Last data update: Jul 01, 2024. (Total: 47134 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Paulos S [original query] |
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Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells
Kyu S , Ramonell RP , Kuruvilla M , Kraft CS , Wang YF , Falsey AR , Walsh EE , Daiss JL , Paulos S , Rajam G , Wu H , Velusamy S , Lee FE . PLoS One 2021 16 (11) e0259644 BACKGROUND: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes. METHODS: We introduce two new methods for diagnosing S. pneumoniae infections by measuring the presence of newly activated, pathogen-specific, circulating Antibody Secreting Cells (ASC). First, ASC were detected by ELISpot assays that measure cells secreting antibodies specific for signature antigens. Second, the antibodies secreted by isolated ASC were collected in vitro in a novel matrix, MENSA (media enriched with newly synthesized antibodies) and antibodies against S. pneumoniae antigens were measured using Luminex immunoassays. Each assay was evaluated using blood from S. pneumoniae and non-S. pneumoniae-infected adult patients. RESULTS: We enrolled 23 patients with culture-confirmed S. pneumoniae infections and 24 controls consisting of 12 non-S. pneumoniae infections, 10 healthy donors and two colonized with S. pneumoniae. By ELISpot assays, twenty-one of 23 infected patients were positive, and all 24 controls were negative. Using MENSA samples, four of five S. pneumoniae-infected patients were positive by Luminex immunoassays while all five non-S. pneumoniae-infected patients were negative. CONCLUSION: Specific antibodies produced by activated ASC may provide a simple diagnostic for ongoing S. pneumoniae infections. This method has the potential to diagnose acute bacterial infections. |
Tuberculosis screening, testing, and treatment of U.S. health care personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019
Sosa LE , Njie GJ , Lobato MN , Bamrah Morris S , Buchta W , Casey ML , Goswami ND , Gruden M , Hurst BJ , Khan AR , Kuhar DT , Lewinsohn DM , Mathew TA , Mazurek GH , Reves R , Paulos L , Thanassi W , Will L , Belknap R . MMWR Morb Mortal Wkly Rep 2019 68 (19) 439-443 The 2005 CDC guidelines for preventing Mycobacterium tuberculosis transmission in health care settings include recommendations for baseline tuberculosis (TB) screening of all U.S. health care personnel and annual testing for health care personnel working in medium-risk settings or settings with potential for ongoing transmission (1). Using evidence from a systematic review conducted by a National Tuberculosis Controllers Association (NTCA)-CDC work group, and following methods adapted from the Guide to Community Preventive Services (2,3), the 2005 CDC recommendations for testing U.S. health care personnel have been updated and now include 1) TB screening with an individual risk assessment and symptom evaluation at baseline (preplacement); 2) TB testing with an interferon-gamma release assay (IGRA) or a tuberculin skin test (TST) for persons without documented prior TB disease or latent TB infection (LTBI); 3) no routine serial TB testing at any interval after baseline in the absence of a known exposure or ongoing transmission; 4) encouragement of treatment for all health care personnel with untreated LTBI, unless treatment is contraindicated; 5) annual symptom screening for health care personnel with untreated LTBI; and 6) annual TB education of all health care personnel. |
Development and validation of a robust multiplex serological assay to quantify antibodies specific to pertussis antigens
Rajam G , Carlone G , Kim E , Choi J , Paulos S , Park S , Jeyachandran A , Gorantla Y , Wong E , Sabnis A , Browning P , Desai R , Quinn CP , Schiffer J . Biologicals 2018 57 9-20 Despite wide spread vaccination, the public health burden of pertussis remains substantial. Current acellular pertussis vaccines comprise upto five Bordetella pertussis (Bp) antigens. Performing an ELISA to quantify antibody for each antigen is laborious and challenging to apply to pediatric samples where serum volume may be limited. We developed a microsphere based multiplex antibody capture assay (MMACA) to quantify antibodies to five pertussis antigens; pertussis toxin, pertactin, filamentous hemagglutinin and fimbrial antigens 2/3, and adenylate cyclase toxin in a single reaction (5-plex) with a calibrated reference standard, QC reagents and SAS((R)) based data analysis program. The goodness of fit (R(2)) of the standard curves for five analytes was >/=0.99, LLOQ 0.04-0.15 IU or AU/mL, accuracy 1.9%-23.8% (%E), dilutional linearity slopes 0.93-1.02 and regression coefficients r(2)=0.91-0.99. MMACA had acceptable precision within a median CV of 16.0%-22.8%. Critical reagents, antigen conjugated microsphere and reporter antibody exhibited acceptable (<12.3%) lot-lot variation. MMACA can be completed in <3h, requires low serum volume (5muL/multiplex assay) and has fast data turnaround time (<1min). MMACA has been successfully developed and validated as a sensitive, specific, robust and rugged method suitable for simultaneous quantification of anti-Bp antibodies in serum, plasma and DBS. |
Impact of maternally derived pertussis antibody titers on infant whole-cell pertussis vaccine response in a low income setting
Ibrahim R , Ali SA , Kazi AM , Rizvi A , Guterman LB , Bednarczyk RA , Kim E , Park S , Paulos S , Jeyachandran A , Patel D , Gorantla Y , Wong E , Rajam G , Schiffer J , Omer SB . Vaccine 2018 36 (46) 7048-7053 BACKGROUND: Maternal vaccines against pertussis are not yet recommended in the developing world. Besides unclear burden estimates, another concern is that transplacental transfer of maternal pertussis antibodies could result in attenuation of the immune response to whole cell pertussis (DTwP) primary vaccination series in infants. This study was taken up to determine whether higher levels of maternal pertussis antibodies attenuate immune response of infants to DTwP vaccination series given at 6-10-14weeks of age. METHODOLOGY: A total of 261 pregnant women and their infants from four low-income settlements in Karachi, Pakistan were enrolled in this study. The study endpoints were infant antibody titers for Pertussis toxin (PTx), Filamentous hemagglutinin antigen (FHA), Pertactin (PRN) and Fimbriae type 2/3 (FIM) - from birth through 18weeks of age. Cord blood or pre-vaccine pertussis antibody titers indicate the concentration of maternal antibodies transferred to infants. Linear regression models were used to determine the association between higher maternal antibody titers and infant immune response to DTwP vaccine. Geometric Mean Ratio (GMR) was calculated as the ratio of infant antibody titers at specified time points against the maternal antibody titers at the time of delivery. RESULTS: At eighteen weeks of age, the adjusted beta regression coefficient for PTx was 0.06 (95% CI: -0.49-0.61), FHA 0.02 (95% CI: -0.26 -0.29), PRN 0.02 (95%CI -0.38- 0.43), and FIM 0.17 (95%CI: -0.21-0.54). Among infants who received at least two doses of DTwP vaccine, higher maternal antibody titers did not have any attenuating effect on infant post-immunization antibody titers against all four pertussis antigens. CONCLUSION: Maternal pertussis antibodies did not attenuate infant's immune response to pertussis antigens in DTwP primary vaccine given at 6-10-14weeks of age. |
Meningococcal Antigen Typing System (MATS)-based Neisseria meningitidis serogroup B coverage prediction for the MenB-4C vaccine in the United States
Rajam G , Stella M , Kim E , Paulos S , Boccadifuoco G , Serino L , Carlone G , Medini D . mSphere 2017 2 (6) Neisseria meningitidis is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against N. meningitidis serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States. MATS data correlate with killing in the human complement serum bactericidal assay (hSBA) and predict the susceptibility of NmB strains to killing in the hSBA, the accepted correlate of protection for MenB-4C vaccine. A panel of 442 NmB United States clinical isolates (collected in 2000 to 2008) whose data were down weighted with respect to the Oregon outbreak was selected from the Active Bacterial Core Surveillance (ABCs; CDC, Atlanta, GA) laboratory. MATS results examined to determine strain coverage were linked to multilocus sequence typing and antigen sequence data. MATS predicted that 91% (95% confidence interval [CI95], 72% to 96%) of the NmB strains causing disease in the United States would be covered by the MenB-4C vaccine, with the estimated coverage ranging from 88% to 97% by year with no detectable temporal trend. More than half of the covered strains could be targeted by two or more antigens. NHBA conferred coverage to 83% (CI95, 45% to 93%) of the strains, followed by factor H-binding protein (fHbp), which conferred coverage to 53% (CI95, 46% to 57%); PorA, which conferred coverage to 5.9%; and NadA, which conferred coverage to 2.5% (CI95, 1.1% to 5.2%). Two major clonal complexes (CC32 and CC41/44) had 99% strain coverage. The most frequent MATS phenotypes (39%) were fHbp and NHBA double positives. MATS predicts over 90% MenB-4C strain coverage in the United States, and the prediction is stable in time and consistent among bacterial genotypes. IMPORTANCE The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates (n = 442) predicts high MenB-4C vaccine coverage in the United States. |
Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Holmes MV , Dale CE , Zuccolo L , Silverwood RJ , Guo Y , Ye Z , Prieto-Merino D , Dehghan A , Trompet S , Wong A , Cavadino A , Drogan D , Padmanabhan S , Li S , Yesupriya A , Leusink M , Sundstrom J , Hubacek JA , Pikhart H , Swerdlow DI , Panayiotou AG , Borinskaya SA , Finan C , Shah S , Kuchenbaecker KB , Shah T , Engmann J , Folkersen L , Eriksson P , Ricceri F , Melander O , Sacerdote C , Gamble DM , Rayaprolu S , Ross OA , McLachlan S , Vikhireva O , Sluijs I , Scott RA , Adamkova V , Flicker L , Bockxmeer FM , Power C , Marques-Vidal P , Meade T , Marmot MG , Ferro JM , Paulos-Pinheiro S , Humphries SE , Talmud PJ , Mateo Leach I , Verweij N , Linneberg A , Skaaby T , Doevendans PA , Cramer MJ , Harst Pv , Klungel OH , Dowling NF , Dominiczak AF , Kumari M , Nicolaides AN , Weikert C , Boeing H , Ebrahim S , Gaunt TR , Price JF , Lannfelt L , Peasey A , Kubinova R , Pajak A , Malyutina S , Voevoda MI , Tamosiunas A , Maitland-van der Zee AH , Norman PE , Hankey GJ , Bergmann MM , Hofman A , Franco OH , Cooper J , Palmen J , Spiering W , Jong PA , Kuh D , Hardy R , Uitterlinden AG , Ikram MA , Ford I , Hypponen E , Almeida OP , Wareham NJ , Khaw KT , Hamsten A , Husemoen LL , Tjonneland A , Tolstrup JS , Rimm E , Beulens JW , Verschuren WM , Onland-Moret NC , Hofker MH , Wannamethee SG , Whincup PH , Morris R , Vicente AM , Watkins H , Farrall M , Jukema JW , Meschia J , Cupples LA , Sharp SJ , Fornage M , Kooperberg C , LaCroix AZ , Dai JY , Lanktree MB , Siscovick DS , Jorgenson E , Spring B , Coresh J , Li YR , Buxbaum SG , Schreiner PJ , Ellison RC , Tsai MY , Patel SR , Redline S , Johnson AD , Hoogeveen RC , Hakonarson H , Rotter JI , Boerwinkle E , Bakker PI , Kivimaki M , Asselbergs FW , Sattar N , Lawlor DA , Whittaker J , Davey Smith G , Mukamal K , Psaty BM , Wilson JG , Lange LA , Hamidovic A , Hingorani AD , Nordestgaard BG , Bobak M , Leon DA , Langenberg C , Palmer TM , Reiner AP , Keating BJ , Dudbridge F , Casas JP . BMJ 2014 349 g4164 OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health. |
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