Legionnaires' disease outbreak investigation toolbox

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Legionella effects on individuals

Infectiousness of aerosolised organisms

The locations of infection for cases of Legionnaires' disease have occasionally been epidemiologically-linked to sources up to several kilometres from the point of presumptive release of aerosolised organisms. An expected reduction in aerosol concentration away from source, combined with environmental and meteorological effects, would suggest that the doses of inhaled organisms required to induce symptoms in humans can be low. However, given the likely geographic extent of the exposed population, the probability of infection may also be low. It is notable that no evidence has been found to indicate that cases infected nearer a source, and therefore more likely to have received a higher dose, had shorter incubation periods than those at some distance away from it.

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Incubation period

The incubation period is the time interval between initial infection and the appearance of the first symptom or sign of disease. As with most other infections, the incubation period is right skewed about the mean and has a relatively long tail. The distribution of incubation periods from an outbreak appears to be effectively described by a range of parametric mathematical probability distributions.

Three past outbreak investigations have reported incubation periods with a median value of 6 days, but with a significant proportion of cases having incubation periods in excess of the classic 10 day limit. Choosing an upper limit of 14 days for the purpose of outbreak control is arguably more inclusive and could reduce the number of missed or misclassified cases.

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Immune response to a Legionella infection

The mammalian immune response to a Legionella infection can be summarised as follows:

  • Innate immune response - When Legionella pneumophilla enters the lungs it is engulfed by macrophages where it is able to replicate. The Legionella replication causes the macrophage to release cytokines which attract the attention of Natural Killer cells. These then stimulate the macrophages, by releasing IFN-γ, enabling them to restrict Legionella growth.
  • Adaptive immune response - Immature dendritic cells (DCs) present in the lung are infected by the Legionella bacteria. The bacteria inside the DC are not destroyed but are prevented from further growth. The DC then goes through a process of maturation enabling it to produce Legionella antigens. The DCs then present the intracellularly-produced antigen to T-cells thus allowing the T-cells to produce IFN-γ and assist in the removal of the infection.

In a wide variety of mammals, this system works well enough to prevent an infection of Legionella pneumophilla from becoming a fully symptomatic disease. However, in the case of humans and guinea-pigs, there is no innate response thus allowing the bacteria to exist in the lungs until the adaptive response is able to react.

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An atypical pneumonia diagnosis of Legionnaires' disease is not obvious. Initially the patient will have non-specific symptoms including fever, malaise, loss of appetite and headache. Gastrointestinal symptoms are also prominent, with diarrhoea occurring in about 20 - 40% of cases. If left undiagnosed and untreated, the patient could go on to suffer respiratory- and even multi-organ failure. A chest x-ray alone will be insufficient evidence for the observer to distinguish between legionellosis and other more usual causes of pneumonia, so specialised laboratory tests are required (see here for further discussion on the microbiological tests used).

The gold standard test for Legionnaires' disease is to culture the organism using sputum or bronchial lavage from a suspected patient. However, as the organism can take some time to grow, it is not always the most efficient method in an ongoing outbreak setting. Legionella urinary antigen tests are significantly quicker and have high sensitivity and specificity.

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Experimental studies in animals exposed to aerosolised Legionella

Examination of available studies appears to suggest that some variation in reported incubation periods between studies may be due to experimental (exposure) methodology rather than any potential differences in the intrinsic biological susceptibility of the different strains of guinea pig used. Similar, relatively limited and consistent, dose-dependent trends, suggest only a relatively small increasing risk of infection and death with increasing dose, once a particular threshold has been passed.

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Background immunity/antibody level in population

One study found that out of 286 human sera only 1 tested positive for Legionella ; suggesting that humans are rarely infected by Legionella or that protection wanes and so most of the population are likely to have little or no pre-existing acquired-immunity against Legionnaires' disease. However another study found raised antibody levels in a population up to one year after an outbreak.

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