m. a. el-farrash. virology of pharyngitis, gastroenteritis and meningitis prof. mohamed el-farrash...

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M. A. El- Farrash In the name of Allah, Most Gracious, Most Merciful

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M. A. El-Farrash

In the name of Allah, Most Gracious, Most Merciful

Virology of Pharyngitis, Gastroenteritis

and Meningitis

Prof. Mohamed El-Farrash2015

PharyngitisPharyngitis “not tonsillitis” is the most

common cause of a sore throat.

Like many types of inflammation, pharyngitis

can be Acute  “characterized by a rapid onset

and typically a relatively short course”

or Chronic (relatively long course with milder

clinical form).

M. A. El-Farrash

Most (40–80%) acute cases of pharyngitis are

caused by viral infections.

The remainder (20 – 60 %) are caused by

bacterial infections, fungal infections, or

irritants as pollutants or chemical substances. 

Acute Pharyngitis

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Viral and Bacterial Pharyngitis

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Viral PharyngitisPharyngitis can be a feature of many different

types of viral infections.

Adenovirus is the most common of the viral

causes.

In Adenoviral pharyngitis the degree of

neck lymphadenitis is modest and the throat

often does not appear red, although it is very

painful. M. A. El-Farrash

Adenoviruses Morphology

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Icosahedral,

non-enveloped

virus containing

double stranded

linear DNA genome.

Human adenoviruses are classified into 6

subgroups (A – F) containing 56 serotypes.

Adenoviruses Pathogenesis

Infections by adenoviruses are very common.

Most infections are asymptomatic.

Virus was isolated from tonsils/adenoids

surgically removed, indicating latent infections.

It is transmitted by droplet, contact or feco-oral.

Adenovirus infections are difficult to distinguish

from Influenza, Parainfluenza or RSV. M. A. El-Farrash

Adenoviruses can cause:

1. Acute febrile pharyngitis and pneumonia

2. Conjunctivitis and keratoconjuctivitis

3. pharyngo-conjunctival fever

4. Gastroenteritis and intussusceptions in infants

5. Acute hemorrhagic cystitis

6. Sever pneumonia in AIDS patients.

M. A. El-Farrash

Adenoviruses Pathogenesis

Diagnosis and Treatment

Laboratory diagnosis is done by:

1. Virus isolation by culture on human fibroblasts

and founding the CPE (rounding, clustering and

swelling)

2. PCR for DNA detection

3. Antibody detection by CF, NT and HI tests.

Management: No specific antiviral agents and

no vaccine. M. A. El-Farrash

Herpesviruses

Eight human herpes virus species are known.

All have the ability to enter a latent state

following primary infection and to be reactivated

at a later time.

Structure:

Capsid: Icosahedral.

Genome: Double stranded, linear DNA.

Envelope: With glycoprotein spikes.

Human Herpes Viruses

M. A. El-Farrash

1- Alpha herpesvirinae:

Human herpesvirus 1, 2 (HSV-1, HSV-2)

Varicellovirus (HHV-3 or VZV).

2- Beta herpesvirinae:

Cytomegalovirus (CMV),

Roseolovirus (HHV-6, HHV-7).

3- Gamma herpesvirinae:

Epstien-Barr virus (EBV),

Kaposi sarcoma associated virus (HHV-8).

Herpes viruses Classification

M. A. El-Farrash

The Epstein-Barr virus (EBV) or Human herpes

virus 4 (HHV-4) is one of the most common

viruses in humans (more than 70%

seropositivity).

EBV has a dual cell tropism for human B-

lymphocytes and epithelial cells.

EBV often causes asymptomatic infection but

may cause infectious mononucleosis in few cases.

Epstein-Barr virus (EBV)

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Also known as glandular fever, or Mono.

Transmission occurs from exchanging saliva

(Kissing disease) and also by airborne infection.

It is associated with the appearance of unusually

large lymphocytes (atypical lymphocytes) in

blood.

Symptoms are fever, general malaise, sore throat

and generalized lymphadenitis.

Infectious Mononucleosis

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Burkitt's lymphoma is a type of Non-Hodgkin's

lymphoma most common in equatorial Africa

and co-exists with the presence of malaria.

Malaria infection causes reduced immune

surveillance of EBV immortalized B cells, so

allowing their proliferation.

Burkitt's lymphoma commonly affects the jaw

bone, forming a huge tumor mass.

EBV-associated malignancies

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Burkitt's lymphoma

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It is found predominantly in Southern China

and Africa, due to genetic and environmental

factors.

It is more common in people of Chinese ancestry

(genetic), and is also linked to Chinese diet (high

amount of smoked fish, which contain

nitrosamines) a well known carcinogens.

Nasopharyngeal carcinoma

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Nasopharyngeal carcinoma

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1. Blood film: lymphocytosis and many abnormal

lymphocytes.

2. Detection of EBV in lymphocytes by PCR.

3. Paul-Bunnel test: It is non specific test in which

we add serum of the patient + sheep RBCs

agglutination of RBCs (positive).

4. Detection of specific antibodies to viral antigens.

5. Virus isolation from saliva.

EBV Laboratory Diagnosis

M. A. El-Farrash

Myxoviruses

Name is from the Greek 'myxo' = mucus.

The first isolated and known member of the

group was Influenza virus.

The group has 2 families:

1. Orthomyxoviridae: which contains the influenza

viruses and other non human viruses.

2. Paramyxoviridae: containing the parainfluenza,

mumps, measles and respiratory syncytium

virus.

Myxoviruses

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Orthomyxoviridae: Particle size: 80-120 nm (highly pleomorphic)

Core diameter: 9 nm.

Genome: Segmented (-) sense RNA.

Replication: Nuclear.

Paramyxoviridae: Particle size: 125-250 nm (somewhat pleomorphic)

Core diameter: 14-20 nm.

Genome: Non-segmented (-) sense RNA.

Replication: Cytoplasmic.

Myxoviruses

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Influenza VirusInfluenza virus belongs to Orthomyxoviridae

family (s/s, negative-sense RNA viruses).

The particles are mostly spherical.

The virus has a lipid envelope from which project

prominent glycoprotein spikes of two types:

1. Haemagglutinin (HA or H),

2. Neuraminidase (NA or N).

The genome is composed of 8 segments (7 in type B). M. A. El-Farrash

Influenza Virus

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Virus MutationEvery now and then (10 - 15 years) a major new

pandemic strain appears in man, with a totally

new H and sometimes a new N as well (Antigenic

Shift).

This new variant may cause a major epidemic

around the world.

Over the subsequent years this strain undergoes

minor changes (Antigenic Drift) every two to

three years. M. A. El-Farrash

Serotypes

There are 16 known (H) serotypes and 9 known

(N) types of Influenza A virus giving a large

number of subtypes due to different associations.

Fifteen subtypes of influenza A virus are known

to infect birds, thus providing a reservoir of

influenza viruses circulating in bird populations.

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Types and Host range

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Influenza is characterized by fever, myalgia, headache and pharyngitis. There is usually no coryza (runny nose) which characterizes common cold infections. Symptoms may be very mild, (even asymptomatic) moderate or very severe.Spread: rapid via aerial droplets with inhalation into the pharynx or lower respiratory tract. Incubation: short: 1-3 days. Rapid spread leads to epidemics.

Influenza

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Laboratory DiagnosisA. Viral Isolation :

Samples: Respiratory secretions: obtained by

direct aspirate, gargle or nasal washings.

Rapid examination of cells by IF then

inoculation on cell cultures (or egg embryo).

PCR and genotyping or serotyping.

B. Serology :Detection of antibodies in the serum by HAI.

M. A. El-Farrash

Amantadine and Rimantadine are active against

influenza A viruses (but not B).

Recently, they became not effective against

seasonal strains.

Tamiflu: is an inhibitor of neuraminidase taken

in pill form which causes decreased severity and

duration of symptoms.

M. A. El-Farrash

Treatment of Influenza

Vaccines are produced by re-assortment of egg-adapted strains with strains having the season HA type.

Large amounts of virus are then grown in embryonated eggs (cheap and efficient), purified and formalin inactivated.

The vaccine is given sub-cutaneously.

For new antigenic type, 2 doses are necessary for adequate protection (which depends on age of patient).

M. A. El-Farrash

Influenza vaccines

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Diarrhea VirusesDiarrhoa is not as dramatic

illness as AIDS.

However, the viruses

causing diarrhea are of

great economic importance.

Diarrhea viruses include : Astroviruses,

Adenoviruses, Reoviruses and Caliciviruses.

ReovirusesRespiratory Enteric Orphan viruses, i.e. viruses

that infect the human respiratory and intestinal

tracts, without causing a known disease.

There are more than 150 species in the family

Reoviridae. The most important one is Rotavirus.

They are unified by their most unique feature;

the composition of their genome d/s RNA.

M. A. El-Farrash

RotavirusesRotaviruses have three shells: an outer capsid,

inner capsid and core which surrounds the 11

segments of double-stranded RNA.

M. A. El-Farrash

Infections cause endemic/epidemic gastroenteritis

and infantile diarrhea (a major cause of death in

the developing world).

Rotaviruses cause generally self-limited

infections rare in adults and trivial in

consequence, but may kill infants unless properly

treated (oral rehydration keeps children alive).

Rotaviruses

Rotaviruses are the most common cause of severe

diarrhea worldwide.

In developing countries, rotavirus infection may

cause up to one million deaths each year,

accounting for an estimated 20-25% of all deaths

due to diarrhea and 6% of all deaths among

children less than five years old.

Rotaviruses

M. A. El-Farrash

Infection occurs by feco-oral route.

Diagnosis is confirmed by virus detection in stool

by E/M or isolation by culture.

Treatment : oral rehydration therapy with

isotonic glucose/mineral salt solution.

Diagnosis and Management

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Astroviruses

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Astroviruses are 28–35 nm, icosahedral viruses

that have a characteristic five- or six pointed

star-like surface structure when viewed by

electron microscopy.

 Astrovirus has a non-segmented, single stranded,

positive sense RNA genome within a non-

enveloped icosahedral capsid. 

They have been shown to be an important cause

of gastroenteritis in young children worldwide.

Norwalk Virus

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Norovirus is a genus of single-stranded RNA,

non-enveloped viruses in the Caliciviridae family.

The known viruses in the genus are all

considered a single species called  Norwalk virus.

Noroviruses are the most common cause of

viral gastroenteritis in humans, and affect people

of all ages.

Norwalk “Norovirus”

The viruses are transmitted  by contaminated

food or water; by person-to-person contact; and

via aerosolization of the virus and subsequent

contamination of surfaces.

The virus causes over 200,000 deaths each year;

these deaths are usually in less developed

countries and in the very young, elderly and

immunosuppressed.

Norwalk “Norovirus”

Norovirus infection is characterized by nausea,

forceful vomiting, watery diarrhea, and

abdominal pain, and in some cases, loss of taste.

General lethargy, weakness, muscle aches,

headache, coughs, and low-grade fever may

occur.

The disease is usually self-limiting, and severe

illness is rare.

Norwalk “Norovirus”

Viral Meningitis

Viral Meningitis

Viral meningitis is sometimes referred to as

"aseptic meningitis" in contrast to meningitis

caused by bacteria.

Viral meningitis is most commonly caused

by enteroviruses, however, only a small

number of people with enterovirus infections

actually develop meningitis.

Causative organisms include:1. Enteroviruses

i. Echovirus

ii. Poliovirus (PV1, PV2, PV3)

iii. Coxsackie A virus .

Other viral infections that can lead to meningitis include

2. Herpesviruses,

3. Arboviruses

Viral Meningitis

5. LCMV (lymphocytic choriomeningitis

virus), which is spread by rodents,

6. Human Immunodeficiency Virus (HIV)

7. Measles

8. Mumps

9. St. Louis Encephalitis virus

10.West Nile virus

Viral Meningitis

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