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Chapter: Medical Microbiology: An Introduction to Infectious Diseases: Legionella

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Legionellosis : Clinical Aspects

Legionnaires’ disease is a severe toxic pneumonia that begins with myalgia and headache, followed by a rapidly rising fever.

LEGIONELLOSIS : CLINICAL ASPECTS

MANIFESTATIONS

Legionnaires’ disease is a severe toxic pneumonia that begins with myalgia and headache, followed by a rapidly rising fever. A dry cough may develop and later become productive, but sputum production is not a prominent feature. Chills, pleuritic chest pain, vomiting, diar-rhea, confusion, and delirium may all be seen. Radiologically, patchy or interstitial infiltrates with a tendency to progress toward nodular consolidation are present unilaterally or bilater-ally. Liver function tests often indicate some hepatic dysfunction. In the more serious cases the patient becomes progressively ill and toxic over the first 3 to 6 days, and the disease terminates in shock, respiratory failure, or both. The overall mortality is about 15%, but has been higher than 50% in some hospital outbreaks. It is particularly high in patients with serious underlying disease or suppression of cell-mediated immunity.

 

A less common form of disease called Pontiac fever (named for a 1968 Michigan outbreak), is a nonpneumonic illness with fever, myalgia, dry cough and a short incu-bation period (6 to 48 hours). Pontiac fever is a self-limiting illness and may represent a reaction to endotoxin or hypersensitivity to components of the Legionella or their protozoan hosts.

DIAGNOSIS

The best means of diagnosis is direct fluorescent antibody (DFA) smears combined with cul- ture of infected tissues. For this purpose, a high-quality specimen such as lung aspirates, bronchoalveolar lavage, or biopsies are preferred, because the organism may not be found in sputum. Typically, the Gram smear shows no bacteria, but the organisms are demonstrated by DFA using L. pneumophila – specific conjugates. These conjugates utilize monoclonal anti-bodies, which bind to all serotypes of L. pneumophila but not the non – L. pneumophila species. DFA is rapid, but it is positive in only 25 to 50% of culture-proved cases.

Cultures must be made on buffered charcoal yeast extract (BCYE) agar medium that meets the growth requirements of Legionella. BCYE contains amino acids, vitamins, L-cysteine, ferric pyrophosphate, and charcoal to adsorb toxic fatty acids. It is buffered opti-mally for Legionella growth (pH 6.9). The isolation of large Gram-negative rods on BCYE after 2 to 5 days that have failed to grow on routine media (blood agar, chocolate agar), is presumptive evidence for Legionella. Diagnosis is confirmed by DFA staining of bacterial smears prepared from the colonies. BCYE also allows isolation of species of Le-gionella other than L. pneumophila.

The diagnosis of legionellosis can also be established by polymerase chain reaction (PCR) amplification of a rRNA gene common to all Legionella species or detection of antigen by immunoassay of urine. The antigenuria test was originally limited to L. pneu-mophila serogroup 1 but has been recently expanded to all L. pneumophilaserogroups.Demonstrating a significant rise in serum antibody is used primarily for retrospective di-agnosis and in epidemiologic studies. Diagnostic procedures for legionellosis are likely to be available only in reference facilities and the laboratories of hospitals treating immuno-compromised patients. Even here, DFA and culture remain the mainstay until the newer methods prove cost-effective.

TREATMENT

The best information on antimicrobial therapy is still provided by the original Philadel-phia outbreak. Because the etiology was completely obscure at the time, the cases were treated with many different regimens. Patients treated with erythromycin clearly did bet-ter than those given the penicillins, cephalosporins, or aminoglycosides. Subsequently, it was shown that most Legionella produce β-lactamases. In vitro susceptibility tests and animal studies have confirmed the activity of erythromycin and showed that tetracycline, rifampin, and the newer quinolones are also active. Although the other antimicrobics are sometimes used in combination, erythromycin and the newer macrolides (azithromycin, clarithromycin) remain the agents of choice.

PREVENTION

The prevention of legionellosis involves minimizing production of aerosols in public places from water that may be contaminated with Legionella. Although outbreaks con-nected with large buildings have received the most attention, cases have been traced to sources as common as the mists used in supermarkets to make the vegetables look shiny and fresh. Prevention is complicated by the fact that, compared with other environmental bacteria, Legionella bacteria are relatively resistant to chlorine and heat. They have been isolated from hot water tanks held at over 50°C. Methods for decontaminating water sys-tems are still under evaluation. Some outbreaks have been aborted by hyperchlorination, by correcting malfunctions in water systems, or by temporarily elevating the system tem-perature above 70°C. The installation of silver and copper ionization systems similar to those used in large swimming pools has been effective as a last resort in hospitals plagued with recalcitrant nosocomial legionellosis.

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