Legionnaires' disease

The length of time between exposure to the bacteria and the appearance of symptoms (incubation period) is generally 2–10 days, but more rarely can extend to as long as 20 days. For the general population, among those exposed, between 0.1 and 5.0% develop the disease, while among those in hospital, between 0.4 and 14% develop the disease. "Relative bradycardia" may also be present, which is low to normal heart rate despite the presence of a fever. Laboratory tests may show that kidney functions, liver functions, and electrolyte levels are abnormal, which may include low sodium in the blood. Chest X-rays often show pneumonia with consolidation in the bottom portion of both lungs. Distinguishing Legionnaires' disease from other types of pneumonia by symptoms or radiologic findings alone is difficult; other tests are required for definitive diagnosis. People with Pontiac fever, a much milder illness caused by the same bacterial genus, experience fever and muscle aches without pneumonia. They generally recover in 2–5 days without treatment. For Pontiac fever, the time between exposure and symptoms is generally a few hours to two days. ==Cause==

image of L. pneumophila, responsible for over 90% of Legionnaires' disease cases Over 90% of cases of Legionnaires' disease are caused by Legionella pneumophila. Other types include L. longbeachae, L. feeleii, L. micdadei, and L. anisa. Transmission Legionnaires' disease is usually spread by the breathing in of aerosolized water or soil contaminated with the Legionella bacteria. In 2014, one case of possible spread from someone sick to the caregiver occurred. Rarely, it has been transmitted by direct contact between contaminated water and surgical wounds. Sources where temperatures allow the bacteria to thrive include hot water tanks, cooling towers, and evaporative condensers of large air conditioning systems, such as those commonly found in hotels and large office buildings. Before 1988, energy conservation programs from the late 1970s and early 1980s still mandated a maximum hot water generation, storage, and distribution temperature of , unknowingly, Legionella bacteria's ideal breeding temperature. To minimize risks of bacterial growth, the American Society of Heating, Refrigerating and Air-Conditioning Engineers' 1988 ASHRAE Standard 188 and subsequent ASHRAE Guideline 12-2000 increased recommended hot water generation and storage temperatures to with minimum distribution temperatures of . Legionella bacteria survive in water as intracellular parasites of water-dwelling protozoa, such as amoebae. Amoebae are often part of biofilms, and once Legionella and infected amoebae are protected within a biofilm, they are particularly difficult to destroy. The bacteria may also be transmitted from contaminated aerosols generated in hot tubs if the disinfection and maintenance programs are not followed rigorously. Freshwater ponds, creeks, and ornamental fountains are potential sources of Legionella. The disease is particularly associated with hotels, fountains, cruise ships, and hospitals with complex potable water systems and cooling systems. Respiratory-care devices such as humidifiers and nebulizers used with contaminated tap water may contain Legionella species, so using sterile water is very important. Other sources include exposure to potting mix and compost. ==Mechanism==

Legionella species enter the lungs either by aspiration of contaminated water or inhalation of aerosolized contaminated water or soil. In the lung, the bacteria are consumed by macrophages, a type of white blood cell, inside of which the Legionella bacteria multiply, causing the death of the macrophage. Once the macrophage dies, the bacteria are released from the dead cell to infect other macrophages. Virulent strains of Legionella kill macrophages by blocking the fusion of phagosomes with lysosomes inside the host cell; normally, bacteria are contained inside the phagosome, which merges with a lysosome, allowing enzymes and other chemicals to break down the invading bacteria. ==Diagnosis==

People of any age may develop Legionnaires' disease, but the illness most often affects middle-aged and older people, particularly those who smoke cigarettes or have chronic lung disease. Immunocompromised people are also at higher risk. Pontiac fever most commonly occurs in those who are otherwise healthy. The most useful diagnostic tests detect the bacteria in coughed-up mucus, find Legionella antigens in urine samples, or allow comparison of Legionella antibody levels in two blood samples taken 3–6 weeks apart. A urine antigen test is simple, quick, and very reliable, but only detects L. pneumophila serogroup 1, which accounts for 70% of disease caused by L. pneumophila, which means use of the urine antigen test alone may miss as many as 30% of cases. This test was developed by Richard Kohler in 1982. When dealing with L. pneumophila serogroup 1, the urine antigen test is useful for early detection of Legionnaire's disease and initiation of treatment, and has been helpful in early detection of outbreaks. However, it does not identify the specific subtypes, so it cannot be used to match the person with the environmental source of infection. The Legionella bacteria can be cultured from sputum or other respiratory samples. Legionella spp. stain poorly with Gram stain, stain positive with silver, and are cultured on charcoal yeast extract with iron and cysteine (CYE agar). A significant under-reporting problem occurs with legionellosis. Even in countries with effective health services and readily available diagnostic testing, about 90% of cases of Legionnaires' disease are missed. This is partly due to the disease being a relatively rare form of pneumonia, which many clinicians may not have encountered before, thus may misdiagnose. A further issue is that people with legionellosis can present with a wide range of symptoms, some of which (such as diarrhea) may distract clinicians from making a correct diagnosis. ==Prevention==

Although the risk of Legionnaires' disease being spread by large-scale water systems cannot be eliminated, it can be greatly reduced by writing and enforcing a highly detailed, systematic water safety plan appropriate for the specific facility involved (office building, hospital, hotel, spa, cruise ship, etc.) • System design (or renovation) can reduce the production of aerosols and reduce human exposure to them, by directing them well away from building air intakes. An effective water safety plan also covers such matters as training, record-keeping, communication among staff, contingency plans, and management responsibilities. The format and content of the plan may be prescribed by public health laws or regulations. The legionella risk assessment identifies the hazards, the level of risk they pose and provides recommendations of control measures to put in place within the overarching water safety plan. ==Treatment==

Effective antibiotics include most macrolides, tetracyclines, ketolides, and quinolones.) because the antibiotics used (including penicillins, cephalosporins, and aminoglycosides) had poor intracellular penetration. Mortality has plunged to less than 5% if therapy is started quickly. Delay in giving the appropriate antibiotic leads to higher mortality. ==Prognosis==

The fatality rate of Legionnaires' disease has ranged from 5–30% during various outbreaks and approaches 50% for nosocomial infections, especially when treatment with antibiotics is delayed. ==Epidemiology==

Legionnaires' disease acquired its name in July 1976, when an outbreak of pneumonia occurred among people attending a convention of the American Legion at the Bellevue-Stratford Hotel in Philadelphia. Of the 182 reported cases, mostly men, 29 died. On 18 January 1977, the causative agent was identified as a previously unknown strain of bacteria, subsequently named Legionella, and the species that caused the outbreak was named Legionella pneumophila. Following this discovery, unexplained outbreaks of severe respiratory disease from the 1950s were retrospectively attributed to Legionella. Outbreaks of Legionnaires' disease receive significant media attention, but this disease usually occurs in single, isolated cases not associated with any recognized outbreak. When outbreaks do occur, they are usually in the summer and early autumn, though cases may occur at any time of year. Most infections occur in those who are middle-aged or older. National surveillance systems and research studies were established early, and in recent years, improved ascertainment and changes in clinical methods of diagnosis have contributed to an upsurge in reported cases in many countries. Environmental studies continue to identify novel sources of infection, leading to regular revisions of guidelines and regulations. About 8,000 to 18,000 cases of Legionnaires' disease occur each year in the United States, according to the Bureau of Communicable Disease Control. Between 1995 and 2005, over 32,000 cases of Legionnaires' disease and more than 600 outbreaks were reported to the European Working Group for Legionella Infections. The data on Legionella are limited in developing countries, and Legionella-related illnesses likely are underdiagnosed worldwide. During the COVID-19 pandemic, some researchers and organisations raised concerns about the impact of the COVID-19 lockdowns on Legionnaire's disease outbreaks. Additionally, at least two people in England died from a co-infection of Legionella and SARS-CoV-2. Outbreaks An outbreak is defined as two or more cases where the onset of illness is closely linked in time (weeks rather than months) and space, where a suspicion or evidence exists of a common source of infection, with or without microbiological support (i.e. common spatial location of cases from travel history). == References ==