Ebola Virus & Marburg

Filoviridae family The Marburg virus was isolated for the first time in 1967
As a result of three simultaneous outbreaks among laboratory staff in Marburg, Frankfurt, and Belgrade

Ebola: Four strains

Ebola-Zaire, Ebola-Sudan, EbolaCote dIvoire, Ebola-Reston

The subtypes of Ebola virus Zaire and Sudan are highly virulent.
Probable reservoir rodent or bat

Common name: Ebola

Both

Ebola and Marburg Causes hemorrhagic fever

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General features

Filoviruses are pleomorphic, long filamentous thread like forms with RNA
Coiled RNA in spike-covered envelope from host cell Long rods (800-1000 nm) Replication = 8 hours Therefore, spreads rapidly

History

First identified in Sudan

Ebola virus after a river in Zaire

Outbreaks occurred all over Sudan, Zaire, Congo, Gabon, and the Ivory Coast. Between 1976 and 1996, over 1000 deaths have been recorded.
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Modes of Transmission
There are 3 modes of infection: 1. Unsterilized needles 2. Suboptimal Hospital conditions 3. Personal contact

Clinical features contd..

Symptoms are abrupt and unexpected. Incubation between 2 and 21 days Starts with red eyes, then leads to fever, headache Flu-like symptoms, fatigue, internal/external bleeding, massive hemorrhage (uncontrollable bleeding) Severe vomiting, Abdominal pain , Diarrhea, Pharyngitis, Conjunctivitis
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Clinical features contd..

Extremely high body temperature

Impaired liver function

The infected body is also corroding away from the inside. A cadaver's internal organs have been compared to black and red tapioca pudding

Diagnosis

Viral antigens can be detected by ELISA

Patients sera may contain virulent virus

Vero, MA-104 cell lines can bee used for cultivation. PCR can be used for diagnosis.

Treatment and Prevention

There is no cure for Ebola

Maintaining renal function and electrolyte balance and combating hemorrhage and shock No vaccine
Due to the extreme biohazard, doctors must wear Level 4 containment suits. They are the equivalence of a spacesuit.

RUBELLA (GERMAN MEASLES)

Rubella

From Latin meaning "little red" Discovered in 18th century - thought to be variant of measles

First described as distinct clinical entity in German literature

Congenital rubella syndrome (CRS) described by Gregg in 1941

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Rubella Virus

Togavirus
Rubrivirus genus RNA virus

One antigenic type

Rapidly inactivated by chemical agents ultraviolet light, low pH, and heat

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Rubella Pathogenesis

Respiratory transmission of virus Replication in nasopharynx and regional lymph nodes Viremia 5-7 days after exposure with spread to tissues

Placenta and fetus infected during viremia

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Rubella Clinical Features

Incubation period 14 days

(range 12-23 days)

Prodrome of low-grade fever Maculopapular rash 14-17 days after exposure Lymphadenopathy in second week
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Rash of Rubella

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Congenital Rubella Syndrome

Infection may affect all organs May lead to fetal death or premature delivery Severity of damage to fetus depends on gestational age Up to 85% of infants affected if infected during first trimester

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Congenital Rubella Syndrome

Deafness Cataracts Heart defects Microcephaly Mental retardation Bone alterations Liver and spleen damage

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Rubella Laboratory Diagnosis

Isolation of rubella virus from specimen (e.g., nasopharynx, urine)

clinical

Positive serologic test for rubella IgM antibody Significant rise in rubella IgG by any standard serologic assay (e.g., enzyme immunoassay)

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Prevention

Since 1968, a highly effective live attenuated vaccine has been available with 95% efficacy

Universal vaccination is now offered to all infants as part of the MMR regimen.

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Rabies Virus

Member of the Lyassavirus of the Rhabdoviridae. ssRNA enveloped virus, characteristic bullet-shaped appearance with 6-7 nm spike projections. Virion 130-240nm -ve stranded RNA codes for 5 proteins
Nucleocapsid (N), polymerase proteins (L, P), matrix (M), and glycoprotein (G)

Exceedingly wide range of hosts.

There are 5 other members of Lyassavirus : Mokola, Lagosbat, Duvenhage, EBL-1, and EBL-2. Duvenhage and EBL-2 have been associated with human rabies.
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Rabies Virus

Structure of rabies virus

Rabies virus particles

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Epidemiology
Rabies is a zoonosis which is prevalent in wildlife. The main animals involved differs from continent to continent.
Europe Middle East Asia Africa N America S America fox, bats wolf, dog dog dog, mongoose, antelope foxes, skunks, raccoons, bats dog, vampire bats

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Pathogenesis

The commonest mode of transmission in man is by the bite of a rabid animal, usually a dog. Rabies is an acute infection of the CNS which is almost invariably fatal Following inoculation, the virus replicates in the striated or connective tissue at the site of inoculation Enters the peripheral nerves through the neuromuscular junction.

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Pathogenesis contd

It then spreads to the CNS in the endoneurium of the Schwann cells. Terminally, there is widespread CNS involvement
But few neurons infected with the virus show structural abnormalities.

The nature of the profound disorder is still not understood Site of bite determine the speed of progression of clinical manifestation

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Clinical Findings

An acute, fulminant, fatal encephalitis The incubation period in humans is typically 12 months
May be as short as 1 week or as long as many years (up to 19 years) Usually shorter in children than in adults

The clinical spectrum can be divided into three phases

A short prodromal phase An acute neurologic phase Coma.
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Clinical Findings contd..

The prodrome lasting 210 days May show any of the following nonspecific symptoms
Malaise Anorexia Headache, photophobia, nausea and vomiting, sore throat, and fever Usually there is an abnormal sensation around the wound site.
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Clinical Findings contd..

Acute neurologic phase lasts 27 days Patients show signs of nervous system dysfunction
Nervousness, apprehension, hallucinations, and bizarre behavior General sympathetic over activity is observed, including lacrimation, pupillary dilatation, and increased salivation and perspiration A large fraction of patients will exhibit hydrophobia (fear of water) The act of swallowing precipitates a painful spasm of the throat muscles.

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Clinical Findings contd..

Coma

Convulsive seizures or coma and death

The major cause of death is respiratory paralysis

Paralytic rabies occurs in about 20% of patients, most frequently in those infected with bat rabies virus

The disease course is slower, with some patients surviving 30 days

Recovery and survival are extremely rare.

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Laboratory Diagnosis

Histopathology - Negri bodies are pathognomonic of rabies. However, Negri bodies are only present in 71% of cases Rapid virus antigen detection - in recent years, virus antigen detection by IF had become widely used Corneal impressions or neck skin biopsy are taken The Direct Fluorescent Antibody test (DFA) is commonly used

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Laboratory Diagnosis

Virus cultivation - The most definitive means of diagnosis

From saliva and infected tissue Cell cultures may be used or more commonly, the specimen is inoculated intracerebrally into infant mice.

Serology - circulating antibodies appear slowly in the course of infection

But they are usually present by the time of onset of clinical symptoms.

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Diagnosis of Rabies contd.

Negri Body in neuron cell

Positive DFA test

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Treatment and Prevention

Pre-exposure prophylaxis - Inactivated rabies vaccine may be administered to persons at increased risk
E.g. vets, animal handlers, laboratory workers etc.

Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a rabies endemic area should be held for 10 days for observation. If signs develop in the dog or cat, they should be killed and their tissue examined for diagnosis

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Treatment and Prevention

Wild animals are not observed but if captured, the animal should be killed and examined The essential prophylaxis components of postexposure

The local treatment of wounds and active and passive immunization.

Once rabies is established, there is nothing much that could be done except intensive supportive care.

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Postexposure Prophylaxis

Wound treatment - surgical debridement should be carried out Experimentally, the incidence of rabies in animals can be reduced by local treatment alone. Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an I.m. dose to confer short term protection. Active immunization - the human diploid cell vaccine (HDCV) is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given.
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Postexposure Prophylaxis

Combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG

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Rabies Vaccines
The vaccines which are available for humans are present are inactivated whole virus vaccines.
Nervous Tissue Preparation e.g. Simple Vaccine associated with the rare complication of demyelinating allergic encephalitis. Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck eggs

This vaccine has a lower risk of allergic encephalitis but is considerably less immunogenic.

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Rabies Vaccines
Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine available with an efficacy rate of nearly 100% Rarely any severe reactions. However it is very expensive.
Other Cell culture Vaccines - because of the expense of HDCV, other cell culture vaccines are being developed for developing countries However recent data suggests that a much reduced dose of HDCV given intradermally may be just be effective.
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Control of Rabies

Urban - canine rabies accounts for more than 99% of all human rabies. Control measures against canine rabies include;
stray dog control. Vaccination of dogs Quarantine of imported animals

Wildlife - this is much more difficult to control than canine rabies.

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