fatal Ebola infection is desperately needed, it is the everyday things, such as gloves, gowns, and patient charts, that will ultimately help in the fight against this virus.

Personalizing protective equipment can be psychologically comforting to patients who are confused and afraid. Photo courtesy of Dr. Thomas Fletcher.

The lack of personal protective equipment "really holds back the ability to deliver care," he explained. He showed photographs of piles of contaminated waste in a Conakry hospital, and described medical teams sharing a few sets of personal protective equipment between them. In fact, a nurse he was working with in Conakry recently contracted the virus and died.

There is also a pressing need for clinicians on the frontline of the outbreak to communicate the clinical information being gathered to the international medical community.

"It is vitally important to get some clinical data from these outbreaks," he told Medscape Medical News. "Observational data are useful because we don't understand the pathogenesis of the disease in humans yet. If we're going to try to match the pathogenesis in clinical cases to the pathogenesis in nonhuman primates — which is relatively well understood — then we need to start reporting," he said.

There is cautious optimism that the number of cases in the current outbreak is decreasing. However, "we never call an end to the epidemic until we've had 2 full 21-day cycles without any new cases, and we haven't even done 1 cycle without a few new cases," Dr. Fletcher explained.

As of May 9, there were 236 confirmed cases and 158 fatalities in Guinea. Of the 24 healthcare workers infected, 17 had died.

In the Conakry isolation facility where Dr. Fletcher was based, preliminary data were collected on 80 patients who were isolated; Ebola was confirmed in 34 of those.

A Spectrum of Disease Activity

For the particular variant of the Ebola virus (Zaire ebolavirus) seen at the facility, the mortality rate is encouraging, at just over 50%. Elsewhere, rates for that variant are 70% to 90%.

Hospital admission ranged from 1 to 20 days in Conakry. Diarrhea, which occurred in 90% of patients, was "profuse and significant," and lasted, on average, 4 days. Gastrointestinal (GI) hemorrhage occurred in 40% of patients, and included hemorrhage from intravenous points, "which is a marker of severity, understandably," Dr. Fletcher reported.

Initial symptoms of Ebola infection are relatively nonspecific, and include fever with joint, muscle, and chest pain, eventually leading to nausea, vomiting, and diarrhea. Occasionally there is respiratory involvement.

The hallmark bleeding (particularly upper GI), hiccups (a sign of diaphragmatic contraction), and dementia are bad prognostic signs. Patient confusion presents the most serious risk to staff because of the potential for needle sticks, he explained.

"Diarrhea is the big issue and, in this environment, leads to significant hypovolemia, electrolyte imbalance, and renal impairment," he said.

It has become evident that there is a spectrum of disease activity.

"There are people who have a relatively mild disease course with a febrile illness and some GI upset who recover. They probably don't need much more than some oral rehydration salts," he said. "And then there are people with severe disease who either present late or gravely unwell with hemorrhage; there's very little you can do for them apart from palliate them."

The group in the middle is probably the most interesting. Dr. Fletcher said he thinks that outcome can be affected in these patients, and significant GI upset can probably be managed with supportive care.

He emphasized that enhanced treatment protocols are important in the management of Ebola. These are simple, and include "intravenous fluids, supportive antimicrobials particularly for secondary infections, oxygen support when required, and potentially vasopressors and inotropes for people who develop a degree of septic shock," he said.

Therapy for Ebola patients "has really revolved around noninvasive treatments. Giving everyone rehydration salts is incredibly important for the GI aspect, but clearly there are people who will not get away with just oral rehydration salts; they're sick and septic and hypovolemic, and they're so lethargic they just cannot drink. Therefore, you have to deliver some intravenous fluids," he said.

"A number of patients have had dual infection with malaria, and there's some unpublished evidence that a number of severe cases have dual infection with Gram-negative bacteria," he reported. "Our policy is for all severe cases to be treated with intravenous antibiotics, mainly ceftriaxone; milder cases get oral treatment."

Symptom-based palliative care with morphine and diazepam — either intravenously or subcutaneously — is also important, as is psychological support. "I've never encountered such a frightened group of patients," he said. "Bear in mind they have often seen their family members die, and they can almost chart their progression through the symptoms, especially the healthcare workers who obviously have an increased knowledge."

Combating patient fear is important, not only for delivering care, but also in terms of infection control cooperation in the surrounding community. "People have to understand that if you get isolated in an Ebola treatment center, you'll get a level of care that should increase your chance of survival," said Dr. Fletcher. "Fear and misperceptions can lead to reluctance within the community to identify and isolate possible patients."

Improving survival rates in the isolation center will improve outside cooperation. "If it becomes apparent that most of the people who enter isolation die, then the community will not isolate their cases. However, if you start to have survivors leave the facility, that is a positive message that will support the community teams," he explained.

The Search for Treatment or a Vaccine

The wait continues for a treatment or vaccine for Ebola; even the most promising possibilities have not reached phase 1 human clinical trials, according to Heinz Feldmann, MD, PhD, who conducts research on Ebola and other hemorrhagic fever viruses at the National Institute of Allergy and Infectious Diseases.

"If we are to practice cutting-edge medicine, rather than simply outbreak control, we need to advance leading approaches toward approval and licensing," he wrote in a recent commentary (N Engl J Med. Published online May 7, 2014).

But he too acknowledges that such a breakthrough cannot happen without more data.

"Owing to poor infrastructure, biosafety concerns associated with processes of patient care and autopsy, and the essential focus on disease containment during outbreaks, there has been little empirical study to elucidate the pathogenesis or pathology of human ebolavirus infection," he observed.

Although clinical data such as Dr. Fletcher's is important for informing research, Dr. Feldmann also believes strongly that research should be funneled back immediately to help those in the field. At this stage, such research can be used to keep the diagnosis of Ebola on the cutting-edge.

"To optimize diagnostic-response capabilities, it is essential that information be shared in real time, as it was during the pandemic of the severe acute respiratory syndrome and during recurrent outbreaks of influenza," he wrote.

Conakry is fortunate to have onsite molecular diagnosis capabilities, but established assays that are used in such situations might not always be reliable when applied to new variants, strains, or viruses, said Dr. Feldmann. "Real-time sharing of sequence data is absolutely critical for our response capacity, since any delay could have disastrous consequences for public health."

"I have not been to Guinea and cannot speak to the local situation," he told Medscape Medical News. "In an outbreak situation like this one in Guinea, you take your broad assay to make sure that you have the best chance to detect the virus."

"The molecular diagnostic assays are based on existing sequence data," he explained. "Once you have the specific sequence, you do refine your diagnostic to make it specific for the new variant if needed (dependent on sequence changes). This can be adapted very quickly, as molecular diagnostics these days are extremely flexible but totally dependent on real-time sequence information. Thus, why it is so important to get the information out real-time."

Dr. Fletcher and Dr. Feldmann have disclosed no relevant financial relationships.

24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Presented May 12, 2014.


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