Maternal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination During Pregnancy: Impact on Infant Anti-Pertussis Antibody Concentrations by Maternal Pertussis Priming Series.

BACKGROUND: Acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccines for the US childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy may be impacted. METHODS: Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMCs) of pertussis-specific immunoglobulin G antibodies (international units per milliliter) in cord blood of infants born to women born after 1997 (aP-primed) were compared with those born to women born before 1992 (wP-primed). RESULTS: 253 and 506 infants born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger, more likely to be Hispanic or non-Hispanic Black, and had lower-birthweight infants (P < .01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed vs wP-primed women (PT, 17.3 vs 36.4; GMC ratio, .475; 95% confidence interval [CI], .408-.552 and FHA, 104.6 vs 121.4; GMC ratio, 0.861; 95% CI, .776-.958). No differences were observed for anti-fimbriae or anti-pertactin antibodies. CONCLUSIONS: Transplacental anti-pertussis antibody concentrations in infants of women vaccinated with Tdap during pregnancy differed by type of childhood vaccine the women received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP-primed vs wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in infants born to aP-primed vs those born to wP-primed women.

Invasive Group B Streptococcal Disease In Childhood.

Invasive group B streptococcal disease in childhood is uncommon and occupies a unique clinical niche. We present 10 children, 1-17 years of age, with invasive group B streptococcal disease from 2010 to 2020. Seven had conditions predisposing to infection and 3 had no identifiable risk factors. With appropriate consideration of pathogenesis, source control, and treatment, all children recovered.

Group B Streptococcal Cellulitis-Adenitis Syndrome in Infants: Insights From 24 Years of Experience.

This series of 28 infants with group B streptococcal (GBS) cellulitis-adenitis from a single institution over 24 years offers insights important to the early recognition, spectrum of findings, and optimal management of this rare manifestation of invasive GBS disease.

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy.

BACKGROUND: Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5-6 weeks. METHODS: 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated. RESULTS: Tdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28-32.7). Mean neonatal gestation was 39.1 weeks (36-41.1) and mean birthweight was 3379 g (2580-4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6-78.6) to 21.1 IU/ml (14.7-30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3-31.7) for PT, 29.8 (95% CI 27.7-32.2) for FHA, 31.2 (95% CI 28.9-33.7) for PRN, and 35.8 (95% CI 30.1-44.3) for FIM. CONCLUSION: The half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29-36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.

Association Between Third-Trimester Tdap Immunization and Neonatal Pertussis Antibody Concentration.

Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.

Prevalence and Capsular Types of Group B Streptococci Colonizing Indian Women Living in the United States.

Group B streptococcal rectovaginal colonization prevalence in women of Indian descent living in the United States was 24.7% comparable with US rates but higher than rates reported from India. The capsular polysaccharide types were distinct in that type V was most common and 33% of group B streptococcal strains were nontypeable.

Group B Streptococcal Colonization Among Pregnant Women in Delhi, India.

BACKGROUND: Little is known regarding maternal group B streptococcal (GBS) colonization prevalence and capsular (CPS) serotype distribution among pregnant women in India. The objective of this prospective cohort study was to determine GBS recto-vaginal colonization prevalence in pregnant women at Dr. Ram Manohar Lohia Hospital in Delhi, India. METHODS: Literature review identified reports from India assessing GBS colonization prevalence in pregnant women. Rectal and vaginal swabs were inoculated into Strep B Carrot Broth (Hardy Diagnostics, Santa Maria, CA) and subcultured onto GBS Detect plates (Hardy Diagnostics, Santa Maria, CA). Isolates were serotyped using ImmuLex Strep-B latex kits (Statens Serum Institut, Copenhagen, Denmark). RESULTS: Thirteen studies were identified citing GBS colonization prevalence during pregnancy as 0.47%-16%. Among 300 pregnant women (mean age: 26.9 years; mean gestation: 34 weeks) enrolled (August 2015 to April 2016), GBS colonization prevalence was 15%. Fifteen percent of women had vaginal only, 29% had rectal only and 56% had both sites colonized. CPS types were Ia (13.3%), Ib (4.4%), II (20%), III (22.2%), V (20%) and VII (6.7%); 13.3% were nontypable. Fetal loss in a prior pregnancy at ≥20-weeks gestation was more common in colonized than noncolonized women (15.6% vs. 3.5%; P = 0.004). Employing recent census data for the birth cohort and estimating that 1%-2% of neonates born to colonized women develop early-onset disease, at least 39,000 cases of early-onset disease may occur yearly in India. CONCLUSIONS: Using optimal methods, 15% of third trimester pregnant women in India are GBS colonized. A multivalent vaccine containing 6 CPS types (Ia, Ib, II, III, V and VII) would encompass ~87% of GBS carried by pregnant women in India.

Immune Responses to Invasive Group B Streptococcal Disease in Adults.

Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. We defined capsular polysaccharide (CPS) and pilus island (PI) surface antigen distribution and expression and immune responses to GBS infection in nonpregnant adults. Prospective surveillance from 7 hospitals in Houston, Texas, USA, identified 102 adults with GBS bacteremia; 43% had skin/soft tissue infection, 16% bacteremia without focus, and 12% osteomyelitis. CPS-specific IgG was determined by ELISA and pilus-specific IgG by multiplex immunoassay. CPS types were Ia (24.5%), Ib (12.7%), II (9.8%), III (16.7%), IV (13.7%), and V (12.7%); 9.8% were nontypeable by serologic methods. Pili, expressed by 89%, were most often PI-2a. CPS and pilus-specific IgG increased during convalescence among patients with strains expressing CPS or PI. All GBS expressed CPS or PI; 79% expressed both. Increased antibodies to CPS and PI during recovery suggests that GBS bacteremia in adults is potentially vaccine preventable.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.

BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. METHODS: Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSIONS: Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.

Molecular characterization of the first G24P[14] rotavirus strain detected in humans.

Here we report the genome of a novel rotavirus A (RVA) strain detected in a stool sample collected during routine surveillance by the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The strain, RVA/human-wt/USA/2012741499/2012/G24P[14], has a genomic constellation of G24-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3. The VP2, VP3, VP7 and NSP3 genes cluster phylogenetically with bovine strains. The other genes occupy mixed clades containing animal and human strains. Strain RVA/human-wt/USA/2012741499/2012/G24P[14] most likely is the product of interspecies transmission and reassortment events. This is the second report of the G24 genotype and the first report of the G24P[14] genotype combination in humans.

Perinatal Screening for Chagas Disease in Southern Texas.

Perinatal screening for Trypanosoma cruzi in a cohort of 4000 predominantly Hispanic women in southern Texas revealed that Chagas disease occurs with sufficient frequency (0.25%) that targeted perinatal screening should be considered to identify infected mothers and infants at risk for congenital infection.

Knowledge and attitiudes of pregnant women and their providers towards recommendations for immunization during pregnancy.

OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) and influenza vaccination is recommended during each pregnancy but uptake is suboptimal. We evaluated knowledge and acceptance of vaccination recommendations among pregnant women. METHODS: Prospective, convenience survey of pregnant women presenting for antenatal care at the Pavilion for Women, Texas Children's Hospital, Houston, and their healthcare providers. RESULTS: 796 of 825 (96.5%) of women and 63 of 87 (72.4%) providers completed surveys. Mean age of pregnant women was 30.2 (18-45) years. Self-identified race/ethnicity was 45% white, 26% Hispanic, 13% black, 12% Asian and 4% other. Most women had college degrees (84%) and private health insurance (83%). Mean gestation was 28.5 weeks with 4.8%, 37.8% and 57.4%, in the 1st, 2nd and 3rd trimesters, respectively. Women used various sources for pregnancy information (personal contacts, providers, print, audiovisual and online media) but 89.1% cited a provider as their most trusted source, predominantly (85.8%) their physician. 668 (84%) knew vaccines are recommended during pregnancy, specifically influenza (77%) and Tdap (61%) vaccines. 659 (83%) were willing to receive vaccines if recommended by their physician. Factors impacting vaccination decisions included safety for baby, safety for mother and sufficient information, scoring 4.7, 4.5 and 4.2, respectively, on a 5-point scale; less important were additional visit time (2.6), cost (1.9) or needle phobia (1). Women surveyed in the 3rd trimester showed greater acceptance than those earlier in gestation (87% vs 78%; P0.003). Maternal education, ethnicity, insurance, multiple gestation or history of serious illness in a prior infant did not affect willingness to receive vaccines. CONCLUSIONS: Pregnant women are willing to accept vaccination in pregnancy if recommended by their physician and if sufficient discussion of safety and rationale occurs. Strong physician recommendation, as reported for pediatric vaccination, is essential to optimizing uptake of vaccines during pregnancy.

Tetanus and diphtheria toxoids and acellular pertussis vaccine uptake during pregnancy in a metropolitan tertiary care center.

OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) vaccine is recommended during each pregnancy, but national uptake is poor. We assessed Tdap uptake in a tertiary referral hospital served by university-affiliated and private obstetrical offices. METHODS: Review of women delivering at Texas Children's Hospital Pavilion for Women, Houston, Texas, during April 2013-June 2014. RESULTS: 6577 deliveries occurred during the study period. Mean maternal age was 29.8 years (range 13-49); race/ethnicity was 43.6% White, 27% Hispanic, 21% Black, 7.1% Asian, and 1.3% other. 252 were multiple gestations; 229 sets of twins, 21 triplets and 2 quadruplets. 3678 (56%) women received Tdap during pregnancy, 249 (3.8%) postpartum and 100 (1.5%) received Tdap pre-conception only. Tdap uptake during pregnancy increased from 36% in April 2013 to a sustained uptake of greater than 61% since November 2013, with increases noted coincidental with presentations highlighting Tdap maternal immunization recommendations at faculty and staff meetings, and the release of the ACOG "toolkit". When antenatal Tdap vaccine was administered, mean gestation at receipt of Tdap was 31.4 weeks and 95% of vaccinated women received Tdap at the recommended gestation interval of 27-36 weeks, 71.6% during the 28-32 week window believed optimal for placental transport and 98.5% at least 7 days before delivery. Of 19 women with two pregnancies during the study period, four (21%) had Tdap during both. Black women were less likely to receive antenatal Tdap than women of other race/ethnicity (41% versus 60%; P<0.001). CONCLUSIONS: Sustained antenatal Tdap uptake rates exceeding 61% were achieved after strategies to increase awareness of recommendations were introduced and 95% of women were immunized at a gestation optimal for efficient maternal antibody placental transport. Further increases in uptake will require system changes such as best practice alerts in electronic medical records.

Relevance of age at diagnosis to prevention of late-onset group B streptococcal disease by maternal immunization.

Among 248 infants with late-onset group B streptococcal (GBS) disease from 1993 to 2012, approximately two thirds (63%) had a gestation of at least 35 weeks and 72% of these became ill within 6 weeks of life (median 27 days), suggesting that third trimester maternal GBS immunization could substantially reduce the late-onset GBS disease burden in the United States.

Evaluation of the impact of a pertussis cocooning program on infant pertussis infection.

BACKGROUND: Tetanus, diphtheria and acellular pertussis immunization of infant contacts (cocooning) is recommended by the Centers for Disease Control and Prevention to prevent infant pertussis. We determined whether implementing a cocooning program at Ben Taub General Hospital, Houston, reduced severe pertussis in young infants. METHODS: Infants ≤6 months of age, diagnosed with pertussis (determined by International Classification of Diseases, Ninth Revision codes and microbiology records) at 4 hospitals, and born at times when only postpartum women (January 2008 through May 2009) and all infant contacts (June 2009 through August 2011) were offered tetanus, diphtheria and acellular pertussis vaccine at Ben Taub General Hospital were compared with infants born preintervention (May 2004 through December 2007). RESULTS: One hundred ninety-six (49%) infants with pertussis were born preintervention, 140 (35%) during maternal postpartum (PP) and 64 (16%) during cocooning (C) periods. Infants were similar in age at diagnosis (81.2 vs. 71.3 [PP] vs. 72.5 [C] days; P 0.07), sex (male 59% vs. 51% [PP] vs. 48% [C]; P 0.17), hospitalization (68% vs. 71% [PP] vs. 78% [C]; P 0.27) and outcome (2 deaths in the PP period; P 0.15), but more were admitted to intensive care units during cocooning (24% vs. 35% [PP] vs. 68% [C]; P < 0.001). Similar proportions of infants were born at Ben Taub General Hospital throughout the study (8% vs. 9% [PP] vs. 5% [C]; P 0.53). CONCLUSIONS: Postpartum immunization and cocooning did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed toward increasing tetanus, diphtheria and acellular pertussis immunization during pregnancy, combined with cocooning, to reduce life-threatening young infant pertussis.

Acceptability of immunization in adult contacts of infants: possibility of expanding platforms to increase adult vaccine uptake.

OBJECTIVE: Adult vaccination coverage is low and current strategies are unlikely to achieve Healthy People 2020 targets. We determined the attitude of adult infant contacts toward recommended adult vaccines and their willingness to receive vaccines should they be available during hospital visits or prenatal or infant clinic appointments. METHODS: Survey of predominantly Hispanic, underinsured and medically underserved infant contacts at a county hospital in Houston, Texas where a pertussis cocooning program is offered. RESULTS: Two hundred and eighty-five contacts (mean age 32.8 years [18-73]; 94.8% Hispanic) participated. Most were fathers (58.2%), followed by aunts (19%), and grandparents (12.3%). Participants used many health information sources. 221 (77.5%) considered healthcare providers the most influential on their decisions but only 51.6% reported healthcare visits within the prior year. Forty-one (14.4%) discussed family vaccinations during prenatal visits. Preferred locations for adult vaccination were hospital or clinic-based (96.5%). Lack of knowledge (22.8%), fear of pain/needles (14.7%), work commitments (14%), lack of transport (11.2%), cost (10.2%) and fear of side effects (5.3%) were barriers to vaccination. More males than females reported fear of pain/needles and work commitments (P 0.01 and P 0.02, respectively), and more females lack of transport (P<0.001) as barriers. Most planned to (76.1%) or had received (7%) pertussis vaccine; if available, 73.3%, 53.3% and 50.5% expressed willingness to receive vaccines against influenza, pneumonia and meningitis, respectively. Age, ethnicity or education was not associated with willingness to be vaccinated. Vaccine acceptance was higher in females than males for pertussis (P 0.04), influenza (P 0.008), pneumonia (P 0.04), and meningitis (P 0.006) vaccines by multiple regression analysis. CONCLUSIONS: Most adults were willing to be vaccinated if offered during hospital visits or clinic appointments for mother or infant. Development and expansion of recommended immunization platforms, such as the cocooning platform, offers the opportunity to increase adult vaccination coverage.

Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

BACKGROUND: Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization. METHODS: We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with early onset GBS infection (cases), and 99 age- and ethnicity-matched mothers colonized with the same capsular polysaccharide (CPS) types delivering healthy neonates (controls). Relative risk and absolute risk were calculated for early onset disease associated with concentrations of type Ia, III, or V CPS-specific antibody in maternal serum. RESULTS: For GBS types Ia and III, maternal CPS-specific antibody concentrations of ≥ 0.5 µg/mL were associated with a relative risk of approximately 0.1 (95% confidence intervals [CIs], .01-.74 and 0-.72, respectively; P = .02 for each), corresponding to a 90% risk reduction (by logistic regression). For type V, the relative risk was 0.3 (95% CI, .01-3.1), corresponding to a 70% risk reduction. By Bayesian modeling, the risk of early onset disease would decrease by 70% if maternal CPS-specific antibody concentrations for these 3 GBS types were ≥ 1 µg/mL. CONCLUSIONS: Maternal CPS-specific antibody serum concentrations of ≥ 1 µg/mL at the time of delivery appear to protect most neonates from early onset GBS type Ia and III disease.

Knowledge and attitudes of postpartum women toward immunization during pregnancy and the peripartum period.

Influenza and pertussis prevention in young infants requires immunizing pregnant women and all caregivers (cocooning). We evaluated the knowledge and attitude of postpartum women about these two recommendations. A survey of predominantly Hispanic, underinsured, medically underserved postpartum women in Houston, Texas was performed during June 2010 through July 2012. Five hundred eleven postpartum women [mean age 28.8 y (18-45); 94% Hispanic] with a mean of 3 children (1-12) participated. Ninety-one (17.8%) were first-time mothers. Four hundred ninety-six (97.1%) received prenatal care; care was delayed in 24.3%. Only 313 (61.3%) received vaccine education while pregnant, and 291 (57%) were immunized. Four hundred seventy-four women (93%) were willing to be immunized during pregnancy if recommended by their healthcare provider, (the most trusted information source for 62%). Immunization of infants or infant caregivers had been discussed with 41% and 10% of mothers, respectively. Two hundred thirty women (45%) had received influenza vaccine; most intended to (79%) or had already received (15%) tetanus, diphtheria, and acellular pertussis (Tdap) vaccine. Preferred locations for cocooning were hospital or community clinics (97%). Insufficient knowledge (46.6%), cost (31.4%), lack of transportation (26%), work commitments (13.3%), and fear of needles (13.3%) were perceived barriers to cocooning. Level of formal education received by mothers had no effect on the quantity or quality of immunization education received during PNC or their attitude toward immunization. Immunization during pregnancy and cocooning, if recommended by providers, are acceptable in this high-risk population. Healthcare providers, as reported in infant studies, have the greatest influence on vaccine acceptance by pregnant and postpartum women.