Legionella

Failure of oxidative burst REF: Harrison’s 17^th edition, chapter 141

Pathogenesis of legionella infection

Legionella enters the lungs through aspiration or direct inhalation. Attachment to host cells is mediated by bacterial type IV pili, heat-shock proteins, and the major outer-membrane protein. Because the organisms possess pili that may mediate adherence to respiratory tract epithelial cells, conditions that impair mucociliary clearance, including cigarette smoking, lung disease, or alcoholism, predispose to Legionnaires’ disease.

Cell-mediated immunity is the primary mechanism of host defense against Legionella, as it is against other intracellular pathogens. Thus Legionnaires’ disease is more common and its manifestations are more severe among patients with depressed cell-mediated immunity

Alveolar macrophages readily phagocytose Legionella. The attachment of the bacteria to phagocytes is mediated via Fc receptors and complement receptors, which attach to the bacterial major outer-membrane protein. Binding to these receptors promotes phagocytosis but fails to trigger an oxidative burst.

Gram negative

Intracellular survival of the Legionella attributed to following factors:

• Reduced oxidative burst
• Failure of phagosome to acidify
• Failure of phagosome to fuse with lysosome
• Bacterial resistance to lysosomal contents

In fact, the bacterial growth within infected macrophages has been estimated at 100- to 1000-fold within 48-72 hours of infection, which is considered remarkable compared to that of other intracellular opportunistic bacteria (e.g., Salmonella, Mycobacterium, Listeria).

Legionella is a gram-negative rod that stains with difficulty.

The toxicity of L pneumophila lipopolysaccharide (LPS) is significantly less than that of other Gram-negative bacteria such as Neisseria and the Enterobacteriaceae.

Side chains are hydrophobic.

It has been postulated that this hydrophobicity may promote adherence of bacterial cells to membranes or their concentration in aerosols.

Infections are associated with aerosols distributed by humidifying and cooling systems.

Amoebas in fresh water habitat act as reservoir. Person-to-person transmission or carriers are unknown.

The prevention of legionellosis involves minimizing production of aerosols in public places from water that may be contaminated with Legionella.

Prevention is complicated by the fact that, compared with other environmental bacteria, Legionella bacteria are relatively resistant to chlorine and heat.

The bacteria have been isolated from hot water tanks held at over 50°C.

Ans. is ‘c’ i.e., Legionella are communicable from infected patients to others

.       The source of legionella is water. Man of man transmission does not occur.

LEGIONELLA

Morphology

.         Gram negative

.         Coccobacilli

.         Non capsulated

.         Motile by polar or subpolar flagella.

.        Best visualized by direct flurescent antibody (DFA)

Culture

.          Strict aerobe

.         Has fastidious requirements and grow on complex media such as buffered charcol, yeast extract (BCYE) agar.

Transmission

.         The nature habitats for L. pneumophila are aquatic bodies, including lakes and streams.

.         The legionellae survive and multiply inside freeliving amebae and other protozoa.

.         Mode of transmissions :

1)  Aerosolization – Inhalation of aerosols produced by cooling towers, air conditioners and shower heads which act as disseminators.

2)  Aspiration –         Is the predominant mode of transmission – 

3)  Direct instillation in to the lung

.  The source of legionella is water

.  No animal reservoir exists

.  No carrier state is estabilished

.  Man to man transmission does not occur.

About option d

.   Because of its intracellular location legionella is not effectively killed by the polymorphs and humoral antibodies.

.   Cell mediated immunity is the primary mechanism of host defense against legionella.

About option b

.   At least 14 serogroups of L. pneumophila have been identified.

.   L. pneumophila serogroup 1 (SG 1) accounts nearly all severe infections.

.   L. pneumophila serogroup 6 is more commonly involved in hospital – acquired legionnaire’s disease.

Ans. is ‘a’ i.e., Consumption of contaminated water

Inhalation of aerosols containing ligionella is no more considered common mode of transmission of legionella.

Aspiration is the most common mode of transmission of legionella.

• Earlier the most popular theorey was that organism is aerosolized in water and people inhale the droplets containing legionella.
• However, new evidence suggests that another way of contracting legionella is more common.
• Aspiration now appears to the most common mode of transmission of legionella.

Ans. is ‘c’ i.e., From inhalation of the aerosols in air conditioned room at convention centre

“Human infection is typically by inhalation of aerosals is produced by cooling towers, air conditioners, and shower heads which act as disseminators.”

• In this question, consumption of water is not provided in the option. Thus, the best answer is inhalation of aerosols.

Ans is ‘b’ i.e., BCYE medium 

Laboratory diagnosis

.   Legionella is grown on complex media such as Buffered Charcoal Yeast Extract agar (BCYE) with alpha ketoglutarate at pH 6.9, temp 35°C and 90% humidity. Antibiotics can be added to make the medium selective for legionella.

. The definitive method for diagnosis of legionella is isolation of the organism from respiratory secretions and specimens.

Treatment

.  Pontiac fever requires only symptom – based treatment, not antimicrobial therapy.

.  Legionnaire’s disease :

–  Azithromycin are DOCs

–  Quinolones

Levofloxacin Gemifloxacin Moxifloxacin

Alternatives Tetracyclines, Co-trimoxazole, Rifampin (in combination with macrolide or quinolone).

.  For transplant recipients quinolones are prefered.

Ans. is ‘a’ i.e., Epidemics (+) 

Legionnaire’s disease may be either epidemic or sporadic.

About other options

Option `b,’

Legionella has been identified in lymphnodes, spleen, liver or kidneys in autopsied cases of legionnaire’s disease. But it does not cause splenomegaly.

Option ‘c & d’

Gram stain smear of sputum typically reveal numerous leukocytes but no organism.

Ans. is `b’ i.e., Can be isolated from lung biopsy 

.  Legionella is gram negative and non-acid fast.

.  Legionella can be isolated from lung biopsy.

.  Sputum shows numerous neutrophils but no organism.

Answer is B (Erythromycin is the drug of choice):

‘Azithromycin, Clarithromycin or a fluoroquinolone (eg Levofloxacin) and not erythromycin is the drug of choice for treatment legionellosis because of their excellent intracellular penetration and in vitro activity as well as desirable pharmacokinetic properties that permit oral administration and once or twice daily dosing –

Ans. D: Unilateral pneumonitis