Stacey W. Martin

Impact of the serogroup A meningococcal conjugate vaccine, MenAfriVac, on carriage and herd immunity.

BACKGROUNDnThe 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.nnnMETHODSnWe 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.nnnRESULTSnIn 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).nnnCONCLUSIONSnThe disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.

Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data

BACKGROUNDnAn 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.nnnMETHODSnWe 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.nnnFINDINGSnDuring 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).nnnINTERPRETATIONnEarly 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.nnnFUNDINGnNone.

Pertactin-Negative Bordetella pertussis Strains: Evidence for a Possible Selective Advantage

BACKGROUNDnA recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN(-)) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed.nnnMETHODSnWe retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis.nnnRESULTSnAmong 753 isolates, 640 (85%) were PRN(-). The age distribution differed between cases caused by PRN(-) B. pertussis and cases caused by B. pertussis producing pertactin (PRN(+)) (P = .01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN(+) case-patients reported apnea (P = .005). Twenty-two case-patients were hospitalized; 6% in the PRN(+) group compared to 3% in the PRN(-) group (P = .11). Case-patients having received at least 1 pertussis vaccine dose had a higher odds of having PRN(-) B. pertussis compared with unvaccinated case-patients (adjusted OR = 2.2; 95% confidence interval [CI], 1.3-4.0). When restricted to case-patients at least 1 year of age and those age-appropriately vaccinated, the adjusted OR increased to 2.7 (95% CI, 1.2-6.1).nnnCONCLUSIONSnThe significant association between vaccination and isolate pertactin production suggests that the likelihood of having reported disease caused by PRN(-) compared with PRN(+) strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN(-) strains.

Effects of a Reduced Dose Schedule and Intramuscular Administration of Anthrax Vaccine Adsorbed on Immunogenicity and Safety at 7 Months: A Randomized Trial

CONTEXTnIn 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).nnnOBJECTIVEnTo determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.nnnDESIGN, SETTING, AND PARTICIPANTSnAssessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).nnnINTERVENTIONnHealthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.nnnMAIN OUTCOME MEASURESnNoninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.nnnRESULTSnAt week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.nnnCONCLUSIONSnThe 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.

Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure — United States, September 2016

CDC has updated its interim guidance for persons with possible Zika virus exposure who are planning to conceive (1) and interim guidance to prevent transmission of Zika virus through sexual contact (2), now combined into a single document. Guidance for care for pregnant women with possible Zika virus exposure was previously published (3). Possible Zika virus exposure is defined as travel to or residence in an area of active Zika virus transmission (http://www.cdc.gov/zika/geo/index.html), or sex* without a condom† with a partner who traveled to or lived in an area of active transmission. Based on new though limited data, CDC now recommends that all men with possible Zika virus exposure who are considering attempting conception with their partner, regardless of symptom status,§ wait to conceive until at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Recommendations for women planning to conceive remain unchanged: women with possible Zika virus exposure are recommended to wait to conceive until at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic). Couples with possible Zika virus exposure, who are not pregnant and do not plan to become pregnant, who want to minimize their risk for sexual transmission of Zika virus should use a condom or abstain from sex for the same periods for men and women described above. Women of reproductive age who have had or anticipate future Zika virus exposure who do not want to become pregnant should use the most effective contraceptive method that can be used correctly and consistently. These recommendations will be further updated when additional data become available.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae prior to introduction of the 10-valent pneumococcal conjugate vaccine in Brazil, 2000–2007

This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine. The active hospital-based surveillance showed a decline in the annual incidence rates of pneumococcal meningitis during the period of study, from 1.12 cases to 0.83 cases/100,000 persons for all age groups (P<0.001), with an overall case-fatality rate of 28.6% (113 of 395) for all patients and 41.9% (57 of 136) for those <5 years of age. Serotypes 14 (n=55; 13.9%), 3 (n=32; 8.1%), 23F (n=32; 8.1%), 19F (n=31; 7.8%), 6B (n=30; 7.6%), 18C (n=28; 7.1%), and 6A (n=20; 5%) were the most prevalent serotypes. In patients <5 years the estimated projected coverage of 7-, 10- and 13-valent conjugate vaccines was 74.3%, 75.7% and 83.1%, respectively. Antimicrobial susceptibility testing revealed that 22.1% (n=88) of isolates were non-susceptible to penicillin, 56% were non-susceptible to trimethoprim/sulphamethoxazole, and 29.6% were non-susceptible to tetracycline. Nonsusceptibility to penicillin and cefotaxime was detected solely among serotype 14 isolates (n=4; 1%). This study provides an important baseline to assess the impact of conjugate vaccine implantation on the epidemiology of meningitis due to Streptococcus pneumoniae in Salvador, Brazil.

Effect of reduced dose schedules and intramuscular injection of anthrax vaccine adsorbed on immunological response and safety profile: a randomized trial.

OBJECTIVEnWe evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for anthrax vaccine adsorbed (AVA). AVAs 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.nnnMETHODSnThrough 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).nnnRESULTSnThe 8-IM groups 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.nnnCONCLUSIONSnA 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.

Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis Vaccination Program on Preventing Pertussis in Infants <2 Months of Age: A Case-Control Evaluation

BackgroundnInfants aged <1 year are at highest risk for pertussis-related morbidity and mortality. In 2012, Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccine was recommended for women during each pregnancy to protect infants in the first months of life; data on effectiveness of this strategy are currently limited.nnnMethodsnWe conducted a case-control evaluation among pertussis cases <2 months old with cough onset between 1 January 2011 and 31 December 2014 from 6 US Emerging Infection Program Network states. Controls were hospital-matched and selected by birth certificate. Mothers were interviewed to collect information on demographics, household characteristics, and healthcare providers. Provider-verified immunization history was obtained on mothers and infants. Mothers were considered vaccinated during pregnancy if Tdap was received ≥14 days before delivery; trimester was calculated using Tdap date, infants date of birth, and gestational age. Odds ratios were calculated using multivariable conditional logistic regression; vaccine effectiveness (VE) was estimated as (1 - odds ratio) × 100%.nnnResultsnA total of 240 cases and 535 controls were included; 17 (7.1%) case mothers and 90 (16.8%) control mothers received Tdap during the third trimester of pregnancy. The multivariable VE estimate for Tdap administered during the third trimester of pregnancy was 77.7% (95% confidence interval [CI], 48.3%-90.4%); VE increased to 90.5% (95% CI, 65.2%-97.4%) against hospitalized cases.nnnConclusionsnVaccination during pregnancy is an effective way to protect infants during the early months of life. With a continuing resurgence in pertussis, efforts should focus on maximizing Tdap uptake among pregnant women.

Estimating the Effectiveness of Acellular Pertussis Vaccines

TO THE EDITOR—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 8to 12-year-olds, and 79% for 13to 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. Second, Witt et al state that VE was estimated using the screening method, often used when precise attack rates cannot be calculated for vaccinated and unvaccinated individuals. However, the authors describe a cohort study and report attack rates, as well as discuss vaccination rates among cases and age-

Health-related quality of life in the Anthrax Vaccination Program for workers in the Laboratory Response Network.

BACKGROUNDnIn 2002 CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure vaccination with Anthrax Vaccine Adsorbed (AVA) for persons at high risk of exposure to Bacillus anthracis spores. There has been concern that AVA could be associated with long term impairment of physical and/or mental health.nnnOBJECTIVESnTo ascertain whether physical and mental functional status, as measured by the SF-36v2 health survey (Medical Outcomes Trust, Boston, MA), of AVA recipients and controls changed differently over time.nnnMETHODSnWe enrolled 437 exposed (received AVA) and 139 control subjects. The exposed group received AVA under then-current Advisory Committee on Immunization Practices (ACIP) recommendations. SF-36v2 surveys were completed at 0, 12, and 30 months. SF-36v2 physical and mental scores both range from 0 to 100 with an estimated national average of 50 points.nnnRESULTSnFor physical scores, the average change from baseline was -0.53 for exposed vs. -0.67 for controls at 12 months (p=0.80) and -1.09 for exposed vs. -1.97 for controls at 30 months (p=0.23). For mental scores, the average change from baseline was -1.50 for exposed vs. -1.64 for controls at 12 months (p=0.86) and -2.11 for exposed vs. -0.24 for controls at 30 months (p=0.06). In multivariable analysis, the difference in mental score change between exposed vs. controls at 30 months was less pronounced (p=0.37) but other findings were similar to univariate analyses.nnnCONCLUSIONSnThese results do not favor an association between receipt of AVA and an altered health related quality of life over a 30-month period.