Legionellosis (Legionnaires Disease)

What is Legionellosis (Legionnaires Disease)?

Legionellosis is a bacterial infection manifested by severe pneumonia, severe intoxication, and impaired function of the central nervous system and kidneys.

Brief historical information
The disease has been known since 1976, when it manifested itself in the form of an outbreak of acute respiratory viral infections with severe pneumonia and high mortality among participants of the congress of the veteran organization “American Legion” in Philadelphia. Among the 4,400 people who took part in the work of the congress, 182 fell ill, of whom 29 died. Then it got the name “Legionnaires disease.” A year later, D. McDaid and C. Shepard isolated the pathogen from the lung tissue of one of the deceased patients, known as Legionella pneumophilia. The clinical and immunological similarity of legionnaires’ disease with other infections caused by various types of legionella and registered in the United States (1965, 1968) and Spain (1973) has been established in retrospect. Since 1982, the term “legionellosis” has been introduced into practice, uniting all diseases caused by various types of legionella.

Causes of Legionellosis (Legionnaires Disease)

The causative agents are gram-negative aerobic motile bacteria of the Legionella genus of the family Legionellaceae. Currently, more than 40 legionella species are known; 22 species are pathogenic for humans. The most common pathogen (more than 90%) is L. pneumophila. There are 18 bacteria serovars; most often the disease is caused by bacteria 1 serovar. L. pneumophila is cultivated on cellular media (chicken embryos, guinea pigs). Bacteria need cysteine ​​and gland to grow on artificial nutrient media. Legionella pathogenicity factors include the lipopolysaccharide complex (endotoxin) and potent exotoxin. The pathogen is stable in the environment: in a liquid medium at a temperature of 25 ° С 112 days can be maintained, at 4 ° С – 150 days. Under the action of 1% formalin solution, 70 ° ethanol, 0.002% phenol solution dies in 1 minute, in 3% solution of chloramine – within 10 minutes. Colonizing connecting nodes, rubber gaskets of water tanks, bacteria multiply rapidly in them.

Reservoir and sources of infection. Legionella’s natural habitat is freshwater and soil. Most often, legionella is isolated from the water of stagnant water bodies, where they live in associations with photosynthetic blue-green algae and aquatic amoebas. Warm habitats favorable for algae breeding are an ecological niche for L. pneumophila. At 35–40 ° C, legionella multiply rapidly in protozoa, such as amoebas, that protect bacteria from exposure to high concentrations of chlorine and other disinfectants. Legionella’s high adaptive abilities allow them to successfully colonize cooling systems, cooling towers, compressor devices, shower sets, swimming pools, decorative fountains, bathrooms for balneological procedures, equipment for respiratory therapy, etc. than in the natural. The person is not the source of the pathogen. Even with close communication with the sick, cases of infection of others are not registered. The isolation of the pathogen from any animals, birds or arthropods is also not established.

The transmission mechanism is aerosol, infection occurs most often through inhalation of a water aerosol. Most outbreaks are associated with water cooling systems, technological cycles, the functioning of which produces a fine aerosol containing bacteria. Possible air and dust (soil) route of infection during construction and earthworks. The pathogen that has accumulated in the soil, air conditioners and showerheads is inhaled in the form of a water or dust spray. Under the conditions of treatment-and-prophylactic institutions, an artifactual method of infection is possible, associated with medical procedures: whirlpool baths, therapy with ultrasonic disintegrators, intubation, etc.

Natural susceptibility is high. Alcohol use, smoking, endocrine disorders, chronic lung diseases, and immunodeficiencies contribute to the disease. The duration of post-infection immunity is not known, however, no recurrences of the disease have been reported.

Major epidemiological signs. Legionellosis is common everywhere; incidence is higher in economically developed countries. Occurs more frequently among hotels, medical workers, and patients in geriatric and psychiatric hospitals. The possibility of infection of people from risk groups during respiratory therapy or nutritional way (through drinking water) has been shown. Outbreaks among the population occur more frequently in the summer-autumn months.

Of particular importance in recent years is the problem of the “travel-associated” legionellosis that occurs during tourist and business trips and is diagnosed, as a rule, upon returning from them. More than 30% of cases of sporadic legionellosis, numerous epidemic cases in hotels, and often fatal outcomes, served as the basis for creating a unified international system of epidemiological monitoring of travel-related legionellosis cases.

Cases associated with nosocomial outbreaks are noted throughout the year. Persons of advanced age are ill mainly, and men are 2-3 times more often than women. Known nosocomial outbreaks of legionellosis. The proportion of legionella-induced pneumonia is 0.5–5%, while acute respiratory disease of a legionella nature (Pontiac fever) occurs in 95% of the total number of individuals infected.

Pathogenesis during Legionellosis (Legionnaires disease)

The main entrance gate of the infection is the various sections of the respiratory system, including lung tissue. Selective primary lesion of epithelial cells of the upper or deeper sections of the respiratory tract and lungs depends on the infectious dose, the size of aerosol particles, and the characteristics of external respiration. In addition, the pathogen can penetrate into the human body, being inside the cells of various protozoa (amoebas, etc.), as well as during medical manipulations and surgical interventions in immunosuppressive individuals. To a certain extent, the nature of the entrance gate determines the shape and severity of the infectious process.

During the development of the inflammatory response, the bacteria absorb phagocytes. Depending on their functional state, including the completeness of phagocytosis, the bacteria either break down or persist for a long time in phagocytes, causing a prolonged course of infection with relapses. Also shown is the ability of bacteria to multiply in phagocytes, leading to their death and the rapid progression of the pathological process. It is believed that with high activity of alveolar macrophages, the disease develops not in the form of severe pneumonia, but in more benign forms, such as Pontiac fever or acute legionella bronchitis. The lack of receptors that allow legionella to “consolidate” in the cells of the mucous membrane of the respiratory tract, explains the lack of contagion in legionellosis. The spread of the pathogen with the blood flow through various organs and systems leads to the development of microcirculation disorders, including distress syndrome, an inflammatory process with a hemorrhagic component, the formation of lymphoplasmacytic infiltrates and necrosis. These reactions are associated with exposure to certain bacterial factors (cytotoxin, cytolysin, phenylalanine amino peptidase). They cause toxic damage to cells, hydrolysis of proteins (including immunoglobulins) and amino acids, peptides and α-antitrypsin, hemolysis of erythrocytes, the development of hemorrhagic and necrotic processes. Particularly often affects the lungs, kidneys, liver, bone marrow. In severe bacteremia, sometimes the disease can occur in a septic type with the development of septic endocarditis, pericarditis, and secondary purulent foci.

The release of the lipopolysaccharide complex (endotoxin) after the death of bacteria and progressive endotoxemia cause clinical manifestations of intoxication up to toxic encephalopathy and infectious toxic shock. With the influence of toxic factors associated with the possibility of inhibition of blood formation in the bone marrow, liver cell necrosis, epithelium of the renal tubules, which, along with microcirculatory disorders in the kidneys, leads to the development of acute renal failure.

Symptoms of Legionellosis (Legionnaires Disease)

Incubation period. In various clinical forms of the disease varies from 2 to 10 days, averaging 4-7 days.

The most often clinically legionellosis is diagnosed as severe pneumonia (actually “legionnaires disease”). In the first days of the disease in some patients prodromal phenomena can be observed in the form of headache, weakness, loss of appetite, and diarrhea may develop. In the acute onset of the disease, the temperature quickly rises to 39–40 ° C, and signs of severe intoxication increase. Patients complain of chills, headache, pain in muscles and joints, severe sweating. General weakness, adynamia develop. There are signs of toxic damage to the central nervous system: emotional lability, lethargy, fainting, hallucinations, loss of consciousness and delusions. Sometimes ataxia, dysarthria, nystagmus, and paralysis of the eye muscles are observed. By the middle of the week, there is a cough, first dry, then with scanty mucopurulent, and in some patients with bloody sputum. Dyspnea and severe chest pain develop, especially with concomitant fibrinous pleurisy. In the lungs, dullness of percussion sound, areas of weakened breathing, a large number of dry and moist finely wheezing are detected. Almost half of the patients listen to pleural friction noise. On the radiograph determine focal infiltrates of diverse localization; subsequently, they merge and form extensive foci of darkening of the type of lobar, and quite often one-sided subtotal and even total pneumonia.

The course of pneumonia is rapid, difficult to treat. The disease can complicate the development of abscesses, exudative pleurisy, and infectious toxic shock. Often despite the treatment, respiratory and cardiovascular insufficiency progresses, requiring the transfer of patients to mechanical ventilation.

Lesions of the cardiovascular system are manifested by hypotension, relative bradycardia, alternating tachycardia. Quite often (about 30% of cases) there are prolonged diarrhea with abdominal pain and rumbling of the intestines, hepatitis with jaundice and changes in blood biochemical parameters. There may be impaired renal function, including kidney failure, which persists for months. When recovering, asthenic syndrome (weakness, dizziness, memory loss, irritability), radiologically determined infiltrates in the lungs and pleural changes persist for many weeks.

Acute alveolitis. The appearance from the first days of the illness of dry cough against the background of high fever and other manifestations of intoxication (headache, myalgia, etc.) is characteristic. In the future, the cough becomes wet with discharge of mucous or muco-purulent sputum, shortness of breath increases. In the lungs during auscultation on both sides listen to abundant diffuse, long-lasting crepitus. The process takes place with sweating in the alveoli of erythrocytes, fibrin, edema of the alveolar septa. In some cases, the disease acquires a protracted progressive course with the development of fibrosis.

Acute respiratory disease (Pontiac fever). Legionella infection occurring without pulmonary lesions. Against the background of temperature, rapidly rising to -40 ° C, chills, headache, diffuse myalgia appear. Respiratory syndrome develops in the form of rhinitis, tracheobronchitis and bronchitis; it is often combined with abdominal pain and vomiting. Often identify neurological disorders: dizziness, insomnia, disorders of consciousness and coordination of varying degrees. The course of the disease is favorable, the duration of the main clinical manifestations is on average several days; residual asthenovegetative syndrome lasts much longer.

Acute febrile illness with exanthema (Fort Bragg fever). A rarer form of legionellosis. Against the background of moderate general toxic and respiratory phenomena (more often in the form of bronchitis), a rash of a large-spotted, core-like, scarlet-like or petechial nature occurs. Elements of the rash do not have a certain characteristic localization, after their disappearance, peeling of the skin, as a rule, is not observed.

In much more rare cases, the disease can occur in other forms: from subclinical to severe generalized forms with multiorgan lesions and sepsis.

The most terrible complication is infectious-toxic shock that occurs during legionella pneumonia. According to the WHO, in these cases the frequency of deaths of the disease reaches 20%.

Diagnosis of Legionellosis (Legionnaires Disease)

Legionellosis should be distinguished from pneumonia of various etiologies – staphylococcal, pneumococcal, mycoplasma, klebsiellosa, caused by Pseudomonas bacillus, etc., as well as SARS, Q-fever, ornithosis, and other diseases of the lungs. Legionella etiology pneumonia is characterized by severe intoxication with the development of toxic encephalopathy, the extensive nature of lung lesions, and a tendency to complications (respiratory and cardiovascular insufficiency, hepatitis, renal impairment).

Laboratory diagnosis
In the hemogram, leukocytosis is detected with a shift to the left, a significant increase in ESR (more than 60 mm / h).

Isolation of the pathogen from the blood, sputum, pleural fluid, bronchial wash water is difficult and rarely used in practice, although the bacteriological method is the most accurate confirmation of the etiology of legionella infection. Bacteria can be distinguished by sowing the test material on special nutrient media or after infection of laboratory animals (guinea pigs). More available is the indication of legionella antigen in the material under investigation by the RIF and FA methods.

In wide practice, methods for the determination of antibodies in microagglutination and HIF reactions are common. A 4-fold increase in antibody titers in paired sera or a diagnostic titer of 1: 128 and higher in a single study is considered to be diagnostically significant results. The enzyme immunoassay method allows detection of soluble legionella antigen in the urine during the acute period of the disease (3-10th day of illness). The method is developed only for the detection of antigens of the first L. pneumophila serogroup. PCR is used to study the material of the lower part of the respiratory tract in the acute phase of the disease. The specificity of the method is 95-99%, the sensitivity is 80-85%.

Legionellosis Treatment (Legionnaires Disease)

The basis of etiotropic therapy of legionellosis is the use of macrolides. In particular, erythromycin is administered orally at a dose of 2-4 g / day, in severe cases administered intravenously (Erythromycin Phosphate at 1 g / day, up to a maximum of 2-3 g / day). In the absence or low severity of the clinical effect of antibiotic therapy supplement the appointment of rifampicin at a dose of 0.6-1.2 g / day. The course of treatment is 2-3 weeks. Fluoroquinolone (pefloxacin) also has a good clinical effect.
Pathogenetic treatment aimed at combating intoxication, bleeding, development of respiratory and renal failure, shock states, is carried out according to generally accepted rules. Needed oxygen therapy, often used mechanical ventilation.

Legionellosis Prevention (Legionnaires Disease)

Epidemiological surveillance includes monitoring the sanitary and hygienic state of water conditioning and cooling systems, shower installations, ventilators, etc. The timely detection of the pathogen’s water reservoir and disinfection are of particular importance.

Preventive measures are carried out to monitor the operation of the air conditioning system, the quality of water used for medical and hygienic procedures, and the ventilation system. Preventive measures are aimed at reducing the concentration or elimination of the pathogen in aquatic systems. The main methods of disinfection are thermal (warming water at a temperature not lower than 80 ° C) and chemical (using chlorine). These methods or their combination are used depending on the type of water body to be disinfected. In industrial plants, power plants, hospitals and hotels, closed water systems must be cleaned and flushed at least 2 times a year. When detected in legionella systems, quarterly disinfection measures are performed, followed by a mandatory bacteriological examination of water. In place of chlorination and heat treatment, often negatively affecting the operation of water systems and devices, they are actively introducing chlorine-free disinfectants, ultraviolet radiation, or devices that enrich the water with silver and copper ions. The means of specific prophylaxis of legionellosis are not developed.

Activities in the epidemic focus
Carry out the identification of patients among those who were in conditions similar to those during infection with Legionella. Hospitalization of patients is carried out only according to clinical indications. Dispensary observation of patients who have not been regulated. Due to the fact that there is no reliable data on the possibility of legionella transmission from person to person, they do not carry out disconnection and emergency prevention of contact persons. Disinfection in the outbreak is not carried out.

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