Ebola virus disease

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ByBy

Ahmed Abudeif Ahmed Abudeif AbdelaalAbdelaal

Assistant Lecturer of Tropical Medicine & Assistant Lecturer of Tropical Medicine & GastroenterologyGastroenterology

Sohag Faculty of MedicineSohag Faculty of MedicineOctober, 2014October, 2014

Ebola Virus DiseaseEbola Virus Disease

Introduction

- Ebola virus disease (EVD) is a severe often fatal disease in humans and non human primates (monkeys, gorillas and chimpanzees).

- The disease is caused by infection with ebola virus, named after a river in the Democratic Republic of the Congo (formerly Zaire) in Africa, where it was first recognized.

Epidemiology

- Ebola virus disease 1st appeared in 1976 with two subsequent outbreaks of acute viral haemorrhagic fever.

- The 1st outbreak occurred in Nazara, South Sudan with 284 cases (151 deaths, CFR 53%). It is caused by Sudan ebola virus.

- The 2nd outbreak occurred in Yambuku “near the Ebola river”, Democratic Republic of the Congo with 318 cases (280 deaths, CFR 88%). It is caused by Zaire ebola virus.

Democratic Republic of the Congo, 2nd outbreak

Ebola river

South Sudan, 1st outbreak

Epidemiology

- Since these original outbreaks, there have been approximately 20 other outbreaks occurring through to 2013.

- Before 2014, the total number of cases 2407 (1582 deaths).

- In 2014, there are two ongoing EVD outbreaks.

•The 1st is the 2013-2014 ebola virus epidemic in west Africa.

•The 2nd is the 2014 Democratic Republic of the Congo ebola virus outbreak, began in August 2014 with 68 cases (49 deaths) “9 October 2014”.

Causative Agent

- EVD is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirals.

- The four disease causing viruses are:

•Bundibugyo ebola virus (BDBV).

•Sudan ebola virus (SUDV), case fatality rate 40-60%.

•Zaire ebola virus (EBOV), associated with more severe disease with case fatality rate 60-90%.

•Taï Forest ebola virus (TAFV), also known as Côte d’Ivoire ebola virus.

Causative Agent

•The 5th virus, Reston ebola virus (RESTV), is not thought to be disease causing in humans.

- Ebolavirons are filamentous particles that may appear in the shape of shepherd’s crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. The virus is 80 nm in width, but vary in length from 974 to 1086 nm.

- Ebolavirons contain linear non-segmented, single stranded, non infectious RNA genomes.

Ebola virus particles under EM

Reservoir

- Bats are considered the most likely natural reservoir of ebola virus.

- Plants, arthropods, and birds were also considered.

- In the wild, transmission may occur when infected fruit bats drop partially eaten fruits or fruit pulp, then land mammals such as gorillas may feed on these fallen fruits.

- Fruit bats are also eaten by people in parts of west Africa where they are smoked, grilled or made into a spicy soup. However, transmission by this method is rare and outbreaks

Reservoir

are usually traceable to a single case where an individual has handled the carcass of gorilla, chimpanzee or duiker.

Fruit bats

Mode of transmission

- Human to human transmission occurs only via direct contact with blood or body fluids from an infected person or by contact with objects contaminated by the virus, especially needles and syringes.

- Body fluids that may transmit ebola virus include saliva, mucous, vomitus, feces, sweat, tears, breast milk, urine and semen.

- Male survivors may be able to transmit the disease via semen Male survivors may be able to transmit the disease via semen for nearly 2 months.for nearly 2 months.

Mode of transmission

- Airborne transmission hasn’t been documented during EVD outbreaks.

Clinical picture

- Incubation period: 2-21 days (mean 8-10 days).

- Onset: sudden.

- Early manifestations include influenza like stage with fever, malaise, chills, myalgia, severe headache and arthralgia.

- Subsequent manifestations indicate multisystem involvement and include:

•GIT: anorexia, nausea, vomiting, diarrhea, abdominal pain “ sometimes associated with elevated serum amylase and true pancreatitis”.

Clinical picture

•Respiratory: chest pain, shortness of breath, cough, nasal discharge.

•Vascular: conjunctival injection, postural hypotension, oedema.

•Neurological: headache, confusion, coma.

- Haemorrhagic manifestations arise in 40-50% of cases, typically 5-7 days after first symptoms and include petechiae, ecchymosis, bleeding from puncture sites and mucous membranes “GIT, nose, vagina and gums”. Heavy bleeding is rare and is usually confined to the GIT. In general the development of bleeding symptoms often indicate a worse prognosis.

Clinical picture

- In about 5-50% of cases a maculopapular rash associated with varying severity of erythema appears 5-7 days of the illness and usually desquamate in survivors.

- In late stages shock, convulsions, severe metabolic disturbances and DIC occurs.

- Death occurs within 7-16 days “usually between 8-9 days”.

Laboratory findings

-Are less characteristic including:

•Early leucopenia “as low as 1000 cells/L” with lymphopenia and subsequent neutrophilia, atypical lymphocytes. In late stages there is leucocytosis.

•Thrombocytopenia “50000-100000/L”.

•Highly raised serum transaminases “typically AST > ALT”.

•Hyperproteinaemia and proteinuria.

•PT and PTT are prolonged and FDP may be detectable.

Diagnosis of EVD

- Ebola virus is a WHO risk group 4 pathogen (i.e. greatest threat to humans). So, it requires a biosafety level 4 (BSL-4) laboratory for diagnosis.

1) Within a few days after beginning of symptoms:

•Antigen capture ELISA.•IgM ELISA.•PCR.•Virus isolation.

2) Later in disease course or after recovery:

•IgM and IgG antibodies.

Diagnosis of EVD

3) Retrospectively in deceased patients:

•Immunohistochemistry testing.•PCR.•Virus isolation.

BSL-4 positive pressure suit

BSL-4 laboratory

Differential diagnosis

-Marburg virus disease.-Other viral hemorrhagic fevers.-Falciparum malaria.-Typhoid fever.-Shigellosis.-Rickettsial diseases such as typhus.-Cholera.-Gram-negative septicemia.-Borreliosis such as relapsing fever.-EHEC enteritis.-Leptospirosis.


-Scrub typhus.-Plague.-Q fever.-Candidiasis.-Histoplasmosis.-Trypanosomiasis.-Visceral leishmaniasis.-Hemorrhagic smallpox.-Measles.-Fulminant viral hepatitis.-Acute promyelocytic leukemia.


-Hemolytic uremic syndrome.-Snake envenomation.-Clotting factor deficiencies/platelet disorders.-Thrombotic thrombocytopenic purpura.-Hereditary hemorrhagic telangiectasia.-Kawasaki disease.-Warfarin poisoning.

Treatment

- No specific treatment is currently approved.

- Treatment is primarily supportive in nature and early treatment improve survival.

- Supportive measures may include:

•Patient isolation.

•Management of pain, nausea, fever, anxiety.

•Oral or IV rehydration with maintenance of electrolyte balance.

•Provision of blood products such as packed RBCs, platelets, fresh frozen plasma or clotting factors when needed.

Treatment

•Heparin to prevent DIC, when needed.

•Antimalarial medications and antibiotics are often used before the diagnosis is confirmed.

•Management of organ failure e.g. dialysis for renal failure and extracorporeal membrane oxygenation may be used for lung dysfunction.

Prevention

- Barrier isolation of patients.

- Wearing of protective clothing by attending personnel including masks, gloves, impermeable gowns and goggles or face shields.

- Sterilizing equipment and surfaces and routine use of disinfectants.

- Avoid touching the bodies of patients who have died from ebola.

A hospital isolation ward

Health care workers wear protective clothing

Prevention

- Quarantine of patients is usually effective in decreasing spread of the disease.

- Burial of dead bodies should be done with extreme caution, incinerate all waste.

- Contact tracing, it involves finding everyone who had close contact with infected individuals and watching for signs of illness for 21 days.

CDC worker incinerates medical waste from Ebola patients in Zaire in 1976

Mass graves for ebola victims

Prognosis

- The disease has a high mortality rate which varies between 25-90% of those infected.

- Early and effective treatment of symptoms may reduce the fatality rate significantly.

- If an infected person survives, recovery may be quick and complete.

- Prolonged infections are often complicated by the occurrence of long term problems such as orchitis, arthralgia, myalgia,

Prognosis

skin peeling or hair loss. Eye symptoms such as photophobia, excess lacrimation, iritis, iridocyclitis, choroiditis and blindness have also been described.

EVD prevention poster used in Kikwit outbreak

The 2013-2014 Ebolavirus The 2013-2014 Ebolavirus Epidemic in West AfricaEpidemic in West Africa

The 2013-2014 ebola virus epidemic in west Africa

- The most severe ebola virus outbreak recorded as regards to both the number of human cases and fatalities exceeding the sum of all previous identified cases.

- It began in Guinea in December 2013 then spread to Liberia and Sierra Leone.

- A small outbreak of twenty cases then occurred in Nigeria where it has been contained, and one case occurred in Senegal, where the outbreak was declared over on 17 October 2014.


- Cases of secondary infections of medical workers in the United States and Spain occurred, neither of which has yet spread to the general population.


- The index case is a 2 years old boy called Emile who died on 6 December 2013 in the village of Meliandou, Guinea. His mother, sister, and grandmother then became ill with similar symptoms and also died. People infected by those victims spread the disease to other villages.

- Although Ebola represents a major public health issue in sub-Saharan Africa, no cases had ever been reported in West Africa and the early cases were diagnosed as other diseases more common to the area. Thus, the disease had several Thus, the disease had several months to spread before it was recognized as ebola.months to spread before it was recognized as ebola.


- The total number of cases is 9216 (4555 deaths, CFR 71%) “ 14 October 2014”

-WHO believes that this substantially understates the magnitude of the outbreak with possibly 2.5 times more cases being under reported.

-WHO stated that there could be as many as 10,000 new ebola cases per week by December 2014.

The 2013-2014 ebola virus epidemic in west Africa- Experimental treatments

- A number of experimental treatments are being studied.

- In the USA, the FDA's animal efficacy rule is being used to demonstrate reasonable safety to obtain permission to treat people who are infected with Ebola.

- This rule is used because the normal path for testing drugs is not possible for diseases caused by dangerous pathogens like ebola.


- WHO released a statement that the use of not yet proven treatments is ethical in certain situations in an effort to treat or prevent the disease.

•Medications

- The WHO has recognized that transfusion of whole blood or purified serum from Ebola survivors is the therapy with the greatest potential to be implemented immediately although there is little information on its efficacy.


-A number of experimental treatments are being considered for A number of experimental treatments are being considered for use in the context of this outbreak, and are currently or will use in the context of this outbreak, and are currently or will soon undergo clinical trial:soon undergo clinical trial:

•Zmapp: a combination of monoclonal antibodies. The limited supply of the drug has been used to treat 7 individuals infected with the Ebola virus. Although some of them have recovered, the outcome is not considered to be statistically significant.

•TKM-Ebola: an RNA interference drug. The drug started Phase 1 trial and has received limited approval from the FDA for emergency use.


•Favipiravir (Avigan): an antiviral drug approved in Japan for treatment of influenza pandemics, appears to be useful in a mouse model of Ebola.

•BCX4430: is a broad-spectrum antiviral drug undergoing animal testing as a potential human treatment for Ebola.

•Brincidofovir: is a broad-spectrum antiviral drug. FDA approved the trial to test its safety and effectiveness in ebola patients.

•JK-05: The drug can selectively inhibit virus replication by inhibiting the RNA polymerase.


•Lamivudine: was reported to be used successfully to treat 13 out of 15 ebola infected patients by a doctor in Liberia, as part of a combination therapy also involving IV fluids and antibiotics to combat bacterial infection. However, western virologists have expressed caution about the results, due to the small number of patients treated and confounding factors present.

•Clomiphene and toremifene: antiestrogens used to treat infertility and breast cancer, its found that they inhibit the progress of Ebola virus in vitro as well as in infected mice.

•Melatonin: has been suggested as a potential treatment for Ebola based on promising in vitro results.

The 2013-2014 ebola virus epidemic in west Africa- Experimental vaccines

-Two vaccines are under development:

•cAd3-ZEBOV vaccine.

•rVSV-ZEBOV vaccine.

Thank Thank youyou

Ebola virus disease

Health & Medicine