Lower respiratory tract infections by tbou28

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									 Lower respiratory tract
       infections

            Mark Jorge
            Colchester
Mark.jorge@colchesterhospital.nhs.uk
Respiratory tract
Anatomy of lower respiratory tract-
             Trachea
   Trachea – 11-12cm tube, thickened by
    cartilage, which extends from the larynx
    into the thoracic cage. It is lined with
    pseudostratified epithelium, containing
    ciliated and mucous-secreting cells, and
    branches to form the left and right
    primary bronchi. It represents the change
    from upper to lower respiratory tract.
                  Bronchi

   One primary bronchus supplies each lung.
    They are lined with pseudostratified,
    ciliated epithelium and, on entering the
    lungs, divide to form the secondary lobar
    bronchi, one for each lobe of the lungs.
    Each secondary bronchus divides to
    produce tertiary bronchi, which in turn
    produce the bronchioles
              Bronchial tree

   This successive branching produces a
    ‘bronchial tree’ of ever decreasing
    diameter which is characterised by a
    gradual loss of cartilage, increase in
    smooth muscle within the wall and change
    from columnar to cuboidal epithelium.
                          Lungs
   Each lung is divided by fissures into lobes: 2 in the left
    (superior and inferior), 3 in the right (superior, middle
    and inferior). The lobes are further subdivided into
    lobules.
   The lungs are housed in a pleural membrane.
   Within the lobules, the bronchial tree is now at the level
    of the bronchioles and subsequently the alveoli. It is
    estimated that the adult human lung contains 300 million
    alveoli, which collectively offer a total surface area of
    70m2 for gaseous exchange.
   The lungs therefore, are primarily composed of alveoli,
    the capillaries of the pulmonary circulation and
    connective tissue. Adequately perfused lungs may
    consist of 40% by weight of blood in the circulation.
    Normal Host Defence Mechanisms

   Mucocilliary escalator
   Phagocytosis
   Alveolar macrophages
   Lysozyme
   s IgA
   Interferons
Mucocilliary escalator
              The normal airway epithelium
               provides an effective barrier
               against penetration of inhaled
               bacteria into deeper lung
               tissues. The mucocilliary
               escalator helps remove
               bacteria that deposit along the
               airways. Viral infection often
               compromises the integrity of
               the epithelial barrier and the
               effective function of the
               mucociliary escalator.
                 Bronchitis

   Inflammation of the bronchial tubes
   Tissues become irritated
   More mucous then usual produced
   Results in cough
              Acute bronchitis
   Only lasts for a few weeks
   Generally viral in origin
   Rhinovirus, parainfluenzae

   Can get secondary bacterial overgrowth
   H. influenzae
   S. pneumoniae
   S.aureus
     Chronic respiratory diseases
   Bronchiectasis
    Localised, irreversible dilation of part of the
    bronchial tree
   COPD
    This is a term used for a number of conditions
    including-
   Emphysema
    Alveoli lose their elasticity resulting in shortness
    of breath
   Chronic bronchitis
                    COPD

   Acute exacerbations generally caused by
    viruses (rhinoviruses, parainfluenza)
   Secondary bacterial invasion is extremely
    common (H.influenzae, Moraxella)
          Prevention of COPD

   Stop smoking
   Avoid cold damp weather
   Influenza vaccination
   Chemoprophylaxis (nebulisers)
   Steroids
   Bronchodilators
   Diet
     Microbial causes of infective exacerbations of
                   chronic bronchitis
                                           Chronic Bronchitis Cases

Organism                   Early disease            Advanced disease
H. Influenzae, Moraxella   ++++                     ++++
S. pneumoniae              +++                      +++
Viruses                    ++                       ++
M. pneumoniae              +                        +
S. aureus                                           +
Coliforms                                           +
Pseudomonas                                         +
Non-sporing anaerobes                               +
++++ Very common cause
+++ Common cause
++ Frequent cause
+ Occasional cause
                Pneumonia

   Inflammation of the alveoli of the
    parenchyma of the lung with consolidation
    and exudation

   Cough
   Pleuritic pain
   Production of purulent sputum
                   Pneumonia
   Risk factors

   COPD
   Diabetes
   Cardiac / Renal failure
   Immunosuppression
   Reduced levels consciousness
   Anything that inhibits the gag / cough reflex
         Causes of pneumonia acquired outside or inside hospital in patients

                                                 other than those with AIDS
Types of pneumonia                                              General Practice patient                            Hospital patient
                                            Primary*                           Secondary@                           Nearly all secondary
Bacterial Pneumonias eg
Strep pneumonia                             Common                             Common                               Common
Staph aureus                                Rare                               Occasional                           Occasional (o)
H.Influenzae, Moraxella                     Rare                               Occasional                           Occasional
Coliform (Kleb)                             Rare                               Rare                                 Occasional (o)
P. aeruginosa                                                                  Rare                                 Occasional (o)
Anaerobes(bacteroides)                                                         Rare                                 Occasional (o)
Legionnaire’s disease
L.pnemophilia                               Rare                               Occasional                           Rare (o)
Tuberculosis
M. tuberculosis                             Rare                               Occasional                           Rare (o)

 (o) Includes ‘opportunistic infections’, occurring in special units such as intensive care or transplant units where these infections are more common.
                                                           *Patients who are previously healthy.
                            @ Patients who are debilitated, elderly or have some specific predisposing factor for pneumonia.
    Causes of pneumonia acquired outside or inside hospital in
        patients other than those with AIDS (continued)
Types of pneumonia                                           General Practice patient                             Hospital patient
                                       Primary*                              Secondary@                           Nearly all secondary
Primary atypical
    pneumonia
M. pneumoniae, C.pneumoniae            Common                                Occasional                           Rare
C. psittaci                            Occasional                            Rare                                 Rare
C. burnetti                            Rare                                  Rare                                 Rare
Viruses
Influenza                              Rare
RSV                                    Rare
Para-influenza viruses                 Rare
Adenovirus                             Rare
Measles                                Rare                                  Rare (o)                             Rare (o)
Varicella-zoster                       Rare                                  Rare (o)                             (except outbreaks)
Other viruses, protozoa,                                                     Rare (o)                             Rare (o)
   fungi and worms
       (o) Includes ‘opportunistic infections’, occurring in special units such as intensive care or transplant units where these infections are more
       common.
       *Patients who are previously healthy. @ Patients who are debilitated, elderly or have some specific predisposing factor for pneumonia
Community acquired pneumonia

   S. pneumoniae
   H. influenzae
   Moraxella
   K. pneumoniae (Friedlander’s bacillus)

   Pasturella
   N. meningitidis
    Hospital acquired pneumonia

   Risk factors include mechanical ventilation

   Enterobactericiae
   Acinetobacter
   Pseudomonas apecies
   S.aureus (MRSA)
           Atypical pneumonia
    Mycoplasma pneumoniae (Eaton agent)

   Obligate human pathogen
   Epidemics occur at 4-6 year intervals
   Spread requires close contact
   Common in children <5 years – mild illness
   Most common in 5-20 year age group – walking
    pneumonia
          Atypical pneumonias

   Chlamydia pneumoniae
   Chlamydia psittaci
   Legionairre’s disease
   Q fever (Coxiella burnetti)

   Hantavirus (ARDS)
    Investigations for pneumonia
   Blood culture
   Resp specimens/blood for viruses,
    chlamydia & mycoplasma
   Urine for legionella & pneumococcal
    antigen testing
   Sputum
   BAL
   Pleural fluid
                   Pleurisy
   Inflammation of the pleura, the lining of
    the pleural cavity

   Pain
   Shortness of breath, cough, fever, chills,
    Unexplained weight loss, Sore throat
    followed by pain in and swelling in joints,
    rapid shallow breathing
             Pleurisy - Causes
   Viral infection

   Bacterial infections
   Fungal infections or parasites

   Non-infective causes such as chest
    injuries, cancer, pneumothorax or
    autoimmune diseases
                Pleural effusion
   Transudative – left ventricular failure, cirrhosis

   Exudative
    Bacterial pneumonia
    TB
    Autoimmune
    Trauma
                     Empyma
   Collection of pus in
    the pleura
   Usually starts off as a
    pneumonia
                Cystic fibrosis
   Most common
    autosomal-recessive
    disease in caucasians,
    affecting
    approximately 1 in
    3,000 individuals.
   First described in
    1938 by Andersen.

                             Dorothy Hansine Andersen
                         Genetics
   The CFTR (cystic fibrosis       Chromosome 7
    transmembrane
    conductance                            CFTR gene
    regulator)[ATP-binding
    cassette sub-family C,
    member 7]. Gene is
    located on the long (q)
    arm of chromosome 7 at
    position 31.2. It is located
    from base pair
    116,907,252 to base pair
    117,095,950.
             Diagnosis of CF

   Sweat test – abnormal amounts of sodium
    & chloride
   Newborn Screening – raised
    immunoreactive trypsinogen
   Genetic screening
     Diseases associated with CF
   The abnormal sodium and chloride transport
    leads to obstruction and disease in the lungs,
    pancreas, paranasal sinuses, and sweat glands.
   Common pulmonary findings include bronchitis,
    recurrent pneumonia, and parenchymal scarring.
    In the paranasal sinuses, nasal polyposis and
    bacterial colonization of retained mucus results
    in chronic sinusitis.
   Most people with cystic fibrosis also have
    digestive problems because thick, sticky mucus
    interferes with the function of the pancreas.
           Diseases in adulthood
   Cystic fibrosis used to be considered a fatal disease of
    childhood. With improved treatments and better ways to
    manage the disease, many people with cystic fibrosis
    now live well into adulthood.
   Most men with cystic fibrosis are infertile because the
    vas deferens are blocked by mucus and do not develop
    properly. This condition is known as congenital bilateral
    absence of the vas deferens (CBAVD). Infertility is also
    possible, though less common, in women with cystic
    fibrosis.
                  Acquisition

   Clinical deterioration due to infection with

   EBV
   Influenza A
         Progression of disease

   Streptococcus pneumoniae
   Haemophilus influenzae
   Staphylococcus aureus
   Pseudomonas species

   Mucoid Pseudomonas aeruginosa
   Burkholderia cepacia
            Other infections

   Aspergillus fumigatus
   Mycobacterium avium
   Mycobacterium chelonae
          Pneumocystis jiroveci
   Unicellular Fungus
   Found only in humans
    (although other
    species occur in other
    animals)
   Carried by healthy
    people
   AIDS defining disease
               History of PJP
   Organism first described in 1906 by
    Chagas
   Jirovec first isolated it from humans
   Interstitial pneumonia in central & eastern
    Europe in World War 2 in severely
    malnourished and premature infants
   In the first decade of the HIV epidemic
    100,000 cases were reported in the US
          Morphological stages

   The trophozoite (trophic form), in which it
    often exists in clusters
   The sporozoite (precystic form)
   The cyst, which contains several
    intracystic bodies (spores)
Pneumocystis jiroveci – life cycle
Pneumocystis jiroveci- stains
                  Panel A shows typical pneumocystis
                   cyst forms in a bronchoalveolar-lavage
                   specimen stained with Gomori
                   methenamine (x100). Thick cyst walls
                   and some intracystic bodies are
                   evident. Wright–Giemsa staining can
                   be used for rapid identification of
                   trophic forms of the organisms within
                   foamy exudates, as shown in Panel B
                   (arrows), in bronchoalveolar-lavage
                   fluid or induced sputum but usually
                   requires a high organism burden and
                   expertise in interpretation (x100).
                   Calcofluor white is a fungal cyst-wall
                   stain that can be used for rapid
                   confirmation of the presence of cyst
                   forms, as shown in Panel C (x400).
                   Immunofluorescence staining, shown
                   in Panel D, can sensitively and
                   specifically identify both pneumocystis
                   trophic forms (arrowheads) and cysts
                   (arrows) (x400).
Aspergillus fumigatus
Aspergillus fumigatus
             Aspergillus fumigatus
        bronchopulmonary diseases
   Asthma – type I, immediate hypersensitivity response.
    IgE mediated in bronchii
   Allergic bronchopulmonary aspergillus. Spores reaching
    the lung stimulates extrinsic allergic bronchoalveolitis
    due to type I and III hypersensitivity. Bronchial plugs
    found in sputum.
   Aspergilloma. Chronic infection damages areas of lung
    (eg. Healed TB cavity). Production of a fungus ball.
    Massive haemoptysis and secondary bacterial infections
    common.
   Desseminated Aspergillosis. Invasive lung infection. Can
    spread to brain and liver. Rare implications include
    endocarditis. Very high mortality.
Bronchial plugs
Invasive Aspergillosis (silver stain)
Aspergilloma
               Bronchiolitis

   RSV
   Adenovirus
   Parainfluenzae type 1 & 3
   Influenzae
   Human metapneumovirus
Mycobacteria
               Mycobacteria

    M. tuberculosis complex:
   M. tuberculosis
   M. bovis
   M. africanum

   Mycobacteria other than tuberculosis
    (MOTT)
                                                                            Some Non-
                          Pathogenic              Usual Site of
    Group:                                                                   pathogenic
                             Species:               Infection:
                                                                              Species:

                          M.tuberculosis,
  Tuberculosis
                             M.africanum,       Lungs, Lymph nodes
     Complex
                               M.bovis

Runyan Group I:             M.kansasii,
                                                    Lungs, Skin
 Photochromogens             M.marinum

Runyan Group II:
                          M.scrofulaceum           Lymph nodes               M.gordonae
 Scotochromogens

                            M.avium,
Runyan Group III:          M.intracellulare,
                                                 Lungs, Bone, Skin        M.gastri, M.terrae
   Not Pigmented              M.xenopi,
                             M.ulcerans

Runyan Group IV:           M.fortuitum,
                                                  Lungs, Wounds          M.phlei, M.smegmatis
  Rapid Growers              M.chelonae

Not Culturable in
                             M.leprae          Skin, Peripheral Nerves
        vitro

                        M. avium and M. xenopi can grow at 40 0C.
                 M. marinum and M. ulcerans need to be incubated at 30 0C
                 Mycobacteria
   Obligate aerobe
   Catalase positive

   60% cell wall
    composed of lipids
   Wax D
   Mycolic acids
          Tuberculosis
                   Physicians in ancient Greece called
                    this illness “phthisis" to reflect its
                    wasting character.

                   During the 17th and 18th
                    centuries, TB caused up to 25% of
                    all deaths in Europe. In more
                    recent times, tuberculosis has
                    been called "consumption.“

                   Robert Koch isolated the tubercle
                    bacillus in 1882 and established
                    TB as an infectious disease.




Robert Koch
              TB Virulence factors
   Cell entry - TB can bind directly to mannose receptors of
    macrophage cell wall-associated mannosylated glycolipid,
    Lipoarabinomannan (LAM), or indirectly via certain complement
    receptors or Fc receptors.

   Intracellular survival - TB can survive in macrophages by preventing
    phagosome - lysosome fusion. The organism may remain in the
    phagosome or may escape from there to another intra-cellular site.

   Interference with toxic effects of reactive oxygen intermediates
    glycolipids and cell wall-associated mannosylated glycolipid down
    regulate the oxidative cytotoxic mechanism

   Macrophage uptake via complement receptors may bypass the
    activation of a respiratory burst.
           TB Virulence factors
   Antigen 85 complex - These proteins bind
    fibronectin and may aid in walling off the
    bacteria from the immune system and may
    facilitate tubercule formation
   Slow generation time
   High lipid concentration in cell wall
   Cord factor – surface glycolipid. Toxic to
    mammalian cells & prevent polymorphonucleur
    cell migration
   Infective droplet size 5µ.
   5-200 inhaled bacilli required for infection.
   Bacteria deposited into alveoli.
   Alveolar macrophages phagocytose but do not
    kill them. Bacteria continue to multiply.
   Carried to regional lymph nodes.
   Lymphohaematogenous dissemination to other
    lymph nodes eg in kidneys, bones, meninges.
    Cell mediated immunity (CMI)
   After 2-3 weeks the CMI halts the unimpeded
    growth of TB.
   CD4 helper T cells activate the macrophages to
    kill intracellular bacteria.
   CD8 T cells lyse the macrophages infected with
    mycobacteria. This results in caseating
    granulomas. The extracellular environment is
    too acidic for mycobacterial growth.
   Most people infected with M. tuberculosis do not
    develop active disease.
Risk factors for acquisition of TB

   Nodular lesions have 100-10,000
    organisms, cavitary lesions have 10 million
    to 1 billion bacilli.
   Antibiotic treatment.
   Ventilation & exposure to UV light – poor
    housing, overcrowding.
                   Treatment of TB


                                  Streptomycin, the first
                                   antibiotic to fight TB,
                                   was introduced in
                                   1946.


Bill McLaren'voice of rugby'
              Treatment of TB
   The standard treatment for TB is a combination
    of three or four antibiotics for a period of two
    months, and then two antibiotics for a further
    four months. The four main antibiotics for
    treating TB are ISONIAZID, RIFAMPICIN,
    PYRAZINAMIDE and ETHAMBUTOL. RIFATER
    (rifampicin, isoniazid, pyrazinamide) AND
    RIFINAH (rifampicin, isoniazid) are single tablets
    which contain a combination of drugs to make it
    easier for the patient.
                MOTT                                Clinical features
Mycobacterium avium-intracellulare      Also known as MAC (Mycobacterium avium complex)
                                        Most common non-tuberculous mycobacterial infection
                                         associated with AIDS
                                        Symptoms include fever, swollen lymph nodes,
                                         diarrhoea, fatigue, weight loss and shortness of breath
                                        May develop into pulmonary MAC



Mycobacterium kansasii                  May cause a chronic infection of the lungs similar to
                                         pulmonary TB
                                        Second most common non-tuberculous mycobacterial
                                         infection associated with AIDS
                                        Symptoms include fever, swollen lymph nodes and lung
                                         crackles and wheezing
                                        Skin lesions may occur either alone or as part of a more
                                         widespread disease

Mycobacterium chelonae                  Worldwide distribution: found in tap water and other
                                         water sources
                                        May cause lung disease, joint infection, eye disease and
                                         other organ infections
                                        May result in non-healing wound, subcutaneous nodule
                                         or abscess
                                        Immunosuppression may cause disseminated lesions
                                         throughout the body
               Treatment of MOTT
   Treatment of atypical mycobacterial infections depends upon the
    infecting organism and the severity of the infection. In most cases a
    course of antibiotics is necessary. These include rifampicin,
    ethambutol, isoniazid, minocycline, ciprofloxacin, clarithromycin,
    azithromycin and cotrimoxazole. Usually treatment consists of a
    combination of drugs. Some points to consider when treating
    atypical mycobacterial infections:
   Mycobacterium kansasii should be treated for at least 18 months.
   Mycobacterium chelonae is best treated by clarithromycin in
    combination with another agent, Sometimes surgical excision is the
    best approach.
   AIDS patients on HIV protease inhibitor drugs cannot be treated
    with rifampicin because it significantly increases the breakdown of
    these drugs.
AAFB
Mycobacterial culture methods




                            Lowenstein Jensen slopes
            BACT/ALERT 3D

    MGIT
     Mycobacterial culture media

   Egg based
   Ogawa
   Lowenstein Jensen

   Agar
   Middlebrook’s media

   Liquid media
   Kirchner
   Dubos
    BACTEC MGIT & BACT/ALERT 3D

   Both use modified 7H9 Middlebrook broth base

   BACTEC MGIT – Add PANTA contains
    Polymyxin B, Amphotericin B, Nalidixic acid,
    Trimethoprim and Azlocillin
   BACT/ALERT 3D - Add amphotericin B,
    azlocillin, nalidixic acid, trimethoprim, polymyxin
    B, and vancomycin
             Decontamination
   Petroff’s method – 4% NaOH
   N-acetyl-L-cysteine-NaOH method
   Oxalic acid
   Sodium dodecyl (lauryl) sulfate (SDS)-NaOH
   Cetylpyridinium chloride-sodium chloride
   Benzalkonium chloride-trisodium phosphate
   12 % H2SO4 and 1.5% HPC
    (1-Hexadecylpyridinium Chloride)
           Genitourinary tuberculosis
                                                          Common cause of
                                                           extrapulmonary TB
                                                          Insidious onset –
                                                           nonspecific
                                                           presentation



Genitourinary tract tuberculosis. Lobar
calcification in a large destroyed right kidney in a
patient with renal tuberculosis.
      Genitourinary tuberculosis
   Frequency
   Dysuria
   Haematuria
   Flank pain

   Patient often presents with a history of
    sterile pyuria and chronic cystitis
    unresponsive to treatment
            Tuberculous arthritis




Gibbous deformity (humpback) thought to have been caused by tuberculosis.
                      Spinal TB called Pott’s disease.
             Tuberculous arthritis
   Hips
   Knees
   Wrists
   Ankles

   Most cases involve just one joint.
   About 50% have no evidence of pulmonary
    tuberculosis
        Tuberculosis meningitis
                                   Haematogenous
                                    spread
                                   Small caseating
                                    lesions (tubercules) in
                                    meninges & brain
                                    tissue
                                   These rupture
                                    discharging AAFB into
                                    the CSF
Thick exudates at base of the
brain in TB meningitis
                     Tuberculoma

                                       Tumour like mass –
                                        Tuberculoma
                                       Consists of caseous
                                        necrotic material
                                       Rupture releases
                                        AAFB into the sub
                                        arachnoid space
                                        leading to meningitis
Tuberculoma of the right thalamus
        Tuberculosis meningitis

   In some cases, tuberculous meningitis has
    a fulminant presentation
   Sometimes it acts insidiously and
    progresses slowly over weeks or months,
    causing headache, confusion and cranial
    nerve deficits.
Diagnosis of Tuberculosis
       meningitis

                        CSF
                Slightly raised protein
                 & depressed glucose
                Slight lymphocytosis
                AAFB
                Spiderweb clot
Miliary TB
          Widespread
           dissemination -
           haematogenous
          Millet-like seeding of
           organs including
           lungs, liver, spleen &
           brain
Miliary TB
         Primary site in lung
         Non-specific
          presentation – low
          grade fever, enlarged
          lymph nodes
         Can also have
          enlarged spleen, liver,
          inflammation of
          pancreas
Miliary TB - Diagnosis


               Sputum culture
               Blood cultures
               Chest X-ray
               Bronchoscopy
               CT MRI of brain
                      Miliary TB
   100 % mortality in untreated cases
   With early and appropriate treatment, the
    mortality rate is reduced to less than 10%
   Most deaths occur within the first 2 weeks of
    admission to the hospital. This may be related to
    delayed onset of treatment
   Up to 50% of all cases of disseminated TB
    detected at autopsy were missed antemortem in
    reported case series.
    Other extra-pulmonary sites of
               infection

   Lymph glands
   Pleura
   Bowel
   Pericardium
   Skin
           Multi drug resistant TB




                                    Multidrug-resistance
Tuberculosis incidence rate, 2006
                                    among reported
                                    tuberculosis cases, 2006
          Multi drug resistance

    Due to:
   Inappropriate therapy
   Failure to complete treatment
          Multi drug resistant TB
   A 1997 survey of 35 countries found rates above 2% in
    about a third of the countries surveyed.
   Highest rates in the former USSR, the Baltic states,
    Argentina, India and China
   Associated with poor or failing national tuberculosis
    control programmes
   MDR strains of TB do not dominate naturally as they
    appear to be less robust and less transmissible
   Outbreaks tend to occur in people with weakened
    immune systems (e.g., patients with HIV)
          Multi drug resistance

   Risk factors for MDR-TB include HIV
    infection, previous incarceration, failed TB
    treatment, failure to respond to standard
    TB treatment, and relapse following
    standard TB treatment.
   Usually can be cured with second line anti-
    tuberculous drugs
             Treatment MDR-TB
   Aminoglycoside (amikacin) or polypeptide antibiotic
    (capreomycin)
   PZA
   EMB
   Fluoroquinolone (moxifloxacin)
   Rifabutin
   Cycloserine
   Ethionamide
   PAS
   Clarithromycin
   Linezolid
   high-dose INH(if low-level resistance)
            Treatment MDR-TB
   Response to treatment must be obtained by
    repeated sputum cultures (monthly if possible).
   Treatment for MDR-TB must be given for a
    minimum of 18 months and cannot be stopped
    until the patient has been culture-negative for a
    minimum of nine months
   It is not unusual for patients with MDR-TB to be
    on treatment for two years or more
Poverty and MDR-TB
            Problems occur mainly in
             impoverished areas
            Community-based
             treatment programs such
             as DOTS-Plus based on
             short course treatment
            These have been
             successful in Lima, Peru,
             where the program has
             seen cure rates of over
             80%

								
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