EXPERIMENTAL TRANSMISSION OF LEGIONNAIRES' DISEASE BY EXPOSURE TO AEROSOLS OF LEGIONELLA PNEUMOPHILA

doi:10.1016/S0140-6736(81)92803-8

The Lancet

Volume 318, Issues 8260–8261, 26 December 1981, Pages 1389-1390

https://doi.org/10.1016/S0140-6736(81)92803-8 Get rights and content

Abstract

Pyrexia and pneumonia developed in guinea-pigs after exposure to aerosols of Legionella pneumophila in a Henderson apparatus. Mortality was high 1-3 days after exposure. Histopathological changes were of an acute fibrinopurulent pneumonia, with widespread fibrin exudation and accumulation of neutrophils and macrophages in alveoli—lesions similar to those of legionella pneumonia in man. Rhesus monkeys given low doses of bacteria had slight fever and mild histological lesions in the lungs. Aerosol infection of these species offers suitable experimental models of legionnaires' disease.

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The study of virulence of Legionella pneumophila and its interactions with its hosts has been predominantly conducted in cellulo in the past decades. Although easy to implement and allowing the dissection of molecular pathways underlying host-pathogen interactions, these cellular models fail to provide conditions of the complex environments encountered by the bacteria during the infection of multicellular organisms. To improve our understanding of human infection, several animal models have been developed. This review provides an overview of the invertebrate and vertebrate models that have been established to study L. pneumophila infection and that are alternatives to the classical mouse model, which does not recall human infection with L. pneumophila well. Finally we provide insight in the main contributions made by these models along with their pros and cons.
Epidemiological analysis of Legionnaires' disease in Scotland: a genomic study
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Citation Excerpt :
More than 30 Legionella species can invade immune cells and cause opportunistic human respiratory infections.1 However, over 90% of infections are caused by a single species, Legionella pneumophila, which is typically inhaled from contaminated environmental aerosols.2 Legionellosis varies from a mild flu (Pontiac fever) to Legionnaires' disease, an atypical, often severe form of pneumonia with a 10% mortality rate.1
Legionella pneumophila is the main cause of a severe pneumonic illness known as Legionnaires' disease and is a global public health threat. Whole-genome sequencing (WGS) can be applied to trace environmental origins of L pneumophila infections, providing information to guide appropriate interventions. We aim to explore the evolutionary and epidemiological relationships in a 36-year Scottish L pneumophila reference isolate collection.
We investigated the genomic epidemiology of Legionnaires' disease over 36 years in Scotland, comparing genome sequences for all clinical L pneumophila isolates (1984–2020) with a sequence dataset of 3211 local and globally representative isolates. We used a stratified clustering approach to capture epidemiological relationships by core genome Multi-locus Sequence Typing, followed by high-resolution phylogenetic analysis of clusters to measure diversity and evolutionary relatedness in context with epidemiological metadata.
Clustering analysis showed that 111 (57·5 %) of 193 of L pneumophila infections in Scotland were caused by ten endemic lineages with a wide temporal and geographical distribution. Phylogenetic analysis of L pneumophila identified hospital-associated sublineages that had been detected in the hospital environment up to 19 years. Furthermore, 12 (30·0%) of 40 community-associated infections (excluding a single, large outbreak) that occurred over a 13 year period (from 2000 to 2013) were caused by a single widely distributed endemic clone (ST37), consistent with enhanced human pathogenicity. Finally, our analysis revealed clusters linked by national or international travel to distinct geographical regions, indicating several previously unrecognised travel links between closely related isolates (fewer than five single nucleotide polymorphisms) connected by geography.
Our analysis reveals the existence of previously undetected endemic clones of L pneumophila that existed for many years in hospital, community, and travel-associated environments. In light of these findings, we propose that cluster and outbreak definitions should be reconsidered, and propose WGS-based surveillance as a critical public health tool for real-time identification and mitigation of clinically important endemic clones.
Chief Scientist Office, Biotechnology and Biological Sciences Research Council (UK), Medical Research Council Precision Medicine Doctoral Training Programme, Wellcome Trust, and Medical Research Council (UK).
The mysterious illness that drove them to their knees - Ah, that Legionnaires’ disease – A historical reflection of the work in Legionnaires’ disease in New Zealand (1978 to mid-1990s) and the ‘One Health’ paradigm
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Citation Excerpt :
The epidemiological investigation led by David Fraser of the US CDC into the 1976 LD outbreak suggested the disease was most probably spread by the air borne route [49] but the ubiquitous presence of Legionella spp. in the environment was not fully known until 1980. By 1981 evidence for confirmation of human exposure to LD via an airborne route was obtained [50] through inducing experimental respiratory infection in guinea pigs and rhesus monkeys using a strain of L. pneumophila that was isolated from a contaminated domestic water supply. In 1979 the NHI provided the back-up for New Zealand’s first occurrence of L. pneumophila infection via serological immunocytological and histological techniques and was reported in the New Zealand Medical Journal [51].
And so, formed the basis for the song Legionnaires’ disease (LD) composed by the legendry musician Bob Dylan shortly after this mysterious illness dramatically entered the clinical and epidemiological scene in July 1976 at an American hotel. Now more than forty years have passed since Legionella pneumophila, the causative agent of LD, was formally identified in 1977. Once the publicity associated with the outbreak subsided, there was the challenge to science and health professionals of what was an extremely complex and intriguing health concern. In the United States, the outbreak investigation that eventually solved the mystery had taken an array of surprising twists and turns. Globally, it revealed the strengths and weakness of countries’ health systems in response to the outbreak from an unknown agent. Extensive international coverage of the outbreak also marked a turning point in journalism’s efforts to hold officials accountable for their response to epidemics that had the potential to threaten the lives of hundreds of people. In 1979, New Zealand became an active participant in the international efforts towards increasing the understanding of infection caused by Legionella species and set up a centralized laboratory diagnostic service. By 1980 LD had become a notifiable disease making New Zealand one of the first countries globally to do so. This historical narrative in the decade or so from its recognition, provides a unique insight into how the One Health paradigm was instrumental in New Zealand’s early response to LD in tandem with control strategies. The findings show that from 1979 the distribution of the Legionella species in New Zealand did not follow patterns observed in studies carried out globally.
Risk of infection from Legionella associated with spray irrigation of reclaimed water
2018, Water Research
Citation Excerpt :
When guinea pigs are exposed to aerosols of L. pneumophila they develop a pneumonic illness characterized by fever, weight loss and labored respirations that sometimes results in death. This syndrome resembles Legionnaires disease in humans (Berendt et al., 1980; Baskerville et al., 1981; Breiman and Horwitz, 1987). Berendt et al. (1980) carried out experiments to determine the infectivity and lethality of exposure to L. pneumophila, using guinea pigs.
Legionella pneumophila has been detected in reclaimed water used for spray irrigation of turfgrass in public parks and golf courses. This study determined the risks of infection from exposure to various levels of Legionella in reclaimed waters considering: the method of spray application; and the duration and frequency of exposure. Evaluation of these factors resulted in a risk of infection greater than 1:10,000 for several scenarios when the number of Legionella in the reclaimed water exceeded 1000 colony-forming units (CFU) per ml. Most current guidelines for control of Legionella in distribution systems recommend that increased monitoring or remedial action be taken when Legionella levels exceed 1000 to 10,000 CFU/ml. Based upon our risk assessment, these guidelines seem appropriate for reclaimed water systems where spray irrigation is practiced.
Greywater reuse - Assessment of the health risk induced by Legionella pneumophila
2017, Water Research
Greywater (GW), domestic wastewater excluding the streams generated by toilets and kitchens, can serve as an alternative water source. The main options for GW reuse are toilet flushing and garden irrigation, both generating aerosols. These may transmit inhalable pathogens like Legionella and present a potential health risk. This study quantified the health risk that may arise from inhalation of Legionella-contaminated aerosols due to non-potable GW reuse. Data on Legionella concentrations in potable water and GW was collected. Then, Quantitative Microbial Risk Assessment (QMRA) was performed for two possible exposure scenarios: garden irrigation and toilet flushing. This was performed while considering Legionella seasonality. In order to determine the safety of GW reuse regarding Legionella transmission, the obtained results were compared with estimated tolerable risk levels of infection and of disease. Both limits were expressed as Disability-Adjusted Life Years index (DALY) being 10⁻⁴ and 10⁻⁵, respectively. The QMRA revealed that the annual risk associated with reuse of treated and chlorinated GW for garden irrigation and toilet flushing was not significantly higher than the risk associated with using potable water for the same two purposes. In all studied scenarios, the health risk stemming from reusing treated and chlorinated GW was acceptable regarding Legionella infection. In contrast, reuse of untreated or treated but unchlorinated GW should not be practiced, as these are associated with significantly higher health risks.
From Single Cells to Engineered and Explanted Tissues: New Perspectives in Bacterial Infection Biology
2015, International Review of Cell and Molecular Biology
Citation Excerpt :
Tissue explants play an important role in in vitro analysis of bacterial pathogens showing restrictive species-specificities such as the human pathogen of Legionnaires' disease L. pneumophila for the human lung. Until recently, mammalian models such as guinea pigs, mice, rhesus monkeys, and marmosets were employed to address immunological, pathological, and pharmacological questions (Baskerville et al., 1981; Blanchard et al., 1987; Fitzgeorge et al., 1983), although data from these animal models cannot be easily generalized because of important interspecies differences in the expression, function, and localization of immune molecules (e.g., receptors, signaling intermediates, response molecules). Cell culture assays on the other hand lack the complex interaction networks between the specialized cell types and extracellular components in the human lung.
Cell culture techniques are essential for studying host–pathogen interactions. In addition to the broad range of single cell type-based two-dimensional cell culture models, an enormous amount of coculture systems, combining two or more different cell types, has been developed. These systems enable microscopic visualization and molecular analyses of bacterial adherence and internalization mechanisms and also provide a suitable setup for various biochemical, immunological, and pharmacological applications. The implementation of natural or synthetical scaffolds elevated the model complexity to the level of three-dimensional cell culture. Additionally, several transwell-based cell culture techniques are applied to study bacterial interaction with physiological tissue barriers. For keeping highly differentiated phenotype of eukaryotic cells in ex vivo culture conditions, different kinds of microgravity-simulating rotary-wall vessel systems are employed. Furthermore, the implementation of microfluidic pumps enables constant nutrient and gas exchange during cell cultivation and allows the investigation of long-term infection processes. The highest level of cell culture complexity is reached by engineered and explanted tissues which currently pave the way for a more comprehensive view on microbial pathogenicity mechanisms.

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Preliminary CommunicationsEXPERIMENTAL TRANSMISSION OF LEGIONNAIRES' DISEASE BY EXPOSURE TO AEROSOLS OF LEGIONELLA PNEUMOPHILA

Abstract

Legionnaires' disease: Description of an epidemic of pneumonia

N Engl J Med

Legionnaires' disease in Nottingham

Lancet

Legionnaires' disease-the Benidorm episode

Scot Med J

Illness associated with 'package tours': A combined Spanish-Scottish study

Bull WHO

Classification of the legionnaires' disease bacterium-an interim report

Curr Microbrol

Legionnaires' disease: Pathological and historical aspects of a "new" disease

Arch Pathol Lab Med

Legionellosis

J Pathol

Legionnaires' disease: Isolation of a bacterium and demonstration of its role in other respiratory disease

N Engl J Med

Primary isolation media and methods

A mobile form of the Henderson apparatus

J Hyg (Camb)

Preliminary Communications
EXPERIMENTAL TRANSMISSION OF LEGIONNAIRES' DISEASE BY EXPOSURE TO AEROSOLS OF LEGIONELLA PNEUMOPHILA