Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
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Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)
Cohn AC , MacNeil JR , Clark TA , Ortega-Sanchez IR , Briere EZ , Meissner HC , Baker CJ , Messonnier NE . MMWR Recomm Rep 2013 62 1-28 Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided. |
Demographic Characteristics of Persons Vaccinated During the First Month of the COVID-19 Vaccination Program - United States, December 14, 2020-January 14, 2021.
Painter EM , Ussery EN , Patel A , Hughes MM , Zell ER , Moulia DL , Scharf LG , Lynch M , Ritchey MD , Toblin RL , Murthy BP , Harris LQ , Wasley A , Rose DA , Cohn A , Messonnier NE . MMWR Morb Mortal Wkly Rep 2021 70 (5) 174-177 In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel(†) and residents and staff members of long-term care facilities (LTCF) during the first phase of the U.S. COVID-19 vaccination program (1). Both vaccines require 2 doses to complete the series. Data on vaccines administered during December 14, 2020-January 14, 2021, and reported to CDC by January 26, 2021, were analyzed to describe demographic characteristics, including sex, age, and race/ethnicity, of persons who received ≥1 dose of COVID-19 vaccine (i.e., initiated vaccination). During this period, 12,928,749 persons in the United States in 64 jurisdictions and five federal entities(§) initiated COVID-19 vaccination. Data on sex were reported for 97.0%, age for 99.9%, and race/ethnicity for 51.9% of vaccine recipients. Among persons who received the first vaccine dose and had reported demographic data, 63.0% were women, 55.0% were aged ≥50 years, and 60.4% were non-Hispanic White (White). More complete reporting of race and ethnicity data at the provider and jurisdictional levels is critical to ensure rapid detection of and response to potential disparities in COVID-19 vaccination. As the U.S. COVID-19 vaccination program expands, public health officials should ensure that vaccine is administered efficiently and equitably within each successive vaccination priority category, especially among those at highest risk for infection and severe adverse health outcomes, many of whom are non-Hispanic Black (Black), non-Hispanic American Indian/Alaska Native (AI/AN), and Hispanic persons (2,3). |
Country data for action: The MenAfriNet experience in strengthening meningitis surveillance in Africa
Novak RT , Moisi JC , Tall H , Preziosi MP , Hadler SC , Messonnier NE , Mihigo R . J Infect Dis 2019 220 S137-s139 Epidemic meningitis has posed a recurrent threat for more than a century for the approximately 430 million people living in the 26 countries in the sub-Saharan region of Africa known as the “meningitis belt.” This population experiences high rates of endemic meningitis, annual seasonal outbreaks, and explosive epidemics occurring every 5–12 years. Hope to eliminate this devastating public health threat came in the form of a novel meningococcal serogroup A conjugate vaccine (MACV [MenAfriVac]) developed by the Meningitis Vaccine Project (MVP; available at: http://www.meningvax.org) specifically for use in the meningitis belt and priced at less than $1.00 per dose [1]. Licensed in 2009, MACV was subsequently prequalified by the World Health Organization (WHO) on the basis of its safety and immunogenicity data but without phase 3 efficacy studies. Starting in 2010, MACV was rolled out across the meningitis belt via mass campaigns to vaccinate all persons 1–29 years of age. By the end of 2018, >300 million people in 22 African countries had been immunized with MACV [2]. The vaccine has been a remarkable public health success, effectively eliminating serogroup A meningitis epidemics in sub-Saharan Africa [3]. |
Progress in vaccine-preventable and respiratory infectious diseases - first 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006-2015
Schuchat A , Anderson LJ , Rodewald LE , Cox NJ , Hajjeh R , Pallansch MA , Messonnier NE , Jernigan DB , Wharton M . Emerg Infect Dis 2018 24 (7) 1178-1187 The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful. |
Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Liang JL , Tiwari T , Moro P , Messonnier NE , Reingold A , Sawyer M , Clark TA . MMWR Recomm Rep 2018 67 (2) 1-44 This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks' gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria. |
Effectiveness and duration of protection of one dose of a meningococcal conjugate vaccine
Cohn AC , MacNeil JR , Harrison LH , Lynfield R , Reingold A , Schaffner W , Zell ER , Plikaytis B , Wang X , Messonnier NE . Pediatrics 2017 139 (2) BACKGROUND: Meningococcal conjugate vaccines were licensed beginning in 2005 on the basis of serologic end points and recommended for use in adolescents. A single dose at age 11 to 12 years was expected to provide protection through late adolescence. We conducted a case-control evaluation of vaccine effectiveness (VE) and duration of protection of a meningococcal (groups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D). METHODS: Cases of culture- or polymerase chain reaction-confirmed serogroup A, C, W, and Y meningococcal disease among adolescents were identified through meningococcal disease surveillance sites in the United States from January 1, 2006, through August 31, 2013. Attempts were made to enroll 4 friend and school controls per case. VE was calculated using the generalized estimating equation, controlling for underlying medical conditions and smoking. RESULTS: Serogroup C accounted for 88 (49%), serogroup Y 80 (44%), and serogroup W 13 (7%) of enrolled cases. Thirty-six (20%) cases and 87 (44%) controls received MenACWY-D. The overall VE estimate 0 to 8 years postvaccination was 69% (51% to 80%); VE was 79% (49% to 91%) at <1 year, 69% (44% to 83%) at 1 to <3 years, and 61% (25% to 79%) at 3 to <8 years. VE was 77% (57% to 88%) against serogroup C and 51% (1% to 76%) against serogroup Y. CONCLUSIONS: MenACWY-D was effective in the first year after vaccination but effectiveness waned 3 to <8 years postvaccination. The estimates of VE from this evaluation informed the Advisory Committee on Immunization Practices in its decision to add a booster dose of MenACWY. |
Population-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States.
Harcourt BH , Anderson RD , Wu HM , Cohn AC , MacNeil JR , Taylor TH , Wang X , Clark TA , Messonnier NE , Mayer LW . Open Forum Infect Dis 2015 2 (3) ofv117 ![]() BACKGROUND: Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. RESULTS: All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008-16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. CONCLUSIONS:. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use. |
Tdap vaccine effectiveness in adolescents during the 2012 Washington State pertussis epidemic
Acosta AM , DeBolt C , Tasslimi A , Lewis M , Stewart LK , Misegades LK , Messonnier NE , Clark TA , Martin SW , Patel M . Pediatrics 2015 135 (6) 981-9 BACKGROUND: Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited. METHODS: To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993-2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993-1997) or all acellular vaccines (1998-2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls. RESULTS: Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: -0.03% to 58%). CONCLUSIONS: Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents. |
Changes in the Population Structure of Invasive Neisseria meningitidis in the United States After Quadrivalent Meningococcal Conjugate Vaccine Licensure.
Wang X , Shutt KA , Vuong JT , Cohn A , MacNeil J , Schmink S , Plikaytis B , Messonnier NE , Harrison LH , Clark TA , Mayer LW . J Infect Dis 2015 211 (12) 1887-94 ![]() BACKGROUND: Meningococcal conjugate vaccines (MenACWY) against serogroups A, C, W and Y are recommended for routine use in adolescents aged 11-18 years. Impact of these vaccines on meningococcal population structure in the US remained to be evaluated. METHODS: Meningococcal isolates from 2006-10 (post-MenACWY) collected through Active Bacterial Core surveillance (ABCs) were characterized; serogroup distribution and molecular features of these isolates were compared to previously published data on ABCs isolates from 2000-05 (pre-MenACWY). p values were generated using chi-squared statistics and exact methods. RESULTS: There was a significant change (p<0.05) in serogroup distribution among all age groups between the two periods. A small proportion of isolates has shown evidence of capsular switching in both periods. Between the two periods, significant changes were observed in the distribution of PorA, FetA, and strain genotypes among vaccine and non-vaccine serogroups. CONCLUSIONS: The population structure of U.S. meningococcal isolates is dynamic; some changes occurred over time but the basic structure remained. Vaccine-induced serogroup replacement was not observed, although a small proportion of isolates had undergone capsule switching possibly driven by non-vaccine mediated selection. Changes in the distribution of molecular features are likely due to horizontal gene transfer and changes in serogroup distribution. |
Meningococcal carriage among Georgia and Maryland high school students
Harrison LH , Shutt KA , Arnold KE , Stern EJ , Pondo T , Kiehlbauch JA , Myers RA , Hollick RA , Schmink S , Vello M , Stephens DS , Messonnier NE , Mayer L , Clark TA . J Infect Dis 2014 211 (11) 1761-8 BACKGROUND: Meningococcal disease incidence in the U.S. is at an all-time low. In a previous study of Georgia high school students, meningococcal carriage prevalence was 7%. The purpose of this study was to measure the impact of a meningococcal conjugate vaccine on serogroup Y meningococcal carriage and to define the dynamics of carriage in high school students. METHODS: This was a prospective cohort study at 8 high schools, 4 each in Maryland and Georgia during a school year. In each state, 2 high schools were randomized for participating students to receive MCV4-DT at the beginning of the study and 2 at the end. Oropharyngeal swab cultures for meningococcal carriage were performed three times during the school year. RESULTS: Among 3,311 students, prevalence of meningococcal carriage was 3.21%- 4.01%. Phenotypically non-groupable strains accounted for 88% of carriage isolates. There were only 5 observed acquisitions of serogroup Y strains during the study; therefore, the impact of MCV4-DT on meningococcal carriage could not be determined. CONCLUSIONS: Meningococcal carriage rates in U.S. high school students were lower than expected and the vast majority of strains did not express capsule. These findings may help explain the historically low incidence of meningococcal disease in the U.S. |
Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel
Patel M , Romero-Steiner S , Broderick MP , Thomas CG , Plikaytis BD , Schmidt DS , Johnson SE , Milton AS , Carlone GM , Clark TA , Messonnier NE , Cohn AC , Faix DJ . Vaccine 2014 32 (30) 3805-9 Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWYD group. rSBA GMT increased to 703 at 5-7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWYD group at 5-7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWYD recipients achieving an rSBA titer of ≥8 decreased from 87% at 5-7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ≥8 at any time-point. GMC for the MenACWYD group was 0.14mug/mL at baseline, 1.07mug/mL at 5-7 months, and 0.66mug/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYWD; a booster dose is needed to maintain protective levels of circulating antibody. |
Neisseria meningitidis serogroup W, Burkina Faso, 2012
Macneil JR , Medah I , Koussoube D , Novak RT , Cohn AC , Diomande FV , Yelbeogo D , Kambou JL , Tarbangdo TF , Ouedraogo-Traore R , Sangare L , Hatcher C , Vuong J , Mayer LW , Djingarey MH , Clark TA , Messonnier NE . Emerg Infect Dis 2014 20 (3) 394-9 In 2010, Burkina Faso became the first country to introduce meningococcal serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported increases in Neisseria meningitidis serogroup W, raising questions about whether these cases were a natural increase in disease or resulted from serogroup replacement after PsA-TT introduction. We analyzed national surveillance data to describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates. In 2012, a total of 5,807 meningitis cases were reported through enhanced surveillance, of which 2,353 (41%) were laboratory confirmed. The predominant organism identified was N. meningitidis serogroup W (62%), and all serogroup W isolates characterized belonged to clonal complex 11. Although additional years of data are needed before we can understand the epidemiology of serogroup W after PsA-TT introduction, these data suggest that serogroup W will remain a major cause of sporadic disease and has epidemic potential, underscoring the need to maintain high-quality case-based meningitis surveillance after PsA-TT introduction. |
Geotemporal analysis of Neisseria meningitidis clones in the United States: 2000-2005.
Wiringa AE , Shutt KA , Marsh JW , Cohn AC , Messonnier NE , Zansky SM , Petit S , Farley MM , Gershman K , Lynfield R , Reingold A , Schaffner W , Thompson J , Brown ST , Lee BY , Harrison LH . PLoS One 2013 8 (12) e82048 ![]() ![]() BACKGROUND: The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic. METHODS: Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA) genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model. RESULTS: Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases) were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases), C (n = 11 clusters, 27 cases), and Y (n = 9 clusters, 35 cases); 20 clusters (62.5%) were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States. CONCLUSIONS: Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of transmission in populations. |
Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial
Wright JG , Plikaytis BD , Rose CE , Parker SD , Babcock J , Keitel W , El Sahly H , Poland GA , Jacobson RM , Keyserling HL , Semenova VA , Li H , Schiffer J , Dababneh H , Martin SK , Martin SW , Marano N , Messonnier NE , Quinn CP . Vaccine 2013 32 (8) 1019-28 OBJECTIVE: We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. METHODS: Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 "annual" boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). RESULTS: The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months. CONCLUSIONS: A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response. |
Prolonged university outbreak of meningococcal disease associated with a serogroup B strain rarely seen in the US
Mandal S , Wu HM , Macneil JR , Machesky K , Garcia J , Plikaytis BD , Quinn K , King L , Schmink SE , Wang X , Mayer LW , Clark TA , Gaskell JR , Messonnier NE , Diorio M , Cohn AC . Clin Infect Dis 2013 57 (3) 344-8 BACKGROUND: College students living in residential halls are at increased risk of meningococcal disease. Unlike for serogroups prevented by quadrivalent meningococcal vaccines, public health response to outbreaks of serogroup B meningococcal disease is limited by lack of a US licensed vaccine. METHODS: In March 2010 we investigated a prolonged outbreak of serogroup B disease associated with a university. In addition to case ascertainment, molecular typing of isolates was performed to characterize the outbreak. We conducted a matched case-control study to examine risk factors for serogroup B disease. Five controls per case, matched by college year, were randomly selected. Participants completed a risk factor questionnaire. Data were analyzed using conditional logistic regression. RESULTS: Between January 2008 and November 2010, we identified 13 meningococcal disease cases (seven confirmed, four probable, and two suspected) among university students (ten) or university-linked persons (three). One student died. Ten cases were determined to be serogroup B. Isolates from six confirmed cases had an indistinguishable pulse-field gel electrophoresis pattern and belonged to sequence type ST-269, clonal complex 269. Factors significantly associated with disease were Greek Society membership (matched odds ratio [mOR] 15.0; p=0.03), >1 kissing partner (mOR 13.7; p=0.03) and attending bars (mOR 8.1; p=0.04). CONCLUSIONS: The outbreak was associated with a novel serogroup B strain (CC269) and risk factors indicative of increased social mixing. Control measures were appropriate but limited by lack of vaccine. Understanding serogroup B transmission in college and other settings will help inform use of serogroup B vaccines currently under consideration for licensure. |
Waning immunity to pertussis following 5 doses of DTaP
Tartof SY , Lewis M , Kenyon C , White K , Osborn A , Liko J , Zell E , Martin S , Messonnier NE , Clark TA , Skoff TH . Pediatrics 2013 131 (4) e1047-52 OBJECTIVE: To assess the risk of pertussis by time since vaccination in children in Minnesota and Oregon who received 5 doses of acellular pertussis vaccines (DTaP). METHODS: These cohort analyses included Minnesota and Oregon children born between 1998 and 2003 who had 5 DTaP doses recorded in state Immunization Information Systems. Immunization records and statewide pertussis surveillance data were combined. Incidence rates and risk ratios for pertussis were calculated for the 6 years after receipt of the fifth DTaP dose. RESULTS: The cohorts included 224 378 Minnesota children and 179 011 from Oregon; 458 and 89 pertussis cases were identified in Minnesota and Oregon, respectively. Pertussis incidence rates rose each year of follow-up: 15.6/100 000 (95% confidence interval [CI]: 11.1-21.4) at year 1 to 138.4/100 000 (CI: 113.3-166.9) at year 6 (Minnesota); 6.2/100 000 (CI: 3.3-10.6) in year 1 to 24.4/100 000 (CI: 15.0-37.8) in year 6 (Oregon). Risk ratios increased from 1.9 (CI: 1.3-2.9) in year 2 to 8.9 (CI: 6.0-13.0) in year 6 (Minnesota) and from 1.3 (CI: 0.6-2.8) in year 2 to 4.0 (CI: 1.9-8.4) in year 6 (Oregon). CONCLUSIONS: This evaluation reports steady increase in risk of pertussis in the years after completion of the 5-dose DTaP series. This rise is likely attributable in part to waning immunity from DTaP vaccines. Continuing to monitor disease burden and vaccine effectiveness in fully vaccinated children in coming years will be important to assess ongoing risk as additional cohorts vaccinated solely with acellular pertussis vaccines are introduced. |
Impact of the serogroup A meningococcal conjugate vaccine, MenAfriVac, on carriage and herd immunity
Kristiansen PA , Diomande F , Ba AK , Sanou I , Ouedraogo AS , Ouedraogo R , Sangare L , Kandolo D , Ake F , Saga IM , Clark TA , Misegades L , Martin SW , Thomas JD , Tiendrebeogo SR , Hassan-King M , Djingarey MH , Messonnier NE , Preziosi MP , Laforce FM , Caugant DA . Clin Infect Dis 2013 56 (3) 354-63 BACKGROUND: The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of 1-29-year-olds in Burkina Faso in 2010. It is not known whether MenAfriVac has an impact on NmA carriage. METHODS: We conducted a repeated cross-sectional meningococcal carriage study in a representative portion of the 1-29-year-old population in 3 districts in Burkina Faso before and up to 13 months after vaccination. One district was vaccinated in September 2010, and the other 2 were vaccinated in December 2010. We analyzed 25,521 oropharyngeal samples, of which 22,093 were obtained after vaccination. RESULTS: In October-November 2010, NmA carriage prevalence in the unvaccinated districts was comparable to the baseline established in 2009, but absent in the vaccinated district. Serogroup X N. meningitidis (NmX) dominated in both vaccinated and unvaccinated districts. With 4 additional sampling campaigns performed throughout 2011 in the 3 districts, overall postvaccination meningococcal carriage prevalence was 6.95%, with NmX dominating but declining for each campaign (from 8.66% to 1.97%). Compared with a baseline NmA carriage prevalence of 0.39%, no NmA was identified after vaccination. Overall vaccination coverage in the population sampled was 89.7%, declining over time in 1-year-olds (from 87.1% to 26.5%), as unvaccinated infants reached 1 year of age. NmA carriage was eliminated in both the vaccinated and unvaccinated population from 3 weeks up to 13 months after mass vaccination (P = .003). CONCLUSIONS: The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect. |
Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010
Misegades LK , Winter K , Harriman K , Talarico J , Messonnier NE , Clark TA , Martin SW . JAMA 2012 308 (20) 2126-32 CONTEXT: In 2010, California experienced its largest pertussis epidemic in more than 60 years; a substantial burden of disease was noted in the 7- to 10-year-old age group despite high diphtheria, tetanus, and acellular pertussis vaccine (DTaP) coverage, indicating the possibility of waning protection. OBJECTIVE: To evaluate the association between pertussis and receipt of 5 DTaP doses by time since fifth DTaP dose. DESIGN, SETTING, AND PARTICIPANTS: Case-control evaluation conducted in 15 California counties. Cases (n = 682) were all suspected, probable, and confirmed pertussis cases among children aged 4 to 10 years reported from January through December 14, 2010; controls (n = 2016) were children in the same age group who received care from the clinicians reporting the cases. Three controls were selected per case. Vaccination histories were obtained from medical records and immunization registries. MAIN OUTCOME MEASURES: Primary outcomes were (1) odds ratios (ORs) for the association between pertussis and receipt of the 5-dose DTaP series and (2) ORs for the association between pertussis and time since completion (<12, 12-23, 24-35, 36-47, 48-59, or ≥60 months) of the 5-dose DTaP series. Logistic regression was used to calculate ORs, accounting for clustering by county and clinician, and vaccine effectiveness (VE) was estimated as (1 - OR) x 100%. RESULTS: Among cases and controls, 53 (7.8%) and 19 (0.9%) had not received any pertussis-containing vaccines, respectively. Compared with controls, children with pertussis had a lower odds of having received all 5 doses of DTaP (OR, 0.11; 95% CI, 0.06-0.21 [estimated VE, 88.7%; 95% CI, 79.4%-93.8%]). When children were categorized by time since completion of the DTaP series, using an unvaccinated reference group, children with pertussis compared with controls were less likely to have received their fifth dose within the prior 12 months (19 [2.8%] vs 354 [17.6%], respectively; OR, 0.02; 95% CI, 0.01-0.04 [estimated VE, 98.1%; 95% CI, 96.1%-99.1%]). This association was evident with longer time since vaccination, with ORs increasing with time since the fifth dose. At 60 months or longer (n = 231 cases [33.9%] and n = 288 controls [14.3%]), the OR was 0.29 (95% CI, 0.15-0.54 [estimated VE, 71.2%; 95% CI, 45.8%-84.8%]). Accordingly, the estimated VE declined each year after receipt of the fifth dose of DTaP. CONCLUSION: Among children in 15 California counties, children with pertussis, compared with controls, had lower odds of having received the 5-dose DTaP series; as time since last DTaP dose increased, the odds increased, which is consistent with a progressive decrease in estimated vaccine effectiveness each year after the final dose of pertussis vaccine. |
Haemophilus influenzae type B disease and vaccine booster dose deferral, United States, 1998-2009
Briere EC , Jackson M , Shah SG , Cohn AC , Anderson RD , Macneil JR , Coronado FM , Mayer LW , Clark TA , Messonnier NE . Pediatrics 2012 130 (3) 414-20 BACKGROUND: Since the introduction of effective vaccines, the incidence of invasive Haemophilus influenzae type b (Hib) disease among children <5 years of age has decreased by 99% in the United States. In response to a limited vaccine supply that began in 2007, Hib booster doses were deferred for 18 months. METHODS: We reviewed national passive and active surveillance (demographic and serotype) and vaccination status data for invasive H. influenzae disease in children aged <5 years before (1998-2007) and during (2008-2009) the vaccine shortage years to assess the impact of the vaccine deferral on Hib disease. We estimated the average annual number of Hib cases misclassified as unknown (not completed or missing) serotype. RESULTS: From 1998 to 2007 and 2008 to 2009, the annual average incidence of Hib disease per 100,000 population was 0.2 and 0.18, respectively; no significant difference in incidence was found by age group, gender, or race. Among Hib cases in both time periods, most were unvaccinated or too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown serotype. CONCLUSIONS: The booster deferral did not have a significant impact on the burden of invasive Hib disease in children <5 years of age. Continued surveillance and serotype data are important to monitor changes in Hib incidence, especially during vaccine deferrals. Hib booster deferral is a reasonable short-term approach to a Hib vaccine shortage. |
Estimating the effectiveness of acellular pertussis vaccines
Misegades LK , Martin SW , Messonnier NE , Clark TA . Clin Infect Dis 2012 55 (10) 1432-3; author reply 1435-6 In the 15 June 2012 issue of Clinical Infectious Diseases, Witt et al reported that vaccine effectiveness (VE) of acellular pertussis vaccines was 41% for children aged 2–7 years, 24% for 8- to 12-year-olds, and 79% for 13- to 18-year-olds [1]. The authors conclude that their data “confirms markedly lower than expected protection afforded by the pre-school series of acellular pertussis vaccinations in the 8–12 year age group” and poor durability of protection from the vaccine. While we agree that protection wanes over time, there are important limitations to the Witt et al analysis. | VE estimates are predicated on comparing disease risk in a vaccinated group with disease risk in an unvaccinated group. When calculating VE for multiple dose vaccines, partially vaccinated persons should not be grouped with unvaccinated individuals [2, 3]. Doing so compromises the vaccine-naive comparison group and lowers VE estimates. Although the authors do not specify how undervaccinated individuals were handled in the analyses, the results presented in their Tables 1 and 2 indicate that undervaccinated and unvaccinated individuals were inappropriately categorized together, rather than excluding undervaccinated persons from the analysis. This bias explains the surprisingly low estimates in the 2 younger and combined overall age groups. |
Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data
Novak RT , Kambou JL , Diomande FV , Tarbangdo TF , Ouedraogo-Traore R , Sangare L , Lingani C , Martin SW , Hatcher C , Mayer LW , Laforce FM , Avokey F , Djingarey MH , Messonnier NE , Tiendrebeogo SR , Clark TA . Lancet Infect Dis 2012 12 (10) 757-64 BACKGROUND: An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA-TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11.4 million people aged 1-29 years. We analysed national surveillance data around PsA-TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics. METHODS: We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA-TT implementation. We assessed the risk of meningitis disease and death between years. FINDINGS: During the 14 year period before PsA-TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0.29, 95% CI 0.28-0.30, p<0.0001) and a 64% decline in risk of fatal meningitis (0.36, 0.33-0.40, p<0.0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0.38, 95% CI 0.31-0.45, p<0.0001), and among children aged less than 1 year (54%, 0.46, 0.24-0.86, p=0.02) and people aged 30 years and older (55%, 0.45, 0.22-0.91, p=0.003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory-confirmed serogroup A N meningitidis dropped significantly to 0.01 per 100,000 individuals per year, representing a 99.8% reduction in the risk of meningococcal A meningitis (CIR 0.002, 95% CI 0.0004-0.02, p<0.0001). INTERPRETATION: Early evidence suggests the conjugate vaccine has substantially reduced the rate of meningitis in people in the target age group, and in the general population because of high coverage and herd immunity. These data suggest that fully implementing the PsA-TT vaccine could end epidemic meningitis of serogroup A in sub-Saharan Africa. FUNDING: None. |
Haemophilus haemolyticus causing clinical disease
Anderson R , Wang X , Briere EC , Katz LS , Cohn AC , Clark TA , Messonnier NE , Mayer LW . J Clin Microbiol 2012 50 (7) 2462-5 We report seven cases of Haemophilus haemolyticus invasive disease detected in the United States, which were previously misidentified as non-typeable Haemophilus influenzae (Hi). All cases had different symptoms and presentations. Our study suggests that a testing scheme that includes reliable PCR assays and standard microbiological methods should be used in order to improve H. haemolyticus identification. |
Does Tdap vaccination interfere with serodiagnosis of pertussis infection?
Pawloski LC , Kirkland KB , Baughman AL , Martin MD , Talbot EA , Messonnier NE , Tondella ML . Clin Vaccine Immunol 2012 19 (6) 875-80 BACKGROUND: An IgG anti-pertussis toxin (PT) enzyme-linked immunosorbent assay (ELISA) was analytically validated for diagnosis of pertussis, using the cut-off of 94 ELISA Units (EU)/mL. Little was known about the performance of this ELISA for diagnosis in adults recently vaccinated with tetanus-diphtheria-acellular pertussis (Tdap), which contains PT. The goal of this study was to determine when the assay can be used following Tdap vaccination. METHODS: A cohort of 102 asymptomatic health care personnel (HCP) vaccinated with Tdap (Adacel, Sanofi Pasteur) were aged 19 to 79 years (median 47 years) at vaccination. For each HCP, specimens were available for evaluation at 2-10 time points (pre-vaccination to 24 months post-vaccination), and geometric mean concentrations (GMC) for the cohort were calculated at each time point. Among 97 HCP who responded to vaccination, a mixed model analysis with prediction and tolerance intervals was performed to estimate the time at which serodiagnosis can be used following vaccination. RESULTS: The GMC was 8, 21, and 9 EU/mL at pre-vaccination, four, and 12 months post-vaccination, respectively. Eight of 102 (8%) HCP reached antibody titers ≥ 94 EU/mL during their peak response but none had these titers by six months post-vaccination. Calculated prediction and tolerance intervals were < 94 EU/mL by 45 and 75 days post-vaccination, respectively. CONCLUSIONS: Tdap vaccination six months prior to testing did not confound result interpretation. This seroassay remains a valuable diagnostic tool for adult pertussis. |
Pertussis control: time for something new?
Clark TA , Messonnier NE , Hadler SC . Trends Microbiol 2012 20 (5) 211-3 ![]() Childhood acellular pertussis vaccines were licensed and implemented in the US in the 1990s following an effort to improve on the safety profile of whole-cell vaccines. However, waning of immunity from acellular vaccines may be driving the recent resurgence of pertussis, raising the need to consider new prevention strategies. |
Inching toward a serogroup B meningococcal vaccine for infants
Cohn AC , Messonnier NE . JAMA 2012 307 (6) 614-5 In the past decade, the introduction of meningococcal conjugate vaccines has led to substantial reductions in meningococcal disease. Monovalent serogroup C vaccines have virtually eliminated serogroup C disease from the United Kingdom and other countries, and serogroup A, C, W, and Y vaccines have reduced disease among adolescents in the United States.1,2 In 2010 and 2011, Burkina Faso, Mali, Niger, and part of Nigeria introduced serogroup A conjugate vaccine, which may eliminate epidemic meningitis from the meningitis belt of Africa. These accomplishments have been dampened by the lack of effective serogroup B meningococcal vaccines. Serogroup B meningococcal disease causes substantial morbidity and mortality globally, especially in young infants.3-5 Serogroup B disease can be devastating; 5% to 10% of children with the disease do not survive and another 10% to 20% experience long-term sequelae such as hearing loss, limb loss, and neurologic deficits.5 Disease burden is lower in the United States than in other countries; incidence of serogroup B disease is 0.16 per 100 000 population but 3.08 per 100 000 population among infants younger than 12 months.4 In contrast, incidence of serogroup B disease in several countries in Europe, including the United Kingdom, is about 10-fold that in the United States.3 | Serogroup B polysaccharide has not been a successful vaccine target because it is similar to human neural cell glycopeptide and therefore poorly immunogenic in humans. For a serogroup B vaccine to have a substantial effect on disease burden, it will need to be immunogenic and safe in young infants, protect against a high proportion of serogroup B strains, and provide long-term protection. |
Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs
Jackson ML , Rose CE , Cohn A , Coronado F , Clark TA , Wenger JD , Bulkow L , Bruce MG , Messonnier NE , Hennessy TW . Emerg Infect Dis 2012 18 (1) 13-20 In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age. |
Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
Mandal S , Tatti KM , Woods-Stout D , Cassiday PK , Faulkner AE , Griffith MM , Jackson ML , Pawloski LC , Wagner B , Barnes M , Cohn AC , Gershman KA , Messonnier NE , Clark TA , Tondella ML , Martin SW . Pediatrics 2012 129 (2) e424-30 ![]() BACKGROUND AND OBJECTIVES: We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. METHODS: We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. RESULTS: Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. CONCLUSIONS: A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens. |
Early impact of the US Tdap vaccination program on pertussis trends
Skoff TH , Cohn AC , Clark TA , Messonnier NE , Martin SW . Arch Pediatr Adolesc Med 2012 166 (4) 344-9 OBJECTIVE: To evaluate the impact of the adolescent Tdap vaccination (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine) program on pertussis trends in the United States. DESIGN: Retrospective analysis of nationally reported pertussis cases, January 1, 1990, through December 31, 2009. SETTING: United States. PARTICIPANTS: Confirmed and probable pertussis cases. Intervention The US Tdap vaccination program. MAIN OUTCOME MEASURE: Rate ratios of reported pertussis incidence (defined as incidence among 11- to 18-year-olds divided by the combined incidence in all other age groups) modeled through segmented regression analysis and age-specific trends in reported pertussis incidence over time. RESULTS: A total of 200,401 pertussis cases were reported in the United States from 1990 to 2009. Overall incidence ranged from 1.0 to 8.8 per 100,000 persons (1991 and 2004, respectively). Slope coefficients (estimated annual rate of change in rate ratios) from segmented regression showed a steady increase in pertussis incidence among adolescents 11 to 18 years old compared with all other age groups before Tdap introduction (slope = 0.22; P < .001), and a steep decreasing trend postintroduction (slope = -0.48; P < .001) suggesting a direct impact of vaccination among adolescents. Indirect effects of adolescent vaccination were not observed among infants younger than 1 year. CONCLUSIONS: Changes in pertussis incidence in the United States from 2005 to 2009 revealed a divergence between 11- to 18-year-olds and other age groups, suggesting that targeted use of Tdap among adolescents reduced disease preferentially in this age group. Increased Tdap coverage in adolescents and adults is needed to realize the full direct and indirect benefits of vaccination. |
Clinical validation of multiplex real-time PCR assays for detection of bacterial meningitis pathogens.
Wang X , Theodore MJ , Mair R , Trujillo-Lopez E , du Plessis M , Wolter N , Baughman AL , Hatcher C , Vuong J , Lott L , von Gottberg A , Sacchi C , McDonald JM , Messonnier NE , Mayer LW . J Clin Microbiol 2011 50 (3) 702-8 ![]() Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect Nm ctrA, Hi hpd and Sp lytA, and serogroup-specific genes in the cap locus for Nm serogroups A, B, C, W135, X and Y. However, the assay sensitivity for serogroups B, W135 and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays B-synD, W-synG, and Y-synF showed 100% specificity for detecting Nm species, with high sensitivity [B-synD, 99%(75/76); W-synG, 97%(38/39); and Y-synF, 100%(66/66)]. The lower limit of detection (LLD) was 9, 43 and 10 copies/reaction for B-synD, W-synG, and Y-synF assays, respectively, a significant improvement compared to the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of: (i) Nm ctrA, Hi hpd and Sp lytA (NHS); (ii) Nm serogroups A, W135 and X (AWX), and (iii) Nm serogroups B, C and Y (BCY). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for singleplex. Pairwise comparison of real-time PCR between multiplex and singleplex showed that cycle threshold values of the multiplex were similar to those for singleplex. There were no substantial differences in the sensitivity and specificity between these multiplex and singleplex real-time PCR assays. |
Comparative study of different sources of pertussis toxin (PT) as coating antigens in IgG anti-PT ELISAs
Kapasi A , Meade BD , Plikaytis B , Pawloski L , Martin MD , Yoder S , Rock MT , Coddens S , Haezebroeck V , Fievet-Groyne F , Bixler G , Jones C , Hildreth S , Edwards KM , Messonnier NE , Tondella ML . Clin Vaccine Immunol 2011 19 (1) 64-72 In an effort to improve the reliability and reproducibility of serological assays for Bordetella pertussis, a collaborative study was conducted to compare four different sources of pertussis toxin (PT) as coating antigens in the immunoglobulin G (IgG) anti-PT enzyme-linked immunosorbent assay (ELISA). Four sources of PT were used as coating antigens in the IgG anti-PT ELISA in four different testing laboratories (Labs A-D) to determine if the different antigen preparations and different laboratories influenced assay results. A panel of 60 sera consisting of de-identified human specimens from previous vaccination trials of normal healthy adults and infants and clinical specimens from outbreak settings was tested. In the four laboratories, each sample was tested three times with the four PT antigens according to the standard coating optimization and IgG anti-PT ELISA testing procedures used in that laboratory. Differences among the antigens, as well as intra- and inter-laboratory variability, were evaluated. Excellent agreement was observed with the test panel results among the four antigens within each laboratory. Concordance correlation coefficient (r(c)) measurements among the different antigens ranged from 0.99, 0.99-1.00, 1.00, and 0.97-1.00 for Labs A-D, respectively. The comparisons between pairs of laboratories also indicated a high degree of concordance for each PT preparation, with r(c) measurements between 0.90-0.98, 0.93-0.99, 0.92-0.98 and 0.93-0.99 for antigens 1-4, respectively. Relatively minor differences in results were observed among laboratories or among antigens, suggesting that the four PT antigens are quite similar and could be considered for acceptance in harmonized immunoassays used for serodiagnosis or vaccine evaluation. |
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