1. Atypical pneumonia 1938, H.A.Reimann,
atypical pneumonia : not caused by influenza virus, psittacosis
different from other pneumonia
Causes of Community-Acquired Atypical Pneumonia
Mycoplasma
M.pneumoniae
Respiratory tract virus
Influenza, adenovirus, RSV, parainfluenza virus
Other viral agents
Varicella-zoster, measles, EBV
Rickettsia
C. burnetii (Q fever)
Chlamydia
C.psittaci (psittacosis), C.pneumoniae
Bacteria
Legionella, F.tularensis, Y.pestis, B.anthracis
Fungi
Histoplasma, Blastomyces, Coccidioides
From Fishman’s pulmonary diseases and disorders. 3rd Ed. Morton NS.

2. Nonzoonotic atypical pneumonia (not spread from animal to human)
Mycoplasma pneumonia (M.pneumoniae)
Legionnaires’ diseases (Legionella species)
Chlamydia pneumonia (Chlamydia pneumoniae)
Zoonotic atypical pneumonia (spread from animal to human)
Psittacosis(Chlamydia psittaci)
Q fever (Coxiella burnetii)
Tularemia (Francisella tularensis)

3. Mycoplasma infection Pathogenesis
Smallest free living organism( nm)
Lack of cell wall : no Gram staining, resistant to -lactam
M.pneumoniae
M.hominis
Ureaplasma urealyticum : urinary calculi
Pathogenesis
Adhesion to host cell  induction of ciliostasis
Non-specific stimulation of B lymphocyte
 trigger autoAb
 reactive with brain, heart, muscle, erythrocyte I Ag
IgM autoAb(cold agglutinins)
 agglutinate human erythrocyte at 4℃

4. Mycoplasma pneumonia Epidemiology 10-20% of all pneumonia
Mycoplasma infection
Mycoplasma pneumonia
Epidemiology
10-20% of all pneumonia
Common causes of tracheobronchitis, bronchiolitis, pharyngitis
Symptoms persist for weeks or month
Spread by aerosol from person to person
Incubation period 1-3weeks
Common misconception that M.pneumoniae disease is rare among the very young and among older adults has led to a failure of physicians even to consider this conditon in the differential diagnosis.

5. Clinical Features Tracheobronchitis is the most frequent.
Mycoplasma pneumonia
Clinical Features
Tracheobronchitis is the most frequent.
Primary cause of “walking” or “atypical” pneumonia(3-10%).
Sore throat, headache, chills, coryza, general malaise(rigors very rare)
Sometimes myringitis(5%), otitis
Lung abscesses, pneumatoceles, extensive lobar consolidation, respiratory distress and pleural effusion(20%) may develop.
<P/E>
No findings on chest auscultation even if pneumonia is present
Rales, wheeze present later
Sinus tenderness, pharyngeal erythema, erythema or bulla of tympanic membrane, nonprominent cervical adenopathy

6. Extrapulmonary Complication
Mycoplasma pneumonia
Extrapulmonary Complication
⑴ Hemolytic anemia
antibodies to I Ag on erythrocyte membrane
 cold agglutinin response(60%)
positive Coombs’ test, reticulocytosis
⑵ Mucocutaneous lesions(25%)
erythematous maculopapular and vesicular exanthems
ulcerative stomatitis, conjunctivitis
⑶ Gastrointestinal symptoms(25%)
nausea, vomiting(common), pancreatitis(rare)
⑷ CNS(0.1%)
meningoencephalitis, aseptic meningitis, encephalitis,
ascending paralysis, transverse myelitis
 slow recovery, permanent neurologic deficit sometimes
⑸ Rheumatologic symptoms
arthralgia(common), actual arthritis(rare)
⑹ Cardiac involvement(rare)
myopericarditis, hemopericardium, CHF, complete heart block

7. Laboratory Abnormalities
Mycoplasma pneumonia
Laboratory Abnormalities
① Routine lab is usually normal.
Thrombocytosis
Leukocytosis(1/4)
ESR(1/3)
② Subclinical hemolytic anemia
positive Coombs’ test , reticulocytosis
Chest X-ray
① Peribronchial pneumonia : most common
thickened bronchial shadow
streaks of interstitial infiltration
atelectasis
② Pleural effusion(20%)
③ Nodular infiltration
④ Hilar adenopathy
uncommon

8. Mycoplasma pneumonia
Diagnosis
There are no distinguishing clinical or radiologic manifestations that allow a secure diagnosis of mycoplasma pneumonia versus other causes of atypical pneumonia such as chlamydia or legionella.
⑴ Serologic test (IgM and IgG antibody to M.pneumoniae by ELISA or CF test)
① A fourfold or greater increase in titer in paired sera
② A single titer of greater than or equal to 1:32
* Antibody titers rise 7-10 days after infection and peak at 3-4 weeks
⑵ Cold agglutinin test : neither sensitive nor specific for M.pneumoniae
⑶ Antigen capture-enzyme immunoassay (Ag-EIA)
⑷ Direct PCR
⑸ Isolation of M.pneumoniae

9. Treatment of Mycoplasma Pneumonia
No rapid way to make the diagnosis of mycoplasm pneumonia.
Empiric therapy for atypical pneumonia for day course
① erythromycin : drug of choice
② tetracyclin, doxycycline : suitable alternatives
③ new drug : clarithromycin, azithromycin

10. Chlamydial infection
Chlamydia : obligate intracellular parasites, possess cell wall, both DNA & RNA
extracellular elementary body (infective form)
intracellular reticulate body
Chlamydia psittaci : pneumonia, psittacosis
Chlamydia trachomatis : STD & perinatal infection
Chlamydia pneumoniae : URI, pneumonia
Attack to target cells
Rupture of inclusion
Enter the cells within phagosome
Releasing elementary bodies
Reorganize into reticulate bodies
Infection of adjacent cells
Multiplication in inclusion body

11. Chlamydial infection
C. trachomatis inclusion showing a dividing reticulate body, two elementary bodies and an intermediate form with its typical nucleoid
Electron micrograph of an inclusion containing C trachomatis cultured for 40hours in L929 cells. Most of the reticulate bodies are at the periphery of the inclusion (X 7500).

12. 1. STD Due to C. Trachomatis
Chlamydial infection
1. STD Due to C. Trachomatis
At least 20 serotypes for C.trachomatis
LGV(lymphogranuloma venereum)
: more invasive, disease in lymphatic tissue
Non-LGV strains
: superficial infections of eye,genitalia,respiratory tract
Epidemiology
Peak incidence : late teens and early twenties
Prevalence
① urethritis 3-5% in general medical settings
10% for asymptomatic soldiers under routine P/E
15-20% for heterosexual men in STD clinics
② cervicitis 5% for asymptomatic college students and prenatal patients
10% in family planning clinics
> 20% in STD clinics

13. Clinical Features of STD
Chlamydial infection
Clinical Features of STD
⑴ Nongonococcal and postgonococcal urethritis
⑵ Epididymitis
⑶ Reiter’s syndrome
⑷ Proctitis
⑸ Mucopurulent cervicitis
⑹ Pelvic inflammatory disease(PID)

14. Chlamydial infection ㅊ
Fig 1. Chlamydial cervicitis with granulation tissue of the zone of transformation

15. Fig 2. Colposcopic exam of a cervix.
Chlamydial infection
Fig 2. Colposcopic exam of a cervix.
Erythema and mucopurulent discharge coming from the ciervical os

16. Fig 3. Unilateral chronic follicular conjunctivitis
Chlamydial infection
Fig 3. Unilateral chronic follicular conjunctivitis

17. Chlamydial infection
Fig 4. Unilateral follucular conjunctivitis caused autoinoculation from the genital tract

18. Chlamydial infection
Fig 5. Fluorescein-conjugated monoclonal antibody detects the EBs in a cervical smear from a patient. EB are apple green, fluorescing,round extracellular particles.

19. Chlamydial infection
Fig 6. Iodine stain of a tissue cultures specimen from patient with C. trachomatis infection showing the darkly staining glycogen-containing inclusion

20. Chlamydial infection
Fig 7. Chronic salpingitis and obstruction of the distal portion of the tube caused by infection with C.trachomatis

21. Chlamydial infection
Fig 8. C. trachomatis epididymitis with unilateral scrotal erythema and edema

22. Ulcerated inguinal bubo in a patient with secondary LGV
Chlamydial infection
Ulcerated inguinal bubo in a patient with secondary LGV
Inguinal bubo
Ulcerative lesion

23. 2. C. Pneumniae Infections
Chlamydial infection
2. C. Pneumniae Infections
C.pneumoniae : more difficult to culture than other chlamydiae
Peak incidence : young adults
Secondary episode : older adults
Transmission : from person to person, primarily in schools and family units
Clinical spectrum : acute pharyngitis, sinusitis, bronchitis, pneumonitis
Clinical features
① resembles that of M.pneumoniae pneumonia
(leukocytosis(-), antecedent URI symptoms, fever,
nonproductive cough,minimal findings on chest auscultaton
small segmental infiltrates on chest x-ray)
② severe especially in elderly patients
Diagnosis
acute and convalescent-phase sera for chlamydial CF antibody
( but not distinguish C.pneumoniae from C.trachomatis or C.psittaci)
Treatment
erythromycin or tetracycline 2g/day for 10-14days

24. 3. Psittacosis Infectious disease of birds caused by C.psittaci
Chlamydial infection
Infectious disease of birds caused by C.psittaci
Transmissin from birds to humans -> febrile illness
Almost always transmitted to humans by the respiratory route
(rarely bite of a pet bird)
upper respiratory tract ->bloodstream -> pulmonary alveoli, RES
-> lymphocytic inflammation in alveolar walls and interstitium
Clinical Features
incubation period : 7-14 days
more gradual onset with fever, headache, nonproductive cough
untreated cases -> sustained or remittent fever for 10days to 3weeks
-> gradually abate
Diagnosis
acute and convalescent-phase sera for chlamydial CF antibody
Differential diagnosis
Mycoplasma pneumonia, C.pneumoniae pneumonia, legionellosis
viral pneumonia, Q fever
Treatment
tetracycline 2g/day for 7-14days

25. Legionella Infection Etiology
Legionellosis : two clinical syndromes by genus Legionella
Pontiac fever : acute,febrile,self-limited illness by Legionella species
Legionnaires’ disease : pneumonia by Legionella species
Legionnaires’ disease
1976 outbreak of pneumonia at a hotel in Philadelphia during American
Legion Convention  aerobic G(-) bacterium named Legionella
pneumophila in lung specimens
Etiology
Family Legionellaceae : 41 species with 63 serogroups
L.pneumophila
aerobic G(-) bacilli
80-90% of human infections
at least 14 serogroups (most common serogroups 1,4, 6)
17 species other than L.pneumophila associated with human infections
L. micdadei, L. bozemanii, L. dumoffii, L. longbeachae

26. Imprint smear of lung in Legionnaires’ disease.
Legionella infection
Imprint smear of lung in Legionnaires’ disease.
The bacilli are red and clustered in alveolar macrophages.

27. Legionella infection
L.pneumophilla bacilli are enclosed by envelope,which consists of inner and outer triple-layered membranes.most organisms contain vacuoles.

28. Epidemiology Transmission Epidemiology
Legionella infection
Epidemiology
Transmission
natural habits for L.pneumophila : aquatic bodies(lakes, streams)
enter aquatic reservoirs(cooling towers or water-distribution systems)
grow and proliferate ( enhance colonization in warm temperature 25-42℃)
aerolization, aspiration, direct instillation into the lung
Epidemiology
3-15% of community-acquired pneumonia
10-50% of nosocomial pneumonias
when a hospital’s water system is colonized with the organisms
Most common risk factors
cigarette smoking, chronic lung disease, old age, immunosuppression
Most often develops in elderly.
Surgery is a prominent predisposing factor in nosocomial infection

29. Pathogenesis Enter the lungs via aspiration or direct inhalation
Legionella infection
Enter the lungs via aspiration or direct inhalation
Adherence to respiratory tract epithelial cells
1. Conditions that impair mucociliary clearance
smoking, lung disease, alcoholism
2. Cell-mediated immunity is the primary mechanism.
transplant recipients, HIV patients, patients receiving glucocorticoid
hairy cell leukemia(monocyte deficiency and dysfunction)
3. Role of neutrophil : minimal
4. Humoral immune system
IgM, IgG witin weeks ofinfection
promote killing of legionellae by neutrophils,monocytes,alveolar M
neither enhance lysis by complememt nor intracellular multiplication

30. Legionella infection
Pontiac Fever
Acute, self-limiting, flulike illness with a 24-48h incubation period
Pneumonia does not develop.
Fever, headache, malaise, fatigue, myalgias : the most frequent symptoms
Complete recovery within only a few days without antibiotic therapy
Diagnosis by antibody seroconversion

31. Legionnaires’ disease(pneumonia)
Legionella infection
Legionnaires’ disease(pneumonia)
Clinical Clues suggestive of Legionnaires’ Disease
Diarrhea
High fever ( > 40℃ )
Numerous neutrophils but no organisms revealed by Gram’s staining of
respiratory secretions
Hyponatremia (serum sodium level of < 131 meq/L)
Failure to respond to -lactam drugs and aminoglycoside antibiotics
Occurrence of illness in an environment in which the potable water
supply is known by be contaminated with Legionella
Onset of symptoms within 10 days after discharge from the hospital

32. Legionella infection

33. Diagnosis Utility of Special laboratory Test for the Diagnosis of
Legionella infection
Utility of Special laboratory Test for the Diagnosis of
Legionnaires’ Disease
Test
Culture
sputum
transtracheal aspirate
DFA staining of sputum
Urinary antigen testing *
Antibody serology **
Sensitivity,% 80 90
50-70 70
40-60
Specificity,%
100
96-99
* Serogroup 1 only
** IgG and IgM testing of both acute- and convalescent-phase sera.
A single titer of ≥ 1:128 is considered presumptive,
while a single titer of ≥ 1:256 or fourfold seroconversion is considered definitive.

34. Extrapulmonary Legionellosis
Legionella infection
Extrapulmonary Legionellosis
Usually result from bloodborne dissemination from the lung
Sinusitis, peritonitis, pyelonephritis, cellulitis, pancreatitis
: predominantly in immunosuppressed patients
The most common extrapulmonary site  Heart
: myocarditis, pericarditis, postcardiotomy syndrome, prosthetic-valve
endocarditis
Most cases hospital-acquired

35. Direct immunofluorescence of
Legionella infection
Direct immunofluorescence of
L. pneumophila of lung. Numerous bacilli in alveolar macrophages

36. Treatment Prevention Antibiotics for 10-14 days
Legionella infection
Antibiotics for days
* longer period(3 weeks) for immunosuppressed
① Erythromycin
② New macrolides(azithromycin, clarithromycin, roxithromycin, josamycin)
③ Ciprofloxacin : transplanted patient
④ Rifampin + macrolides or quinolone
Pontiac fever requires only symptom-based treatment, not antibiotics
Prevention
Disinfection of the water supply is the ultimate preventive measure.
① Superheat and flush method
heating of the water( 70-80℃ )
flushing with hot water for at least 30 min.
② copper and silver ionization method
③ hyperchlorination is no longer recommended