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Objective: To study the epidemiologic manifestations of a large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water., Patients: In June 2000 at Ishioka City, Ibaraki Prefecture, a large outbreak of Legionnaire's disease occurred, as a result of an inadequate circulating and filtration system for communal bath water. This outbreak was the worst ever experienced in Japan, involving a total of 34 patients (20 confirmed, 14 probable), 3 of whom died., Measurements and Results: Legionella pneumophila serogroup 1 was isolated from sputum culture in two patients. Bacteriological culture of the public bath water subsequently yielded large numbers of Legionella species. Cleavage of genomic DNA showed that restriction fragment patterns coming from clinical and environmental isolates of L. pneumophila serogroup 1 were closely related, focusing the inquiry to a public bathhouse where a circulating filtration system was suspected as the source of infection., Conclusions: It was later concluded that the circulating filtration system adopted for bath water was marred by a serious design flaw that subsequently caused the mass outbreak. Specifically, a line of the bath water was being returned to the bath without undergoing heat exchange or sterilization by chlorine; and the Legionella species that had proliferated in the filter and the bright stone filtration unit were allowed to return to the bath, eventually culminating in a mass infection.

Background and Objectives: Hospital-acquired legionnaires' disease can be prevented by disinfection of hospital water systems. This study assessed the long-term efficacy of copper-silver ionization as a disinfection method in controlling Legionella in hospital water systems and reducing the incidence of hospital-acquired legionnaires' disease. A standardized, evidence-based approach to assist hospitals with decision making concerning the possible purchase of a disinfection system is presented., Design: The first 16 hospitals to install copper-silver ionization systems for Legionella disinfection were surveyed. Surveys conducted in 1995 and 2000 documented the experiences of the hospitals with maintenance of the system, contamination of water with Legionella, and occurrence of hospital-acquired legionnaires' disease. All were acute care hospitals with a mean of 435 beds., Results: All 16 hospitals reported cases of hospital-acquired legionnaires' disease prior to installing the copper-silver ionization system. Seventy-five percent had previously attempted other disinfection methods including superheat and flush, ultraviolet light, and hyperchlorination. By 2000, the ionization systems had been operational from 5 to 11 years. Prior to installation, 47% of the hospitals reported that more than 30% of distal water sites yielded Legionella. In 1995, after installation, 50% of the hospitals reported 0% positivity, and 43% still reported 0% in 2000. Moreover, no cases of hospital-acquired legionnaires' disease have occurred in any hospital since 1995., Conclusions: This study represents the final step in a proposed 4-step evaluation process of disinfection systems that includes (1) demonstrated efficacy of Legionella eradication in vitro using laboratory assays, (2) anecdotal experiences in preventing legionnaires' disease in individual hospitals, (3) controlled studies in individual hospitals, and (4) validation in confirmatory reports from multiple hospitals during a prolonged time (5 to 11 years in this study). Copper-silver ionization is now the only disinfection modality to have fulfilled all four evaluation criteria.

A case-control study of three cases of Legionella pneumophila pneumonia identified transesophageal echocardiography (TEE) as a risk factor. Patient isolates and environmental strains from water used for rinsing TEE probes were identical by pulsed-field gel electrophoresis. This is the first report of endoscopy as a potential source of legionellosis.

The virulence factor Mip (macrophage infectivity potentiator) contributes to the intracellular survival of Legionella pneumophila, the causative agent of Legionnaires' disease. The protein consists of two domains that are connected via a very long alpha-helix (A. Riboldi-Tunnicliffe et al., Nat. Struct. Biol. 8:779-783, 2001). The fold of the C-terminal domain (residues 100 to 213) is closely related to human FK506-binding protein (FKBP12), and like FKBP12, Mip exhibits peptidylprolyl cis/trans isomerase (PPIase) activity. The alpha-helical N-terminal domain is responsible for the formation of very stable Mip homodimers. In order to determine the importance of the homodimeric state of Mip for its biochemical activities and for infectivity of Legionella, a truncated, monomeric Mip variant [Mip((77-213))] was overexpressed in Escherichia coli and characterized biochemically. In vitro isomerase activity assays revealed that the altered protein exhibits full isomerase activity towards peptide substrates. However, the deletion resulted in a dramatic loss in the efficiency of refolding of reduced and carboxy-methylated RNase T(1). By cis complementation of the Mip-negative mutant strain L. pneumophila JR32-2, we constructed the strain L. pneumophila JR32-2.4, which expresses an N-terminally truncated variant of Mip. Infection studies with these strains revealed that the N-terminal part and the dimerization of Mip but not its PPIase activity are necessary for full virulence in Acanthamoeba castellanii. Infection of guinea pigs showed that strains with dimerization-deficient Mip (JR32-2.4) or a very low PPIase activity (JR32-2.2) were significantly attenuated in the animal model. These results suggest a different role of the PPIase activity and the N-terminally mediated dimeric state of Mip in monocellular systems and during the infection of guinea pigs.

A sporadic case of Legionnaires' disease was linked to travel on a cruise ship. Investigation identified two further cases of Legionnaires' Disease and one case of non-pneumonic Legionella infection. An Incident Team confirmed the source to be the ship's water system and control measures were instituted that included pasteurisation, super chlorination and chlorine dioxide dosing. The Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC), through the European Surveillance Scheme for Travel Associated Legionnaires' Disease, identified three previous cases associated with the same ship's water system including one fatality. Lessons for the international surveillance and control of Legionnaires' disease on cruise ships are discussed.

We report a case of Legionella pneumophila pneumonia in a patient with interstitial lung disease. Intensive environmental investigations revealed that a system of all-day-running bathwater was the source of infection. In this case, the concentration of L. pneumophila in the hospital bathwater was low. We therefore emphasize that even a low concentration of L. pneumophila in environmental water can cause serious infections to immunocompromised patients in a hospital.

We report the first case of neonatal Legionnaires' disease associated with water birth in a spa bath at home. Legionella pneumophila serogroup 6 was detected from postmortem lung tissue.

Tandem autologous transplant actually represents a challenge in multiple myeloma treatment, but the best conditioning regimen is still under investigation. With the aim of evaluating the feasibility of a modified tandem transplant strategy, we treated 10 multiple myeloma patients after conventional first line chemotherapy with a two step conditioning regimen consisting of high-dose melphalan (200 mg/m2) followed by high-dose melphalan (180 mg/m2) together with indarubicin (15 mg/sqm2 c.i. x 3 days) both with peripheral stem cell support. At first transplant, the median age wasyears, performance status was good and disease status was CR in 2 patients and PR in the rest. At the end of the first transplant, 70% of patients achieved CR and only mild toxicity was observed. After the second transplant further improvement of the response rate was obtained with 90% CR. However, we observed three toxic early infection-related deaths from CMV and legionella pneumonia at day + 17, +26, +54 after transplantation. Although this schedule seems to be effective in terms of response rate, the 30% TRM imposes an anthracycline dose-reduction with careful patient selection. This approach could reduce the toxic effects and maintain the efficacy of therapy at the same time.

An outbreak of infections caused by Legionella pneumophila serogroup 5 was detected in a university hospital, and nosocomial reservoirs of the legionella epidemic were examined. Clinical isolates from two patients who had been affected by the L. pneumophila serogroup 5 outbreak, and from another patient with a legionella infection caused by the same serogroup 3 years later, were compared to L. pneumophila serogroup 5 isolates from the hospital water supply by two molecular methods, amplified fragment length polymorphism (AFLP) analysis and random amplified polymorphic DNA analysis (RAPD). Genotyping confirmed the epidemiological linkage of the first two patients, and linked their infections with the hospital water supply. The third clinical strain, which was also linked to the hospital water, was very similar to the epidemic strain. Even though the water distribution system was sanitized (superheat and flush sanitation), the epidemic strain was shown to be persisting in the hospital water outlets several years after its initial discovery.

There have been reported outbreaks of Legionnaires' disease at hospitals and industrial facilities, which prompted the development of various preventive measures. For example, Ford has been developing and implementing such a measure at its facilities worldwide to provide technical guidance for controlling Legionella in water systems. One of the key issues for implementing the measure is the selection of a disinfectant(s) and optimum conditions for its use. Therefore, available publications on various disinfectants and disinfection processes used for the inactivation of Legionella bacteria were reviewed. Two disinfection methods were reviewed: chemical and thermal. For chemical methods, disinfectants used were metal ions (copper and silver), oxidizing agents (halogen containing compounds [chlorine, bromine, iodine, chlorine dioxide, chloramines, and halogenated hydantoins], ozone, and hydrogen peroxide), non-oxidizing agents (heterocyclic ketones, guanidines, thiocarbamates, aldehydes, amines, thiocyanates, organo-tin compounds, halogenated amides, and halogenated glycols), and UV light. In general, oxidizing disinfectants were found to be more effective than non-oxidizing ones. Among oxidizing agents, chlorine is known to be effective and widely used. Among non-oxidizing agents, 2,2-dibromo-3-nitropropionamide appears to be the most effective followed by glutaraldehyde. Isothiazolin (known as Kathon), polyhexamethylene biguanide, and 2-bromo-2-nitropropionamide (known as Bronopol) were found to be less effective than glutaraldehyde. Thermal disinfection is effective at > 60 degrees C (140 degrees F).

In order to determine the role of ferrous iron transport in Legionella pathogenesis, we identified and mutated the feoB gene in virulent Legionella pneumophila strain 130b. As it is in Escherichia coli, the L. pneumophila feoB gene was contained within a putative feoAB operon. L. pneumophila feoB insertion mutants exhibited decreased ferrous but not ferric iron uptake compared to the wild type. Growth on standard buffered charcoal yeast extract agar or buffered yeast extract broth was unaffected by the loss of L. pneumophila FeoB. However, the L. pneumophila feoB mutant had a reduced ability to grow on buffered charcoal yeast extract agar with a reduced amount of its usual iron supplementation, a phenotype that could be complemented by the addition of feoB in trans. In unsupplemented buffered yeast extract broth, the feoB mutant also had a growth defect, which was further exacerbated by the addition of the ferrous iron chelator, 2,2'-dipyridyl. The feoB mutant was also 2.5 logs more resistant to streptonigrin than wild-type 130b, confirming its decreased ability to acquire iron during extracellular growth. Decreased replication of the feoB mutant was noted within iron-depleted Hartmannella vermiformis amoebae and human U937 cell macrophages. The reduced intracellular infectivity of the feoB mutant was complemented by the introduction of a plasmid containing feoAB. The L. pneumophila feoB gene conferred a modest growth advantage for the wild type over the mutant in a competition assay within the lungs of A/J mice. Taken together, these results indicate that L. pneumophila FeoB is a ferrous iron transporter that is important for extracellular and intracellular growth, especially in iron-limited environments. These data represent the first evidence for the importance of ferrous iron transport for intracellular replication by a human pathogen.

As part of a case-control study of community-acquired Legionnaires' disease, several factors related to residential water distribution systems and public drinking water systems were studied in the homes of 124 patients with community-acquired Legionnaire's disease and in the homes of 354 controls. The presence of water reservoirs and hot water tanks was studied in residential systems. Factors such as deficient chlorine levels, pipe repairs and other work, water flow interruptions, the use of alternative water sources, inadequate cleaning operations in public water reservoirs, and the position of the home within the public network (and whether this location constituted an endpoint) were studied in public water supply systems. Levels of legionellae in domestic water samples were also measured. Although the use of water reservoirs and hot water tanks promotes colonization by legionellae in residential systems, none of the variables studied seems to increase the incidence of community-acquired Legionnaires' disease.

Legionnaires' disease is a community-acquired or hospital-acquired pneumonia, and the immunocompromised patient is at particular risk. We report a case of serogroup 1 pneumonia in a renal transplant patient shortly after grafting. No source of infection was identified in the hospital unit, but an extended investigation located patient exposure to a shower during a weekend home stay. Sampling at the hospital, in the patient's flat, other flats, and the laundry of the same building returned only one positive result from the patient's showerhead. Strain identity was confirmed by pulsed-field electrophoresis and amplified fragment length polymorphism. Guidelines recommend -free water for transplant units, but further epidemiologic evidence is required before extending this preventive approach to the patient's home.

A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3 occurred in four patients following hematopoietic stem cell transplantation (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period. The causative organism was recovered from the water supply system to the same unit just before the outbreak. Nineteen other BMT patients were hospitalized in the same unit at the same time, giving a frequency of proven infection of 4/23 = 17%. Immediately after recognition of the outbreak, use of tap water was forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was started for all patients in the unit, until decontamination of the water was achieved. No other cases were detected. In conclusion, contamination of the hospital water supply system with legionella carries a high risk for legionella pneumonia among BMT patients. Early recognition of the outbreak, immediate restrictions of water use, antibiotic prophylaxis for all non-infected patients, and water decontamination, successfully terminated the outbreak.

Microbiological contamination of hot spring waters is a public health problem, and hot spring waters have been thought to be a potential source of Legionella infections. In this study, 209 water samples collected from 69 thermal pools of 36 hot springs in the Central Anatolia Region were examined for the presence of Legionella spp. between September and November 2001. The water samples were concentrated via filtration, and the filtrates were decontaminated by low-pH method. Then the samples were cultured on non-selective (Buffered Charcoal Yeast Extract Agar, BCYE) and selective (GVPC; BCYE supplemented with glycine, vancomycin, polymyxin B, cycloheximide, and MWY; BCYE supplemented with glycine, anisomycin, polymyxin B, vancomycin, bromthymol blue, bromcresole purple) media, and suspected colonies were confirmed by Legionella Latex Kit (Oxoid) and direct fluorescent antibody test. As a result, 24 out of 209 (11.5%) water samples were found positive for Legionella pneumophila, and a total 26 L. pneumophila strains were isolated from these 24 samples. Two of these isolates were found reactive with serogroup 1, 20 were reactive with serogroup 2-14 antisera in agglutination test, while 2 samples collected from the same thermal pool, have yielded 2 strains, of which one was serogroup 1 and the other was serogroup 2-14. L. pneumophila was detected in 22.2% of hot springs (8 of 36) and 14.5% of thermal pools (10 of 69). L. pneumophila concentrations which were detected in water samples ranged from 10 to 430 CFU/100 ml. This is the first data for the prevalence of Legionnaires' disease agent in hot spring spas in the Central Anatolia Region of Turkey. Colonization of bacterium in some spas indicates that the certain hot springs might be endemic focuses for Legionnaires' disease in our country.

Inhalation of contaminated aerosols is considered the most common route of Legionella transmission. The aim of this study was to determine whether contact with water contaminated by Legionella was related to oropharyngeal colonization in immunosuppressed patients. Eighty-five oropharyngeal swabs (April 1996 to June 1996) were seeded on selective and nonselective buffered charcoal-yeast extract media. Legionella was not isolated.

Objective: To describe the incidence and mortality of legionnaires' disease (LD) in the Netherlands on the basis of registration, with a focus on possible sources of infection, and geographic and seasonal variations., Design: Retrospective, descriptive., Method: The incidence and mortality rate of LD from July 1987 until December 2000 was described using registration data from the Dutch Health Inspectorate. Possible sources of infection were also listed (patients involved in the Bovenkarspel outbreak (1999) were excluded). Geographic variations in occurrence of LD were investigated by incidences computed per province. To gain insight into the possible existence of seasonal variations the mean numbers of patients per month were compared., Results: During the period of interest a total of 806 persons with LD were reported, 36 of whom were excluded. The mean incidence rose from 0.27 cases per 100,000 inhabitants in the 1987-1998 period to 0.91 cases per 100,000 inhabitants in the 1999-2000 period. The male:female ratio was 2.6:1. A total of 96 persons (12.5%) died as a result of LD. There were more deaths in the group of patients with confirmed LD compared to the group of patients with probable LD. After 1998 the case fatality rate was lower than in the previous period (Fisher's exact test: p = 0.005). The potential source of infection was situated in the open population in 92.9% of cases. In 7.1% of cases the potential source was situated in a hospital. The incidence per province varied from 0.13 per 100,000 (Drente) to 0.66 per 100,000 (Limburg). During the summer months more patients were reported, most of whom had contracted the infection abroad. In contrast to the 1987-1998 period, after 1998 the incidence in the Netherlands was higher than the European mean and the incidence of confirmed LD was higher than in the United States.

Objective: To investigate the presence and clonal distribution of Legionella species in the water supply of 20 hospitals in Catalonia, Spain., Setting: 20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain., Methods: Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence of Legionella species. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained were characterized microbiologically and genotyped by SfiI pulsed-field gel electrophoresis (PFGE)., Results: 73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive for Legionella pneumophila (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its own Legionella DNA subtype, which was not shared with any other hospitals., Conclusions: Legionella was present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity of Legionella in the aquatic environment.

A 57-year-old man presented with pneumonia, respiratory distress, and myelodysplastic syndrome. A diagnosis of Legionnaires' disease due to Legionella pneumophila (L. pneumophila) was established. The patient had long been drinking tap water via a conduit from a hot spring resource, from which L. pneumophila was also isolated. Both the patient's strain and the water strain of L. pneumophila were identified as serogroup 1, and the genetic relatedness between the two strains as seen by pulsed-field gel electrophoresis was 87%. The patient was successfully treated with erythromycin, fluoroquinolone, and rifampicin. This case raises an important issue on public health represented by legionellosis in Japan.

Construction and renovation projects in health care facilities are a risk for certain patients, particularly those who are immunocompromised. A proactive approach must be taken to limit construction-related nosocomial infections. This requires having a multidisciplinary team, supported by administration, to plan and implement preventive measures throughout the duration of the construction project. The ICP should be an active team member in all phases of the project. The ICP plays a major role by providing education to personnel; ensuring that preventive measures are identified, initiated, and maintained; and carrying out surveillance for infections in patients. By ensuring that the appropriate preventive measures are in place and clear lines of communication exist among the personnel, patient safety will be enhanced.

Legionella pneumophila produces several extracellular proteins, but their role in the pathogenesis of Legionnaires' disease is unclear. This study examined the effects of the L. pneumophila major secretory protein (Msp), a zinc metalloprotease, on the oxidative burst and chemotaxis of human phagocytes. Polymorphonuclear leucocytes (PMNLs) and adherent monocytes treated with sublethal amounts of Msp protease were stimulated with formyl-leucyl-methionyl-phenylalanine (fMLP) and opsonised zymosan particles (ZAP). A dose-dependent inhibition in superoxide anion production in response to both stimuli was seen, and complete inhibition was achieved in PMNLs and monocytes treated with Msp at concentrations of 1500 and 1000 U/ml, respectively. ZAP-induced chemiluminescence by PMNLs and mononuclear cells and fMLP-induced PMNL nitroblue tetrazolium dye reduction were both significantly inhibited. The chemotactic response of PMNLs to fMLP was inhibited in a dose-dependent manner and substantial inhibition (11% of control) was achieved with Msp 1200 U/ml. These results suggest that the L. pneumophila Msp protease alters human phagocyte functional responses significantly and may contribute to the pathogenesis of Legionnaires' disease.

Legionelosis is an environment-related disease with particular pulmonary tropism. Reporting is mandatory in France. Legionellosis may result from nosocomial or community-acquired infection. In both cases, humans are contaminated from a humid environmental reservoir that must be identified. Cellular immunity is the main mechanism of defense and transplant recipients, particularly those on an immunosuppressor regimen, are at risk. There is no clinical, biological or radiographic sign specific of nosocomial legionellosis. Culture provides the diagnosis. Treatment is based on prevention and curative antibiotic treatment using compounds with an intracellular activity. Preventive measures have been reinforced by legislation regulating the steps required in case of nosocomial legionellosis.

Two cases of legionellosis occurring 3 years apart were acquired in the same French thermal spa and were apparently due to the same strain of Legionella pneumophila serogroup 1, as shown by genomic macrorestriction analysis. Minor differences between the two isolates were found by random amplification PCR profiling which showed an additional band with one of the isolates. Analysis of 107 L. pneumophila strains isolated from the spa waters by genome macrorestriction failed to identify the infective strain, but a closely related L. pneumophila serogroup 3 strain differing from the clinical isolates by only one band was found. To determine if the clinical L. pneumophila serogroup 1 isolates was better adapted for intracellular multiplication than related serogroup 3 environmental isolates, the growth kinetics of six isolates were determined in co-culture with Acanthamoeba lenticulata. One clinical isolate failed to grow within amoeba, while the other clinical isolate yielded the highest increase in bacterial cell count per amoeba (1,200%) and the environmental isolates gave intermediate values. Genetic analysis of L. pneumophila isolates by DNA macrorestriction does not therefore appear to reflect their growth kinetics within amoeba, and is not sufficiently discriminatory to identify potentially virulent strains.

A 62-year-old male with rheumatoid arthritis (RA) who was taking nonsteroid anti-inflammatory drug for controlling synovitis developed a flare of his arthritis, hepatitis, and pneumonia due to infection with Legionella pneumophila serotype 1. Adult respiratory distress syndrome (ARDS) occurred following the development of pneumonia. After the introduction of erythromycin and ventilator support with positive end expiratory pressure (PEEP), his condition stabilized and he recovered gradually. We suggest that L. pneumophila should be considered early in the differential diagnosis of pneumonia in RA patients due to their immunocompromised status.

A case of Legionella pericarditis caused by a Legionella pneumophila isolate other than serogroup 1 is reported in a 59-year-old man after allogeneic peripheral blood stem cell transplantation. On admission a 5 mm pericardial effusion was detected on echocardiography. Antibodies were detected against L. pneumophila serogroups 7 to 14 using the antigen pool and against serogroup 12 alone. Antibodies were not detected against the serogroup 1 to 6 antigen pool. The patient's clinical condition improved dramatically after treatment with clarithromycin and an echocardiography revealed the total disappearance of the pericardial effusion.

Objectives: To determine whether a newly-constructed long-term care facility would become colonized with Legionella and whether Legionnaires' disease would occur in residents of this new facility., Design: Prospective environmental surveillance of the hospital's water distribution system for the presence of Legionella pneumophila during construction. Utilization of diagnostic tests for Legionnaires' disease in cases of nosocomial pneumonia., Setting: The Pittsburgh VA Health Care System, Aspinwall Division, a two-building 400-bed complex., Participants: Six patients who acquired Legionnaires' disease while in the facility., Intervention: Installation of copper-silver ionization systems., Measurements: Isolation of L. pneumophila from potable water and the occurrence of Legionnaires' disease., Results: L. pneumophila serogroup 1 was recovered from the water distribution system within 1 month of operation; 74% (61/82) of distal sites were positive during construction. In the first 2 years of occupancy, six cases of legionellosis were diagnosed. Both clinical isolates of L. pneumophila were identical to environmental isolates by pulsed field gel electrophoresis (PFGE). Copper-silver ionization systems were installed to control Legionella in the water system., Conclusions: We conclude that long-term care residents are at risk for acquiring nosocomial Legionnaires' disease in the presence of a colonized water system, even in a newly constructed building.

Since Legionnaires' Disease (LD) was first reported in 1976, outbreaks have been associated with airborne transmission of Legionella bacteria through cooling towers, showers, and other aerosolizing devices (1). However, most LD cases are sporadic, and the source and mode of infection in many cases are unknown. Infections with one species, Legionella longbeachae, have been associated with gardening and use of potting soil in Australia and Japan (2,3). This report summarizes the findings of LD investigations in California, Oregon, and Washington, that suggest that transmission from potting soil has occurred for the first time in the United States, and that active surveillance and case finding are warranted to explore this association.

Prior genetic and physical mapping has shown that the Naip gene cluster on mouse chromosome 13D1-D3 contains a gene, Lgn1, that is responsible for determining the permissivity of ex vivo macrophages to Legionella pneumophila replication. We have identified differences in the structure of the Naip array among commonly used inbred mouse strains, although these gross structural differences do not correlate with differences in L. pneumophila permissiveness. A physical map of the region employing clones of the C57BL/6J haplotype confirms that there are fewer copies of Naip in this strain than are in the physical map of the 129 haplotype. We have also refined the genetic location of Lgn1, leaving only Naip2 and Naip5 as candidates for Lgn1. Our genetic map suggests the presence of two hotspots of recombination within the Naip array, indicating that the 3' portion of Naip may be involved in the genomic instability at this locus.

We report an uncommon presentation of Legionella pneumophila infection following a placentalblood transplantation in an immunodeficient child. The patient presented with lung nodules and liver abscesses. We discuss how a digestive contamination can be suspected.

We describe the case of a 53-month-old girl with juvenile rheumatoid arthritis (JRA), complicated by the occurrence of Hodgkin's lymphoma and Legionella pneumophila infection during immunosuppressive treatment with methotrexate (MTX) and cyclosporine A (CSA). The girl had received variable anti-inflammatory combination therapy, including MTX for 28 months and CSA for 3 months. Thirty-six months after the onset of arthritis, the girl presented with an enlargement of the lymph nodes of the mediastinum, the hilum of the lungs, and the abdomen. Concomitantly, a diagnosis of Legionella pneumonia was rendered. Autopsy showed Epstein-Barr virus (EBV)-associated nodular sclerosing Hodgkin's lymphoma. The neoplastic cells were positive for CD15, CD 30, and latent membrane protein 1 (LMP 1). The present case is the second reported to occur in a child, and it lends support to the hypothesis that immunosuppressive treatment may contribute to an increased risk of the development of EBV-associated lymphoproliferative disorders (LPD) in pediatric patients suffering from JRA.

Legionella pneumophila first commanded attention in 1976, when investigators from the Centers for Disease Control and Prevention identified it as the culprit in a massive outbreak of pneumonia that struck individuals attending an American Legion convention (). It is now clear that this gram-negative bacterium flourishes naturally in fresh water as a parasite of amoebae, but it can also replicate within alveolar macrophages. L. pneumophila pathogenesis is discussed using the following model as a framework. When ingested by phagocytes, stationary-phase L. pneumophila bacteria establish phagosomes which are completely isolated from the endosomal pathway but are surrounded by endoplasmic reticulum. Within this protected vacuole, L. pneumophila converts to a replicative form that is acid tolerant but no longer expresses several virulence traits, including factors that block membrane fusion. As a consequence, the pathogen vacuoles merge with lysosomes, which provide a nutrient-rich replication niche. Once the amino acid supply is depleted, progeny accumulate the second messenger guanosine 3',5'-bispyrophosphate (ppGpp), which coordinates entry into the stationary phase with expression of traits that promote transmission to a new phagocyte. A number of factors contribute to L. pneumophila virulence, including type II and type IV secretion systems, a pore-forming toxin, type IV pili, flagella, and numerous other factors currently under investigation. Because of its resemblance to certain aspects of Mycobacterium, Toxoplasma, Leishmania, and Coxiella pathogenesis, a detailed description of the mechanism used by L. pneumophila to manipulate and exploit phagocyte membrane traffic may suggest novel strategies for treating a variety of infectious diseases. Knowledge of L. pneumophila ecology may also inform efforts to combat the emergence of new opportunistic macrophage pathogens.

Background and Objectives: During a hot and humid summer period workers became ill with fever and flu-like symptoms after repairing a decanter for sludge concentration at a sewage treatment plant. The work took place over a period of 10 days in a small closed room, while another decanter was in operation and was consequently emitting aerosol to the environment, to which the workers were exposed. The aim of this study was to determine the cause of this outbreak of febrile illness so that additional cases could be prevented., Methods: All 5 patients were seen and examined in the Department of Occupational Medicine. Furthermore 2 of the workers had recurrent illness and were examined during hospitalization. As Pontiac fever (nonpneumonic legionellosis) was suspected, antibodies to legionellae were measured in blood samples. After positive antibody titers to Legionella pneumophila were found, samples of the sludge were collected for legionellae culture., Results and Conclusions: The clinical picture agreed with that described for Pontiac fever, and positive antibody titers to L. pneumophila serogroup 1 were found in blood from all 5 patients. L. pneumophila serogroup 1 was cultured in high amounts from sludge from the decanter. It was concluded that the fever was caused by L. pneumophila emitted to the environment by the uncovered decanter. Procedures for preventing new cases were established.