In this learning unit, we are going to discuss the clinical presentation of

Ebola virus disease patients.

The learning objectives are to quickly recap the essential

modes of infection and to discuss the incubation period.

We will discuss main clinical signs and symptoms and

laboratory findings in Ebola virus disease patients.

And we will briefly look at outcomes and characteristics of

patients during this current West African epidemic.

To recapitulate, the primary transmission in an epidemic is zoonotic.

We discussed that extensively in a previous learning unit.

Subsequent transmission occurs from person to person through contact

with infected bodily fluids, with mucous surfaces or broken skin.

Infectious bodily fluids are blood, feces, vomit, urine, saliva,

breast milk, semen and sweat, in other words, virtually every bodily fluid,

and the first three being considered as the possibly most infectious.

The incubation time varies.

It's usually considered to be fairly short.

We assume that the majority of patients who are infected and

who become diseased develop symptoms within 6 to 12 days following exposure,

but the range is considered to be from 2 to 21 days.

However, recent modeling from the current outbreak suggests that a small

proportion of patients may have an extended incubation period, and

extended would then mean probably maybe four, five days longer actually.

Signs and symptoms are unspecific in the beginning, which makes it so

difficult to tell Ebola virus disease apart from other hemorrhagic fevers or

from other viral diseases with the same symptoms, and

also to differentiate them from virtually almost all

febrile conditions which one may pick up in a tropical setting.

The onset of symptoms is usually abrupt.

It is nonspecific flu-like fever, a profound weakness,

malaise, myalgia, may be the lead symptoms in the beginning.

Gastrointestinal symptoms may develop swiftly and

ensue which is, at least in the current outbreak,

predominately high-volume watery diarrhea, vomiting, abdominal pain.

Diffuse erythematous, non-pruritic, maculopapular rashes may evolve.

Actually, it is not seen very frequently and

also more difficult to detect on a dark skin.

Relative bradycardia may be encountered, and hemorrhages occur in many, many forms,

internal and external hemorrhages, but only in a minority of patients.

And this became very, very clear during the extra outbreak where

only a tiny fraction of all patients with severe disease, 2 to 3% maybe,

develop some sort of bleeding in the end stage of the disease.

Laboratory findings as well are puzzlingly difficult to disentangle or

to differentiate from many other tropical diseases.

Mild leukopenia may be seen or thrombopenia may be encountered.

Multifocal hepatic necrosis may lead to a transaminitis.

There are multiple coagulation abnormalities such

as prolonged bleeding time, elevated D-dimers, and

renal failure may develop in patients when they progress to more severe

disease with the usual markers, creatinine, urea, being elevated.

What we should say at this stage again is not every individual,

of course, which gets infected will progress to disease at all.

There is certainly a, so far ill-described or

not clearly defined proportion of individuals

infected who will not progress to disease,

will not exhibit any signs of infection.

And in the wake of the current outbreak, there will be certainly several

prevalence studies which will shed more light on the proportion of

patients who will never develop disease signs and, of course,

then, consequently also not progress to more severe disease.

The differential diagnosis of Ebola virus disease is really broad.

Why is it so broad?

Because the signs and symptoms, at least in the beginning of the disease,

are very unspecific, could be described as a flu-like illness,

which is a feature which is shared with, as I said before,

the majority of infectious diseases.

The differential diagnosis has to be constructed from

the clinical presentation and epidemiological characteristics.

For West and Central Africa, the main differentials will always include

malaria in the first place, but also the other viral hemorrhagic fevers.

There is a whole range of bacterial infections which may mimic Ebola virus

disease as well as they may complicate Ebola virus disease in later stages.

Bacterial sepsis, typhoid fever, leptospirosis,

the rickettsioses may form important differential diagnosis.

Parasitological diseases other than malaria, maybe amoebiasis,

maybe in certain areas, African trypanosomiasis.

And then, of course, there are the viral afflictions.

A flu-like infectious agent and the whole range of the viral

hepatitis may form an important differential diagnosis.

And as I mentioned before, there are other viral hemorrhagic fevers which may

also be present in the area of an outbreak.

At present, for example, Lassa fever

is an important differential diagnosis in the area of the current outbreak.

Complications and outcome.

If an individual which falls ill does not progress to

severe disease, then an average rule of thumb is that the majority

of patients will show signs of improvement between 6 and 11 days.

Of course, this has to be handled flexibly as well.

In individuals who progress to more severe disease, death ensues usually or

most frequently within a period of 6 to 16 days after onset of symptoms.

Complications in an individual which

becomes diseased are multitude with regard to GI symptoms.

Dehydration, of course, is very important, if not most important, and of course with

dehydration, come electrolyte disbalances which may lead to cardiac arrhythmias.

There are coagulation abnormalities.

Major bleeding is not a rarity, but

not encountered as frequently as the old term hemorrhagic fevers would suggest.

Actually we discussed that before.

Renal failure, multifocal hepatitis may ensue in patients who are severely ill,

and the fatality rates, actually they vary.

In the beginning of an outbreak we usually encounter higher fatality rates.

At the end of an outbreak this is usually then brought down a bit.

In the beginning of this extra outbreak, the death rates exceeded 70%.

Now towards what may constitute the end of the outbreak in retrospect,

we are down to a mortality rate between 40 to 50%, which is still very high.

As I said before, the Zaire Ebola virus is known to be the most virulent one and

usually claims the highest death toll amongst all the various Ebola viruses.

Now what did we learn about clinical characteristics from the current massive,

large-scale outbreak?

First of all, and one cannot say this too frequently,

the hemorrhagic events occur only in a minority of patients.

Or at least to be a bit more cautious, we may say that in the current outbreak,

only in a minority of patients, severe hemorrhages, internal or

externally, were witnessed actually, and the estimates run at least below 5%.

GI symptoms, including massive watery diarrhea and vomiting,

are very common and seem to be associated with fatal outcomes, actually.

Early oral rehydration may improve outcomes.

If people are unable to take oral rehydrations actually,

wherever this is possible, early intravenous rehydration seems to be a key

measure to keep patients alive to see them through the organ complication phase.

Case fatality rates seem to be comparable to previous epidemics,

and patients younger than 21 years

old seem to have a better survival chance compared to older individuals.

Probably we have to exclude very young children from this age range calculation.

Diagnostics.

Ebola Virus Disease is confirmed by detection of viral antigens or

RNA from bodily fluids.

Of course, also the visualization by electron microscopy

and cell cultivation methods are possible, but the current gold standard

of the diagnosis is RT-PCR, and

rapid diagnostic tests are under development.

Serology by means of an immunoassay in ELISA,

is well possible and also helpful, but

the RT-PCR is the current gold standard, at least up to the time now.

Negative tests for more than 72 hours after

symptom onset excludes Ebola as a causative

agent if the methodology is good actually,

if we are talking about RT-PCR.

However, to gain confidence and

to gain security, these tests should be repeated,

particularly when patients are symptomatic actually.

Two negative tests separated by at least 48 hours

in patients whose symptoms have resolved can be considered as providing

enough safety to discharge patients from an isolation area, actually.

And I would like to conclude with a referral to the rapidly growing

body of knowledge particularly gained from these current outbreaks

by pointing at our list of references, which is, of course,

still in the stage of rapid growth.

Thank you very much.

Introduction lecture

Ebola: Essential Knowledge for Health Professionals

Meet the Instructors