RESPIRATORY TRACT INFECTIONS

Department of MicrobiologyFaculty of MedicineBrawijaya University

The Respiratory tract Most common entry point for infections Pathogens that enter the respiratory

system can infect other parts of the body Upper respiratory tract :

nose, nasal cavity, sinuses, throat and associated structures such as the middle ear and auditory tube

Lower respiratory tract Trachea, bronchi, bronchioles, and alveoli

in the lungs

Protective Mechanisms

Normal flora: Commensal organisms Limited to the upper tract can include

pathogenic microorganisms Mostly Gram positive or anaerobic Microbial antagonist (competition) The lower respiratory system is usually sterile

because of the action the ciliary escalator

Clearance of particles and organisms from the respiratory tract

Cilia and microvilli move particles up to the throat where they are swallowed.

Alveolar macrophages migrate and engulf particles and bacteria in the alveoli deep in the lungs.

Protective Mechanisms

Other Protective Mechanisms

Nasal hair, nasal turbinates Mucus Involuntary responses (coughing) Secretory IgA Immunocompetent cells

Microbial Diseases of The Upper Respiratory System Specific areas of the upper respiratory

system can become infected to produce pharyngitis, laryngitis, tonsilitis, sinusitis and epiglottitis

These infections may be caused by several bacteria and viruses, often in combination

Bacterial Diseases of The Upper Respiratory System Streptococcal Pharyngitis (Strep Throat) Scarlet Fever Otitis Media Diphteria

Streptococcal Pharyngitis (Strep Throat) This infection is caused by group A beta-

hemolytic streptococci (Streptococcus pyogenes)

Gram positive cocci, katalase : negative

Streptococcus pyogenes Capsule -resistant to

phagocytosis Enzymes damage host

cells M protein adhesin

The M protein has many antigenic varietiesand thus, different strain of S.pyogenes cause repeat infections

Strep Throat

Fever Tonsillitis Enlarged lymph

nodes Middle-ear infection

Treatment :

Antibiotic Penicillin

Scarlet Fever

Strep throat, caused by an erythrogenic toxin-producing S.pyogenes, result in Scarlet Fever

S.pyogenes produces erythrogenic toxin when lysogenized by a phage

Symptoms include a red rash, high fever, and a red, enlarge tongue (strawberry tongue)

Scarlet FeverCaused by ErythrogenicToxin secreted by S. pyogenes

Scarlet Fever

The erythrogenic toxin is coded by a genelysogenic bacteriophage within the genome of S. pyogenes

Rash is an inflammatory reaction to the toxin

Infected Middle Ear(otitis media)

Otitis Media

Can occur as a complication of nose and throat infections

Pus accumulation causes pressure on the eardrum

Bacterial causes include : Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus

Diphtheria

Diphtheria

Caused by Corynebacterium diphtheriae Transmitted by droplets or fomites Infects the upper respiratory tract Begins with severe sore throat, low-grade

fever and swollen lymph nodes or with skin rash, 1-6 days after infection

Corynebacterium diphtheriae Aerobic Gram + bacillus,

club-shaped morphology, metachromatic granules, form V and Y-shaped figures

Exotoxin inhibits protein synthesis of cells to which it binds, and heart, kidney, or nerve damage may result

Destroyed cells and WBC form "pseudomembrane" which blocks airways

Corynebacterium diphtheriae

To produce exotoxin,

C. diphtheriae must be infected with a bacteriophage carrying the toxin gene

An “AB” toxin

B = binding subunit A = active subunit

which binds to and inhibits a eucaryotic ribosomal translation factor

Vaccine is diphtheria toxoid

Diphtheria

Diphtheria

Laboratory diagnosis : isolation of the bacteria and the appearance of growth on differential media, ELEK test, PCR for detection tox gene

Antitoxin must be administered to neutralize the toxin, and antibiotics can stop growth of bacteria

Routine immunization diphtheria toxoid in the DTaP vaccine

Slow –healing skin ulcerations are characteristic of cutaneous diphtheria

Viral Diseases of The Upper Respiratory SystemTHE COMMON COLD Any one of approximately 200 different viruses can

cause the common cold; Rhinoviruses cause about 50% of all, Coronaviruses 15 – 20 %. In about 40% of cases no causative agent can be identified

Symptoms include sneezing, nasal secretions, and congestion

Sinus infections, lower respiratory tract infections, laryngitis, and otitis media can occur as complication

THE COMMON COLD Colds are most often transmitted by indirect contact Rhinovirus grow best slightly below body temperature The incidence of colds increases during cold weather,

possibly because increased interpersonal indoor contact or physiological changes

Antibodies are produced against the specific viruses

Microbial Diseases of The Lower Respiratory Tract Many of the same microorganisms that

infect the upper respiratory system also infect the lower respiratory system

Diseases of the lower respiratory include bronchitis and pneumonia

Bacterial, viral and fungal infection can cause Inflammation of the lung with fluid filled alveoli

Bacterial Diseases of The Lower Respiratory System Bacterial Pneumonias Pertussis (Whooping Cough) Tuberculosis (module) Melioidosis

Bacterial Pneumonias

Typical Pneumonia is caused by Streptococcus pneumoniae

(= Diplococcus pneumoniae = Pneumococcus)

Atypical Pneumonias are caused by other microorganisms

Pneumococcal Pneumonia

Pneumococcal Pneumonia

Is caused by encapsulated S.pneumoniae The bacteria can be identified by the production

of alpha hemolysin, inhibition by optochin, bile solubility, and through serological test

Symptoms are fever, breathing difficulty, chest pain, and rust-colored sputum

Treatment : penicillin, fluoroquinolones Prevention : pneumococcal vaccine consist of

23 serotypes of S.pneumoniae

Haemophilus influenzae Pneumonia H.influenzae is a gram-negative coccobacil Alcoholism, poor nutrition, cancer, and diabetes

are predisposing factors for H.influenzae Treatment : 2nd generation of cephalosporins

that are resistant to beta-lactamases produced by many H.influenzastrains

Mycoplasmal Pneumonia

Mycoplasma pneumoniae causes mycoplasmal pneumonia; it is an endemic disease

The mycoplasmas, which do not have cell walls, do not grow under the condition normally used to recover most bacterial pathogens

M.pneumoniae produces small “fried egg” colonies after two weeks incubation on enriched media containing horse serum and yeast extract

Diagnosis is by PCR or serological test Treatment : tetracycline

Legionellosis

This disease is caused by aerobic gram-negative rod Legionella pneumophila

The bacterium can grow in water, such as air-conditioning cooling towers, and then disseminated in the air

This pneumonia does not appear to be transmitted from person to person

Bacterial culture, FA test, and DNA probes are used for laboratory diagnosis

Treatment : Erythromycin

Psittacosis (Ornithosis)

The term “psittacosis” is applied to the human Chlamydia psittaci disease acquired from contact with birds and also the infection of psittacin birds (parrots,parakeets,etc)

Elementary bodies allow the bacteria to survive outside a host

Commercial bird handlers are most susceptible to this disease

The bacteria are isolated in embryonated eggs, mice, or cell culture. Identification is based on FA staining

Treatment : tetracyclines

Chlamydial Pneumonia

Chlamydia pneumoniae, causes pneumonia; it is transmitted from person to person

C.pneumoniae produces round,dense, glycogen-negative inclusion that are sulfonamide-resistant

The elementary bodies some time have a pear-shaped appearance

Suggesting that C.pneumoniae associated with atherosclerotic coronary artery and cvd

Tetracycline is used for treatment

Chlamydia pneumoniae

Q Fever

Obligately parasitic, intracellular Coxiella burnetii causes Q Fever

The disease is usually transmitted to humans through unpasteurized milk or inhalation of aerosols in dairy barns

Mild respiratory disease lasting 1 – 2 weeks; occasional complication such as endocarditis occur

Treatment : doxycycline and chloroquin

Melioidosis Melioidosis is caused by

Burkholderia pseudomallei, a gram-negative rod formerly placed in the genus of Pseudomonas

Melioidosis is transmitted by inhalation, ingestion, or through puncture wounds

Symptoms include pneumonia, sepsis, and encephalitis

Most common in Southeast Asia and northern Australia

Treatment : Ceftazidime

Pertussis (Whooping Cough)

Pertussis is caused by Bordetella pertussis B.pertussis is a small, obligately aerobic gram-

negative coccobacillus The virulent strain posses a capsule The bacteria attach specifically to ciliated cells in

the trachea, first impeding their ciliary action and then progressively destroying the cells

The filamentous hemagglutinin mediates adhesion to ciliated epithelial cells

Pertussis (Whooping Cough)

B.pertussis produce several toxins. The tracheal toxin damage to the ciliated cells, pertussis toxin blood stream and associated with systemic symptoms of the disease

The initial stage of pertussis resemble a cold and is called catarrhal stage

The paroxismal (second) stage deep cough The convalescence stage can last for months Regular immunization decreases the incidence of

pertussis (DTaP) Treatment : erythromycin

Viral diseases of The Lower Respiratory System

VIRAL PNEUMONIA Viral pneumonia can occur as a

complication of influenza, measles, or even chickenpox

The etiologies are not usually identified in a clinical laboratory because of the difficulty in isolating an identifying viruses

Respiratory Syncytial Virus (RSV)

Respiratory syncytial virus is probably the most common cause of viral respiratory disease in infants

RSV is an RNA virus, member of Paramyxoviridae family, genus Pneumovirus

RSV replication occur initially in epithelial cells of the nasopharynx spread into the lower repiratory tract and cause bronchiolitis and pneumonia

The symptoms are coughing and wheezing that last for more than a week

The most recent approved treatment : humanized monoclonal antibody, Palivizumab (Synagis)

BRONCHIOLITIS

RSV

Influenza (Flu)

History of influenza

412 BC - first mentioned by Hippocrates

1580 - first pandemic described

1580-1900 - 28 pandemics

Pandemic influenza in the 20th Century

1920 1940 1960 1980 2000

H1N1 H2N2 H3N2

1918 “Spanish Flu” 1957 “Asian Flu” 1968 “Hong Kong Flu”

20-40 million deaths 1 million deaths 1 million deaths

Influenza Virus

Family Orthomyxoviridae

Three main types Type A

Multiple species

Type B Humans

Type C Humans and swine

15 HA and 9 NA for influenza A All in aquatic birds

Hemagglutinin (HA) Function: Sites for attachment

to infect host cells Neuraminidase (NA)

Function: Remove neuraminic acid from mucin and release from cell

Antigenic drift Changes in proteins by genetic point

mutation & selection Immune response no longer protects

fully Ongoing and basis for change in

vaccine each year

Antigenic shift Changes in proteins through genetic

reassortment Produces different viruses not covered

by annual vaccine pre-existing antibodies do not protect may get pandemics

Influenza A Virus

AGE SHIFTS IN MORTALITY

Concept of “The Doctrine of Original Antigenic Sin,” by Thomas Francis (1960) - immune response is greatest to antigens to which first exposure occurred in childhood.

Persons born before 1957 who were exposed in childhood to influenza A (H1N1) viruses might be better protected against this viral subtype than those who were first exposed to other influenza A subtypes, H2N2 and H3N2, at a later date .

Ecology of Influenza Virus A

Avian InfluenzaAvian Influenza is an infection caused by avian (bird)

influenza (flu) virusesFlu viruses occur naturally among birds worldwide Wild birds carry the viruses in their intestines, but usually

do not get sick Easily transmitted to domesticated birds like chickens,

ducks, and turkeys and usually acquire them by coming in contact with contaminated excretions—they usually die.

May be transmitted to other speciesMay mutate to cause human to human infections

>300 million domestic poultry culled

186 human cases/ 105 fatalities

24 March 06

REASSORTMENT

α2-3 α2-6Sebaran reseptor Sebaran reseptor αα2-3 atau 2-3 atau αα2-6 2-6 sialic acidssialic acids pada saluran pada saluran

pernafasan manusiapernafasan manusiaInfluenza virus Receptors in Human air way, Nature vol. 440, 23 March 2006

f. Bronchiole g. Alveolus

c. Pharynx

e. Bronchusd. Trachea

b. Paranasal sinus

a b

c

d

e

f g

Novel Influenza A (H1N1) 2009 Virus SWINE FLU

New strain of A (H1N1) Not previously detected in swine or human Unusual mix of genetic segments including of swine, avian

and human influenza viruses Originated from pigs and at some point of time transmitted

to human Cases began to appear from 17th March’09 in Mexico with

human – to – human transmission No cases in swine population and no infections from pork.

Pigs are responsible only for mutation of virus.

PIG THE CREATOR

Treatment & Prevention

Amantadine and rimantadine are effective prophylactic and curative drugs against Influenza virus A

The NA inhibitors zanamivir and oseltamivir were approved in 1999 for tx both influenza A and B

Multivalent vaccines are available for the eldery and other high-risk group

Fungal Diseases of The Lower Respiratory System Fungal spores are easily inhale ; they may

germinate in the lower respiratory tract

The incidence of fungal diseases has been increaseing in recent years

Histoplasmosis Histoplasma capsulatum

causes a subclinical respiratory infection that only occasionally progresses to severe, generalized disease

The disease is acquired by inhalation of airborne conidia

Isolation of the fungus or identification in tissues sample is necessasry for diagnosis

Treatment : Ampotericin B

Coccidioidomycosis Inhalation of the airborne

arthroconidia of Coccidioides immitis can result Coccidioidomycosis

Most cases are subclinical, but when there are predisposing factors such as fatigue and poor nutrition, a progressive disease resembling tuberculosis can result fever, coughing, weight loss; occasionally fatal

Treatment : Ampotericicn B

Pneumocystis Pneumonia Pneumocystis jeroveci

(formerly P.carinii) is sometimes found in healthy human lung

Pneumonia; a common serious complication of AIDS

Treatment : Co-trimoxazole

Blastomycosis (North American Blastomycosis) Blastomyces dermatitidis is

the causative agent of blastomycosis

The infection begins in the lungs and can spread to cause extensive abcesses

Treatment : Amphotericin B

Aspergillosis

Many other opportunistic fungi may cause

respiratory disease

Aspergillus fumigatus can cause: Allergic bronchopulmonary aspergillosis

Aspergilloma: in patients with pre-existing

lung disease mass of hyphae produce fungus ball

Disseminated aspergillosis

Aspergillosis