Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-24 (of 24 Records) |
Query Trace: Brown JM[original query] |
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Prenatal exposure to poly- and perfluoroalkyl substances (2009-2014) and vaccine antibody titers of measles, mumps, rubella, and varicella in children four to eight years old from the Healthy Start Cohort
Zell-Baran LM , Dabelea D , Norris JM , Glueck DH , Adgate JL , Brown JM , Harrall KK , Calafat AM , Starling AP . Environ Health Perspect 2023 131 (12) 127018 BACKGROUND: Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations. OBJECTIVE: We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization. METHODS: We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in > 65% of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture. RESULTS: Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males. DISCUSSION: Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863. |
Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood
Zell-Baran LM , Venter C , Dabelea D , Norris JM , Glueck DH , Adgate JL , Brown JM , Calafat AM , Pickett-Nairne K , Starling AP . Environ Res 2023 239 117311 EXPOSURE TO POLY: and perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma. |
Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data
Stepniewska K , Allen EN , Humphreys GS , Poirot E , Craig E , Kennon K , Yilma D , Bousema T , Guerin PJ , White NJ , Price RN , Raman J , Martensson A , Mwaiswelo RO , Bancone G , Bastiaens GJH , Bjorkman A , Brown JM , D'Alessandro U , Dicko AA , El-Sayed B , Elzaki SE , Eziefula AC , Gonçalves BP , Hamid MMA , Kaneko A , Kariuki S , Khan W , Kwambai TK , Ley B , Ngasala BE , Nosten F , Okebe J , Samuels AM , Smit MR , Stone WJR , Sutanto I , Ter Kuile F , Tine RC , Tiono AB , Drakeley CJ , Gosling R , Stergachis A , Barnes KI , Chen I . BMC Med 2022 20 (1) 350 BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185. |
Editorial: Immune Mechanisms in the Pathologic Response to Particles, Fibers, and Nanomaterials
Ma Q , Pollard KM , Brown JM , Italiani P , Moghimi SM . Front Immunol 2021 12 665810 It may come as a surprise that a Research Topic in Frontiers in Immunology is devoted to “Immune mechanisms” in the pathologic response to “particles, fibers, and nanomaterials,” a large group of natural and man-made particulates with dimensions in micro and nano ranges. Unlike pathogens, many particulate materials do not possess apparent antigenic structures and are assumed to be non-immunogenic. But because of their small size and airborne propensity, inhaled particulates can penetrate deep into the lung and pleura to cause inflammation, fibrosis, and cancer, exemplified by silicosis, asbestosis, and mesothelioma that are progressive and have high mortality rates (1, 2). Notwithstanding, the role of immune responses in the pathogenesis of particulate-induced diseases has gained increasing attention. A plethora of studies have shown that particulates activate various immune cells to promote physiological responses to particulate deposition and, under pathological conditions, development of fibrosis, malignancy, and autoimmunity (3, 4). The past two decades have also witnessed rapid advancement of nanotechnology and commercialization of nanomaterials, raising concerns on their possible adverse immune effects in exposed individuals (5–7). Understanding the interactions between particulates and immune functions has emerged as a new frontier for researchers in immunology, toxicology, and nanoscience. This Research Topic discusses recent trends in particle immunotoxicology with focus on pathologic immune effects of particulates and mechanisms mediating particle-immune interactions. |
Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission: A WWARN individual patient meta-analysis
Stepniewska K , Humphreys GS , Gonçalves BP , Craig E , Gosling R , Guerin PJ , Price RN , Barnes KI , Raman J , Smit MR , D'Alessandro U , Stone WJR , Bjorkman A , Samuels AM , Arroyo-Arroyo MI , Bastiaens GJH , Brown JM , Dicko A , El-Sayed BB , Elzaki SG , Eziefula AC , Kariuki S , Kwambai TK , Maestre AE , Martensson A , Mosha D , Mwaiswelo RO , Ngasala BE , Okebe J , Roh ME , Sawa P , Tiono AB , Chen I , Drakeley CJ , Bousema T . J Infect Dis 2020 225 (7) 1215-1226 BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected. RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP. |
Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial
Dicko A , Roh ME , Diawara H , Mahamar A , Soumare HM , Lanke K , Bradley J , Sanogo K , Kone DT , Diarra K , Keita S , Issiaka D , Traore SF , McCulloch C , Stone WJR , Hwang J , Muller O , Brown JM , Srinivasan V , Drakeley C , Gosling R , Chen I , Bousema T . Lancet Infect Dis 2018 18 (6) 627-639 BACKGROUND: Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. METHODS: This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali). We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria. G6PD-normal participants with gametocytes detected by blood smear were randomised 1:1:1:1 in block sizes of eight, using a sealed-envelope design, to receive either sulfadoxine-pyrimethamine and amodiaquine, sulfadoxine-pyrimethamine and amodiaquine plus a single dose of 0.25 mg/kg primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days. Laboratory staff, investigators, and insectary technicians were masked to the treatment group and gametocyte density of study participants. The study pharmacist and treating physician were not masked. Participants could request unmasking. The primary efficacy endpoint, analysed in all infected patients with at least one infectivity measure before and after treatment, was median within-person percentage change in mosquito infectivity 2 and 7 days after treatment, assessed by membrane feeding. This study is registered with ClinicalTrials.gov, number NCT02831023. FINDINGS: Between June 27, 2016, and Nov 1, 2016, 80 participants were enrolled and assigned to the sulfadoxine-pyrimethamine and amodiaquine (n=20), sulfadoxine-pyrimethamine and amodiaquine plus primaquine (n=20), dihydroartemisinin-piperaquine (n=20), or dihydroartemisinin-piperaquine plus methylene blue (n=20) groups. Among participants infectious at baseline (54 [68%] of 80), those in the sulfadoxine-pyrimethamine and amodiaquine plus primaquine group (n=19) had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with sulfadoxine-pyrimethamine and amodiaquine alone (n=12; -10.2%, IQR -143.9 to 56.6; p<0.0001). The dihydroartemisinin-piperaquine plus methylene blue (n=11) group had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with dihydroartemisinin-piperaquine alone (n=12; -6.0%, IQR -126.1 to 86.9; p<0.0001). Haemoglobin changes were similar between gametocytocidal arms and their respective controls. After exclusion of blue urine, adverse events were similar across all groups (59 [74%] of 80 participants had 162 adverse events overall, 145 [90%] of which were mild). INTERPRETATION: Adding a single dose of 0.25 mg/kg primaquine to sulfadoxine-pyrimethamine and amodiaquine or 3 days of 15 mg/kg per day methylene blue to dihydroartemisinin-piperaquine was highly efficacious for preventing P falciparum transmission. Both primaquine and methylene blue were well tolerated. FUNDING: Bill & Melinda Gates Foundation, European Research Council. |
Kroppenstedtia pulmonis sp. nov. and Kroppenstedtia sanguinis sp. nov., isolated from human patients.
Bell ME , Lasker BA , Klenk HP , Hoyles L , Sproer C , Schumann P , Brown JM . Antonie Van Leeuwenhoek 2016 109 (5) 603-10 Three human clinical strains (W9323T, X0209T and X0394) isolated from a lung biopsy, blood and cerebral spinal fluid, respectively, were characterised using a polyphasic taxonomic approach. Comparative analysis of the 16S rRNA gene sequences showed the three strains belong to two novel branches within the genus Kroppenstedtia: 16S rRNA gene sequence analysis of W9323T showed close sequence similarity to Kroppenstedtia eburnea JFMB-ATET (95.3 %), Kroppenstedtia guangzhouensis GD02T (94.7 %) and strain X0209T (94.6 %); sequence analysis of strain X0209T showed close sequence similarity to K. eburnea JFMB-ATET (96.4 %) and K. guangzhouensis GD02T (96.0 %). Strains X0209T and X0394 were 99.9 % similar to each other by 16S rRNA gene sequence analysis. The DNA-DNA relatedness was 94.6 %, confirming that X0209T and X0394 belong to the same species. Chemotaxonomic data for strains W9323T and X0209T were consistent with those described for the members of the genus Kroppenstedtia: the peptidoglycan was found to contain LL-diaminopimelic acid; the major cellular fatty acids were identified as iso-C15 and anteiso-C15; and the major menaquinone was identified as MK-7. Differences in endospore morphology, carbon source utilisation profiles, and cell wall sugar patterns of strains W9323T and X0209T, supported by phylogenetic analysis, enabled us to conclude that the strains each represent a new species within the genus Kroppenstedtia, for which the names Kroppenstedtia pulmonis sp. nov. (type strain W9323T = DSM 45752T = CCUG 68107T) and Kroppenstedtia sanguinis sp. nov. (type strain X0209T = DSM 45749T = CCUG 38657T) are proposed. |
Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial
Dicko A , Brown JM , Diawara H , Baber I , Mahamar A , Soumare HM , Sanogo K , Koita F , Keita S , Traore SF , Chen I , Poirot E , Hwang J , McCulloch C , Lanke K , Pett H , Niemi M , Nosten F , Bousema T , Gosling R . Lancet Infect Dis 2016 16 (6) 674-684 BACKGROUND: Single low doses of primaquine, when added to artemisinin-based combination therapy, might prevent transmission of Plasmodium falciparum malaria to mosquitoes. We aimed to establish the activity and safety of four low doses of primaquine combined with dihydroartemisinin-piperaquine in male patients in Mali. METHODS: In this phase 2, single-blind, dose-ranging, adaptive randomised trial, we enrolled boys and men with uncomplicated P falciparum malaria at the Malaria Research and Training Centre (MRTC) field site in Ouelessebougou, Mali. All participants were confirmed positive carriers of gametocytes through microscopy and had normal function of glucose-6-phosphate dehydrogenase (G6PD) on colorimetric quantification. In the first phase, participants were randomly assigned (1:1:1) to one of three primaquine doses: 0 mg/kg (control), 0.125 mg/kg, and 0.5 mg/kg. Randomisation was done with a computer-generated randomisation list (in block sizes of six) and concealed with sealed, opaque envelopes. In the second phase, different participants were sequentially assigned (1:1) to 0.25 mg/kg primaquine or 0.0625 mg/kg primaquine. Primaquine tablets were dissolved into a solution and administered orally in a single dose. Participants were also given a 3 day course of dihydroartemisinin-piperaquine, administered by weight (320 mg dihydroartemisinin and 40 mg piperaquine per tablet). Outcome assessors were masked to treatment allocation, but participants were permitted to find out group assignment. Infectivity was assessed through membrane-feeding assays, which were optimised through the beginning part of phase one. The primary efficacy endpoint was the mean within-person percentage change in mosquito infectivity 2 days after primaquine treatment in participants who completed the study after optimisation of the infectivity assay, had both a pre-treatment infectivity measurement and at least one follow-up infectivity measurement, and who were given the correct primaquine dose. The safety endpoint was the mean within-person change in haemoglobin concentration during 28 days of study follow-up in participants with at least one follow-up visit. This study is registered with ClinicalTrials.gov, number NCT01743820. FINDINGS: Between Jan 2, 2013, and Nov 27, 2014, we enrolled 81 participants. In the primary analysis sample (n=71), participants in the 0.25 mg/kg primaquine dose group (n=15) and 0.5 mg/kg primaquine dose group (n=14) had significantly lower mean within-person reductions in infectivity at day 2-92.6% (95% CI 78.3-100; p=0.0014) for the 0.25 mg/kg group; and 75.0% (45.7-100; p=0.014) for the 0.5 mg/kg primaquine group-compared with those in the control group (n=14; 11.3% [-27.4 to 50.0]). Reductions were not significantly different from control for participants assigned to the 0.0625 mg/kg dose group (n=16; 41.9% [1.4-82.5]; p=0.16) and the 0.125 mg/kg dose group (n=12; 54.9% [13.4-96.3]; p=0.096). No clinically meaningful or statistically significant drops in haemoglobin were recorded in any individual in the haemoglobin analysis (n=70) during follow-up. No serious adverse events were reported and adverse events did not differ between treatment groups. INTERPRETATION: A single dose of 0.25 mg/kg primaquine, given alongside dihydroartemisinin-piperaquine, was safe and efficacious for the prevention of P falciparum malaria transmission in boys and men who are not deficient in G6PD. Future studies should assess the safety of single-dose primaquine in G6PD-deficient individuals to define the therapeutic range of primaquine to enable the safe roll-out of community interventions with primaquine. FUNDING: Bill & Melinda Gates Foundation. |
Nocardia arizonensis sp. nov., obtained from human respiratory specimens.
Lasker BA , Bell M , Klenk HP , Schumann P , Brown JM . Antonie Van Leeuwenhoek 2015 108 (5) 1129-37 In 2008, three clinical isolates (W9405T, W9409 and W9575) were obtained from bronchial wash or sputum specimens from patients from the state of Arizona and characterised by polyphasic analysis. All three clinical isolates 16S rRNA gene sequences were found to be 100 % identical to each other and showed the strains belong in the genus Nocardia. BLASTn searches in the GenBank database of near full-length 16S rRNA gene sequences showed the highest sequence similarities to the type strains of Nocardia takedensis (98.3 %, sequence similarity), Nocardia lijiangensis (97.4 %), Nocardia harenae (97.4 %), and Nocardia xishanensis (97.1 %). The DNA-DNA relatedness between isolate W9405T and the type strain of N. takedensis is 26.0 +/- 2.4 % when measured in silico using genomic DNA sequences. The G+C content of isolate W9405T is 68.6 mol%. Chemotaxonomic analyses of the clinical isolates were consistent with their assignment to the genus Nocardia: whole cell hydrolysates contain meso-diaminopimelic acid as the diagnostic diamino acid of peptidoglycan; the whole-cell sugars are arabinose and galactose; the predominant phospholipids include diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol; MK-8-(H4) omega-cyc as the major menaquinone; mycolic acids ranging from 38 to 62 carbon atoms; and palmitic acid, tuberculostearic acid, palmitelaidic acid and oleic acid are the major fatty acids. Genus and species specific profiles were obtained following analysis by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra of the clinical isolates. All isolates were found to be intermediately resistant or resistant to minocycline and resistant to ciprofloxacin but were susceptible to amikacin, imipenem and linezolid. Our polyphasic analysis suggest the three clinical isolates obtained from patients in Arizona represent a novel species of Nocardia for which we propose the name Nocardia arizonensis, with strain W9405T (=DSM 45748T = CCUG 62754T = NBRC 108935T) as the type strain. |
Nocardia vulneris sp. nov., isolated from wounds of human patients in North America.
Lasker BA , Bell M , Klenk HP , Sproer C , Schumann P , Brown JM . Antonie Van Leeuwenhoek 2014 106 (3) 543-53 Nocardia species are ubiquitous in the environment with an increasing number of species isolated from clinical sources. From 2005 to 2009, eight isolates (W9042, W9247, W9290, W9319, W9846, W9851T, W9865, and W9908) were obtained from eight patients from three states in the United States and Canada; all were from males ranging in age from 47 to 81 years old; and all were obtained from finger (n = 5) or leg (n = 3) wounds. Isolates were characterized by polyphasic analysis using molecular, phenotypic, morphologic and chemotaxonomic methods. Sequence analysis of 16S rRNA gene sequences showed the eight isolates are 100 % identical to each other and belong in the genus Nocardia. The nearest phylogenetically related neighbours were found to be the type strains for Nocardia altamirensis (99.33 % sequence similarity), Nocardia brasiliensis (99.37 %), Nocardia iowensis (98.95 %) and Nocardia tenerifensis (98.44 %). The G+C content of isolate W9851T was determined to be 68.4 mol %. The DNA-DNA relatedness between strain W9851T and the N. brasiliensis type strain was 72.8 % and 65.8 % when measured in the laboratory and in silico from genome sequences, respectively, and 95.6 % ANI. Whole-cell peptidoglycan was found to contain meso-diaminopimelic acid; MK-8-(H4)omega-cyc was identified as the major menaquinone; the major fatty acids were identified as C16:0, 10 Me C18:0, and C18:1 w9c, the predominant phospholipids were found to include diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides; whole-cell sugars detected were arabinose and galactose; and mycolic acids ranging from 38 to 60 carbon atoms were found to be present. These chemotaxonomic analyses are consistent with assignment of the isolates to the genus Nocardia. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra of the clinical isolates showed genus and species level profiles that were different from other Nocardia species. All isolates were resistant to ciprofloxacin, clarithromycin and imipenem but were susceptible to amikacin, amoxicillin/clavulanate, linezolid and trimethoprim/sulfamethoxazole. The results of our polyphasic analysis suggest the new isolates obtained from wound infections represent a novel species within the genus Nocardia, for which the name Nocardia vulneris sp. nov. is proposed, with strain W9851T (= DSM 45737T = CCUG 62683T = NBRC 108936T) as the type strain. |
Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: the NIEHS Nano Go Consortium
Bonner JC , Silva RM , Taylor AJ , Brown JM , Hilderbrand SC , Castranova V , Porter D , Elder A , Oberdorster G , Harkema JR , Bramble LA , Kavanagh TJ , Botta D , Nel A , Pinkerton KE . Environ Health Perspect 2013 121 (6) 676-82 BACKGROUND: Engineered nanomaterials (ENMs) have potential benefits, but also present safety concerns for human health. Inter-laboratory studies in rodents using standardized protocols are needed for ENM toxicity assessment. METHODS: Four labs evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA). Three labs evaluated Sprague-Dawley (SD) or Fisher (F)344 rats following intratracheal instillation (IT). ENMs tested were three forms of titanium dioxide (TiO2); anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), anatase nanobelts (TiO2-NB), and three forms of multiwalled carbon nanotubes (MWCNT); original (O), purified (P), and carboxylic acid "functionalized" (F). Bronchoalveolar lavage fluid was collected after 1 day for differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2) and 21 days (MWCNTs). RESULTS: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in 3 out of 4 labs, respectively. TiO2-NB caused neutrophilia in rats at 1 day in 2 out of 3 labs, while TiO2-P25 or TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in 3 out of 4 mouse labs and all rat labs. Three out of 4 labs observed similar histopathology to O-MWCNT or TiO2-NB in mice. CONCLUSIONS: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although inter-laboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these inter-laboratory comparisons. |
Pattern of antimicrobial susceptibility obtained from blood isolates of a rare but emerging human pathogen, Gordonia polyisoprenivorans
Moser BD , Pellegrini GJ , Lasker BA , Brown JM . Antimicrob Agents Chemother 2012 56 (9) 4991-3 The genus Gordonia, originally described in 1971 by Tsukamura, consisted of both clinical and environmental isolates (9).... |
Nocardia amikacinitolerans sp. nov., an amikacin-resistant human pathogen.
Ezeoke I , Klenk HP , Potter G , Schumann P , Moser BD , Lasker BA , Nicholson A , Brown JM . Int J Syst Evol Microbiol 2012 63 1056-1061 Five isolates from clinical human sources were evaluated. Analysis of the near full length 16S rRNA gene showed 99.9-100 % similarity among the strains. The results of a comparative phylogenetic analysis of the 16S rRNA gene sequences indicated that the isolates belonged to the genus Nocardia. Phenotypic and molecular analyses were performed on the clinical isolates. Traditional phenotypic analyses included morphologic, biochemical/physiological, chemotaxonomic and antimicrobial susceptibility profiling. Molecular studies included 1441-bp 16S rRNA and 1246-bp gyrB gene sequence analyses, as well as DNA-DNA hybridizations. Biochemical analysis failed to differentiate the putative novel species from its phylogenetic neighbors; however, molecular studies were able to distinguish the patient strains and confirm them as a single species. Based on 16S rRNA gene sequence analysis, similarity between the isolates and their closest relatives (Nocardia araoensis, Nocardia arthritidis, Nocardia beijingensis and Nocardia niwae) were less than or equal to 99.3 %. Partial gyrB gene sequence analysis showed 98-99.7 % relatedness among the isolates. Nocardia lijiangensis and Nocardia xishanensis were the isolates' closest related species based on gyrB gene sequence analysis and showed 95.7 and 95.3 % similarity, respectively. Resistance to amikacin and molecular analyses, including DNA-DNA hybridization, distinguished the five patient strains from their phylogenetic neighbors, and the results of this polyphasic study indicated a novel species of Nocardia for which we propose the name Nocardia amikacinitolerans sp. nov., with strain W9988T (=DSM 45539 T = CCUG 59655T) as the type strain. |
Nocardia cyriacigeorgica infections attributable to unlicensed cosmetic procedures -- an emerging public health problem?
Apostolou A , Bolcen SJ , Dave V , Jani N , Lasker BA , Tan CG , Montana B , Brown JM , Genese CA . Clin Infect Dis 2012 55 (2) 251-3 We describe an outbreak of Nocardia cyriacigeorgica soft-tissue infections attributable to unlicensed cosmetic injections and the first report using MLST sequence data for determining Nocardia strain relatedness in an outbreak. All eight cases identified had a common source exposure and required hospitalization, surgical debridement, and prolonged antimicrobial therapy. |
Typhoid fever outbreak associated with frozen mamey pulp imported from Guatemala - western United States, 2010
Loharikar A , Newton A , Rowley P , Wheeler C , Bruno T , Barillas H , Pruckler J , Theobald L , Lance S , Brown JM , Barzilay EJ , Arvelo W , Mintz E , Fagan R . Clin Infect Dis 2012 55 (1) 61-6 BACKGROUND: Fifty-four outbreaks of domestically-acquired typhoid fever were reported between 1960-99. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. METHODS: We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analysis was completed using logistic regression. Traceback investigation was completed. RESULTS: We identified twelve cases in three states with onset from April 15-September 4, 2010. The median age of case-patients was 18 years (range 4-48), eight (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 75% (6/8) of case-patients and no (0/33) controls (matched odds ratio [mOR]=33.9, 95% confidence interval [CI]= 4.9-undefined). Traceback investigations implicated two brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-99 outbreak of typhoid fever in Florida. CONCLUSION: Reporting of individual cases of typhoid fever and subtyping of isolates by pulsed-field gel electrophoresis resulted in rapid detection of an outbreak, associated with a ready-to- eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks from occurring. |
Scalp abscess due to Streptomyces cacaoi subsp. cacaoi, first report in a human infection
Pellegrini GJ Jr , Graziano JC , Ragunathan L , Bhat MA , Hemashettar BM , Brown JM . J Clin Microbiol 2012 50 (4) 1484-6 Streptomyces cacaoi subsp. cacaoi, a gram-positive, branching filamentous bacteria, was isolated from a scalp infection in a patient from Pondicherry, India. Phenotypic tests identified the isolate as a Streptomyces but 16S rRNA sequence analysis provided the species identification required for tracking of this emerging pathogen. |
Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001-2006
Park BJ , Pappas PG , Wannemuehler KA , Alexander BD , Anaissie EJ , Andes DR , Baddley JW , Brown JM , Brumble LM , Freifeld AG , Hadley S , Herwaldt L , Ito JI , Kauffman CA , Lyon GM , Marr KA , Morrison VA , Papanicolaou G , Patterson TF , Perl TM , Schuster MG , Walker R , Wingard JR , Walsh TJ , Kontoyiannis DP . Emerg Infect Dis 2011 17 (10) 1855-64 Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period. |
Mycobacterium chelonae-abscessus complex associated with sinopulmonary disease, northeastern USA
Simmon KE , Brown-Elliott BA , Ridge PG , Durtschi JD , Mann LB , Slechta ES , Steigerwalt AG , Moser BD , Whitney AM , Brown JM , Voelkerding KV , McGowan KL , Reilly AF , Kirn TJ , Butler WR , Edelstein PH , Wallace RJ Jr , Petti CA . Emerg Infect Dis 2011 17 (9) 1692-700 Members of the Mycobacterium chelonae-abscessus complex represent Mycobacterium species that cause invasive infections in immunocompetent and immunocompromised hosts. We report the detection of a new pathogen that had been misidentified as M. chelonae with an atypical antimicrobial drug susceptibility profile. The discovery prompted a multicenter investigation of 26 patients. Almost all patients were from the northeastern United States, and most had underlying sinus or pulmonary disease. Infected patients had clinical features similar to those with M. abscessus infections. Taxonomically, the new pathogen shared molecular identity with members of the M. chelonae-abscessus complex. Multilocus DNA target sequencing, DNA-DNA hybridization, and deep multilocus sequencing (43 full-length genes) support a new taxon for these microorganisms. Because most isolates originated in Pennsylvania, we propose the name M. franklinii sp. nov. This investigation underscores the need for accurate identification of Mycobacterium spp. to detect new pathogens implicated in human disease. |
Characterization of human clinical isolates of Dietzia species previously misidentified as Rhodococcus equi.
Niwa H , Lasker BA , Hinrikson HP , Franzen CG , Steigerwalt AG , Whitney AM , Brown JM . Eur J Clin Microbiol Infect Dis 2011 31 (5) 811-20 In this study, 16 human clinical isolates of Dietzia species previously misidentified as Rhodococcus equi were evaluated using phenotypic methods, including traditional and commercial (API Coryne) biochemical tests, antimicrobial susceptibility testing, and 16S rRNA gene and gyrB gene sequencing. Positive results for both the hydrolysis of adenine and Christie-Atkins-Munch-Petersen (CAMP) reaction allowed for differentiation between the Dietzia isolates and the type strain of Rhodococcus equi; however, traditional and commercial phenotypic profiles could not be used to reliably identify Dietzia species. The analysis of 16S rRNA gene and gyrB gene sequences could discriminate all Dietzia strains from the type strain of R. equi. Most Dietzia species had distinct 16S rRNA gene and gyrB gene sequences; however, the 16S rRNA gene sequences of the type strains of D. schimae and D. cercidiphylli were identical to D. maris and D. natronolimnaea, respectively. Based on comparative sequence analysis, five clinical isolates clustered with D. maris/D. schimae and nine with D. natronolimnaea/D. cercidiphylli. The two remaining isolates were found to be most closely related to the D. cinnamea/D. papillomatosis clade. Even though molecular analyses were not sufficiently discriminative to accurately identify all Dietzia species, the method was able to reliably identify isolates that were previously misidentified by phenotypic methods to the genus level. |
Gordonia bronchialis bacteremia and pleural infection: case report and review of the literature
Johnson JA , Onderdonk AB , Cosimi LA , Yawetz S , Lasker BA , Bolcen SJ , Brown JM , Marty FM . J Clin Microbiol 2011 49 (4) 1662-6 Gordonia species are aerobic actinomycetes recently recognized as causing human disease, often in the setting of intravascular catheter-related infections. We describe a case of Gordonia bronchialis bacteremia and pleural space infection in the absence of an indwelling intravascular catheter, and review the breadth of reported infections with this emerging pathogen. |
Antimicrobial-resistant nocardia isolates, United States, 1995-2004
Uhde KB , Pathak S , McCullum I Jr , Jannat-Khah DP , Shadomy SV , Dykewicz CA , Clark TA , Smith TL , Brown JM . Clin Infect Dis 2010 51 (12) 1445-8 We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole. |
Nocardia niwae sp. nov., isolated from human pulmonary sources.
Moser BD , Klenk HP , Schumann P , Potter G , Lasker BA , Steigerwalt AG , Hinrikson HP , Brown JM . Int J Syst Evol Microbiol 2010 61 438-442 Members of the genus Nocardia are responsible for cutaneous, pulmonary and disseminated human infections. From 2003 to 2008, four nocardioform strains (W8027, W8681, W9071, W9241T) were isolated from persons in the state of Florida, USA. Ribosomal gene sequencing analysis suggested that a novel Nocardia species had been isolated. These strains underwent polyphasic taxonomic analysis. Phenotypic analyses included morphologic examination, biochemical profiling and antimicrobial susceptibility testing. Molecular studies included 16S rRNA and DNA gyrase B subunit (gyrB) gene sequence analyses and DNA-DNA hybridization. Phylogenetic neighbours were determined through 16S rRNA and gyrB gene sequence analyses. Differential phenotypic characteristics of the novel Nocardia species compared to phylogenetically related species were growth at 45C and 3 out of 4 novel strains utilized L-rhamnose. The antimicrobial profiles could not reliably distinguish the novel species from related nocardiae. Analysis showed that the 16S rRNA gene sequences of the four novel isolates were identical. The BLAST analysis of the near full length 16S rRNA gene showed 99.2 % sequence similarity to N. araoensis DSM 44729T, N. arthritidis DSM 44731T and N. beijingensis JCM 10666 T, 98.7 % to N. amamiensis DSM 45066T, 98.2 % to N. pneumoniae JCM 12119T and 97.8 % to N. takedensis JCM 13313T; the analysis of partial gyrB gene sequences showed 95.4 % similarity to N. arthritidis DSM 44731T, 95.3 % to N. gamkensis DSM 44956T, 94.4 % to N. pneumoniae JCM 12119T, 93.8 % to asiatica DSM44668T, 93.5 % to N. amamiensis DSM 45066T, 93.4 % to N. beijingensis JCM 10666 T and 93.2 % to N. araoensis DSM 44729T. The DNA-DNA hybridization percentages among the four novel strains were 86-89 %; the hybridization percentages of W9241T compared to N. beijingensis JCM 10666T was 47 %, to N. araoensis DSM 44729T was 46 %, to N. arthritidis DSM 44731T was 44 %, to N. amamiensis DSM 45066T was 32 % and to N. asiatica DSM 44668T was 20 %. The results of our polyphasic taxonomic analysis suggested that a novel species of Nocardia was identified for which we propose the name Nocardia niwae sp. nov. The type strain is W9241T ( = DSM 45340T = CCUG 57756T). |
Homozygous triplicate mutations in three 16S rRNA genes: responsible for high-level aminoglycoside resistance in Nocardia farcinica clinically isolated in the Canada-wide bovine mastitis epizootic
Kogure T , Shimada R , Ishikawa J , Yazawa K , Brown JM , Mikami Y , Gonoi T . Antimicrob Agents Chemother 2010 54 (6) 2385-90 Nocardia farcinica strains showing high-level resistance to amikacin were isolated from clinical cases in a Canada-wide bovine mastitis epizootic. Shotgun cloning of the resistance genes in the amikacin-resistant mastitis isolate N. farcinica IFM 10580 (= W6220, CDC) using a multicopy vector system revealed that the 16S rRNA gene with an A to G single-point mutation at position 1408 (in E. coli numbering) conferred "moderate" cross-resistance to amikacin and other aminoglycosides to an originally susceptible N. farcinica strain IFM 10152. Subsequent DNA sequence analyses revealed that, in contrast to the susceptible strain, all three chromosomal 16S rRNA genes of IFM 10580, the epizootic clinical strain, contained the same A1408G point mutations. Mutant colonies showing high-level aminoglycoside resistance were obtained when the susceptible strain N. farcinica IFM 10152 was transformed with a multicopy plasmid carrying the A1408G mutant 16S rRNA gene and was cultured in the presence of aminoglycosides for 3-5 days. Of these transformants, at least two of the three chromosomal 16S rRNA genes contained A1408G mutations. A triple mutant was easily obtained from a strain carrying the two chromosomal A1408G mutant genes and one wild-type gene, even in the absence of the plasmid. The triple mutant showed the highest-level of resistance to aminoglycosides, even in the absence of the plasmid carrying the mutant 16S rRNA gene. These results suggest that the homozygous mutations in the three 16S rRNA genes are responsible for the high-level aminoglycoside resistance found in N. farcinica isolates of the bovine mastitis epizootic. |
Nocardia mikamii sp. nov., isolated from human pulmonary infections in the United States
Jannat-Khah DP , Kroppenstedt RM , Klenk HP , Sproer C , Schumann P , Lasker BA , Steigerwalt AG , Hinrikson HP , Brown JM . Int J Syst Evol Microbiol 2009 60 (10) 2272-2276 Four nocardioform bacteria were isolated from clinical respiratory sources (W7467, W7811, W8061T and W9013) in the United States. Macroscopic examination showed scant aerial hyphae and beige-red substrate hyphae. They showed chemotaxonomic markers that were consistent with the classification of Nocardia: i.e., meso-diaminopimelic acid; arabinose and galactose as diagnostic sugars; the phospholipids diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides; a menaquinone with a omega-cyclic isoprene side chain MK-8(H4cycl.); a fatty acid pattern composed of unbranched saturated and monounsaturated fatty acids with considerable amount of tuberculostearic acid; and mycolic acids comprising 52 to 62 carbon atoms with three principal mycolic acids which were mono- and polyunsaturated showing a chain length of C54, C56 and C58. 16S rRNA gene sequence data and phenotypic characters showed they were most closely related to Nocardia aobensis (DSM 44805T ). The G+C content was 68.3 mol %. Analysis of a 1,245-bp fragment of gyrB gene showed a clade separate from N. aobensis and was supported by the DNA relatedness of 67 % of W8061T to N. aobensis. These data indicated that the novel isolates represent a new species within the genus Nocardia, for which the name Nocardia mikamii sp. nov. is proposed, with W8061T (DSM 45174T = JCM 15508T) designated as the type strain. |
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