Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner.

Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested this hypothesis in two ways. First, adult mice were intravenously inoculated with Salmonella typhimurium, resulting in sepsis. Second, newborn mouse pups were intranasally infected with reovirus (serotype 3 Dearing), which induced encephalitis. In both mouse models, wild-type Lrrk2 expression was protective and showed a sex effect, with female Lrrk2-deficient animals not controlling infection as well as males. Mice expressing Lrrk2 carrying the Parkinson's disease-linked p.G2019S mutation controlled infection better, with reduced bacterial growth and longer animal survival during sepsis. This gain-of-function effect conferred by the p.G2019S mutation was mediated by myeloid cells and was abolished in animals expressing a kinase-dead Lrrk2 variant, p.D1994S. Mouse pups with reovirus-induced encephalitis that expressed the p.G2019S Lrrk2 mutation showed increased mortality despite lower viral titers. The p.G2019S mutant Lrrk2 augmented immune cell chemotaxis and generated more reactive oxygen species during virulent infection. Reovirus-infected brains from mice expressing the p.G2019S mutant Lrrk2 contained higher concentrations of α-synuclein. Animals expressing one or two p.D1994S Lrrk2 alleles showed lower mortality from reovirus-induced encephalitis. Thus, Lrrk2 alleles may alter the course of microbial infections by modulating inflammation, and this may be dependent on the sex and genotype of the host as well as the type of pathogen.

Clinical and bacteriological profile and outcome of sepsis in dermatology ward in tertiary care center in New Delhi.

BACKGROUND: There is paucity of data regarding the clinical and bacteriological profile of sepsis in dermatology in-patients. AIMS: To study the frequency, etiology, and outcome of sepsis dermatology in-patients. METHODS: The study was conducted in a 30-bedded dermatology ward of a tertiary care center. Sepsis was defined by presence of ≥2 SIRS (systemic inflammatory response syndrome) criteria along with evidence of infection (clinically obvious/culture proven infection of skin or internal organs). Patients were also assessed for known (common) risk factors of sepsis. In suspected sepsis patients, at least two samples of blood cultures by venepuncture were taken. Pus, skin swab, urine, and sputum samples were also collected for culture as needed with avoidance of contamination. RESULTS: Among 860 admitted patients studied from November 2004 to July 2006, 103 (12%) fulfilled SIRS criteria. Of these, 63 had nonsepsis causes of SIRS positivity, while 40 (4.65%) had sepsis. Majority of the sepsis patient had vesicobullous diseases (42.5%), erythroderma (25%), toxic epidermal necrolysis (TEN) (22.5%). Severe sepsis developed in 17 (42.5%) patients, while 15 (37.5%) died. Methicillin-resistant Staphylococcus aureus (MRSA) was the commonest organism isolated (99; 25.9%) in all culture specimens followed by Acinetobacter spp. (52; 13.6%), Pseudomonas spp. (40; 10.5%), Methicillin-sensitive S. aureus (MSSA: 33; 8.7%), and Klebsiella spp. (22; 5.8%). Various risk factors affecting mortality and sensitivity patterns for various isolates were also analyzed. CONCLUSION: Sepsis occurred in 40 (4.65%) inpatients in dermatology ward. The frequency of sepsis was highest in TEN (90%), followed by drug-induced maculopapular rash (20.0%), erythroderma (17.5%), and vesicobullous diseases (8.5%). MRSA, acinetobacter, pseudomonas, MSSA, and Klebsiella were important etiological agents involved in sepsis in dermatology in-patients.

Case report and review of septicemia due to Serratia ficaria.

Serratia ficaria was first described in 1979 as part of the fig tree ecosystem (P.A.D. Grimont, F. Grimont, and M. P. Starr, Curr. Microbiol. 2:277-282, 1979). Since then, it has been isolated from clinical specimens from a few human patients (C. Bollet, J. Freney, P. de Micco, F. Grimont, and P.A.D. Grimont, Méd. Mal. Infect. 20:97-100, 1990; J.A. Brouillard, W. Hansen, and A. Compere, J. Clin. Microbiol. 19:902-904, 1984; H. Darbas, H. Jean-Pierre, G. Boyer, and M. Riviere, Méd. Mal. Infect. 23:269-270, 1993; V.J. Gill, J.J. Farmer, III, P.A.D. Grimont, M.A. Asbury, and C.L. McIntosh, J. Clin. Microbiol. 14:234-236, 1981; F.D. Pien and J.J. Farmer III, South. Med. J. 76:1591-1592, 1983; C. Richard, J. de Coquet, and C. Suc, Méd. Mal. Infect. 19:45-47, 1989), but the pathogenicity of S. ficaria was always questionable. We are reporting the case of an aged cancer patient who developed S. ficaria septicemia. The habitat of this organism and its potential role as a pathogen are discussed.

Bacillaemia in leprosy: correlation with slit-skin and nasal smears.

Twenty five multibacillary patients (BL/LL) were studied for bacillaemia. Majority (76%) showed acid fast bacilli in peripheral blood. There was good correlation between bacillary load in peripheral blood and bacteriological index (BI) but poor correlation with morphological index (MI) of skin slit smear and BI/MI of nasal smear.

A quick method of demonstrating bacillaemia in patients with lepromatous leprosy and ultrastructural studies of the circulating acid-fast bacilli.

While studying circulating immune complexes (CIC) in the sera of lepromatous patients by the polyethylene glycol (PEG) precipitation technique, we found (by light microscopy) abundant acid-fast bacilli (AFB), morphologically similar to those seen in slit skin smear preparations from these patients, precipitated with the PEG precipitated materials. Both solid and non-solid AFB could be readily identified. Ultrastructures of these AFB in the PEG aggregates showed some similarity with those detected in the PEG precipitates prepared from armadillo-derived lepromin under identical conditions. The most striking difference between the AFB in the test sera and that in the armadillo-derived lepromin was the absence of any transverse band in the former. This suggested that the AFB in the patients' circulation were not in division stage. Furthermore, electron-dense material were deposited on the AFB co-precipitated from the patients' sera, which were not found on the AFB co-precipitated from the armadillo-derived lepromin.

Klebsiella ozaenae septicemia associated with Hansen's disease.

Two cases of Klebsiella ozaenae septicemia from the National Hansen's Disease Center, Carville, La., are discussed: one fatal and one nonfatal. Although both patients had nasal complications of Hansen's disease (leprosy), the organism was grown initially from spinal fluid, blood, and wound cultures. This report confirms the potential pathogenicity of the K. ozaenae species and its widening disease spectrum.

Macrophage culture from untreated leprosy cases.

Macrophage cultures from the peripheral blood were performed in 25 untreated bacteraemic leprosy patients. The monocytes on conversion to macrophages in culture continued to harbour solidly stained M. Leprae till the termination of culture. It is suggested that the majority of these bacilli are viable and capable of multiplication intracellularly in macrophages if cultures could be maintained for sufficiently long periods. It was observed that bacteraemia in Leprosy can be detected by the culture technic. It has been found to be more sensitive than the leukocyte adherence method.

The effect of renal function on the febrile response to bacteremia.

The febrile responses of 73 bacteremic patients were retrospectively studied using peak temperatures and 24-hour areas under the fever curve on the day of the positive cultures. These responses were compared to their respective creatinine clearances calculated with the Nielsen-Hansen nomogram. Patients with clearances greater than or equal to 80 ml/min had a significantly greater febrile response than those with clearances less than or equal to 29 ml/min (P less than .025). Patients with clearances between these groups had responses that were in a mid position but not significantly different from either group. We conclude that patients with impaired renal function do manifest fever in response to infection, but that it is quantitatively less than those with normal renal function. Because of this blunted response, minimal elevations of temperature in such patients warrant a diligent search for the presence of infection.

Evaluation of bacteraemia in leprosy patients.

Thirty five patients of leprosy have been screened for bacteraemia by haemolysis (HL), leucocyte adherence (LA) and buffy coat (BC) methods and the results have been compared. The HL method has yielded not only higher number of acid-fast bacilli (AFB) but also has detected more frequently AFB in blood of leprosy patients as compared to other methods. Further, it has been established that the skin over the cubital fossa does not play any significant role in contaminating blood samples while sampling blood by venepuncture.