Ebola hemorrhagic fever



OVERVIEW

Definition

Ebola hemorrhagic fever (EHF) is an acute infectious disease caused by the Ebola virus, which is characterized by fever, malaise, generalized body aches, vomiting, diarrhea and multiple organ damage.

Because of the 2014 West Africa outbreak reported cases of hemorrhage proportion is small, and only in the late stage of the disease serious bleeding, while vomiting, diarrhea accounted for more, the World Health Organization in the same year, “Ebola hemorrhagic fever” renamed “Ebola virus disease”.

Ebola virus currently has six subtypes, which can cause human disease mainly for the Zaire type, Sudan type, Tay forest type, Bendibujiao type, of which the most serious symptoms are Zaire type.

Incidence

Ebola hemorrhagic fever was first detected in Africa in 1976 and is prevalent mainly in African countries such as Uganda, Congo, Gabon, Sudan, Côte d’Ivoire, South Africa, Guinea, Liberia, Sierra Leone, and Nigeria [1].

In September 2022, there was an outbreak of Ebola in Mubende, a central region of Uganda; this was preceded by several outbreaks of Ebola in Uganda.

Etiology

Causes of the disease

Ebola hemorrhagic fever is caused by infection with the Ebola virus, and there are three basic conditions that lead to epidemics.

Source of infection and host animal

Patients and primates infected with the Ebola virus are the main sources of infection for the disease.

The natural hosts of Ebola virus are fruit bats of the family Foxbatidae, especially hammerhead fruit bats, Fuchs’s front-shouldered fruit bats, and little-collared fruit bats [1].

Typically, a person becomes infected by contact with an infected animal and then spreads the infection from person to person.

Routes of transmission

Direct contact: This is the most important mode of transmission, in which a person is infected by direct contact with blood, body fluids, secretions, excretions and contaminants of patients and infected animals. The blood, feces and vomit of patients have the highest viral content and are the most infectious.

Droplet transmission: Inhalation of secretions and excretions of infected people can cause infection.

Medical infection: The use of unsterilized syringes can also cause infection.

Sexual transmission: It has been reported in the literature that the virus can be isolated from the semen of patients with Ebola hemorrhagic fever, so the possibility of sexual transmission exists [3].

Susceptible population

The population is generally susceptible, the onset of the disease is mainly concentrated in adults, and there is some immunity after infection and vaccination.

Symptoms

Main symptoms

The incubation period of the disease is mostly 2 to 21 days, with an average of 8 to 10 days.

Initial stage

Mostly acute onset, initial fever, and rapid progression to high fever, may be accompanied by fatigue, headache, muscle aches, sore throat, etc..

About half of the patients develop nausea, vomiting, abdominal pain and diarrhea.

Extreme stage

The extreme stage can be entered after the 3rd to 4th day of the disease. There may be persistent fever, malaise, headache, epigastric pain or diffuse abdominal pain, nausea, eructation, vomiting, diarrhea (which may be accompanied by mucus), and the amount of fluid lost in severe diarrhea may exceed 10 liters per day, and there may be hypovolemia and dehydration manifestations such as dryness of the mucous membranes, and poor elasticity of the skin.

Some patients may have multiple bleeding manifestations such as gum bleeding, epistaxis (nosebleed), bleeding from injection site or venipuncture site, vomiting blood, blood in stool, hematuria, and other bleeding manifestations. Conjunctival congestion and skin rash can be seen in a few patients.

The condition of critical patients progresses rapidly, shock, respiratory failure, renal failure, impaired consciousness, multi-site hemorrhage and diffuse intravascular coagulation (DIC), multi-organ dysfunction (MODS) may occur, and most of the fatal cases occur in the second week of the disease.

Recovery period

Body temperature returns to normal, gastrointestinal and other symptoms are relieved, and the function of damaged organs gradually returns to normal.

Some patients still have symptoms such as weakness, fatigue, frequent urination, muscle and joint pain, headache, memory loss, impaired hearing, insomnia, depression, anxiety, etc., which can last for a long time.

Individuals may develop long-term complications such as uveitis and meningitis.

Other symptoms

Some patients may develop red diffuse maculopapular rash without itching, often involving the face, neck, trunk and arms, which may cause skin flaking.

Some patients may develop conjunctival congestion and uveitis, which may manifest as blurred vision, photophobia, and blindness.

Consultation

Department of Medicine

Department of Infectious Diseases

Prompt medical attention is recommended for those with an epidemiologic history of any of the following, such as fever, malaise, nausea, vomiting, abdominal pain, diarrhea, and bleeding from the skin and mucous membranes.

History of residence or travel in an area of active Ebola transmission within 21 days prior to onset of illness.

Contact with patients with Ebola virus disease or their blood, body fluids, secretions, excretions or corpses without proper personal protection within 21 days before the onset of illness.

Contact with or handling of bats or non-human primates from an infected area within 21 days prior to onset of illness without proper personal protection.

Unprotected sexual intercourse with a patient within 3 months of recovery from Ebola virus disease.

Emergency Department

Immediate medical attention is recommended in the event of febrile convulsions, profuse blood in stool, hemoptysis, coma, or shock.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, common problems

Tips for seeking medical treatment

For patients with high fever, physical cooling can be done first, such as applying cold compresses to the forehead and wiping hands, feet and armpits with warm water.

Avoid public transportation, wear a mask, pay attention to hand hygiene, and carry a clean bag (for vomit) on the way to the doctor.

A full body checkup is often required, so it is advisable to wear clothes that are easy to put on and take off.

Checklist for medical care

Pay particular attention to the time of onset of symptoms, special signs, etc.

Is there a fever? What is the highest temperature?

Are there any headaches, muscle aches, sore throats?

Is there nausea, vomiting, abdominal pain, diarrhea?

Is there bleeding from skin and mucous membrane, vomiting blood, hemoptysis, blood in stool, hematuria, etc.?

Is there drowsiness, blurred consciousness?

How long have the above symptoms lasted?

Has there been any contact with patients suffering from Ebola hemorrhagic fever?

Any history of traveling to areas where Ebola hemorrhagic fever is endemic?

Have you come into contact with or handled bats and non-human primates from infected areas?

Any history of food or drug allergies?

Test results from the last 6 months to bring to the doctor’s office

Laboratory tests: routine blood, urine, stool, coagulation function, liver and kidney function, cardiac enzymes, malaria test, Ebola virus nucleic acid test, other infectious diarrhea pathogenetic tests.

Diagnosis

Diagnosis is based on

Medical history

The diagnosis of this disease is mainly based on epidemiologic data, clinical manifestations, and relevant pathogenetic tests to confirm the diagnosis, and the patient may have the following medical history.

History of living or traveling in an area with active Ebola transmission within 21 days prior to the onset of the disease.

Contact with a patient with Ebola virus disease or his/her blood, body fluids, secretions, excretions, or cadaver within 21 days prior to the onset of illness without proper personal protection.

Contact with or handling of bats or non-human primates from an infected area within 21 days prior to onset of illness without proper personal protection.

Unprotected sexual intercourse with a patient within 3 months of recovery from Ebola virus disease.

Clinical manifestations

The main manifestations are fever, malaise, headache, myalgia, nausea, vomiting, abdominal pain and diarrhea.

Some patients may have different degrees of bleeding manifestations, including skin and mucous membrane bleeding, vomiting blood, hemoptysis, blood in stool, hematuria and so on.

In severe cases, consciousness disorder, shock, and multiple organ failure may occur.

Laboratory examination

Examination may reveal a decrease in white blood cell count, mainly lymphocyte count, followed by a decrease in neutrophils. Platelet counts may also be reduced.

In secondary bacterial infections, there may be an elevated blood white blood cell count.

Examination may reveal positive urine protein.

In hepatic insufficiency, there may be an elevation of alanine aminotransferase (AST) and alanine aminotransferase (ALT), with AST elevated more than ALT.

In renal insufficiency, there may be elevated blood urea nitrogen and blood creatinine.

In the presence of disseminated intravascular coagulation (DIC), prolonged prothrombin time and partial thromboplastin time and elevated fibrin degradation products may be present.

Serum specific IgM antibody detection, mostly by ELISA, and a positive serum specific IgM antibody test can help confirm the diagnosis of the disease.

Serum specific IgG antibody detection, mostly using ELISA, immunofluorescence and other methods of detection, double serum specific IgG antibody positive or recovery phase than the acute phase of 4 times and above elevation helps to confirm the diagnosis of the disease.

Viral antigen detection: Since Ebola hemorrhagic fever has high titer viremia, ELISSA and other methods can be used to detect viral antigen in serum.

Nucleic acid detection: Nucleic acid amplification methods such as RT-PCR are used for detection. Generally, viral nucleic acid can be detected in the serum of patients within one week after the onset of the disease.

Virus isolation: Collect serum specimens from patients within one week after the onset of disease and use Vero cells to isolate the virus.

Diagnostic criteria

The diagnosis of this disease requires comprehensive judgment based on epidemiological history, clinical manifestations and relevant pathogenetic examinations, and can be categorized into observation cases, suspected cases and confirmed cases, as described below.

Observation cases

According to the presence or absence of known exposures, cases are categorized into the following two situations: those who have any of the following epidemiologic histories (b, c, or d) and have a temperature >37.3℃ or those who have epidemiologic history (a) and have a temperature >38.6℃.

a. History of residence or travel in an area of active Ebola transmission within 21 days prior to onset of illness;

b.Contact with a patient with Ebola virus disease or his/her blood, body fluids, secretions, excretions, or corpse without proper personal protection within 21 days prior to onset of illness;

c.Contact with or handling of bats or non-human primates from an infected area within 21 days prior to onset of illness without proper personal protection;

d. Unprotected sexual intercourse with a patient within 3 months of recovery from Ebola virus disease.

Suspected cases

A suspected case can be defined as a person who has any of b, c, or d of the above epidemiologic histories and meets one of the following three scenarios

Temperature >38.6°C with severe headache, muscle pain, vomiting, diarrhea, and abdominal pain.

Fever with unexplained bleeding.

Unexplained sudden death.

Confirmed cases

Staying or suspected cases can be defined as confirmed cases if they meet one of the following situations by laboratory testing.

Positive nucleic acid test: the patient’s blood and other specimens are tested by RT-PCR and other nucleic acid amplification methods, and the result is positive. If the nucleic acid test is negative, but the duration of the disease is less than 72 hours, the test should be repeated after 72 hours.

Positive viral antigen test: Collect the patient’s blood or other specimens and test for viral antigen by ELISA or other methods.

Isolation to virus: Collect the patient’s blood and other specimens, and isolate the virus using cells such as Vero and Hela.

Positive serum-specific IgM antibody test: Positive double serum-specific IgG antibody transfer or 4-fold or more elevation in the recovery phase compared to the acute phase.

Positive pathogenetic tests in tissues.

Differential diagnosis

The disease needs to be differentiated from viral hemorrhagic fevers such as Marburg hemorrhagic fever, Crimean Congo hemorrhagic fever, Lassa fever, renal syndrome hemorrhagic fever, etc. This needs to be done by the physician through epidemiologic history, serology and pathogenetic tests.

Treatment

Aim of treatment: prevention and treatment of critical illnesses and improvement of prognosis.

Treatment principle: no specific treatment, mainly symptomatic supportive treatment.

Symptomatic supportive treatment

The infected person should be closely isolated and treated.

Eat fluid, semi-fluid diet during the fever period, drink more water, and rest in bed.

Adequate fluid replacement to maintain water-electrolyte and acid-base balance; patients may lose large amounts of fluid from vomiting and diarrhea, requiring rapid blood volume replacement with balanced saline solutions to prevent shock; antiemetics and antidiarrheals may also be beneficial.

Enhance colloid fluid supplementation such as albumin and low-molecular dextrose to prevent and treat hypotensive shock.

In patients with high fever, treatment with antipyretic drugs such as acetaminophen may be indicated.

Patients with coagulation disorders and bleeding may require transfusion of blood products such as concentrated red blood cells, platelets, and fresh frozen plasma.

Dialysis therapy may be required in acute kidney injury; mechanical ventilation may be required in respiratory failure.

Antiviral treatment

The World Health Organization (WHO) has the following recommendations for antiviral treatment of this disease.

The use of mAb114 or REGN-EB3 is recommended for the treatment of patients with real-time polymerase chain reaction (RT-PCR)-confirmed Ebola virus disease (EVD) and neonates 7 days of age or younger with undiagnosed EVD status born to confirmed ill mothers [6].

For patients with RT-PCR-confirmed EVD, treatment without raltegravir is recommended when available [6].

For patients with RT-PCR-confirmed EVD, treatment with ZMapp is not recommended when available [6].

Concomitant live Ebola virus vaccination should be avoided in patients receiving the above medications.

Specific treatment and medication need to be under the supervision of a physician.

Prognosis

Cure

The prognosis depends on whether the patient has an underlying disease, whether he or she is treated in time, and the conditions of treatment.

In the past, the mortality rate of this disease was high, among which Zaire type can reach 50%~90%, but if timely comprehensive treatment and life support therapy are given in ICU, the mortality rate of Zaire type can be reduced to 25%~30%.

Hazard

The disease is critical and may lead to disseminated intravascular coagulation, shock, multiple organ failure or even death.

The recovery period of this disease is long, and some patients may be left with sequelae such as arthralgia, uveitis, meningitis, memory loss, etc. Rehabilitation is needed in the later stage, which affects the patients’ life.

Daily

Daily management

Daily need to eat a reasonable diet, strengthen the nutrition, fever period can eat fluid or semi-fluid soft food, such as noodles, millet porridge and so on.

Maintain sufficient sleep and pay attention to rest.

Maintain good hygiene habits, wash hands frequently and pay attention to ventilation.

Pay attention to physical exercise to strengthen the body’s resistance.

Follow-up review

WHO suggests that patients need to be followed up two weeks after discharge from the hospital, then once a month for six months, and then every three months until completion of the one-year follow-up, which needs to be carried out under the guidance of the doctor.

Men should have their semen tested during the follow-up period until the semen is negative for Ebola RNA.

Prevention

Avoid traveling to areas where Ebola hemorrhagic fever is endemic.

Avoid contact with blood, body fluids from bats, non-human primates (such as monkeys and chimpanzees), or eating raw meat made from these animals.

Avoid contact with blood and body fluids of sick people, such as urine, feces, saliva, vomit, breast milk, amniotic fluid, semen, and vaginal fluids.

Avoid contact with items that may have come into contact with the blood or body fluids of an infected person, such as clothing, bedding, needles, medical equipment, etc.