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

2. Virology of Pharyngitis, Gastroenteritis and Meningitis Prof
Virology of Pharyngitis, Gastroenteritis and Meningitis Prof. Mohamed El-Farrash 2015

3. Pharyngitis
Pharyngitis “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

4. Acute Pharyngitis
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. 
M. A. El-Farrash

5. Viral and Bacterial Pharyngitis
M. A. El-Farrash

6. Viral Pharyngitis Adenovirus is the most common of the viral causes.
Pharyngitis 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

7. Adenoviruses Morphology
Icosahedral,
non-enveloped
virus containing
double stranded
linear DNA genome.
Human adenoviruses are classified into 6 subgroups (A – F) containing 56 serotypes.
M. A. El-Farrash

8. 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

9. Adenoviruses Pathogenesis
Adenoviruses can cause:
Acute febrile pharyngitis and pneumonia
Conjunctivitis and keratoconjuctivitis
pharyngo-conjunctival fever
Gastroenteritis and intussusceptions in infants
Acute hemorrhagic cystitis
Sever pneumonia in AIDS patients.
M. A. El-Farrash

10. Diagnosis and Treatment
Laboratory diagnosis is done by:
Virus isolation by culture on human fibroblasts and founding the CPE (rounding, clustering and swelling)
PCR for DNA detection
Antibody detection by CF, NT and HI tests.
Management: No specific antiviral agents and no vaccine.
M. A. El-Farrash

11. Herpesviruses

12. Human Herpes Viruses Structure:
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.
M. A. El-Farrash

13. Herpes viruses Classification
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).
M. A. El-Farrash

14. Epstein-Barr virus (EBV)
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.
M. A. El-Farrash

15. Infectious Mononucleosis
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.
M. A. El-Farrash

16. EBV-associated malignancies
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.
M. A. El-Farrash

17. Burkitt's lymphoma
M. A. El-Farrash

18. Nasopharyngeal carcinoma
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.
M. A. El-Farrash

19. Nasopharyngeal carcinoma
M. A. El-Farrash

20. EBV Laboratory Diagnosis
Blood film: lymphocytosis and many abnormal lymphocytes.
Detection of EBV in lymphocytes by PCR.
Paul-Bunnel test: It is non specific test in which we add serum of the patient + sheep RBCs  agglutination of RBCs (positive).
Detection of specific antibodies to viral antigens.
Virus isolation from saliva.
M. A. El-Farrash

21. Myxoviruses

22. 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:
Orthomyxoviridae: which contains the influenza viruses and other non human viruses.
Paramyxoviridae: containing the parainfluenza, mumps, measles and respiratory syncytium virus.
M. A. El-Farrash

23. Myxoviruses Orthomyxoviridae: Paramyxoviridae:
Particle size: nm (highly pleomorphic)
Core diameter: 9 nm.
Genome: Segmented (-) sense RNA.
Replication: Nuclear.
Paramyxoviridae:
Particle size: nm (somewhat pleomorphic)
Core diameter: nm.
Genome: Non-segmented (-) sense RNA.
Replication: Cytoplasmic.
M. A. El-Farrash

24. Influenza Virus
Influenza 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

25. Influenza Virus
M. A. El-Farrash

26. Virus Mutation
Every now and then ( 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

27. 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.
M. A. El-Farrash

28. Types and Host range
M. A. El-Farrash

29. Influenza
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.
M. A. El-Farrash

30. Laboratory Diagnosis A. Viral Isolation : B. Serology :
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

31. Treatment of Influenza
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

32. Influenza vaccines
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

33. M. A. El-Farrash

35. Diarrhea Viruses Diarrhoa 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.

36. Reoviruses
Respiratory 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

37. Rotaviruses
Rotaviruses have three shells: an outer capsid, inner capsid and core which surrounds the 11 segments of double-stranded RNA.
M. A. El-Farrash

38. Rotaviruses
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).

39. 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.
M. A. El-Farrash

40. Diagnosis and Management
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.
M. A. El-Farrash

41. Astroviruses
M. A. El-Farrash

42. 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.

43. Norwalk Virus
M. A. El-Farrash

44. Norwalk “Norovirus”
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.

45. 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.

46. 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.

47. Viral Meningitis

48. 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.

49. Viral Meningitis Causative organisms include: Enteroviruses Echovirus
Poliovirus (PV1, PV2, PV3)
Coxsackie A virus .
Other viral infections that can lead to meningitis include
Herpesviruses,
Arboviruses

50. Viral Meningitis
LCMV (lymphocytic choriomeningitis virus), which is spread by rodents,
Human Immunodeficiency Virus (HIV)
Measles
Mumps
St. Louis Encephalitis virus
West Nile virus

51. Thank you