Transcript Viral Respiratory Tract Infection

Viral Respiratory Tract
Infection-Part 1
Prof. Dr Asem Shehabi
Faculty of Medicine, University of
Jordan
General Respiratory diseases
Viral and bacterial Respiratory infections are
common.. Sore throat, Colds, Sinusitis, Otitis media
Pneumonia .. All ages.. More Infant & Children.
Most infections are mild, self- limiting and confined to
the upper respiratory tract (URT).. Less to Lower
respiratory tract ( LRT).. Pneumonia
Most RT infections are caused by viruses- transmitted
by cough, air droplets-dust (1000-10000 virus
particles), saliva, close contacts ..Some viruses
causes Outbreak diseases.
URT infections may spread to lung, blood cause more
severe infections pneumonia, sepsis meningitis.
Upper Respiratory Diseases-1
1. Colds: watery to mucoid discharge/purulent nasal
discharge .. Often preceded by a sore throat &
accompanied by mild fever .. viral infection may be
followed by opportunistic bacterial infection of lungs.
2. Pharyngitis (sore throat)
Generalized erythema, edema & mild inflammation of
pharynx mucosa..often associated with tonsils &
fever, 90% caused by viruses.
3. Tonsilitis
Local infection of tonsils ..red, swollen with sever
inflammation /exudates on the mucosal surface, fever,
Bacterial agents more common than viruses.
4. Sinusitis & Otitis Media
Painful inflammatory conditions of sinuses & middle
ear.. More bacterial infections than viruses.. Mixed
infection mostly children.
5. Influenza and Influenza-like viruses
Start in upper respiratory tract.. High fever, myalgia,
sore throat, headache, prostration - usually not much
nasal discharge compared to a common cold caused
by other viruses.
Lower Respiratory
1- Laryngo-Tracheo Bronchitis/Laryngitis (Croup)
An acute viral inflammation of larynx and trachea in
infants/small children..less adults.. Often manifested
by fever, hoarseness, cough, Breath difficulty, can be
fatal without treatment.
The following diseases caused by Bacteria/
Viruses or both agents
2- Acute Bronchitis
Inflammation of bronchi, accompanied by fever,
cough, wheezing and noisy chest..All ages
3- Acute Bronchiolitis
Inflammation of terminal bronchioles.. fever, rapid
respiration, exhausting cough and wheezing.. Mostly
in small children.. features can be seen on x-ray.. May
develops into pneumonia.
4-Pneumonia & Bronchopneumonia
Acute inflammation of lung accompanied by high
fever, edema, general weakness, cyanosis.. Can be
life-threatening.. Bacterial infection more than Viruses.
Viral Respiratory Pathogens
Orthomyxovirus: Influenza virus
•
Distribution: Found in humans, aquatic birds, swine,
horses, whales.. Mostly mixed influenza virus types A
+ C found in animals & Birds.
• 3 Genotypes A, B, C .. First isolated & characterized
in tissue culture by electron microscope in 1933
Epidemiology: Type A & B are mostly causing human
flu epidemics/ Pandemic.. because of virus antigenic
variation.. Highly contagious.. target mucus of upper
respiratory tract.. causing first mild sore throat, cough,
high fever ( 39-40C) , fatigue, headache, chills,
running nose.. Infection later may spread to trachea
and lung..Hemorrhagic & necrotizing tracheobronchitis.. bacterial Pneumonia..No viremia.
Influenza Virus Structure
SS-ve sense RNA, 8 segments, helical
nucleocapsid, surrounded by Envelope..
composed of Lipid bilayer .. acquired by
budding through cell plasma membrane.
Virus surface has 2 spike types projected from
Envelop, composed of Glycoproteins (HA, NA)..
Act as specific antigens during mucosal
infection process.
Envelop has 2 M-protein structures: M1
membrane protein, M2 protein-proton ion
channel.. projects through the envelop : Both
control attachment & pH for entrance the virus
through cell membrane to endosomal host cells.
Influenza virus-SS-ve RNA
2/
• Virus attachment to ciliated RT epithelial cells.. with
help (HA)& (NA) .. Attaches to specific receptor in
respiratory mucosal cell membrane.. Virus enter by
endoctyoses.. Start producing essential structures in
cytoplasm & complete virus particles in nucleus
cell..transferred to cell membrane and released by
budding
• Antigenic subtypes: 15 HA, 9 NA..Only HA 1-3
types associated with majority human epidemic
Influenza ..Only NA 1-2 types infect mostly humans.
NA destroys H-receptors bond within host mucosal
cells.. Allow virons to inter & infected cell, later help to
release new developed viruses attached to cell
membranes.
3/ Influenza genetic mutation
• Influenza Type A occurs only in respiratory tract
human, water birds & pigs ..Influenza A+ B types are
found occasionally together in large in epidemics.
• Mutation in Type A.
• 1-Antigenic Drift : Minor mutations in the RNA
segments.. Change slightly virus antigens in (H1N1)..
Develop new subtype strain.. result in decreased
recognition by the host immune system.
2-Antigenic Shift: Sudden major source of antigenic
variation due to re-assortment of RNA segments.. It
leads to changes of geno-subtype of the envelope
glycoproteins.. New genotype. Example:
Example: H1N1 changed to H2N2 .. or Other
genotype variations.
Pandemic Outbreaks Influenza A
• 1918, H1N1.. Swine-like Spanish Influenza..( Killed
20-40 millions)..mostly in Europen countries
1957-H2N2 .. Asia –Influenza..Few millions deaths,
World-wide .. Recorded in Jordan & Arab countries.
1968-H3N2.. Hong Kong influenza..1-2 millions,
World-wide
Last 50-year: mostly H1N1+H3N2 ..Each year about
1 billion infected cases.. 2-3 million deaths.
1997 : Outbreak Avian Influenza strain..H5N1..First
infect Birds, Ducks, Chickens.. spread to humans..
caused high mortality..Rare Human to Human
infection. Other avian genotypes ( H7N2, H7H7),
Large outbreaks in Poultry in South-East Asia..Caused
thousands human infection cases.. few deaths.
Influenza Virus B & C
Influenza virus-B: Infect Only human.. Less common
than type A.. Occasionally mixed infection (A & B)
No antigenic shift..Clinical cases similar to Influenza
virus A.. but less associated with sever complications
& death. No animal reservoir.
Influenza virus C: Found mostly in animal.. mostly
Pigs in China.. rarely in other countries.. human
sporadic infection cases.. Not involved in epidemic..
Mostly young children..mild or asymptomatic upper
respiratory tract infection.
Outbreak of Swine Flu virus.. 2009/New Mexico..First
human cases transmitted directly from swines to
human..later human to human spread.. Similar to AH1N1 type..Cased millions human cases worldwide.
Influenza General Features
Virus Stable at 0-4 C.. for Weeks in moist
environment, clothes associated with organic
material..Survive few min-hrs in organic
dust,saliva, RT droplets..Room-temp, Moistcold temperature, killed rapidly > 45 C.
Clinical Symptoms: lncubation Period 2-3 days ..
Patients highly infectious during clinical illness and
after for one week..No permanent carriers
Complications: Secondary bacterial pneumonia,
Myocarditis, Encephalomyelitis.. Mostly elderly
persons with underlying diseases.. CardiovascularLung disease, Immuno-suppressed.. High mortality.
2/
Immunity: Presence of both specific humoral
antibodies (IgA & IgG), increase secretion of local
Cytotoxic killers & T-cells, Interferons may prevent
developing of acute and severe infection.
Specific viral antibody against haemagglutinin prevent
attachment.. reinfection within 6-12 months
Vaccination: Consisting of purified viral HA & NA
antigens..HA antigens is more important for
production neutralizing antibodies against each
Infuenza virus types.
Influenza Vaccine includes (A+B types): up 80%,
Protection.. Repeat each Year (October-December)
High risk Persons & persons >50-year.. Antiviral
treatment has limited importance.
PARAMYXOVIRUSES Group
• Causes RT diseases in human & animals ..infection
starts in respiratory tract mucosa.
• General Morphology: All have similar virus size,
Envelope , SS-ve RNA genome not segmented..
Nucleocapsid ( RNA+Neuceloprotein)..Complex spikes
All Paramyxo viruses replicate in cytoplasm.. Virions
released by budding.
All Paramyxoviruses are unstable outside body,
environment..surviving only few hours on
environmental surfaces..is readily inactivated with
soap, disinfection agents, water, Temp. above 50 C.
Similar virus structures
• 1-Parainfluenza virus & 2-Mumps virus have
similar virus structure.. Envelope contains (NA
& HA on same spikes).. Other spikes carry MProtein +fusion F-protein.
• Newcastle disease virus.. highly contagious,
causes poultry fatal respiratory disease..Rarely
causes human Influenza-like disease.
•
1-Para-influenzavirus
Causes common cold / Group, 4 Serotypes, infects
only Human.. Worldwide Distribution.. All Seasons..
Associated With 10% of Common URT & Lower RT
Infections..Type-3 is more common & often associated
with bronchiolitis and pneumonia.
Incub. Period:1-7 days.. Mostly Mild Flu-like.
Infection all ages.. More severe in Infants/Jung
Children.. Broncholitis or Laryngotracheo-bronchitis,
fever, dry cough, rare running nose.. Rare respiratory
distress & bronchial obstruction.. Like Asthma.
Short /Partial Immunity.. IgA more important for protection than
other humoral antibodies.. Re-infection is Common in all ages..
Rare Complications.. No Vaccine or antiviral treatment
2- Mumpsvirus
Only one Virus Type.. Children starts as mild Acute
Respiratory Infection.. Flu-like/ Sore throat,. Highly
contagious, Droplet infection..Mostly Children..6 months- 12
Years..Worldwide.. common in Winter-Spring months.
Clinical features: Incubation 2-3 Weeks, Virus shed in Saliva,
RT- Secretions, Fever, Malaise, Running nose, conjunctivitis..
Inflammation & Swelling Salivary glands, Parotid Gland
(Parotitis).. Few Days.. Majority mild infection..recovery within
days.
Complications: About 10% develop Aseptic Meningitis..Less
Encephalitis.. Complication: Arthritis, Nephritis, Pancreatitis,
more sever in children with malnutrition.. Causing deafness,
high mortality.
Infection after puberty.. Painful inflammation testicles (Orchitis)
Less Ovary Inflammation (Oopheritis) .. Rare causes sterility
• Permanent immunity following natural infection..
Humoral /Cell-mediated..Mostly IgM, Live-long.
Vaccination: Live-Attenuated.. Measls-Mumps-Rubella
(MMR).. 9-12 Months, Booster vaccine in elementary
school.
3- Measles/Rebuola
One major virus serotype.. HA surface antigens +
hemolysin activity + F-protein on the same spikes..
infect only human..Children
Infection starts via RT droplets.. Virus multiplies first in
RT mucosa.. Incubation 1-2 Weeks.. Virus spread to
regional lymph tissue.. causing Primary viremia.. Later
spread to reticuloendothelial system.. Secondary
viremia/ Leukopenia.. Later virus disseminate to skin.
Clinical Features: Most cases flu-like, Mild sore throat,
Mild /High Fever, Running Nose, conjunctivitis, Cough,
Intensive skin rash..Face, Trunk, Limbs.. Most rash
disappear with recovery after 1-Week..
Few common asymptomatic cases (5%).. mild skin
rash and fever.
Measles Skin Rush
Measles/ -2
Complications: Bronchitis, Bronchopneumonia with
diarrhea, stomatitis.. Koplick’s spots (small irregular,
red spots with a minute bluish white in the center on
the buccal mucosa near molar teeth.. Otitis media,
Enteritis, Encephalitis.. Conjunctivitis/Corneal
Ulceration.. Blindness.
Post-measles encephalitis.. Rare multiple sclerosis
after many years..giant cell pneumonia developed in
infected adults.
High Fatality among children with malnutrition (< 12
years), Vitamin A Deficiency, most developing &
tropical countries.. Mortality up 15%.
Permanent Immunity.. After natural infection or MMRVaccination (Mumps-Measles-Rubella) .. First shot
age around 1-year,Second 4-5 years, Highly
protective
4-Human respiratory syncytial virus
• RSV is the most common virus that causes high &
lower respiratory tract infections.. more bronchitis in
infants 6-week to less than 2-year.
• Infants under age 1 month may have more severe
lung symptoms and often have the most trouble
breathing.
• Older children than 2-year usually have only mild,
cold-like symptoms, such as cough, stuffy nose, or
low-grade fever.
• Infection in adults is rare.. associated with sever RT
lung disease, asthma, bacterial pneumonia in elderly
persons with chronic diseases.
4- Pneumovirus Group: Respiratory Syncytial
Virus (RSV) & Human metapneumovirus
(hMPV) Both are similar in structures.. have
only a larger surface Gylcoproteins acts like HA
antigens + F-protein
F protein spikes induce fusion & syncytia in
infected cells & tissue culture in vitro
Metapneumovirus
2/
•
RSV often spreads very rapidly in crowded
households and day care centers. The virus can
survive for a half hour to 5 hours on hands,
clothes..More resistant than other RT viruses
Symptoms vary and differ with age. They usually
appear 4 - 6 days after coming in contact with the
virus.
• Outbreaks of RSV infections most often begin in the
fall to continue to spring months..Infection more
acquired nurseries & children hospitals.
• RSV may cause high fatality infections in immunocompromised, bone marrow transplant patients.
• There is still no RSV Vaccine.. Only support therapy
Human Metapneumovirus (HMPV)
HMPV much similar to RSV.. Produces RSV-like
illnesses in infant & young children, ranging from
upper respiratory tract disease to few percentage
severe bronchiolitis and pneumonia.. Easily spread
between Jung children.. Mixed with RSA..Less adults
Serological studies showed that by the age of five
years all children will be exposed to hMPV .This new
discovered virus (2001) has been circulating in
humans for at least the last 50 years.
HMPV may cause severe lower respiratory tract
diseases in high-risk persons.. All ages including
children.. No vaccine, only supportive therapy