atypical by dandanhuanghuang


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

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)
                      Mycoplasma infection
 • Smallest free living organism(100-300nm)
 • Lack of cell wall : no Gram staining, resistant to -lactam
 • M.pneumoniae
  Ureaplasma urealyticum : urinary calculi

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℃
                      Mycoplasma pneumonia

•   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.
                                                               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
•    Sometimes myringitis(5%), otitis
•    Lung abscesses, pneumatoceles, extensive lobar consolidation,
    respiratory distress and pleural effusion(20%) may develop.

• 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
                                                          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
                                            Mycoplasma pneumonia

        Laboratory Abnormalities
① Routine lab is usually normal.
② Subclinical hemolytic anemia
  positive Coombs’ test , reticulocytosis

                Chest X-ray

① Peribronchial pneumonia : most common
   thickened bronchial shadow
   streaks of interstitial infiltration
② Pleural effusion(20%)
③ Nodular infiltration        uncommon
④ Hilar adenopathy
                                                                 Mycoplasma pneumonia


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
                                                       Mycoplasma pneumonia

     Treatment of Mycoplasma Pneumonia

No rapid way to make the diagnosis of mycoplasm pneumonia.
 Empiric therapy for atypical pneumonia for 14-21 day course

① erythromycin : drug of choice
② tetracyclin, doxycycline : suitable alternatives
③ new drug : clarithromycin, azithromycin
                          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
                                                                  Chlamydial infection

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


• 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
                                                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)
                                                       Chlamydial infection


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

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

Fig 3. Unilateral chronic follicular conjunctivitis
                                                     Chlamydial infection

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

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

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

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

                    Ulcerated inguinal bubo in a
                    patient with secondary LGV

Ulcerative lesion                                  Inguinal bubo
                                                                  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
                                                                 Chlamydial infection
                         3. Psittacosis
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
    acute and convalescent-phase sera for chlamydial CF antibody
Differential diagnosis
    Mycoplasma pneumonia, C.pneumoniae pneumonia, legionellosis
    viral pneumonia, Q fever
  tetracycline 2g/day for 7-14days
                       Legionella Infection
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

Family Legionellaceae : 41 species with 63 serogroups
  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
                                         Legionella infection

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

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

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
  Pathogenesis                                                      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
                                                                    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
                                                               Legionella infection
               Legionnaires’ disease(pneumonia)

          Clinical Clues suggestive of Legionnaires’ Disease
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
Legionella infection
                                                                           Legionella infection
           Utility of Special laboratory Test for the Diagnosis of
           Legionnaires’ Disease
    Test                                Sensitivity,%      Specificity,%
       sputum                           80                 100
       transtracheal aspirate           90                 100
    DFA staining of sputum              50-70              96-99
    Urinary antigen testing *           70                 100
    Antibody serology **                40-60              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.
                                                                   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
Most cases hospital-acquired
                                           Legionella infection

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

Antibiotics for 10-14 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

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

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