1. PART TWO SYSTEMIC VIROLOGY Prepared by Professor Dr Hassan J Hasony
Dept Med Microbiology, Basrah Medical College

2. OBJECTIVES:
Viral infections attributed to each system will be discussed concentrating on :
- properties of viral aetiologic agent
- clinical finding and case presentation
- Epidemiology of viral infections
- prevention and control measures
- Laboratory diagnosis and interpretation of lab. Test results

3. LEARNING OBJECTIVES
student should be able to answer the questions attached to each lecture concerning the target system and having a skil to identify and interprept the results of any related investigations for linking the presented case to the viral aetioloigic agent(s)

4. THE FAMILY OF VIRUSES RNA VIRUSES Orthomyxoviridae Paramyxoviridae
Rhabdoviridae
Filoviridae
Flaviviridae
Picornaviridae
Reoviridae
Togaviridae
Retroviridae

5. RESPIRATORY VIRUSES

6. Replication Sites and Clinical Manifestations

7. Why so many? Constant exposure: 21,000 L of air/day
RT is a favorable environment for viruses:
Warm, moist, and dark
Plenty of cell types (25), which are good “tissue culture media”
Optimal temperature
Easy transmission via:
Sneezing – aerosol m particles at 100 ft/sec
Cough – disperses nasopharyngeal content at 850 ft/sec
Intimate and non-intimate contact

8. Determinants of Viral Respiratory Disease
Viral Factors
Tissue tropism
Route of infection
Stability of the virus
Replication and release of viruses into aerosols
Host Factors
Age
Immune status
Underlying disease
adaptation
Environmental Factors
Dosage
Exposure
Occupation
Life Style:
Day care setting
Public transport

9. INFLUENZA VIRUS

10. RNA VIRUSES Enveloped, Single-stranded RNA Viruses
Orthomyxoviruses: Influenza
- spherical particles with an average diameter of nm
- contains 7 structural proteins :
PB1, PB2, PA – bound to viral RNA ; responsible for RNA
transcription and replication
Nucleoprotein ( NP ) – associates with viral RNA to form a
structure 9 nm in diameter that assumes a
helical configuration
Matrix ( M ) protein – forms a shell underneath the viral
lipid envelope; important in particle morphogenesis
HA ( hemagglutinin ) } determines antigenic variation
NA ( neuraminidase ) } of influenza viruses

11. ORTHOMYXOVIRUSES type A, B, C : NP, M1 protein
helical nucleocapsid (RNA plus
NP protein)
HA - hemagglutinin
polymerase complex
lipid bilayer membrane
NA - neuraminidase
type A, B, C : NP, M1 protein
sub-types: HA or NA protein

12. Influenza virus genome:
- divided into eight separate segments  reassorting
during viral assembly  antigenic nature of
proteins change
- antigenic drift : changes in a single amino acid
- antigenic shift : the accumulation of enough changes to
create a new subtype different from the
original strain
H and 9 N ( H= 2 to the power 16 ,N=2 to
power 9

13. Classification and nomenclature :
- antigenic differences between NP and M proteins divides
influenza viruses into :
type A : highly variable antigenically ; responsible
for most cases of epidemic influenza
type B : may exhibit antigenic changes and sometimes
causes epidemics
type C : antigenically stable ; causes only mild illness

14. Properties :
- relatively stable; may be stored at 4 degrees C for a week
- infectivity destroyed by heating at 56 degrees C for a
few minutes, treatment with ether, formaldehyde,
phenol and other protein denaturants
- initial isolation best accomplished by amniotic
inoculation of embryonated chicken eggs and monkey
cell cultures

15. EPIDEMIOLOGY: Influenza A
- acute, highly contagious , respiratory illness afflicting
people of all ages marked by seasonal regularity and
pandemics at predictable intervals
- five pandemics in recorded history : the worst was in
1918 where there were at least 50 million deaths
- the most virulent among the three types of influenza
viruses

17. ( cont. epidemiology )
- influenza A strains are also known for pigs, horses,ducks
and chicken
- antigenic changes in group A > B; group C appears to be
antigenically stable
- interpersonal spread due to formation of virus-laden
aerosol droplets when an infected patient sneezes or coughs
 if virus is not neutralized ( e.g. local IgA specific anti-
hemagglutinin Ab ), initial replication occurs

18. Mode of influenza transmission:
- inhalation of aerosol and droplets major route of infection
- transmission greatly facilitated by crowding and poor ventilation
usually in late fall and winter in temperate countries
throughout the year in the tropics
- occupational contact with ducks, other poultry,and swine constitutes
a special high-risk category for disease
- OVERALL MORTALITY FOR INFLUENZA A : 0.1 % of cases
with deaths occurring among the elderly and small children
Pathogenesis:
Virus binds to ciliated columnar cells (respiratory mucosa)
rapid shedding of mucosal cells together with a load
of viruses trachea and bronchial epithelia are stripped to
the basal layer leading to severe inflammation and irritation
viruses remain in respiratory tract (viremia is rare);
ciliated columnar epithelium restored w/in 1-2 wks

19. FACTORS AFFECTING EFFICIENCY OF
AEROSOL SPREAD:
1. direct proportion to the number of particles generated
2. density of susceptibles
3. physical and temporal contiguity to aerosols
4. degree of stagnation of ambient atmosphere
- high attack rates : nursing homes, classrooms, ships,
barracks, aircraft
- smokers : increased susceptibility to infection
- young children ( pre-school or grade school ) : most
effective disseminators of the disease
- periodicity of influenza epidemics/pandemics:
determined by the surface antigens of the virus and the
antibodies induced within a population

20. Recovery from infection depends on: a. general health
b. immunity from previous
exposure
c. vaccination
d. age

21. DIAGNOSIS:
Virus isolation /detection of viral antigen in respiratory
secretions ( nasal/throat swabs; nasal washes ;
combined nose-and-throat swab ; sputum ) which are
inoculated into :
a. rhesus monkey kidney or Madin-Darby canine
kidney cell cultures  CPE or hemadsorption
b. embryonated hens’ eggs ( allantoic or amniotic cavity )

22. 2. Rapid diagnosis
a. samples centrifuged directly onto cells in shell
vials  detection of viral antigens by IF or
ELISA
* sensitivity higher in nasophrayngeal washes and
swabs
b. PCR

23. 3. serologic testing
- compares acute and convalescent sera ( days
apart ): 4 fold rise in titer
a. CF
b. HAI
4. epidemiologic diagnosis
- when infection is confirmed within a region by the
local health department

24. PREVENTION:
- primary means of prevention : vaccines
- vaccines not used much because:
a. offers only a short duration of protection
b. possibility of sensitization or severe allergic reactions in
persons hypersensitive to eggs ( vaccine viurs grown in chick
embryo )
c. possibility of toxic reactions to the high concentration of
virus material administered parenterally
d. uncertainty of protection because of the changing antigenicity
of the circulating influenza strains
- vaccination recommended for high-risk groups:
a. the chronically ill
b. the elderly ( > 65 years old )
c.persons with high degree of exposure to the public

25. standard vaccines containing viruses grown in
embryonated eggs have an overall effectiveness of 70 %
( accompanied by side effects of chills and fever)
- newer subunit vaccines made by disrupting virus with
detergents or solvents have fewer side reactions but are
more limited in scope of protection
- recent tests being done on influenza vaccine administered
intra-nasally ( greater potential for immunogenicity)

26. CONCEPT QUESTIONS -Mention the major groups of viruses causes RTI.
- What are the determinants of viral respiratory diseases ?
-What are the properties of orthomyxoviruses ?
- What is the major characters of influenza virus genome ?
- On what basis influenza viruse can be classified ?
- What is the possible mechanism for influenza virus antigenic changes?
- What is the mode of influenza virus trasmission ?
- Illustrate the pathogenesis of influenza virus ?
- What are the factors affecting efficiency of aerosole spread ?
- Recovery from influenza virus infection depends on:
- What are the diagnostic methods for influenza infections?
- What are the strategies for influenza prevention ?
- Who are the target for influenza virus vaccinatio ?
-What are the types of influenza vaccines, giving the advantages of each ?

27. ENVELOPED, RNA VIRUSES PARAMYXOVIRUSES
The important human paramyxoviruses:
a. Paramyxovirus ( parainfluenza and mumps )
b. Morbillivirus ( measles virus )
c. Pneumovirus ( respiratory syncytial virus )
- resembles the influenza virus but are larger
all are transmitted thru respiratory droplets
envelope has HN spikes and F glycoprotein spikes that allow the
virus to infect neighboring cells :
HN ( hemaglutinin and neuraminidase ) : responsible
for host cell attachment
F glycoprotein : mediates membrane fusion and
hemolysin activity

28. Paramyxoviridae Properties of the Paramyxoviridae
2. Morphology & structural proteins

29. Paramyxoviridae Properties of the Paramyxoviridae
2. Morphology & structural proteins

30. PARAMYXOVIRUSES:
Mechanism of infection:
cell membrane of infected cell modified by insertion of spikes
HN spikes immediately bind an uninfected neighboring
cell in the presence of F spikes two cells
permanently fuse
chain reaction of multiple cell fusions produce a syncytium or
a multinucleate giant cell (with cytoplasmic inclusion bodies)

31. 2. Parainfluenza virus type 3
I. PARAINFLUENZA
4 major serotypes :
1. Parainfluenza virus types 1 and 2
- usually infects infants and children
2. Parainfluenza virus type 3
- infects infants < 2 years
- year round infections
- more severe than types 1 and 2
3. Parainfluenza virus type 4
- mild disease

32. Epidemiology and Pathology
primary infection with virus occurs throughout the
year ( seasonal peaks in late fall and winter )
droplets and respiratory secretions disseminate the
virus into the air and onto fomites
usual route of transmission: inhalation or inoculation
of mucous membranes by contaminated hands
usually seen most frequently in children
NO transplacental immunity ; babies in first
year are particularly susceptible ( more severe
symptoms )

33. Characteristic symptoms of parainfluenza:
a. minor upper respiratory tract disease (a cold)- caused
by all types
b. bronchitis – usually caused by type 3
c. bronchopneumonia – usually caused by type 3
d. laryngotracheobronchitis ( croup)- afflicts larynx of
infants and young children causing labored ,noisy
breathing with hoarse cough; usually asso. with types
1& 2
* second only to RSV as a cause of lower
respiratory tract infection
* commonly cause croup

34. LABORATORY DIAGNOSIS :
1. Isolation and identification of the virus
* specimens : throat and nasal swabs and
nasal washes
* inoculated on primary human and monkey
kidney cells -> isolates typed by
IF or hemadsorption inhibition
or HI
2. Serology : uses paired sera

35. CONCEPT QUESTIONS Mention the important human paramyxoviruses .
What is the mechanism of infections with paramyxoviruses ?
Four serotypes of parainfluenza, mention the host range and
disease caused by each type .
What are the epidemiologic feature and pathology of
parainfuenza virus infections?
What are the characteristic symptoms of parainfluenza ?
Mention the main laboratory diagnostic methods for
parainfluenza.

38. Adenovirus Penton Fiber What might be its function ?? What are these
components?

47. CONCEPT QUESTIONS: Mention the main characteristic of adenoviruses .
- Describe the pathogenesis of adenovirus infections.
- What are the epidemiological feature of adenovirus infection?
- What are the clinical significane of addenovirus infections?
- What are the main clinical finding associated with acute
febrile pharyngitis?
- In what ways adenovirus can evade host immune response?

48. II. MUMPS ( EPIDEMIC PAROTITIS ) :
- self-limited, mildly epidemic illness associated with painful
at the angle of the jaw with occasional swelling of the testes
- virus bears morphologic and antigenic characteristics similar to
the parainfluenza virus
- has only one serological type
- grows readily in embryonated eggs esp. in the amniotic sac
- can be grown in cell culture to produce large multinucleated giant
cells ( syncytia ) and a hemagglutinin
- infectivity of virus destroyed by heating at 56 degrees C for 20 mins.

49. Mumps
Inflammation, parotitis in a child with mumps

50. Mumps
Parotid gland

51. Epidemiology and Pathology of Mumps:
- humans are the exclusive natural hosts
- occurs worldwide, epidemics occur in the late winter and early
spring
- high rate of infection among crowded populations
- most cases occur in children under 15 years ( 40 % subclinical)
- lasting immunity follows any form of mumps infection
- communicated thru salivary and respiratory secretions
( less contagious than measles or varicella )

52. incubation period : 2-3 weeks  followed by symptoms of
( cont. epidemiology and pathology of mumps )
incubation period : 2-3 weeks  followed by symptoms of
fever, nasal discharge, muscle pain, and malaise
inflammation of salivary glands ( esp. the parotids) produce
the classic “gopher-like” swelling of the cheeks on one or
both sides
viral multiplication in salivary glands  viremia and
invasion of other organs ( e.g. testes, overies, thyroid gland,
pancreas, meninges, heart, kidney)
PROGNOSIS: most will have complete, uncomplicated
recovery

53. Complications of Mumps:
1.Orchitis and epididymitis : occurs in 20-30% of young adult males
: painful but no permanent damage occurs
2. Pancreatitis : virus replicates in beta cells and pancreatic epithelial
cells
3. Viral meningitis : fever, headache, nausea, vomiting, and stiff neck
: common in mumps
: appears 2-10 days after onset of parotitis
: lasts 3-5 days, dissipates with few or no adverse
side effects
4. Hearing loss : a rare occurrence
: affects only one side
: virus replicates in the organ of Corti causing
permanent deafness

54. ( cont. mumps )
Diagnosis:
1. history ( exposure ) and PE ( parotid swelling )
2. serologic studies
* IgM antibodies by ELISA or 4 fold increase between
acute and convalescent sera
3. viral isolation
* virus present in saliva for about 1 week aftre onset
of parotitis
Treatment : Symptomatic treatment usually adequate
Prevention : a live, attenuated mumps vaccine given routinely as part
of the MMR vaccine at 15 months of age ( powerful and
effective control agent )
: protection often lasts a decade

55. CONCEPT QUESTIONS -What are the characteristic of mumps disease ?
- What are the epidemiologic feature and pathology of mumps?
- What are the major complication of mumps ?
- What are the diagnostic methods for mumps?
- What are the main method s for prevention & control of
mumps ?

56. III. MEASLES ( Morbillivirus Infection )
- also known as red measles and rubeola
- entirely unrelated to rubella ( German MEASLES )
- characterized by maculopapular eruption , URTI,conjunctivitis
Epidemiology:
one of the most contagious infectious diseases
- rare under 6 months of age: transplacental IgG
transmitted principally by direct contact with respiratory aerosols
- epidemic spread favored by crowding, a prevalence of nonimmune
children, malnutrition
1986 measles epidemic linked to lack of immunization in children
or the failure of a single dose of vaccine in many children
no reservoir other than humans
person considered infectious during period of incubation, prodrome,
and skin rash
- single attack confers lifelong immunity

57. Measles
(measles or rubeola)
maculopapular rash

58.  “Maculopapular rash” on buttocks of boy
during 3rd day of the rash

59.  Conjunctivitis Eyes of child with measles

60. ( The large syncytia, or multinucleated giant cells, result
CPE typical of measles virus infection of Hela cells
(Hematoxylin & Eosin staining)
( The large syncytia, or multinucleated giant cells, result
from fusion of cell membranes bearing viral glycoproteins e syncytia, or multinucleated giant cells, result
from fusion of cell membranes bearing viral glycoproteins.)

61. Infection and Disease: * incubation period : 2weeks
( cont. Measles )
Infection and Disease:
* incubation period : 2weeks
: invasion of mucosal lining of
respiratory tract, followed by viremia
Symptoms : sore throat, dry cough, headache,
conjunctivitis, lymphadenitis, and fever
Signs : Koplik’s spots( on lateral buccal mucosa ) appear
as a prelude to the red maculopapular exanthem that
erupts on the head which progresses to the trunk and
extremities
: rash gradually coalesce into red patches that fade to
brown

62. “Koplik’s spot”  Patient who presented with Koplik’s spots on
palate due to pre-eruptive measles on day 3 of
the illness

63. Complications : in most instances, a self-limited infection
: may be severe enough to cause death in about 1 in 500 children
: laryngitis, bronchopneumonia, bronchitis,
pneumonitis , bacterial secondary infections ,
otitis media and sinusitis
: children with leukemia predisposed to
pneumonia due to lack of natural T-cell
defense
: SSPE ( subacute sclerosing panencephalitis )
( manifests 5-7 years after initial infection)

64. Diagnosis :
1. Clinical
- age, history of recent exposure to measles,
( useful clues to diagnosis)
- cough, coryza, conjunctivitis, Kopliks’ spots,
a maculopapular rash beginning on the face
2. Laboratory
a. virus isolation
b. identification of measles antigen in infected
tissues ( IF from nasal exudates/urine sedi-
ments and RT-PCR )
c. demonstration of specific serologic response
( ELISA, HI on paired serum samples )

65. Treatment : symptomatic treatment for most cases
: antibiotics may be given for bacterial
complications
: large doses of immune globulin may be
therapeutic
Prevention : vaccination is the most practical, economical,
and enduring strategy to combat measles

66. - immunity persists for about 20 years - may cause atypical infection
Measles vaccine :
- attenuated virus given subcutaneously
- immunity persists for about 20 years
- may cause atypical infection
- recommended for all healthy children at the age of 15
months ( MMR vaccine , with mumps and rubella )
and a booster prior to entering school
- any person who received the vaccine prior to 1980 or
whose immunization history is in doubt should be
revaccinated

67. CONCEPT QUESTIONS
Define measles.
- What are the epidemiologic picture of measles.
- What are the major sign and symptoms of measles.
- What are the complications of measles ?
- What are the basis for the diagnosis of measles
clinically or laboratory?
What are the major preventive measures of measles?
What is the schedule of measles vaccination and
what type of vaccine ?

68. Rubella
Electron micrograph of rubella virus

69. Rubella Epidemiology of Rubella Virus Disease / Viral Factors
- Rubella infects only humans.
- Virus can cause asymptomatic disease.
- There is one serotype.

70. Rubella Epidemiology of Rubella Virus Transmission - Respiratory route
Who Is at Risk?
- Children: mild exanthematous disease.
- Adults: more severe disease with arthritis /
arthragia
- Neonates younger than 20 weeks: congenital

71. Rubella Rash of rubella on skin of child's back.Distribution is
similar to that of measles but the lesions are less intensely red.

72. Rubella Prenatal or congenital rubella
The risk to a fetus is highest in the first few
weeks of pregnancy and then declines in term of both
frequency and severity, although there is still some
risk in 2nd trimester.
The virus infects the placenta and then spreads
to the fetus. If non-immune mothers are infected
in the 1st trimester, up to 80% of neonates may
have sequelae.

73. Rubella The sequelae of congenital rubellar syndrome are:
Hearing loss: This is the most common sequella
of congenital rubella infection
especially when the latter occurs
after 4 months of pregnancy.
Congenital heart defects
Neurologic problems: psychomotor retardation
: mental retardation
Ophthamic problems: cataract, glaucoma,
retinopathy

74. Rubella Prominent Clinical Findings in congenital rubella Syndrome
Cataracts & other ocular defects
Heart defects
Deafness
Intrauterine growth retardation
Failure to thrive

75. Rubella Prominent Clinical Findings in congenital rubella Syndrome
Mortality within the first year
Microcephaly
Mental retardation

76. Rubella This infant has the rash of congenital rubella
(German measles).These infants are at great risk for
severe mental retardation, deafness, blindness
(atrophic eyes, cataracts and chorioretinitis)
as well as congenital heart disease and other abnormalities. .

77. Rubella Baby born with rubella: Thickening of the lens of the eye
that causes blindness (cataracts)   

78. Rubella * Humoral Immunity Immune response
- Specific IgM antibody appears within a few days
of the rash, and is followed soon after by IgG.
The titer of IgM increases rapidly, reaching a
peak about 10 days after onset and thereafter
declining to undetectable amounts over several
weeks or months.   

79. Rubella * Humoral Immunity Immune response
The rapid appearance of specific IgM antibody
is invaluable for diagnostic purposes.
- IgG antibody peaks at about the same time as
IgM, and persists for many years, as does IgA
antibody, which appears in the serum and
nasopharyngeal secretion.   

80. Rubella * Cellular Immunity Immune response
- The cell-mediated response precedes the
appearance of antibody by a few days, reaches
a peak at about the same time, and is also
detectable for many years.   

81. Rubella Diagnosis of rubella - Many (~ 50%) infections are apparently
subclinical and many infections go unrecognized,
even if symptoms develop (rash is not always
present).
- Infections with many other agents give similar
symptoms to rubella (e.g. infection with human
parvovirus, certain arboviruses, many of the
enterovirus group of piconaviruses, some
adenoviruses, EBV, scarlet fever, toxic drug
reactions).   

82. Rubella Diagnosis of rubella - Serological tests or isolation of virus
(immunofluorescence) are needed to confirm
infection of individual
Cord blood rubella- IgM   

83. Rubella Epidemiology - Human is the only host and rubella occurs world
wide.
- Periodic epidemics occur in an unvaccinated
population.
- Natural infection protects for life
(there is a single serotype).   

84. Rubella Prevention - The best means of preventing rubella is
vaccination with the live cold-adapted
RA27/3 vaccine strain of virus.
- The live rubella vaccine is usually administered
with the measles & mumps vaccines
(MMR vaccine) at 24 months of age.   

85. Rubella Prevention - A live vaccine (attenuated strain) is available.
The vaccine virus is grown in human diploid
fibroblasts. Since there is only 1 serotype,
a univalent attenuated vaccine can provide
lifelong immunity.   

86. Rubella Prevention - It is important that women are vaccinated prior
to their 1st pregnancy.
- United States recommendations are for
childhood vaccination to prevent epidemics,
combined with vaccination of susceptible,
non-pregnant adolescent and adult females.   

87. Rubella Prevention - The vaccine is contraindicated for pregnant
women, but when unwittingly used, no problems
have been seen.
- If the patient is pregnant and seronegative, the
pregnancy should be monitored carefully and the
patient vaccinated postpartum.   

88. Rubella Treatment There is no specific treatment. Supportive
care should be used.   

89. CONCEPT QUESTIONS What is the epidemiologic feature of rubella ?
- Who is at risk of rubella infections?
- What are the differences between measles and rubella ?
- What is CRS ?
- Describe the consequences of congenital rubella ?
- What are the sequellae of congenital rubella syndrome ?
- What are the prominant clinical findings in CRS ?
- Describe the humoral responses to rubella virus infection?
- Describe the cellular responses to rubella virus infection?
-Is the diagnosis of rubella virus infection always feasible ?
- What are the diagnostic methods for rubella and CRS ?
- What are the epidemiologic feature of rubella?
- Mention the main methods for rubella prevention?
- In what situations rubella vaccine can be contraindicated ?

90. IV. RESPIRATORY SYNCYTIAL VIRUS
- Also called Pneumovirus
- infects the respiratory tract and produces giant multinucleate cells
- peak incidence in the winter and early spring
- children 6 months or younger are especially susceptible to serious
disease
RSV Infection :
- incidence of RSV in children < one year old is 5/1000 live births
( most prevalent cause of respiratory infection in this age group)
- mortality highest for children with complications ( e.g.,
prematurity, congenital disease, and immunodeficiency )
- immunity is partial or transient, hence, infection could be recurrent
- manifests itself as a common cold in older children and adults

91. - portal of entry : epithelia of the nose and eye
( cont. RSV infections )
Pathogenesis
- transmission : respiratory route
- portal of entry : epithelia of the nose and eye
- main site of replication: nasopharynx
- symptoms : ( 1o infection) fever that lasts for three days
: rhinitis, pharyngitis, and otitis
: infection of the bronchial tree and lung
parenchyma gives rise to croup ( acute bouts of
coughing, wheezing, dyspnea and rales )

92. - major cause of respiratory illness in young children
Clinical Disease:
- major cause of respiratory illness in young children
- < 24 months : devastating disease
-> 4 months : no protective maternal antibody
Lower respiratory tract infections
- pneumonia, bronchiolitis, tracheobronchitis
2. Upper respiratory tract infections
- presents as common cold
3. Complications
- otitis media: common

93. Diagnosis
- critical in babies than in older children
- positive identification of RSV must be made as
rapidly as possible
Viral isolation on nasal wash / naspharyngeal and
throat swab ( done ASAP since virus is labile )
2. Direct and indirect fluorescent staining from a fresh
sample ( the virus is very fragile)
3. ELISA testing and DNA probes

94. ( cont. RSV )
Treatment : Ribavirin (virazole) appears beneficial since
it interferes with the replication of the virus in
infected cells
: Ribavirin is administered as an aerosol
( cannot be given to persons whose ventilation
is compromised)
: costly treatment with some adverse side effects
: supportive measures
Prevention : intranasal live vaccine presently being
developed

95. CONCEPT QUESTIONS
-In what age groups the incidence of RSV is highest ?
- Describe the pathogenesis of RSV .
- Mention the clinical diseases caused by RSV and
their complications .
-What are the diagnostic methods of RSV infections?
- What are the treatment of RSV and the methods
for prevention?

96. HUMAN RHINOVIRUS (HRV )
an extremely large group of picornaviruses ( > 110 serotypes )
associated with the common cold
- characteristics which distinguish the rhinovirus from the other
picornaviruses:
1. Rhinoviruses are sensitive to acidic environments
( e.g. stomach )
2. Optimum temperature for multiplication is not
normal body temperature, but 33o C, the average
temperature in the human nose
structure of the Rhinovirus:
- the capsid units are of two types:
a. protruberances (knobs), which are antigenically diverse
among the rhinoviruses
b. indentations (pockets) of which there are two types

97. 2 Antigenic Sites
1. KNOBS
2. INDENTATIONS
(POCKETS)
RHINOVIRUS 14

98. Pathogenesis and Clinical Manifestations
Portal of entry: nose, mouth, eyes
Replication: in the nose
Primarily infects upper airway  common cold
Binds to ICAM-1 as cellular receptors
Causes lysis of cells
Infected cells release bradykinin and histamine  rhinitis & rhinorrhea
Sore throat, cough, headache, malaise
Immunity is serotype specific

99. Epidemiology and Infection of Rhinoviruses:
the surface antigens are the only ones accessible to the immune
system ( i.e. a successful vaccine would have to contain
hundreds of different antigens- not practical )
-the indented antigens are too deeply situated for either immune
surveillance or antibody fit
Epidemiology and Infection of Rhinoviruses:
infection occurs in all areas, and all age groups at all times of the
year.
- many strains circulate in the population at one time ( occasionally
a single type may cause epidemics)
- children are the most successful disseminators of colds, often
introducing the virus to the whole family
- virus is shed from infected respiratory tract for several days – weeks
- transmission is linked very closely to inoculation by hands and
fomites ( to a lesser extent to droplet nuclei )

100. Rhinovirus Control of infection:
- combined antiviral-antimediator treatment:
In a trial using interferon-alpha 2 + ipratropium (both instilled into the
nose) + oral naproxen - > viral shedding and progression of
illness were reduced in the treatment group
Other measures:
a. hand washing
b. avoiding finger-eye and finger-nose contact
c. covering coughs and sneezes with disposable nasal tissues

101. Rhinovirus Symptomatic therapy:
Combination of a 1st generation antihistamine and a non-steroidal
anti-inflammatory compound effective treatment
-Treatment started a early as symptoms are recognized and
continued every 12 hours for 4-5 days
-Antibiotics have no place in therapy
Antiviral therapy:
the most promising results have been obtained with recombinant
interferon-alpha 2 applied topically in the nose
- interferon-alpha 2 is given prophylactically on doses of
approximately 5 million units or greater per day highly
effective in prevcnting experimental infection or illness
- side effects of chronic topical interferon-alpha 2 include :
nasal irritation, stuffiness, pinpoint mucosal ulcerations

102. CONCEPT QUESTION -What are the characteristics of Rhinoviruses ?
- What are the pathogenesis and clinical manifestation
of rhinoviruses?
- what are the epidemiologic feature of Rhinoviruses?
- How can we control rhinovirus infections?
- mention the strategies for rhinovirus infection therapy
: symptomatic therapy
: antiviral therapy

103. Single-stranded RNA, + strand, enveloped
Coronavirus
Upper respiratory infections

104. SARS Cause: SARS-associated corona (RNA) virus
Respiratory illness with onset
T > 100.5°F (>38° C)
Cough, shortness of breath, difficulty breathing, hypoxia, or radiographic findings of either pneumonia or acute respiratory distress syndrome
Travel within 10 days of onset of symptoms to an area with documented or suspected community transmission of SARS
Close contact with a person with SARS within 10 days of onset

105. Define: Coronaviruses Define: SARS - Mention the main clinical feature of SARS - Mention the main routes of transmission.

106. RHABDOVIRUSES one end and flat on the other end )
Rabies virus ( Lyssavirus ):
- have a distinctive bullet –like appearance ( round on
one end and flat on the other end )
- helical nucleocapsid with spikes that protrude thru the
envelope
- family contains approximately 60 different viruses
- only the rabies virus affect humans ( rarely, other
mammalian lyssaviruses )
- killed by UV irradiation or sunlight

107. RABIES VIRUS

108. - worldwide distribution in various mammals ( skunks,
Epidemiology
- slow , progressive zoonotic disease characterized by a
fatal meningitis
- worldwide distribution in various mammals ( skunks,
foxes, raccoons, wolves, mongooses, and badger )
- humans become accidental hosts thru dog bites, cat
scratches and contact with sylvan animal reservoirs
1.Sylvatic rabies
- rabies in wild animals ( bats, skunks, racoons, foxes )
- fruit and herbivorous bats are known to transmit
rabies
2. Urban rabies
- rabies in domestic animals ( dogs, cats, horses, cattle)
- vampire bats in S. America ( source of rabies in cattle)

109. TRANSMISSION
- primarily affects wild animals
- humans and animals : accidentally infected
animal bite – majority
2. via a scratch
3. inhalation of contaminated aerosolized animal material
4. transplantation of infected tissue ( cornea )
inoculation through intact mucous membrane
* virus found in saliva of infected animal few days
before clinical signs
* bat infection : latent ( bats excrete virus in saliva for
months )

110. Note: no viremia
Murray et al., Medical Microbiology

111. site ( it may also be inhaled or inoculated orally)
Infection and Disease
- begins when an infected animal’s saliva enters a puncture
site ( it may also be inhaled or inoculated orally)
- virus multiplies at the trauma site, up to a week upon
transmission
- virus gradually enters sensory nerve endings or
neuromuscular junction and advances toward the sensory
ganglia, spinal cord and brain
- virus multiplies throughout the brain with migration to
other sites ( eye, heart, skin, and oral cavity )
- viral replicates in the salivary glands and is shed into the
saliva
- considered a slow, progressive infection

112. Clinical phases of Rabies:
Average incubation period: 1-2 months ( extremes of 1
week to more than a year )
Incubation period : depends on wound site, its severity, virus
concentration in inoculum, host’s age,
host’s immune status
: shorter in facial, neck and scalp wounds
due to their proximity to the brain
: prodrome begins with fever, anorexia,
nausea, vomiting, headache, fatigue,
some may have pain, burning, pricking
or tingling sensation at the site of the
wound

113. Furious form – agitation, disorientation, seizures, and twitching
Forms of Rabies:
Furious form – agitation, disorientation, seizures, and
twitching
- spasms in the neck and pharyngeal
muscles lead to severe pain on swallowing ( even the
sight of liquids can bring about hydrophobia )
- the patient is fully coherent and alert
Dumb form – patient is paralyzed, disoriented and
stuporous
*Both forms eventually lead to coma and death from cardiac
or respiratory arrest.
*Only 3 patients have recovered from rabies with minimal
residua

114. Diagnosis
- when symptoms appear after a rabid animal attack the
diagnosis is readily made
- often the diagnosis is made at autopsy
- the laboratory criteria most diagnostic of rabies are :
1. intracelllular inclusions ( Negri bodies )
2. identification, isolation of rabies virus in saliva or brain
tissue
3. demonstration of rabies virus antigens in brain, serum ,
CSF

115. Section of brain showing rabies viruses
Bullet-shaped
Rabies virus
Section of brain showing rabies viruses

116. Rabies virus infected - Negri body - note dark blue basophilic granules (Sellers stain)

117. Rabies Prevention and Control:
Measures that effectively prevent and limit rabies are:
1. Postexposure vaccination
2. Animal control
3 IM injections of HDCV ( human diploid cell vaccine)
are recommended for high risk groups ( veterinarians, animal
handlers, lab personnel, and travelers to endemic areas )
other control measures such as vaccination of domestic animals
elimination of strays, strict animal quarantine have reduced the virus
reservoir
A new genetically engineered vaccine made with a vaccinia virus
that carries the gene for rabies virus surface antigen have been
incorporated into bait placed in habitats of wild reservoir species.
It is hoped eating this bait will render animals immune to rabies.

118. Postexposure Prophylaxis:
1. A wild animal especially a skunk, raccoon, fox, or coyote
that bites without provocation is considered to be rabid and
treatment is commenced
If the animal is captured, brain samples, and other tissues
are examined for verification of rabies
In an apparently healthy dog or cat they are quarantined for
10 days for observation
Following an animal bite the wound should be scrupulously
washed with soap or detergent and water, followed by
debridement and application of an antiseptic that inactivates
the virus ( alcohol or peroxide )
Combination of passive and active postexposure immunization
is very effective: wound is infused with ( HRIG) human rabies
immunoglobulin to impede spread of virus , also injected IM
-a full course of (HDCV) is given simultaneously

119. CONCEPT QUESTIONS - Is the rabies virus morphology distinctive ?
-Define: rabies
- Mention the epidemiologic feature of rabies virus.
- What is sylvanic rabies, and whatis urban rabies ?
- What are the of rabies virus transmission ?
-Describe infection and disease development of rabies.
- Mention the cliniocal phases of rabies .
- Enumerate the forms of rabies .
-Mention the lab. Criteria most diagnostic to rabies.
- Define negri bodies.
- What are the measures that effectively prevent rabies?
- What are thew postexposure prophylaxis ?

120. OTHER ENVELOPED RNA VIRUSES
Arboviruses: viruses spread by arthropod vectors
: includes members of several virus families
( see table)
: named according to place of discovery
* rubella virus : only member of the genus
Rubiviridae that is also a member of the
Togaviridae family
: not an arbovirus because it is
transmitted from person to person

121. FAMILY STRUCTURAL CHARACTERIS- TICS GENUS EXAMPLES ( virus )
Togviridae
+ RNA
enveloped
Alphaviruses
Eastern equine encephalitis;
Western equineencephalitis;
California equine encepha-
litis; Venezeluan equine encephalitis
Flaviviridae
Flaviviruses
Yellowfever ; Dengue;
St. Louis encephalitis;
Japanese B encephalitis;
Central European ence-
Phalitis
Bunyaviridae
- RNA
Bunyaviruses
Phleboviruses
Nairoviruses
California encephalitis;
Lacross encephalitis;
Sandfly fever
Crimean-Congo hemorrhagic fever
Reoviridae
Segmented, double
Stranded RNA, naked
Orbiviruses
Colorado tick fever

122. Arboviruses
These viruses multiply inside the vertebrate host as well as the vector .
The vector transmits the disease to human and other mammals , through the bite .
Man generally plays no role in the natural history of arboviruses .
Humans are not the natural reservoir for the virus .

123. Arboviruses associated with hemorrhagic fever .
1- Dengue virus . Family: Flaviviridae . 2- Yellow fever virus . family : Flaviviridae . 3- Rift valley fever virus . Family : Bunyaviridae . 4- Crimean congo hemorrhagic fever virus .

124. Arboviruses with hemorrhagic fever
2- yellow fever :
Geographical distribution : Africa and South America .
Vector : Mosquitoes .
Vertebrate host : Human , monkeys.
Symptoms: Most cases are mild or asymptomatic .
The severe form of the disease is characterized by fever, myalgia, arthralgia, nausea, vomiting, jaundice, mucosal bleeding, bleeding under the skin, vomiting blood, seizures and coma .

125. Yellow fever cycle . 1- Jungle yellow fever :
Involves transmission between mosquitoes and non-human primate, with human as accidental host.
2- Urban yellow fever :
Involves transmission between mosquitoes and human

126. 2- Arboviruses associated with encephalitis .
1- West Nile Encephalitis (WNE ) .
Family : Flaviviridae .
2- Eastern Equine Encephalitis ( EEE ) .
Family : Togaviridae .
3-Western Equine Encephalitis (WEE ). .
4-Venezuelan Equine Encephalitis (VEE ). .

127. Rift valley fever .
3- Meningoencephalitis : fever, severe headache, stiffness of neck, back pain, hallucination. Mental confusion, lack of coordination, convulsions and coma .
Transmission :By direct contact with infected animal blood or tissue .
Through the bite of mosquitoes.
Human to human transmission has not been documented..

128. Arboviruses associated with hemorrhagic fever
4- Crimean Congo H F :
Geog. Dist. : Africa, Asia and middle east .
Vector : Ticks .
Vertebrate host : Sheep, goats , cattle and human .
Symptoms : Most cases are mild or asymptomatic .
In severe cases, the symptoms are : fever, headache, myalgia, artheralgia, nausea, vomiting, mucosal bleeding and bleeding under the skin .

129. The major arboviruses pathogenic to man:
1. Togaviruses ( Alphavirus)
2. Flavivirus
3. Bunyaviruses ( Bunyavirus and Phlebovirus )
4. Reoviruses ( Orbivirus )
The chief vectors ( bloodsucking arthropods ) :
a. mosquitos
b. ticks
c. flies
d. gnats

130. Most types of illness caused by the virus:
a. mild undifferentiated fevers
b. some would cause severe encephalitides
c. some would cause life-threatening hemorrhagic fevers
General characteristics of Arbovirus Infections :
sudden , unexpected epidemics, sometimes with previously
unreported viruses are due to the uncertain nature of host
and viral cycles
- travelers entering endemic areas are at special risk
because, unlike
the natives of that region,they have no immunity to the
viruses

131. Arboviruses ( con’t )
The influence of the Vector:
- activity and distribution of arboviruses closely tied to
ecology of vectors
- factors to consider: a. longevity of the arthropod
b. availability of breeding sites
c. climactic influence ( temp. &
humidity )
Epidemiology of arbovirus disease:
- worldwide distribution ( being arthropod-borne )
- vectors and viruses tend to be clustered in the tropics and
subtropics
- many temperate zones report periodic epidemics
- vertebrate host : recovers vector: carries virus for life

132. PATHOGENESIS :
* infected vector bites -> virus injected into capillary circulation
-> viral replication in vascular endothelium -> viremia ( precedes onset
of clinical symptoms ) -> circulating virus reaches the organ for which
it has special tropism
ex. liver ( yellow fever virus ) ; brain ( encephalitis virus )
1. incubation period : short ( 1 week ) because viruses
are introduced directly into the bloodstream
2. morbilliform rash – secondary to :
a. endothelial cell damage
* if severe and disseminated : rash becomes hemorrhagic
and involves the mucous membranes, GIT mucosa
and skin
* may lead to disseminated intravascular coagulation
( DIC ) and thrombocytopenia
b. increased vascular permeability

133. maculopapular rash and usually benign
CLINICAL SYNDROMES:
I. Febrile Illness :
- of undifferentiated type with or without a
maculopapular rash and usually benign
A. infections typified by dengue fever and Colorado tick
fever:
( 1 ) mild, and self-limited, with no sequelae
( 2 ) fever of up to 40o C, prostration, headache,
myalgia , orbital pain, muscle aches, and joint
stiffness
( 3 ) midway thru the illness, a maculopapular or
petechial rash may erupt over trunk and limbs

134. II. Encephalitis:( invasion of brain, meninges and spinal cord )
- caused by alphaviruses, flaviviruses, bunyaviruses
a). exemplified by Western equine, eastern equine, St. Louis,
and California encephalitis
b). viruses cycle between wild animals ( primarily birds )
and mosquitos or ticks – humans are not the reservoir hosts
c). begins with an arthropod bite release of virus into
tissues replication in nearby lymphatics
prolonged viremia establishes virus in brain ->
swelling and inflammation causes damage to various nuclei
and tracts including the meninges
d). symptoms : ( variable ), may include coma, convulsions,
paralysis, tremors, rigidity, loss of coordination, palsies,
memory deficits, changes in speech and personality,
and heart damage.
e). survivors may have permanent brain damage ( young
children and very old patients )

135. III. Hemorrhagic Fevers
a. flu-like syndrome ( mild cases )
- fever, chills, headache, backache, nausea,
vomiting
b. extensive hemorrhage ( severe cases ) in mucous
membranes of nose, GIT , bladder
- melanemesis ( vomiting of digested blood )
- decrease in pulse pressure accompanied by a
paradoxical decrease in pulse rate
- jaundice/proteinuria
- certain arboviruses can disrupt vascular bed which can cause sudden localized bleeding in the tissues leading to shock or death ( e.g. yellow fever and dengue fever viruses )

136. exact mechanisms of pathology are obscure : the virus
causes capillary fragility and disrupts the blood clotting
mechanisms
these “ hemorrhagic syndromes” are caused by a variety of
viruses, carried by variety of vectors, and are distributed
globally
reservoir animals: small mammals
: yellow fever and dengue fever can be
harbored in human population

137. Single-stranded RNA, – strand, multiple RNA strands
Arenavirus
Helical capsids contain RNA-containing granules
Lymphocytic choriomeningitis
VEE and Lassa Fever
Rodent transmitted

138. Single-stranded RNA, – strand, multiple RNA strands
Bunyavirus (CE virus)
Hantavirus-cause hemorrhagic fevers & pulmonary syndrome assoc. with rodents.

139. Single-stranded RNA, + strand, enveloped
Alphavirus
Alphaviruses are transmitted by arthropods; include EEE, WEE
Rubivirus (rubella virus)

140. Single-stranded RNA, – strand, one RNA strand
Filovirus
Enveloped, helical viruses
Ebola and Marburg viruses

141. - transmitted by mosquitoes ( Aedes aegypti )
C. Dengue Fever ( DF) / Dengue Hemorrhagic Fever ( DHF ):
- four serotypes ( Types 1-4 ) of dengue ( in tropics )
- transmitted by mosquitoes ( Aedes aegypti )
* principal mosquito vector which are adapted to breed around human dwellings ( in man made water-
holding receptacles, around human habitation , in tree
holes or plants close to human dwelling )
( intensification of dengue transmission in tropical cities)
* epidemics start often during rainy season when
Aedes aegypti is most abundant

142. ( cont. Dengue )
* viral replication in the mosquito takes about
(1-2 weeks) then undergoes extrinsic incubation
* extrinsic incubation period required before it
can transmit the virus on subsequent feedings
* feeding attempts may number several times a day
depending on the availability of hosts
* lifespan of mosquito is 1-4 weeks
* mosquitoes sheltered indoors and bite during day
at 1-2 hour intervals in the morning and late
afternoon

143. PATHOGENESIS ( DF/ DHF ):
- self-limited dengue is the usual outcome of infection
- an immunopathologic response in some patients
usually in the setting of a heterologous immunity
produces the syndrome DHF-DSS
Infectious mosquito bite viral replication in
local lymph nodes disseminates via the blood to
various tissues (w/in 2-3 days) virus circulates in blood
in infected monocytes , B cells, an T cells (for 4-5 days)
nearly all patients are viremic at the point of clinical
presentation with fever virus cleared from blood
within a day after defervescence local suppression
of erythrocytic, myelocytic, and thrombocyticpoeisis
( within 4-5 days)

144. - shock in DHF-DSS follows sudden extravasation of
plasma into extravascular sites including pleural and
abdominal cavities usually with defervescence of fever
- the increase vascular permeability may be due to:
1. Increased levels of soluble tumor necrosis factor
2. Interferon-gamma
3. Activation of the complement system
- rapid, predictive reversibility of syndrome within
48 hours ( with paucity of histopathologic correlation)
suggests an inflammatory response causing vasculopathies
- the rise of levels of neutralizing antibodies correlates
with clearance of viremia

145. - asymptomatic in 80 % of infants and children
CLINICAL FEATURES:
1. Dengue Fever:
- acute febrile illness with headaches, musculoskeletal pain
and rash
- asymptomatic in 80 % of infants and children
- cannot be distinguished from other common childhood
infections
- in adults more severe and acute incubation period ( 4-7
days) of fever, chills, severe frontal headache, retroorbital
pain scarlatiniform rash develops within (3-4 days)
- virtually all cases are uncomplicated
- hepatitis frequently complicates dengue fever ( deaths
are rare )
- vertical transmission of virus to neonates where mothers
had an onset of 1o or 2o dengue fever ( 0-8 days before
delivery) resulted in acute neonatal dengue fever

146. - may occur in individuals with heterologous dengue
2. DHF-DSS:
- may occur in individuals with heterologous dengue
antibody ( possibly acquired as maternal antibody or
endogenously produced )
- hemorrhagic phenomena and hypovolemic shock due to
increased vascular permeability and plasma leakage
- clinical signs similar to DF but with defervescence within
2-7 days 
condition worsens with associated :
1. hypoprotenemia
2. thrombocytopenia
3. prolonged bleeding time
4. elevated prothrombin time

147. 
may lead to Dengue Shock Syndrome
- cyanosis, restlessness, diaphoresis, cool,
clammy skin
- with support, spontaneous resolution of vasculopathy and circulatory problem within
2-3 days with complete recovery

148. ( cont. Dengue ) Factors responsible for occurrence of DSS:
poorly understood ( ? hypersensitivity reactions ) 
secondary Dengue infection
formation of virus antibody complexes
activation of complement system
vascular dysfunction due to complement products
* due to formation of large amounts of cross-reacting
antibodies at the time of second dengue infection

149. Dengue Prevention:
- relies on public health and community-based A. aegypti
control programs to remove or destroy mosquito-breeding
sites
insecticidal fogging is considered unhelpful
in sealed houses, indoor insecticide sprays should be
effectual
vaccines:
The most advanced is a tetravalent combination
of attenuated dengue strains that is under phase
II clinical evaluation
- travelers can protect themselves by using repellents and
insecticidal sprays indoors

150. DIAGNOSIS: 1. viral isolation ( most accurate )
- most sensitive is intracebrebral inoculation of suckling mice
- successful recovery from blood only before an antibody
response develops
2. PCR
- identifies the presesnce of Dengue virus and serotypes
( used in specialized lanoratories )
3. serum IgM in dengue infection ( within 60 days ) by
a. antibody capture ELISA- preferred technique
b. indirect immunofluorescence for IgM and IgG antibodies
4. Rapid immunochromatographic test
- for dengue and JE IgM and IgG
* high sensitivity and specificity

151. CONCEPT QUESTIONS -Define: Arboviruses
- Name the major arboviruses pathoigenic to man .
The chief vectors of arboviruses include:
- Most types of illnesses caused by arboviruses include:
- What are the general characteristicsa of arboviruses?
- Activity and distribution of arboviruses closely tied to ecology of
vectors, what factors to be considered?
- Mention the epidemiologic feature of arboviruses.
- Describe the pathogenesis of arboviruse with an example to each.
- What are the clinical syndrome associated with arboviral infections?
- Mention the characters , members and mode of transmission of arbov.
- Which viruses causing hemorrhagic and pulmonary syndrome associated
with rodents?

152. What are the members of Togaviridae?
- What are the characteristic of filoviruses? mention the diseases caused .
-Define : Lassa fever, Ebola virus , Marburg HF, Dengue fever
- What are the main epidemiologic characteristics of DHF ?
- Describe the pathogenesis of DF/DHF.
- In DF/DHF, what are the causes for increased vascular permeability?
- What are the clinical feature of DF?
-Dengue shock syndrome(DSS), how its caused ?
- What are the factors responsible for occurrence of DSS?
- What are the conditions that worsens DSS if associated?
- What are the preventive measures of DF?
- Mention the methods for diagnosis of DF/ DHF.

153. NONENVELOPED SINGLE-STRANDED RNA VIRUSES: PICORNAVIRUSES AND CALICIVIRUSES
PICORNA viruses are named for their small ( pico )size
and their RNA core.
Important representatives include:
1. Enterovirus
2. Rhinovirus
3. Cardiovirus ( infects the brain and heart in humans
and other mammals)

154. Selected Characteristics of the human picornaviruses
Genus
Representative
1o Disease
Enterovirus
Poliovirus
poliomyeitis
Coxsackievirus A
Focal necrosis,myositis
Coxsackievirus B
Myocarditis of newborn
Echovirus
Aseptic meningitis,enteritis
Enterovirus 72
Hepatitis A
Rhinovirus
Common Cold
Cardiovirus
Encephalomyocarditis
Aphthovirus
Foot and Mouth Disease

155. - an acute enteroviral infection of the spinal cord that may cause
POLIOVIRUS:
- an acute enteroviral infection of the spinal cord that may cause
neuromuscular paralysis
also called infantile paralysis ( often affects small children)
Properties :
inactivated when heated at 55 degrees C for 30 minutes
purified poliovirus is inactivated by chlorine concentration of
0.1 ppm
requires primate-specific membrane receptor for infection
undergoes replication after attaching to viral receptors : serves
both as its own messenger RNA and as the source of genetic
information

156. HUMAN POLIOVIRUS

157. (poliomyelitis)

158. - respiratory droplets are only rarely involved
Poliomyelitis:
- transmission via mechanical vectors such as flies may occur
- respiratory droplets are only rarely involved
- has been virtually eliminated in North and South America
- prevalence varies in Asia, Africa, and European countries
Infection and Disease:
Ingestion of an infectious dose ( approx virions)
polioviruses adsorb to receptors of mucosal cells in oropharynx
and intestine viral multiplication ( precise
location unknown but may be mucosal epithelia or lymphoid
tissue) large numbers of viruses are shed into the
throat and feces and some leak into the blood

159. Polio
Incubation period: 1-2 weeks
4 types of infections:
a. subclinical infection ( inapparent without symptoms)
b. minor disease
c. aseptic, nonparalytic meningitis
d. paralytic disease
Most infections ( 95% ) are contained as a short-term
asymptomatic viremia
a small number of persons will develop minor disease (with
nonspecific symptoms of fever, headache, nausea, sore
throat, and myalgia )
being neurotropic, it may gain access to the CNS via the
blood-brain barrier -> infiltrate the motor neurons of
the spinal cord -> invasion of nervous tissue without
destruction causes nonparalytic meningitis

160. Paralytic Disease:
highly virulent virus + / or highly susceptible host = destruction
of nervous tissue ( various degrees of
flaccid paralysis )
- flaccid paralysis ensue over a period of a few hours to several days
- depending on the level of damage to the motor neurons of the
anterior horn of the spinal cord ( occasionally, the spinal ganglia,
cranial nerves,and motor nuclei) paralysis of the muscles of the legs
abdomen, back, intercostals, diaphragm, pectoral girdle, and bladder
may occur.
- bulbar poliomyelitis : less frequent
: disintegration of the brain stem , medulla,
cranial nerves
: autonomic cardiorespiratory regulatory
centers, palate, pharynx, and vocal cord
are affected

161. Epidemiology
- has 3 serotypes; Types 1 and 3 cause the most severe forms
of disease
- protective capsid and lack of an envelope confer chemical
stability and resistance to acid and bile detergents
SIGNIFICANCE: the virus is capable of passing thru the
gastric environment undamaged
- incidence is more pronounced during the summer and fall
in temperate
- virus is passed within the population thru food, water, hands,
and objects contaminated with feces

162. Paralytic Disease (con’t)
antibodies to poliovirus: occur locally in the intestine and tonsils
( secretory antibodies), and in the serum
One exposure confers lifelong immunity
DIAGNOSIS:
* suspected when epidemics of neuromuscular disease occurs in
the summer in temperate climates
* must be differentiated from Guillain-Barre syndrome, infant
botulism, and encephalomyelitis caused by other enteroviruses
CSF : increased leucocytes and proteins; glucose normal
2. virus can be isolated by inoculating cell cultures with stool or
throat washings in the early part of the disease
3. stage of infection demonstrated by testing serum samples for
the type and amount of antibody

164. Immune response
- Infection induces antibodies with complement-fixing and
neutralizing activities and they may be used retrospectively
for laboratory confirmation at polio infection.
- There is the usually early specific IgM response, rapidly
followed by a much longer-lasting production of specific
IgG.
- Neutralizing antibodies—IgG in the blood and IgA at
mucous surfaces—are important in protecting against
reinfection.
- However, antibody against one of the 3 serotypes does not
in general protect against the others, although there may be
some cross-protection between types 1 and 2.

165. Treatment and Control of Polio:
no specific therapy, treatment rests largely on alleviating
pain and suffering
respiratory failure may require artificial ventilation
secondary pulmonary infection as a result of impairment
of swallowing and coughing may require antibiotics
after the acute febrile phase, prompt physical therapy to
diminish crippling deformities and to retrain muscles

166. Prevention :
vaccination is the mainstay of prevention.
2 forms of vaccine currently in use:
1. Salk Vacine – inactivated poliovirus vaccine ( IPV )
2. Sabin Vaccine – oral poliovirus vaccine ( OPV )
- both vaccines are prepared from animal cell cultures and are
trivalent ( combinations of 3 serotypes )
- both vaccines are effective
in tropical countries where exposure of infants to wild virus
is common, both vaccines may be given
polio immunization must be instituted as early in life as
possible, usually four doses starting at about two months of
age
adult candidates are travelers and members of the armed
forces.

167. NONPOLIO ENTEROVIRUSES
- commonly cause transient neonatal infections
- Coxsackieviruses A and B, echoviruses, and nonpolio
enteroviruses are like polioviruses in many epidemio-
logic and infectious characteristics
- spread thru fecal contamination
- incidence is highest from late spring to early summer
in temperate climates
- 50 % to 80 % of enteroviral infections are subclinical,
and the remainder fall into the category of
“ undifferentiated febrile illness”
- initial phase of infection is intestinal after which the
virus enters the lymph, blood and disseminates to other
organs

168. COXSACKIE B

169. Coxsackievirus & Echovirus Infection
Coxsackie A virus :
- Herpangina is caused by several types of Coxsackie A virus & is not related to a
herpesvirus infection. Fever, sore throat, pain on
swallowing, anorexia, & vomiting.
The classic finding is vesicular ulcerated lesions around the soft palate & uvula

170. Herpangina

171. Coxsackievirus & Echovirus Infection
Coxsackie A virus :
- Hand-foot-and-mouth disease:
a vesicular exanthem usually caused by
coxsackievirus A16.

172. Hand-foot-and-mouth disease caused by
Coxsackie A virus.

173. Coxsackievirus & Echovirus Infection
Coxsackie B virus :
- Myocardial & pericardial infections
(The symptoms resemble those of myocardial infarction with fever.)

174. Acute Hemorrhagic Conjunctivitis:
caused by Enterovirus 70 ( responsible for tens of
millions of cases since 1969 )
a variant of coxsackie A24 causes a similar, but geographi-
cally more restricted disease
AHC first recognized in Ghana and Indonesia in 1969 and
has spread rapidly in different parts of the world ( in
Africa, some parts of Europe and Asia.)
regions of Asia where it has caused epidemics include:
Vietnam, Bangladesh, Thailand, Sri Lanka, Taiwan,
The Philippines, Samoa, and Japan
large-scale epidemics have occurred predominantly in
crowded costal areas of tropical countries during the hot,
rainy season

175. AHC:
unlike most other enterovirus infections, transmission is
primarily from fingers or fomites directly to the eye
both enterovirus 70 and coxsackie A24 can be isolated
from the conjunctiva early in the illness
highly contagious and spreads rapidly
contagion is favored by crowding and unsanitary living
conditions
reuse of water for bathing and sharing of towels are
implicated as factors contributing to spread of infection
begins abruptly, reaches its peak within 1 day
main symptoms: burning, foreign body sensation, ocular
pain, photophobia, swelling of eyelids, and watery discharge
subconjunctival hemorrhage is the most distinctive feature
of enterovirus infection ( much less with coxsackie)

176. more profuse in the young
AHC:
conjunctival edema more common in the elderly; hemorrhage
more profuse in the young
recovery is noticeable on the 2nd or 3rd day and is complete
by 10 days
Complications:
1. Keratitis occasionally persists but no permanent scarring
occurs
2. Motor paralysis similar to polio occurs in persons who have
recently recovered from AHC ( a rare occurrence consi-
dering the number of AHC cases)
* Bulbar paralysis can occur in half of the cases
* CSF abnormalities are that of aseptic meningitis

177. Treatment: Symptomatic
AHC:
Diagnosis:
- Diagnosed easily in major epidemics but may be confused with
adenovirus infection causing epidemic keratoconjunctivitis in
sporadic cases
- AHC has shorter incubation period ( 1 day) compared to 5-7 days
with epidemic keratoconjunctivitis
- Bacterial and chlamydial conjunctivitis do not cause extensive
outbreaks
Lab:
- Virus can be recovered from conjunctival swabs or scrapings of
patients with AHC
- Rising antibody titers in paired sera
Treatment: Symptomatic
Prevention: hand washing, use separate towels, sterilization of oph-
thalmologic instruments

178. CONCEPT QUESTIONS
-Show the main characteristics of human picornaviruses.
- Mention the properties of polioviruses.
- Define: poliomyelitis
- Describe infection and disease of polioviruses .
- Mention the 4 types of poliovirus infections.
-What is the paralytic poliomyelitis ?
-Mention the characters of bulbar poliomyelitis.
- Show the epidemiologic feature of poliovirus.
- The diagnosis of poliomyelitis include:
- What are the clinical feature of poliomyelitis?
- Describe the immune responses to poliovirus ionfection.
- What are the steps for the treatment of poliomyelitis?
-What are the prevention measures of poliomyelitis ?

179. NON-POLIO ENEROVIRUSES
-What are the general properties of Coxsackie & Echo viruses?
- Mention the types of infections associated with coxsackievirus A & B.
- What is acute hemorrhagic conjunctivitis(AHC) ?
- What are the complications associated with AHC ?
Coxsackieviruses incriminated as a cause of:
- What are the diagnostic methods and preventive measures of AHC?