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Mikroorganisme Penyebab Infeksi Saluran Pernafasan

Dr. Tetty Aman Nasution, M.Med.Sc

Departemen Mikrobiologi FK USU

The Respiratory Tract

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LokasiLokasi ::

• Infeksi Saluran Nafas Bagian Atas

• Infeksi Saluran Nafas Bagian Bawah

MikroorganismeMikroorganisme ::

� Bakteri

� Virus

� Jamur

Wabah yang mengancam nyawa :Wabah yang mengancam nyawa :

� SARS

� Flu Burung

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Sites of upper respiratory infections

Bacterial Upper Respiratory Infections

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• Group A beta hemolytic Streptococcus pyogenes

• Common in children 5-15 yrs old

• Inhaling droplet nuclei from active cases or healthy carriers

• Onset is usually abrupt, with chills, headache, acute throat soreness (upon swelling), nausea and vomiting

• Diagnosis by positive throat culture

• Immediate treatment needed

• 3% cases untreated cases interact with immune system and give rise to rheumatic fever

Streptococcal Pharyngitis

• Haemophilus influenzae type b, S. pneumoniae, S. aureus, H. influenzae type non-b, H. parainfluenzae

Pathogenesis :

• Inflammation and edema of the epiglottis, arytenoids, arytenoepiglottic folds, subglottic area

• Epiglottis pulled down into larynx and occludes the airway

Epiglottitis

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• Corynebacterium diphteriae

• Pseudomembrane block the airway

• Spread by respiratory droplets

• Treated with antitoxin and antibiotics

• Prevented by DPT vaccine

Diphteria

Viral Upper Respiratory Infections

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Microbial Causes of Acute Maxillary Sinusitis

PREVALENCE MEAN (RANGE)

Adults ChildrenMICROBIAL AGENT (Bacteria) (%) (%)Streptococcus pneumoniae 31 (20-35) 36Haemophilus influenzae 21 (6-26) 23

(nonencapsulated)S. pneumoniae and H. influenzae 5 (1-9) --

Anaerobes (Bacteroides, Fusobacterium, 6 (0-10) --Peptostreptococcus, Veillonella)

Staphylococcus aureus 4 (0-8) --

Streptococcus pyogenes 2 (1-3) 2Branhamella (Moraxella) catarrhalis 2 19

Gram-negative bacteria 9 (0-24) 2

Microbial Causes of Acute Maxillary Sinusitis

PREVALENCE MEAN (RANGE)

Adult ChildrenMICROBIAL AGENT(Virus) (%) (%)

Rhinovirus 15 --

Influenza virus 5 --Parainfluenza virus 3 2Adenovirus -- 2

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Viruses Associated with

Respiratory Infections

Syndrome Commonly Associated Viruses

Less Commonly Associated Viruses

Corza Rhinoviruses, Coronaviruses

Influenza and parainfluenza viruses, enteroviruses, adenoviruses

Influenza Influenza viruses Parainfluenza viruses, adenoviruses

Croup Parainfluenza viruses Influenza virus, RSV, adenoviruses

Bronchiolitis RSV Influenza and parainfluenza viruses, adenoviruses

Bronchopneumonia

Influenza virus, RSV, Adenoviruses

Parainfluenza viruses, measles, VZV, CMV

Parainfluenza Virus

• ssRNA virus

• enveloped, pleomorphic morphology

• 5 serotypes: 1, 2, 3, 4a and 4b

• No common group antigen

• Closely related to Mumps virus

(Linda Stannard, University of Cape Town, S.A.)

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Parainfluenza Virus Clinical Manifestations

• Croup (laryngotraheobroncitis) - mostcommon manifestation of parainfluenza virusinfection.

• However other viruses may induce croup e.g.influenza and RSV.

• Other conditions that may be caused byparainfluenza viruses Bronchiolitis,Pneumonia, Flu-like tracheobronchitis, andCoryza-like illnesses.

• Rhinitis, pharyngitis, bronchitis, sometimes pneumonia

• Paramyxoviruses attack the mucous membranes of the nose and throat

• Symptoms can progress to a barking cough and high-pitched, noisy respiration (stridor)

• 2 parainfluenza viruses can cause croup ( acute obstruction of the larynx)

• Inactivated by drying, increased temperature, most desinfectants.

Parainfluenza VirusClinical Manifestations

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Influenza Virus

• RNA virus, genomeconsists of 8 segments

• enveloped virus, withhaemagglutinin andneuraminidase spikes

• 3 types: A, B, and C

• Type A undergoesantigenic shift and drift.

• Type B undergoesantigenic drift only andtype C is relatively stable(Courtesy of Linda Stannard,

University of Cape Town, S.A.)

Influenza Virus

• Antigenic shift

– Changes in H and N spikes

– Probably due to genetic recombination between different strains infecting the same cell

• Antigenic drift

– Mutations in genes encoding H or N spikes

– May involve only 1 amino acid

– Allows virus to avoid mucosal IgA antibodies

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Influenza Virus• Orthomyxoviruses

• Enzyme neuraminidase, penetrate the mucus layer protecting the respiratory epithelium, budding of new virus particles from infected cells

• Tendency to undergo antigenic variations or mutations that affect viral antigens

• Inhalation of virus-containing droplets or indirect contact with infectious respiratory secretions

•Hemagglutinin (H) : attachment to host cells

•Neuraminidase (N) :release virus from cell

Influenza Virus

Figure 24.16

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Influenza VirusEpidemiology

• Pandemics - influenza A pandemics arisewhen a virus with a new haemagglutininsubtype emerges as a result of antigenic shift.

• As a result, the population has no immunityagainst the new strain. Antigenic shifts hadoccurred 3 times in the 20th century.

• Epidemics - epidemics of influenza A and Barise through more minor antigenic drifts as aresult of mutation.

Influenza VirusDiagnosis

• Viral culture - tissue culture

• Fluorescent-labeled murine monoclonal Ab - shell viral cell culture - viral Ag

• PCR

• CF - at onset and 2 weeks

4-fold-rise in Ab titre

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Influenza VirusComplications

• Bacterial superinfection

– Otitis media

– Sinusitis

– S. pneumoniae, H. influenzae, B. catarrhalis

• Guillain-Barre Syndrome

• Asthma attacks

Past Antigenic Shifts

1918 H1N1“Spanish Influenza” 20-40 million deaths

1957 H2N2“Asian Flu” 1-2 million deaths

1968 H3N2“Hong Kong Flu” 700,000 deaths

1977 H1N1 Re-emergence No pandemic

At least 15 HA subtypes and 9 NA subtypesoccur in nature.Up until 1997, only viruses of H1, H2, and H3are known to infect and cause disease inhumans.

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Avian Influenza (Flu Burung)

H5N1

• An outbreak of Avian Influenza H5N1 occurred in HongKong in 1997, 18 persons were infected of which 6 died.

• The source of the virus probably from infected chickensand the outbreak controlled by a mass slaughter ofchickens in the territory.

• All strains of the infecting virus were totally avian in originand there was no evidence of reassortment.

• However, the strains involved were highly virulent for theirnatural avian hosts.

H9N2

• Several cases of human infection with avian H9N2 virus occurred in Hong Kong and Southern China in 1999.

• The disease was mild all patients made a complete recovery & there was no evidence of reassortment

Avian Influenza (Flu Burung)

• A(H5N1) avian influenza

• No signs from person to person

• Epidemic among poultry allows more and more opportunities for person-to-person contact to occur

• Right recombination event between the H5N1 strain and a coexisting human influenza strain."

• People and equipment are responsible for spreading about from farm to farm

• Persons with symptoms cover their nose, mouth with a tissue when coughing or sneezing; making hand hygiene products, tissues available in waiting areas; containers for disposal of used tissues; masks to symptomatic patients.

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Theories Behind Antigenic Shift1. Reassortment of the H and N genes

between human and avian influenza virusesthrough a third host.

There is good evidence that this occurred inthe 1957 H2N2 and the 1968 H3N2pandemics.

2. Recycling of pre-existing strains – this probably occurred in 1977 when H1N1 re-surfaced.

3. Gradual adaptation of avian influenzaviruses to human transmission. There issome evidence that this occurred in the1918 H1N1 pandemic.

Avian Influenza (Flu Burung)Laboratory Diagnosis

• Detection of Antigen - a rapid diagnosis canbe made by the detection of influenza antigenfrom nasopharyngeal aspirates and throatwashings by IFT and ELISA

• Virus Isolation - virus may be readily isolatedfrom nasopharyngeal aspirates and throatswabs.

• Serology - a retrospective diagnosis may bemade by serology. CFT most widely used.HAI and EIA may be used to give a type-specific diagnosis

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Common cold

• Rhinoviruses the most common cause of colds

• Coronaviruses the 2nd most common cause

• Cold viruses more often spread by fomites than by close contact with infected persons

• Treatment with remedies that alleviate some symptoms

• Different combinations of interferons and other factors being explored to control rhinovirus infections

Common ColdOver 200 viruses

Virus typeSerotypes

Adenoviruses 41

Coronaviruses 2

Influenza viruses 3

Parainfluenza viruses 4

Respiratory syncytial virus 1

Rhinoviruses100+

Enteroviruses60+

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Lower respiratory tract disorders

Bacterial Lower Respiratory Infections

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Bordetella pertussis, small, aerobic, encapsulated, Gram-neg coccobacillus

• Transmitted by respiratory droplets

• Treated with antitoxin and erythromycin

• Vaccine prevents the disease

• Complications and deaths

Whooping cough or pertussis (“violent cough, cough of 100 days”)

• Classified by site of infection as lobar or bronchial

• Transmitted by respiratory droplets and carriers

• Klebsiella pneumonia is more severe than Pneumococcal pneumonia

• Klebsiella usually treated with cephalosporins

• PNC is drug of choice for Pneumococal pn.

• Mycoplasma pneumoniae causes primary atypical pneumonia.

• The disease called walking pneumonia

Pneumonia

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Mycoplasma Pneumonia

Figure 24.14

• Mycoplasma

pneumoniae: pleomorphic, wall-less bacteria

• Also called primary atypical pneumonia and walking pneumonia

• Common in children and young adults

• Diagnosis by PCR or by IgM antibodies

• 1976 war veterans attending a convention in Philadelphia, 29 deaths

• Legionella pneumophila, a weakly Gram-neg, strictly aerobic bacillus with fastidious nutritional requirements.

• Most Legionella are free living in soil or water and do not ordinarily cause disease.

• Some strains live as intracellular parasites of amoebas, Acanthamoeba, Naegleria, Hartmanella, and Echinamoeba.

Legionnaires’ disease

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• Some of these amoebas colonize wet areas.

• Legionellosis is transmitted when organisms growing in soil or water become airborne and enter patient’s lungs as an aerosol

• Air conditioners, ornamental fountains, cooling tower, shower heads, humidifiers, vaporizers in patient rooms should be regularly desinfected

• 2-10 days incubation; fever, chills, headache, diarrhea, vomiting, fluid in the lungs, pain in the chest and abdomen

•

Legionnaires’ disease

Tuberculosis

• Mycobacterium tuberculosis, Robert Koch in 1882

• White plague of Europe

• Atypical mycobacteria, M. avium-intracellulare complex (MAC) in AIDS patients.

• Straight or slightly curved rods that stain acid-fast.

• Waxes and long-chain mycolic acids in mycobacterial cell walls, difficult to Gram stain

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Tuberculosis

• Obligate aerobes sensitive to slight decreases in O2 conc., in apical or upper portions of the lungs which highly oxygenated.

• Pathogenic mycobacteria long generation time (12-18 hours), up to 8 weeks to produce a visible colony on laboratory

• Highly resistant to drying and remain viable for 6-8 months in dried sputum, sensitive to direct sunlight

Mycobacterial cell wall

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TB Transmission

• Infectious disease cause by the bacterium, Mycobacterium tuberculosis

•Spread by airborne droplets, “droplet nuclei,” 1 to 5 microns in size

•Droplet nuclei generated when a person with TB disease coughs, sneezes, speaks, or sing

•TB infection occurs when a susceptible person inhales droplet nuclei containing the bacteria becomes established in the body

Probability TB Will Be Transmitted

• Infectiousness of person with TB

• Environment in which exposure occurred

• Duration of exposure

• Virulence of the organism

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Psittacosis or parrot fever• Associated with psittacine birds, parrots, and parakeets.

• At least 130 different species of birds, including ducks, chickens, and turkeys, disease referred to ornithosis

• Chlamydia psittaci, by direct contact from birds.

• Most cases are mild and self-limiting, but some developed a serious pneumonia

• Incubation 1-2 weeks, sore throat, coughing, difficulty in breathing, headache, fever and chills.

• Diagnosis by inoculation into tissue culture

Q Fever

• 1st described in Queensland, Australia.

• Q : query, which organism caused it remained a question for a long time

• Caused by Coxiella burnetti, among the rickettsias

• Exist all over the world, especially in cattle-and sheep-raising areas.

• Transmitted via tick bites, feces, and genital secretions of infected animals

• Treatment with antibiotics

• A vaccine for workers with occupational exposure

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Q fever

Figure 24.15

Nocardiosis• Characterized by tissue lesions and abscesses

• Nocardia asteroides, aerobic, acid-fast staining, filamentous bacterium

• Found in soil and water

• By inhalation

• Primary site is the lungs, can originate in the skin and other organs

• Usually occurs in immunosuppressed patients

• Diagnosis based finding the organism in sputum or other specimens

• Sulfonamide and trimethoprim

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Viral Lower Respiratory Infections

Respiratory Syncytial Virus (RSV)

• ssRNA enveloped virus.

• belong to the genus Pneumovirus of the Paramyxovirus family.

• Considerable strain variation exists, may be classified into subgroups A and B by monoclonal sera.

• Both subgroups circulate in the community at any one time.

• Causes a sizable epidemic each year.

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Respiratory Syncytial Virus Clinical Manifestations

• Most common cause of severe lowerrespiratory tract disease in infants,responsible for 50-90% of Bronchiolitis and 5-40% of Bronchopneumonia

• Other manifestations include croup (10% ofall cases).

• In older children and adults, the symptomsare much milder: it may cause a coryza-likeillness or bronchitis.

Respiratory Syncytial Virus Infants at Risk of Severe Infection

1. Infants with congenital heart disease –

2. infants who were hospitalized within the first fewdays of life with congenital disease

3. Infants with underlying pulmonary disease -especially bronchopulmonary dysplasia, are at riskof developing prolonged infection with RSV.

4. Immunocompromized infants - children who areimmunosuppressed or have a congenitalimmunodeficiency disease may develop lowerrespiratory tract disease at any age.

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Acute Respiratory Disease

• Mild to severe

• Sore throat, cough, cold symptoms, fever, headache, and malaise

• Adenoviruses cause about 5% of ARD cases in children under 5 yrs old.

• Symptom are mild and nonspecific-stuffy nose, cough, and nasal discharge

• Adenovirus pneumonia accounts for about 10% of all childhood pneumonia and is occasionally fatal

Adenovirus

• ds DNA virus

• non-enveloped

• At least 47 serotypes are known

• classified into 6 subgenera: A to F

(Linda Stannard, University of Cape Town, S.A.)

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SARS

(Severe Acute Respiratory Syndrome)

• Coronaviridae•The coronaviruses (order Nidovirales, family Coronaviridae, genus Coronavirus) are members of a family of large, enveloped, positive-sense single-stranded RNA viruses that replicate in the cytoplasm of animal host cells

SARS

• Multiple specimens, extracts of lung and

kidney tissue by virus isolation or PCR;

bronchoalveolar lavage specimens by

virus isolation, electron microscopy and

PCR; sputum or upper respiratory tract

swab, aspirate, or wash specimens by

PCR

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Coronavirus

• ssRNA Virus

• Enveloped, pleomorphic morphology

• 2 serogroups: OC43 and 229E

• Fever with a body temperature of > 38.0°C (100.4°F), a main criteria in the current WHO case definition for suspected or probable SARS.

• Sputum production, sore throat, coryza, nausea, and vomiting are less common

• Ribavirin, a "broad spectrum" agent, which is active against various RNA viruses which has been used extensively in SARS patients

• There are currently no commercial veterinary vaccines to prevent respiratory coronavirus infections, except for infectious bronchitis virus infections in chickens.

SARS

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Fungal Respiratory Infections

Coccidioides immitis, soil fungus

• Inhaling dust particles with fungal spores

• Dogs, cattle, sheep, and wild rodents deposit spores in feces, easily become airborne

• An acute, self limiting infection.

• In disseminated disease, therapy needed

• Amphotericin B the most effective agent

Coccidioidomycosis

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Coccidioidomycosis

Figure 24.19

• Coccidioides immitis

Histoplasmosis

• Histoplasma capsulatum, soil fungus

• Thrives in soil mixed with feces and especially in chicken houses and in caves containing bat feces

• Enters the body by the inhalation of conidia

• Diagnosis by microscopic identification

• Supportive therapy and amphotericin B

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Histoplasmosis

Figure 24.17

• Histoplasma capsulatum, dimorphic fungus

(a) 37˚ (a) >35˚

Cryptococcosis

• Filobasidiella (Cryptococcus) neoformans, budding, encapsulated yeast

• Through the skin, nose or mouth

• Thrives in pigeon droppings

• Birds do not suffer from cryptococcosis, but disseminate the opportunistic yeast

• Mild symptoms can became systemic in large quantities of the spores inhaled by debilitated patients

• Flucytosine and amphotericin B

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Pneumocystis pneumonia

• Pneumocystis carinii, an opportunistic fungus

• Occurs in infants, elderly and the immunocompromised

• Invade cell of the lungs and causes alveolar septa to thicken and the epithelium to rupture

• Can spread to other organs and cause extrapulmonary infections

• Diagnosis by finding organisms in biopsied lung tissue or bronchial lavage

• Combination of trimethoprim and sulfametoxazole

Pneumocystis

Figure 24.21

The mature cyst contains 8 intracystic bodies.

The cyst ruptures, releasing the bodies.

The bodies develop into trophozoites.

1

2

3The trophozoites divide.

4

Each trophozoite develops into a mature cyst.

5

Cyst

Intracystic bodies

Trophozoite

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Aspergillosis

• Farmer’s lung disease

• Aspergillus fumigatus or A. flavus occurs in the lungs

• Fungal spores inhaled from piles of rotting vegetation or compost may cause clinical allergy such as asthma, or invasive infection in the lower respiratory tract.

• Fungus ball or aspergilloma may be seen on X rays

•

Aspergillosis

• Obstruct gas exchange, cause death by asphyxiation

• Aspergillus growing in the lungs may serve as antigens that trigger chronic asthma

• Immunosuppresed, immunodeficient (AIDS), diabetic patients are at higher than normal risk

• Amphotericin B

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• Aspergillus

• Rhizopus

• Mucor

Opportunistic fungi involved in respiratory disease:

Mucor rouxii

Figure 12.2b, 12.4

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