Epidemiology

• The Health Protection Agency (HPA) data is derived from laboratory confirmed reports and follow up questionnaires that collect information on whether the case is community, hospital acquired or travel associated.^[1]
• LD is an uncommon form of pneumonia. The disease has no particular clinical features that clearly distinguish it from other types of pneumonia, and laboratory investigations must therefore be carried out in order to obtain a diagnosis. Epidemiological definitions are given in the table below.
• Between 1980 and 2001 the HPA received reports of between 150 and 250 cases a year but since 2002 cases of LD have exceeded 300. In 2006 there were over 500 cases, reducing to 359 cases in 2008.^[1] From these figures it can be derived that:
  • It is 2 to 5 times more common in men.
  • The death rate is about 10 to 15%.
  • 40 to 50% of all cases are related to travel, usually abroad.
  • These numbers are an underestimate because of failure to diagnose and hence report less severe cases (CDC estimates that <10% of cases are reported).
  • Older people are more likely to be infected and are more likely to die.
  • Numbers are highest between June and September.
• The HPA give an epidemiological classification to clarify what their statistics refer to:

Pathophysiology

This organism lives naturally in water. It causes disease when water droplets containing the bacterium enter the atmosphere as fine particles or in an aerosol that enables them to be inhaled deep into the lungs. There they replicate and cause disease. Cooling towers are often a source of infection, as they produce a very fine aerosol. Spa baths, misting machines and showers have also been identified as sources of infection in the past. So too have air conditioning systems, especially if poorly maintained. The disease is not spread from person-to-person. 50% of Pontiac fever outbreaks have been linked to whirlpool spas or hot tubs.

Risk factors

These are all factors that impair immunity and include:

• Smoking
• Malignancy (particularly lung cancer and haematological malignancy)
• AIDS
• End stage chronic renal failure
• COPD
• Advanced age
• Alcohol abuse
• Recent surgery

Presentation

History

Two distinct clinical syndromes can be caused by different species, "pneumonic" and "non-pneumonic" (primarily Pontiac fever).

• Pneumonic - the more severe, Legionnaires' disease:
  • The incubation period is usually 2-10 days.
  • There is a prodrome for a day or two of mild headache and myalgia, followed by high fever, chills, and multiple rigors.
  • 90% present with a cough that is usually unproductive at first but may progress to being productive.
  • Up to a third may have dyspnoea, pleuritic chest pain and haemoptysis.
  • There may be nausea, vomiting, diarrhoea and anorexia.
  • Headache is common and the mental state may be impaired but focal signs are rare.
  • Symptoms outside the chest predominate in the early stages but pulmonary symptoms predominate later.
• Non-pneumonic:
  • Has a higher attack rate in outbreaks.
  • A shorter 1-2 days incubation period than the pneumonic form.
  • The influenza-like illness with myalgia, fever, and headache is almost invariable. Only 50% having a cough.
  • The disease is self-limiting.
  • This similarity to other viral illnesses, coupled with an understandable lack of urgency in even seeking diagnosis, let alone the difficulties in actually achieving one, mean most cases and outbreaks are undiagnosed.

Examination

Pneumonic:

• Pyrexia and tachypnoea are common but for the level of temperature, there is a relative bradycardia in two thirds. This means that the pulse rate is not as high as would be expected for that level of temperature and not that it is slower than usual.
• There are no abnormalities in the upper respiratory tract but examination of the chest may show rales, rhonchi or consolidation.
• Rarer features include pericarditis, hepatomegaly and impaired mental state.

Investigations

• It can be an issue deciding when and how to investigate community-acquired pneumonias (CAP). British Thoracic Society guidelines^[3] recommend investigations for legionella infection for all patients with severe CAP, for other patients with specific risk factors, and for all patients with CAP during outbreaks.^[3]
• For the purpose of confirmation of a case the HPA require one of the following:
  • The Gold standard is isolation and culture of legionella species from clinical specimens, usually sputum - note: non-pneumophilic cases are almost universally culture negative.
  • Seroconversion, meaning at least a four-fold increase in titre of indirect immunofluorescent antibody test (IFAT) incorporating a monovalent L. pneumophila serogroup 1 antigen by a validated technique.
  • Confirmation of L. pneumophila urinary antigen using validated reagents or kits. Culture of sputum and serology have been the standard tests for many years but the development of urine testing gives faster results, improves the rate of correct diagnosis and because the result is swifter it allows earlier correct treatment resulting in a lower mortality.^[4]
  • There are no commercial tests to confirm specific non-pneumophilic infections, and serological conversion rates are variable. The shift towards urine testing is likely to further limit detection of non-pneumophilic cases unless better tests for the full range of legionella species are developed.
• A presumptive case is where there is:
  Either:
  • a clinical diagnosis of pneumonia with a single high titre of 128 using IFAT or a single titre of 64 in an outbreak.
  Or:
  • A positive direct fluorescence (DFA) on a clinical specimen using validated monoclonal antibodies (also referred to as a positive result by Direct Immunofluoresence).
• Other investigations include:
  • FBC that will show a leukocytosis and possibly disseminated intravascular coagulation.
  • U&E and creatinine as there may be dehydration and occasionally inappropriate secretion of ADH produces hyponatraemia.
  • Alkaline phosphatase may be low and along with abnormal LFTs this is an uncommon feature of pneumonia that may suggest the diagnosis.
  • Blood gases in pneumonia.
  • CXR is not specific but may show patchy consolidation and up to half may have pleural effusion. This may take 1 to 4 months to resolve
  • With alteration in mental state lumbar puncture and CT of the brain may be required to exclude other causes. They are both normal in LD.

Differential diagnosis

• Other causes of pneumonia, especially mycoplasma or viral.
• Left ventricular failure.
• Severe acute respiratory syndrome (SARS).

Legionnaires' disease must be in the differential diagnosis for any community-acquired pneumonia.

Management

• Pain and temperature may require drugs such as paracetamol, and oxygen is indicated if there is hypoxia.
• The antibiotic of choice is probably erythromycin although gastrointestinal upset from the disease and the tendency of this drug to do the same may make it less attractive. Doxycycline is an excellent alternative.^[5] Tetracycline, ciprofloxacin, other fluoroquinolone and macrolide drugs may be indicated.^[6] The course should be 10 to 21 days.^[7] In critically ill patients the newer macrolides and fluoquinones should be used as first line therapy.^[8]

Complications

Respiratory insufficiency, dehydration, multiple organ failure, acute renal failure.

Prognosis

About 10 to 15% die overall representing about 10% of those who are treated and not immunocompromised but rising to 80% in those who are untreated and immunocompromised. The death rate in nosocomial infection is around 50% but figures on death rates are very much complicated by other pathology. Early detection and treatment improves outcome.^[9]

Prevention

• Travel associated Legionnaires' disease is linked to stays in holiday accommodation where intermittent use of facilities, variable temperatures and seasonal fluctuations of water flow may increase the risk of infection.
• Prevention needs to be a collaborative effort between health professionals, governments and the tourist industry and enormous progress has been made since EWGLI (European working group for legionella infections) began in 1986 to coordinate such activities in Europe - as a result a legionellosis surveillance network now connects 36 countries that report travel-associated cases to a computerised database in London.^[10]
• Travellers in the highest risk groups must seek medical attention as soon as possible if they suspect they might have Legionnaires' disease. The increasing number of whirlpool spas and hot tubs in hotels and cruise ships, and the difficulty in tracking outbreaks of Pontiac fever, emphasise the importance of adequate filtration and disinfection measures, coupled with strict application of bather capacity. If doctors are suspicious of chest infections acquired abroad then erythromycin or doxycycline are preferable to amoxicillin.
• Legionella species are ubiquitous in water supplies and the role of hospital water supplies in the spread of nosocomial infection is unclear. Water should be kept above 55?C and probably the bacterium should be sought, even in the absence of known infection, especially in places like transplant units where patients are very vulnerable.^[11]
• Public opinion about hospital-acquired infection is also creating pressure for a pro-active approach.^[12]
• Detection of outbreaks and detection of clusters is important and secondary preventive measures can then be undertaken.^[13]