|Year : 2018 | Volume
| Issue : 3 | Page : 324-333
Legionella and Legionnaires' disease: Time to explore in India
Rama Chaudhry1, K Sreenath1, Sonu Kumari Agrawal1, Arvind Valavane2
1 Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Microbiology, Indira Gandhi Medical College and Research Institute, Puducherry, India
|Date of Web Publication||14-Nov-2018|
Dr. Rama Chaudhry
Department of Microbiology, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Legionella pneumophila was first recognised as a fatal cause of pneumonia more than four decades ago, during the 1976-American Legion convention in Philadelphia, USA. Legionella spp. continue to cause disease outbreaks of public health significance, and at present, Legionnaires' disease (LD) has emerged as an important cause of community and hospital-acquired pneumonia. Parallel to this, the understanding of LD has also increased exponentially. However, the disease is likely to be underreported in many countries because of the dearth of common definitions, diagnostic tests and active surveillance systems. In this review, we outline the basic concepts of Legionella including clinical presentations, epidemiology, laboratory diagnosis and the status of LD in India. This article also summarises the progress of research related to Legionella in this country, identifying the research gaps and discussing priorities to explore this unexplored pathogen in India.
Keywords: Legionella, Legionnaires' disease, pneumonia
|How to cite this article:|
Chaudhry R, Sreenath K, Agrawal SK, Valavane A. Legionella and Legionnaires' disease: Time to explore in India. Indian J Med Microbiol 2018;36:324-33
|How to cite this URL:|
Chaudhry R, Sreenath K, Agrawal SK, Valavane A. Legionella and Legionnaires' disease: Time to explore in India. Indian J Med Microbiol [serial online] 2018 [cited 2019 Nov 15];36:324-33. Available from: http://www.ijmm.org/text.asp?2018/36/3/324/245389
| ~ Introduction|| |
Legionella pneumophila was first discovered in 1976, following a sudden epidemic of fever with pneumonia among the delegates of the American Legion conference in Philadelphia, USA. The US Centers for disease control and Prevention (CDC) had sent a team of scientists led by David Fraser for investigating the outbreak and by December 1976, Joseph Mc Dade isolated a new bacterium from guinea pigs exposed with infected lung tissue of a patient. The pathogen was named Legionella for its association with the American veterans who were the first victims.
The genus Legionella comprises >50 species; among these around 30 species can infect humans producing infections mainly in the lower respiratory tract (LRT). Legionella spp. are aerobic, Gram-negative, nonspore forming gamma proteobacteria with strict growth requirements. Legionella are ubiquitous in freshwater environments including rivers, lakes, streams, fountains and hot springs where they survive in association with complex biofilm communities and can replicate inside various protozoan hosts. Legionella spp. survive in aquatic systems having a temperature range of 25°C–37°C but can also withstand temperatures of >50°C for several hours and may propagate at low temperatures of <20°C.,
Pneumonia attributable to any Legionella species is known as Legionnaires' disease (LD) which is mostly transmitted via inhalation of infected aerosols. Other modes of transmissions are microaspiration of contaminated water in hospital settings and direct contact with Legionella in open wounds during surgery.,, Nature of infectious form, infective dose, etc., is still not known. Different strains of Legionella vary clearly in their virulence. Among all species, L. pneumophila is the most pathogenic accounting 90% of reported cases worldwide and L. pneumophila serogroup 1 (Lp1) is the most virulent serogroup causing >80% of LD., Legionella spp. are intracellular pathogens and in lungs, they infect mononuclear cells (alveolar macrophages). In addition to a normal phagocytic process, phagocytosis of L. pneumophila also occur by a unique mechanism (engulfment within a pseudopod coil) termed as coiling phagocytosis.
| ~ Legionnaires' Disease: Clinical Presentations|| |
Clinical manifestations of Legionella infections include fever with pulmonary involvement (LD) or without pneumonia (Pontiac fever) and an extrapulmonary infection. LD occurs, in the form of community-acquired pneumonia (CAP) that might clinically resemble other bacterial pneumonias. Symptoms range from mild infection to severe life-threatening pneumonia requiring hospital admission. The incubation period for LD is variable (2–14 days); the symptoms of LD include: fever at >38.8°C (67%–100%), cough (41%–92%), chills (15%–77%), dyspnoea (36%–56%), neurological abnormalities (38%–53%), myalgia or arthralgia (20%–43%), loose stools (19%–47%), chest pain (14%–50%), headache (17%–43%) and nausea or vomiting (9%–25%).,,, Legionella may spread to internal organs via the blood and the lymphatics involving liver, kidney, spleen, heart, bone marrow, lymph nodes, gastrointestinal tract and central nervous system. Diarrhoea, nausea, vomiting and abdominal pain are the common gastrointestinal symptoms. Neurological findings include headache, seizures and focal neurological deficits., In immunosuppressed individuals, the most common clinical presentation of LD is pneumonia, which may disseminate to other parts of the body.
The laboratory findings in LD are non-specific including hyponatraemia, elevated serum creatine kinase, myoglobinuria, leucocytosis with relative lymphopenia, high erythrocyte sedimentation rate and C-reactive protein levels. The chest X-ray of LD show unilobar, patchy infiltrates progressing to consolidation; and pleural effusion is evident in 15%–50% of the individuals. In immunosuppressed patients round nodular opacities is a prominent finding and cavitations is seen in about 10% of the cases. Pontiac fever is non-pneumonic disease associated with exposure to Legionella bacteria.,
| ~ Legionella and Legionnaires' Disease: Global Epidemiology, Incidence and Summary of Outbreaks|| |
The global incidence of LD is unknown; it is under-reported in many countries mainly due to lack of awareness, scarcity of diagnostics and active LD surveillance systems. It is estimated that LD accounts for 2%–9% of cases of CAP worldwide., Legionnaire's disease is a notifiable disease in the USA and approximately 10,000–20,000 cases of LD occur each year in the United States. Reports from the USA point out 192% increase in the crude national incidence of LD, escalating from 3.9 cases per million inhabitants in 2000 to 11.5 cases per million inhabitants in 2009. This is mainly due to a sharp increase in diagnostic testing for LD, changes in case reporting methods and enlargement of the susceptible population. LD was confirmed using urinary antigen testing (UAT) in 97% of cases, and only 5% were diagnosed by culture.
Majority of LD cases were occurring during summer and early autumn showing a seasonal variation. The disease affects usually males >50 years of age having lung diseases or immunosuppression. Susceptibility of disease is also associated with old age, smoking, alcohol misuse, recent overnight travel, underlying medical conditions including diabetes, malignancies, HIV infection and end-stage renal diseases.,, LD surveillance data from 20 states and a large metropolitan area from US in 2015 showed that health care associated LD cases were reported from 72 centres; and infections were fatal in one-fourth of the individuals.
LD cases reported to the European LD surveillance network were 4000–5000 in 2011; and the disease prevalence was 9.7 cases per million inhabitants. Afterward, between 2011 and 2015, 29 countries reported 30,532 LD cases to European Centers for Disease Control and Prevention. Among the European Union member countries, France, Germany, Italy, and Spain accounted for 70.3% of all reported cases.,,
In the USA and Europe, Lp1 is responsible for 70%–92% of cases and this serogroup account for 50% of LD cases in Australia. Other serogroups and species including L. pneumophila serogroup 6, L. longbeachae, L. micdadei, L. bozemanii etc., account for most of the remaining cases. In Australia and New Zealand, 30%–55% of reported LD cases are caused by L. longbeachae. LD is associated with substantial CAP severity and higher fatality rates (up to 30%) than other atypical pathogens., Outbreaks of LD in hotels, cruise ships, office buildings and health-care facilities have been reported.,, Notable worldwide outbreaks of LD from 1976 to 2017 are depicted in [Table 1].
|Table 1: Summary of selected notable outbreaks of Legionnaires' disease from 1976 to 2018|
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| ~ Laboratory Detection of Legionella spp. and Legionnaires' Disease|| |
Legionella spp. require special media and preferably pre-treatments (heat or acid) for growth. Culturing LRT specimen on selective media; buffered charcoal yeast extract agar is the gold standard and is the most specific method (specificity near 100%) for detection of L. pneumophila., Isolation of Legionella from clinical specimens allows epidemiological typing possible, thereby providing valuable data for control and prevention of further cases. Monoclonal direct fluorescent antibody (DFA) staining is a rapid method for detecting Legionella in respiratory secretions and tissue sample. At present, DFA is not widely used for Legionella diagnosis due to limitations in sensitivity and specificity.,,
Detection of soluble antigen in urine provides rapid qualitative detection of Legionella infections. At present, the UAT is available as a card/strip based immunochromatographic assay (Binax NOW Legionella urinary antigen test) that is easy to perform and having a turnaround time of 15 min. The captured antibody used in these assays is specific for Lp1; hence solely depending UAT can create a blind spot for LD caused by non-Lp1 strains., Concentrating the urine sample improves the sensitivity of antigen detection, but prolonged storage of specimens may hamper the test performance due to degradation of Legionella urinary antigen.
Serologic tests (indirect immunofluorescence assay [IFA] and enzyme-linked immunosorbent assays (ELISA) are valuable for epidemiological investigations, but the requirement of a convalescent sample for testing has limited the utility of these tests in patient treatment. The diagnosis is based on a four-fold increase in antibody titre to 1:128 or more between acute and convalescent-phase serum samples taken 4–8 weeks apart. Challenges in serological assays are cross-reactivity among Legionella spp. and non-Legionella bacteria; besides a proportion of people having LD do not have detectable seroconversion.,,,
Nucleic acid amplification tests (NAAT) allows specific amplification of Legionella DNA, report results within a short time frame and can detect all Legionella spp. and serogroups. When testing a LRT specimen, polymerase chain reaction (PCR) offer sensitivity equal to or greater than culture (80%–100%). Legionella DNA can be detected in urine, serum and leukocyte samples but sensitivity is variable (30%–86%). Sensitivity of molecular assays is likely to increase when samples are collected in the early course of the infection. Currently, real-time PCR is considered as the molecular method of choice for detecting Legionella infections providing sensitivity, specificity and rapid results. CDC has developed multiplex real-time PCR assays for detecting Legionella spp., L. pneumophila, Lp1 and other clinically important non-pneumophila species such as L. anisa, L. bozemanii, L. longbeachea and L. micdadei.,, Summary of laboratory detection of Legionella spp. and LD is depicted in [Table 2] and [Figure 1].
|Table 2: Summary of diagnostic tests for Legionnaires' disease and associated infections|
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|Figure 1: Type of specimens and diagnostic tests for detecting Legionella infections: Lower respiratory tract secretions, urine and blood samples can be collected and diagnosis of LD should be done by a panel of tests including culture, urinary antigen detection, serological assays and nucleic acid amplification test. Legionella infection in extrapulmonary sites including soft tissues, synovial fluid and dissemination via blood to internal organs such as spleen, heart, lymph node is very rare. Routine testing of specimens from these sites are not recommended.|
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| ~ Legionella and Legionnaires' Disease: Trends in India|| |
Legionella-preliminary studies and initial evidence in India, 1990–2000
In a preliminary study involving 45 patients having pneumonia; Agrawal et al. in 1991 demonstrated that 9% of clinical specimens were positive for L. pneumophila. Subsequent environmental screening for Legionella at that time showed 76% positivity among the water samples tested. This was the first report of isolation of L. pneumophila in India. Later on, in 1992, Bahl et al. studied 100 patients suffering from LRT infection over a period of 2 years in North India. Culture, DFA staining and serology (IIF and ELISA) were used for LD detection, but the presence of Legionella was not evident in the samples tested. Chaudhry et al., in 2000 reported serologic evidence of recent Legionella infection in 15% of patients having CAP. These reports suggested that L. pneumophila can be one important cause of CAP and warranted empirical treatment with macrolides while treating patients having pneumonias.
Detection rates in clinical specimens, 2000–2010
Few studies based on serologic tests were conducted during this period to detect L. pneumophila in CAP patients. Chaudhry et al. in 2010 reported a total seropositivity of 27.43% by ELISA; anti L. pneumophila IgG, IgM and IgA positivities were 7.96%, 15.92% and 11.50%, respectively. L. pneumophila antigenuria (microwell ELISA) was positive in 17.69% of individuals and there was no culture positivity. Anbumani et al. during the same period had reported isolation rate of 2.55% for Legionella spp. from clinical specimens in Tirupati, South India. The study did not use other tests including UAT and DFA staining for Legionella detection. However, these reports confirmed that Legionella spp. is not so uncommon in India.
Legionella detection rates in clinical specimens, 2010 to present
During 2014, Chaudhry et al. reported L. pneumophila infection causing fatality in an immunocompromised patient undergoing treatment for sarcoidosis. The authors used PCR targeting 16S r RNA gene of Legionella along with UAT for rapid detection of the pathogen. This was the first known fatal case due to L. pneumophila from India. Afterwards, Angrup et al., in 2016 detected L. pneumophila infections by real-time PCR (targeting mip gene), PCR and serology; and the positivity's were 6%, 4.4% and 23%, respectively. Chaudhry et al. investigated the role of atypical pathogens including L. pneumophila in CAP patients in a multi centric study involving three major hospitals (All India Institute of Medical Sciences, VMMC and Safdarjung Hospital and Vallabhbhai Patel Chest Institute) in New Delhi. Legionella infection was detected by PCR and UAT in one patient; whereas 11% of the patients showed seropositivity by IgM ELISA. The study underscored the utility of multiple laboratory assays (PCR, culture, UAT and serology) for Legionella detection.
Changing patterns of Legionella diagnosis in India
Initially, most of the studies reported from India used culture, serology and DFA staining for LD detection;,,,, but recently, there was a shift towards NAATs including PCR and real-time PCR.,,, Angrup et al. used real-time PCR assays to detect Legionella in an early course before antibodies develops. Notably, PCR targeting Pan Legionella spp. can detect infections caused by all Legionella strains. However in a developing country like India Legionella PCR is available only in few reference laboratories that use either an in-house assay or commercial kits.
Similarly, the use of UAT for Legionella detection has also increased significantly in recent times. Para RA et al., in 2018 detected L. pneumophila in 17.5% of CAP patients by UAT. Antigenuria in Legionella infections can be detected shortly after the onset of clinical symptoms (2–3 days) and the antigen may be excreted for several days to >10 months, even during antibiotic treatment and after disease resolution.
Application of UAT along with PCR can detect LD rapidly, but it is to be noted that decrease in culture-based diagnosis may limit the detection of infections due to non-Lp1 strains. Besides, it is impossible to study the epidemiology of LD in detail without clinical isolates. Altogether when Legionella infection is suspected, UAT, PCR and culture should be performed; so that rapid diagnosis of Lp1, other strains of Legionella and availability of an isolate will be accomplished.
Clinical patterns of Legionnaires' disease in Indian patients
The exact incidence of LD is not known in India due to lack of: awareness, common disease definitions, diagnostic methods and reporting of cases. Due to the absence of national-level active LD surveillance systems, disease prevalence, seasonality, etc., are not clear in this country. However, most of the reported cases from India were sporadic and not associated with a known outbreak or possible cluster. Mostly, studies were conducted in patients having CAP, and hospital-acquired LD cases were so far not reported from this country.
Similar to reports from the USA and Europe studies from India also indicated that LD affect usually males >50 years of age, and in most instances, risk factors in patients including smoking and alcohol consumption were identified. Underlying medical conditions such as chronic obstructive airway disease, bronchial asthma, malignancy, diabetes mellitus, hypertension and end-stage renal disease were reported in our patient's population.
Fever and respiratory symptoms including cough, dyspnoea, chest pain and wheezing were the most common findings among patients with LD by any detection methods. Chaudhry et al. in 2000 reported the presence of extrapulmonary symptoms such as diarrhoea, abdominal pain and headache in Legionella seropositive cases; but such significant findings were not evident in successive studies. Gastrointestinal symptoms such as diarrhoea, abdominal pain and vomiting were noted frequently in association with Legionella infection. In addition, neurological symptoms due to Legionella spp. including disorientation, headache, drowsiness, confusion and coma were reported by Panagariya et al. in 2011. Positive chest X-ray findings were noted in 75%–80% of LD cases diagnosed by serology and/or PCR. Consolidations and infiltrations were the most common radiological abnormalities seen in patients with LD.
The fatality rate of Legionella infection was unknown in most of these studies. However, Chaudhry et al. in 2014 have reported a fatal case due to Legionella causing infection complicated by renal failure in an immunocompromised patient. The patient was presented with systemic and respiratory symptoms along with bilateral infiltrations and nonspecific laboratory findings such as leucocytosis and hyponatraemia. Even though Legionella infection was detected and treated in the early course; the patient died eventually due to LD accompanied with sepsis and renal failure.
In general, the pulmonary manifestations of Legionella CAP are non-specific; similarly, the radiographic and laboratory findings seen in LD may overlap with other typical and atypical pulmonary pathogens. Hence, it is difficult to distinguish LD from other atypical pathogens including Mycoplasma pneumoniae and Chlamydophila pneumoniae and typical pneumonia on the basis of these criteria.
Detection of Legionella from environmental reservoirs in India, 1991–2017
Understanding the epidemiology of Legionella infection is obvious for making decisions about whether to test for Legionella infections and what tests have to be used in a geographical region. Legionella spp. are omnipresent in both natural and humanmade aqueous environments. Rapid monitoring of suspected hospital and environmental water systems for L. pneumophila is essential for risk assessment, to detect possible sources of infection and to prevent further cases. Few studies from India investigated the presence of Legionella in the water distributions systems of health-care facilities. Agrawal et al. in 1992 tested water samples from cooling towers, respirator-humidifier, etc., and reported a culture positivity of 76% for Legionella spp. Later on, in 2010, Anbumani et al. detected L. pneumophila in 33.3% of water samples from hospital outlets by culture and biochemical identification.
Valavane et al. in 2017 isolated L. pneumophila in 21.5% and 6.3% of non-potable and potable water, respectively, by culture and identification by PCR. The authors also studied five markers (annotated to L. pneumophila plasmid pLPP [11A2], lipopolysaccharide synthesis [19H4], CMP-N-acetylneuraminic acid synthetase [10B12], conjugative coupling factor [24B1] and hypothetical protein (8D6)) in Legionella environmental isolates to predict their pathogenic potential to human. The presence of these markers were evident in most of the isolates indicating the virulence of these strains to cause infections in individuals. Successive proactive environmental surveillance by Chaudhry et al. in 2017 reported the presence of Lp1 in 15.2% of water samples tested in a tertiary healthcare center in New Delhi. The authors used culture for isolation of Legionella spp.; and Lp1 was identified by real-time PCR targeting wzm gene. The study was useful for formulating infection control strategies to eradicate Legionella spp. in that setting.
These studies provided new information on the extent of Legionella colonisation in few health-care facilities in India, provided baseline data for measuring the effectiveness of intervention strategies and demonstrated the presence of genes encoding pathogenic potential in Legionella isolates. Clinical and environmental studies regarding Legionella spp. and LD from India are listed in [Table 3].
|Table 3: Summary of studies regarding Legionella spp. and Legionnaires' disease in India from 1992 to 2018|
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| ~ Status of Legionella Research in India|| |
Research work involving Legionella spp. has a vast potential to grow in developing countries such as India. The focus is needed to assess the disease burden, factors affecting the susceptibility in our population, to identify potential sources of infection and to understand the difference in the virulence of strains. Multicentric studies are needed in this country to estimate the incidences of LD, to document the morbidity and mortality and the economic burden associated with Legionella infections. In addition, Legionella risk assessment should be implemented in different environmental and clinical settings and optimum methods for environmental control of this pathogen has to be developed.
Disease caused by Legionella spp. still remains to be noticed as a public health problem in India. Sporadic cases go unnoticed and are overshadowed by burden caused by other diseases including tuberculosis, bacterial, and viral pneumonias. Hence, research to upgrade the diagnostic accuracy of Legionella tests is also needed; such tests should be standardised and used routinely in all patients with pneumonia. Application of molecular tools such as real-time PCR can be implemented for detecting Legionella spp. in our population so that LD will be diagnosed rapidly to meet patient management.
Studies regarding the environmental reservoirs of L. pneumophila have been reported from India, but more focus has to be given for understanding the epidemiology of LD in this country. There is a lacuna in phenotypic and genotypic characterisation and sequence-based typing data. Studies mentioning the antimicrobial susceptibilities of Legionella strains were reported from few countries, but such studies were not yet conducted in India. As L. pneumophila has the potential to become resistant to certain classes of drugs including macrolides and fluoroquinolones, resistance in clinical and environmental strains should be evaluated systematically.
Data suggested that few strains of Legionella are likely to cause infection than many others in human; hence, studies have to be conducted to investigate the environmental distribution of strains and to identify virulence markers in Legionella isolates. At present, advanced techniques such as next-generation sequencing are in the arsenal of researchers and application of such methods could help to explore genotypic factors in the causation of LD. As outbreaks are mostly associated with certain human-made aquatic sources, infection by Legionella spp. is considered as preventable. However, basic research on certain ecological parameters is underexplored.
Ecological parameters that influence L. pneumophila to colonize a water system includes the presence of a suitable microbial consortium such as protozoa and other bacterial species,, presence or absence of divalent cations and nanoparticles,, availability of organic carbon content, etc. Optimal temperature of the water system, relative humidity of the climate,,, flow conditions of the plumbing systems, and the intrinsic capacity of the strain for quorum sensing is also important., In resource limited settings, it may not be possible to study all the above-mentioned parameters. To begin with, the combination of temperature and humidity may be considered as an environmental clue for implementation of control measures to treat high-risk sources, such as cooling towers. Outbreak investigations have shown that the aerosols produced by cooling towers can reach long distances.
Although there are no seasonal predilections for Legionella outbreak to occur, all through the year there are specific months which are optimal for the proliferation and spreading of the bacterium which differs with geographical locations. Besides, dormant or viable but non-cultivable forms of the bacterium can persist, but they may occur only during unfavourable conditions where the numbers are not enough to cause an infection or outbreak. For public buildings, health-care settings, hotels and other institutions the recommendations provided by CDC can be followed regarding detection of Legionella spp. from environmental water samples. Procedures for isolation and identification of Legionella spp. from environmental reservoirs are summarised in [Figure 2].
|Figure 2: Isolation and identification of Legionella spp. from environmental water samples: Guidelines issued by the US Centers for Disease Control and Prevention can be followed regarding the isolation of Legionella spp. Pretreated (heat treatment in a water bath at 50°C for 30 min; acid treatment in equal volume of HCl-KCl acid buffer [pH 2.2]) concentrates of water samples (0.1 ml) are inoculated onto buffered charcoal yeast extract agar supplemented with glycine, vancomycin, polymyxin B and cycloheximide. Colonies growing only on buffered charcoal yeast extract but not on blood agar can be presumptively identified as Legionella spp. Further confirmation shall be done by nucleic acid amplification tests and sub typing of isolates is possible using monoclonal antibodies. In the Figure 2, swabs are dipped in initial water samples collected (5 ml) and 0.2 ml of samples can be directly plated on to BCYE agar; presumptive identification of Legionella spp.; confirmation and typing can be done as mentioned above|
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| ~ Treatment and Prevention of Legionnaires' Disease|| |
As Legionella are intracellular pathogens, antibiotic should be bioactive within the cells, therefore certain classes including beta-lactams and aminoglycosides are ineffective. Macrolides, doxycycline, tetracyclines, ketolides and fluoroquinolones are proved to be effective against Legionella spp. The mainstay of anti-Legionella therapy in healthy as well as immunocompromised individuals is azithromycin and fluoroquinolones., Rifampicin is having good activity against Legionella spp. both in vitro and in vivo models, but this drug is recommended only as a part of combination therapy. Duration of treatment recommended by IDSA/ATS is 5–14 days, but the course is shorter for azithromycin due to its long half-life.,,
As LD is generally not transmitted from person-to-person (except a case reported in 2016; which can be a probable person-to-person transmission), infections can be prevented by proper maintenance of water systems in buildings and health-care facilities. Nosocomial legionellosis can be prevented by environmental monitoring (routine culturing of potable and non-potable water samples for Legionella) in hospitals even in the absence of reported LD cases. Once the bacteria is detected, the hospitals should follow one reliable disinfection method such as superheating the water to 70°C–80°C and flushing, installation of copper-silver ionisation units, hyperchlorination (concentration 2–6 ppm) and installation of point-of-use filters, etc.,,
| ~ Conclusions|| |
LD is undoubtedly considered as an infection that is under reported and under diagnosed. Physicians should be aware of these infections and should include LD in the differential diagnosis of patients with pneumonias. Legionella infection can be suspected in patients when there is a lung finding with or without extrapulmonary features and suboptimal response to aminopenicillins. Specific diagnostic tests including culture, urinary antigen detection, NAAT and antibody detections should be performed to verify the diagnosis. With limited resources, developing nations including India has a long road to travel to know the disease burden caused by these bacteria. Identification of environmental niches of Legionella, improvements in risk assessment, proper detection and control of cases, identification of demographic changes and new risk factors in our patient population need high priorities.
“On the summer of seventy-six, I got a name only to sing some veterans' fame,
Every corner I took the blame, like you never played the vexing game.
Little aerosols made the incident and your ailing was a mere accident.”
- The Summer of seventy-six-Legionella pneumophila monologue.
We would like to thank CMET, AIIMS, New Delhi for their kind help regarding preparation of [Figure 1] and [Figure 2].
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Mercante JW, Winchell JM. Current and emerging Legionella
diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev 2015;28:95-133.
Fields BS, Benson RF, Besser RE. Legionella
and Legionnaires' disease: 25 years of investigation. Clin Microbiol Rev 2002;15:506-26.
Phin N, Parry-Ford F, Harrison T, Stagg HR, Zhang N, Kumar K, et al.
Epidemiology and clinical management of Legionnaires' disease. Lancet Infect Dis 2014;14:1011-21.
Cunha BA, Burillo A, Bouza E. Legionnaires' disease. Lancet 2016;387:376-85.
Cunha BA. Clinical features of Legionnaires' disease. Semin Respir Infect 1998;13:116-27.
Cunha BA. Severe Legionella pneumonia
: rapid presumptive clinical diagnosis with Winthrop-University hospital's weighted point score system (modified). Heart Lung 2008;37:311-20.
Edelstein PH. Legionnaires' disease: History and clinical findings. In: Heuner K, Swanson M, editors. Legionella
Molecular Microbiology. 1st
ed. Norfolk, UK: Caister Academic Press; 2008. p. 1-18.
Roig J, Aguilar X, Ruiz J, Domingo C, Mesalles E, Manterola J, et al.
Comparative study of Legionella pneumophila
and other nosocomial-acquired pneumonias. Chest 1991;99:344-50.
Edelstein PH, Cianciotto NP. Legionella
. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 7th
ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 2969-84.
Stout JE, Yu VL. Legionellosis. N Engl J Med 1997;337:682-7.
Cunha BA, Pherez FM, Nouri Y. Legionella
community-acquired pneumonia (CAP) presenting with spontaneous bilateral pneumothoraces. Heart Lung 2008;37:238-41.
Cordes LG, Fraser DW. Legionellosis: Legionnaires' disease; Pontiac fever. Med Clin North Am 1980;64:395-416.
Centers for Disease Control and Prevention (CDC). Legionellosis – United States, 2000-2009. MMWR Morb Mortal Wkly Rep 2011;60:1083-6.
European Centre for Disease Prevention and Control 2013. Legionnaires Disease in Europe, 2011. Stockholm, Sweden: European Centre for Disease Prevention and Control. Available from: http://www.dx.doi.org/10.2900/78974
. [Last accessed on 2018 Oct 25].
Marston BJ, Lipman HB, Breiman RF. Surveillance for Legionnaires' disease. Risk factors for morbidity and mortality. Arch Intern Med 1994;154:2417-22.
Soda EA, Barskey AE, Shah PP, Schrag S, Whitney CG, Arduino MJ, et al.
Vital signs: Health care-associated Legionnaires' disease surveillance data from 20 states and a large metropolitan area – United States, 2015. MMWR Morb Mortal Wkly Rep 2017;66:584-9.
Benin AL, Benson RF, Besser RE. Trends in Legionnaires disease, 1980-1998: Declining mortality and new patterns of diagnosis. Clin Infect Dis 2002;35:1039-46.
Yu VL, Plouffe JF, Pastoris MC, Stout JE, Schousboe M, Widmer A, et al.
Distribution of Legionella
species and serogroups isolated by culture in patients with sporadic community-acquired Legionellosis: An international collaborative survey. J Infect Dis 2002; 186:127-8.
Jernigan DB, Hofmann J, Cetron MS, Genese CA, Nuorti JP, Fields BS, et al.
Outbreak of Legionnaires' disease among cruise ship passengers exposed to a contaminated whirlpool spa. Lancet 1996;347:494-9.
Okada M, Kawano K, Kura F, Amemura-Maekawa J, Watanabe H, Yagita K, et al.
The largest outbreak of legionellosis in Japan associated with spa baths: Epidemic curve and environmental investigation. Kansenshogaku Zasshi 2005;79:365-74.
Silk BJ, Moore MR, Bergtholdt M, Gorwitz RJ, Kozak NA, Tha MM, et al.
Eight years of Legionnaires' disease transmission in travellers to a condominium complex in Las Vegas, Nevada. Epidemiol Infect 2012;140:1993-2002.
Pasculle AW, McDevitt D. Legionella
cultures. In: Garcia LS, editor. Clinical Microbiology Procedures Handbook. 3rd
ed. Washington, DC: American Society for Microbiology Press; 2010.
Edelstein PH, Meyer RD, Finegold SM. Laboratory diagnosis of Legionnaires' disease. Am Rev Respir Dis 1980;121:317-27.
Shimada T, Noguchi Y, Jackson JL, Miyashita J, Hayashino Y, Kamiya T, et al.
Systematic review and metaanalysis: Urinary antigen tests for Legionellosis. Chest 2009;136:1576-85.
Elverdal PL, Jørgensen CS, Krogfelt KA, Uldum SA. Two years' performance of an in-house ELISA for diagnosis of Legionnaires' disease: Detection of specific IgM and IgG antibodies against Legionella pneumophila
serogroup 1, 3 and 6 in human serum. J Microbiol Methods 2013;94:94-7.
Murdoch DR, Podmore RG, Anderson TP, Barratt K, Maze MJ, French KE, et al.
Impact of routine systematic polymerase chain reaction testing on case finding for Legionnaires' disease: A pre-post comparison study. Clin Infect Dis 2013;57:1275-81.
Cross KE, Mercante JW, Benitez AJ, Brown EW, Diaz MH, Winchell JM, et al.
Simultaneous detection of Legionella
species and L. anisa
, L. bozemanii
, L. longbeachae
and L. micdadei
using conserved primers and multiple probes in a multiplex real-time PCR assay. Diagn Microbiol Infect Dis 2016;85:295-301.
Benitez AJ, Winchell JM. Clinical application of a multiplex real-time PCR assay for simultaneous detection of Legionella
species, Legionella pneumophila
, and Legionella pneumophila
serogroup 1. J Clin Microbiol 2013;51:348-51.
Agrawal L, Dhunjibhoy KR, Nair KG. Isolation of Legionella pneumophila
from patients of respiratory tract disease and environmental samples. Indian J Med Res 1991;93:364-5.
Bahl S, Wali JP, Handa R, Rattan A, Aggarwal P, Kindo AJ, et al. Legionella
as a lower respiratory pathogen in North India. Indian J Chest Dis Allied Sci 1997;39:81-6.
Chaudhry R, Dhawan B, Dey AB. The incidence of Legionella pneumophila
: A prospective study in a tertiary care hospital in India. Trop Doct 2000;30:197-200.
Javed S, Chaudhry R, Passi K, Sharma S, Padmaja K, Dhawan B, et al.
Sero diagnosis of Legionella
infection in community acquired pneumonia. Indian J Med Res 2010;131:92-6.
] [Full text]
Anbumani S, Gururajkumar A, Chaudhury A. Isolation of Legionella pneumophila
from clinical and environmental sources in a tertiary care hospital. Indian J Med Res 2010;131:761-4.
] [Full text]
Chaudhry R, Valavane A, Mohan A, Dey AB. Legionella pneumophila
infection associated with renal failure causing fatality in a known case of sarcoidosis. Indian J Med Microbiol 2014;32:324-7.
] [Full text]
Angrup A, Chaudhry R, Sharma S, Valavane A, Passi K, Padmaja K, et al.
Application of real-time quantitative polymerase chain reaction assay to detect Legionella pneumophila
in patients of community-acquired pneumonia in a tertiary care hospital. Indian J Med Microbiol 2016;34:539-43.
] [Full text]
Chaudhry R, Valavane A, Sreenath K, Choudhary M, Sagar T, Shende T, et al.
Detection of Mycoplasma pneumoniae
and Legionella pneumophila
in patients having community-acquired pneumonia: A multicentric study from New Delhi, India. Am J Trop Med Hyg 2017;97:1710-6.
Para RA, Fomda BA, Jan RA, Shah S, Koul PA. Microbial etiology in hospitalized North Indian adults with community-acquired pneumonia. Lung India 2018;35:108-15.
] [Full text]
Panagariya A, Sharma AK, Dev A, Kankane A, Sharma B, Dubey P, et al.
Reversible neurological syndromes with atypical pneumonia. Ann Indian Acad Neurol 2011;14:127-9.
] [Full text]
Valavane A, Chaudhry R, Malhotra P. Multiplex polymerase chain reaction of genetic markers for detection of potentially pathogenic environmental Legionella pneumophila
isolates. Indian J Med Res 2017;146:392-400.
] [Full text]
Chaudhry R, Sreenath K, Arvind V, Vinayaraj EV, Tanu S. Legionella pneumophila
serogroup 1 in the water facilities of a tertiary healthcare center, India. Emerg Infect Dis 2017;23:1924-5.
Steinert M, Hentschel U, Hacker J. Legionella pneumophila
: An aquatic microbe goes astray. FEMS Microbiol Rev 2002;26:149-62.
Rogers J, Dowsett AB, Dennis PJ, Lee JV, Keevil CW. Influence of temperature and plumbing material selection on biofilm formation and growth of Legionella pneumophila
in a model potable water system containing complex microbial flora. Appl Environ Microbiol 1994;60:1585-92.
Yaradou DF, Raze D, Ginevra C, Ader F, Doléans-Jordheim A, Vandenesch F, et al.
Zinc-dependent cytoadherence of Legionella pneumophila
to human alveolar epithelial cells in vitro
. Microb Pathog 2007;43:234-42.
Koubar M, Rodier MH, Frère J. Involvement of minerals in adherence of Legionella pneumophila
to surfaces. Curr Microbiol 2013;66:437-42.
Temmerman R, Vervaeren H, Noseda B, Boon N, Verstraete W. Necrotrophic growth of Legionella pneumophila.
Appl Environ Microbiol 2006;72:4323-8.
Piao Z, Sze CC, Barysheva O, Iida K, Yoshida S. Temperature-regulated formation of mycelial mat-like biofilms by Legionella pneumophila
. Appl Environ Microbiol 2006;72:1613-22.
Konishi T, Yamashiro T, Koide M, Nishizono A. Influence of temperature on growth of Legionella pneumophila
biofilm determined by precise temperature gradient incubator. J Biosci Bioeng 2006;101:478-84.
Berendt RF. Survival of Legionella pneumophila
in aerosols: Effect of relative humidity. J Infect Dis 1980;141:689.
van der Kooij D, Veenendaal HR, Scheffer WJ. Biofilm formation and multiplication of Legionella
in a model warm water system with pipes of copper, stainless steel and cross-linked polyethylene. Water Res 2005;39:2789-98.
Storey MV, Långmark J, Ashbolt NJ, Stenström TA. The fate of Legionellae
within distribution pipe biofilms: Measurement of their persistence, inactivation and detachment. Water Sci Technol 2004;49:269-75.
Vandersmissen L, De Buck E, Saels V, Coil DA, Anné J. A Legionella pneumophila
collagen-like protein encoded by a gene with a variable number of tandem repeats is involved in the adherence and invasion of host cells. FEMS Microbiol Lett 2010;306:168-76.
Kimura S, Tateda K, Ishii Y, Horikawa M, Miyairi S, Gotoh N, et al. Pseudomonas aeruginosa
las quorum sensing autoinducer suppresses growth and biofilm production in Legionella
species. Microbiology 2009;155:1934-9.
Addiss DG, Davis JP, LaVenture M, Wand PJ, Hutchinson MA, McKinney RM, et al.
Community-acquired Legionnaires' disease associated with a cooling tower: Evidence for longer-distance transport of Legionella pneumophila
. Am J Epidemiol 1989;130:557-68.
Delgado-Viscogliosi P, Solignac L, Delattre JM. Viability PCR, a culture-independent method for rapid and selective quantification of viable Legionella pneumophila
cells in environmental water samples. Appl Environ Microbiol 2009;75:3502-12.
US Centres for Disease Control and Prevention. Procedures for the Recovery of Legionella
from the Environment. U.S. Department of Health and Human Services: Public Health Service. Atlanta, GA: US Centres for Disease Control and Prevention; 2005. p. 1-13.
Cunha BA. Legionnaires' disease: Clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am 2010;24:73-105.
Lin YE, Stout JE, Yu VL. Prevention of hospital-acquired legionellosis. Curr Opin Infect Dis 2011;24:350-6.
Correia AM, Ferreira JS, Borges V, Nunes A, Gomes B, Capucho R, et al.
Probable person-to-person transmission of Legionnaires' disease. N Engl J Med 2016;374:497-8.
Sabrià M, Mòdol JM, Garcia-Nuñez M, Reynaga E, Pedro-Botet ML, Sopena N, et al.
Environmental cultures and hospital-acquired Legionnaires' disease: A 5-year prospective study in 20 hospitals in Catalonia, Spain. Infect Control Hosp Epidemiol 2004;25:1072-6.
Yu PY, Lin YE, Lin WR, Shih HY, Chuang YC, Ben RJ, et al.
The high prevalence of Legionella pneumophila
contamination in hospital potable water systems in Taiwan: Implications for hospital infection control in Asia. Int J Infect Dis 2008;12:416-20.
Valavane A, Chaudhry R. The summer of seventy-six-Legionella pneumophila
monologue. Emerg Inf Dis 2017;23:1202-3.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]