Susan Hariri’s research while affiliated with Centers for Disease Control and Prevention and other places

Background Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11-12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. Methods Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015-2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. Results Overall, 93.8% of the U.S. population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥90% had protective sero-immunity through age 69 years but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio (aPR): 0.89, 95% CI: 0.85-0.92) and being born outside the United States (aPR: 0.96, 95% CI: 0.93-0.98) were significantly associated with lower prevalence of sero-immunity. Conclusion The majority of the U.S. population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program.

Many illnesses can become especially serious when contracted within the first year of life; pertussis remains quite deadly despite recent medical advances in disease prevention. Current guidance on vaccination in the United States includes 3 doses of the DTaP (diphtheria, tetanus toxoid, and acellular pertussis) vaccine beginning at 2 months of age, but this regimen leaves infants younger than that very vulnerable to illness. Research has shown both that vaccinating mothers with tetanus toxoid reduces tetanus, diphtheria, and pertussis (Tdap) between 27 and 36 weeks of gestation significantly reduces instances of pertussis in infants younger than 2 months, and that maternal vaccination rates have risen in the last few years. However, research is lacking in analyzing the relationship between vaccination rates in pregnant mothers and the burden of pertussis in infants in the United States. This study was designed to assess data from 2000 to 2019 and examine the association of Tdap vaccination during pregnancy with trends in infant pertussis. This analysis included data obtained from the National Notifiable Diseases Surveillance System between 2000 and 2019. This included a total of 57,460 cases of pertussis in infants younger than 1 year and a total of 19,322 cases in infants younger than 2 months. The rate of pertussis incidence for infants younger than 2 months in the time period before the implementation of prenatal Tdap was calculated to be 165.3 per 100,000 individuals, with no significant trend observed annually ( P = 0.28). After the implementation of routine maternal Tdap, incidence decreased to 80.9 per 100,000 infants between 2017 and 2019. Accounting for both time periods, the mean annual incidence was calculated as 121.8 per 100,000 infants younger than 2 months. Annual incidence also showed a significant decreasing trend in the period after implementation of maternal Tdap vaccination (slope: −14.53 per 100,000 infants per year; P = 0.001). The change in trends before and after this implementation was also significant ( P = 0.01). In a slightly older age group of 6 to 12 months of age, mean annual incidence of pertussis was 19.7 per 100,000 infants. In the time period before implementation of maternal Tdap, incidence among infants aged 6 to 12 months was consistently 4 to 12 times less than infants younger than 2 months and did not significantly change after the implementation of the maternal vaccine. Comparing the 2 age groups, there was no significant change in the difference in incidence between infants younger than 2 months and those between 6 and 12 months in the period before the maternal vaccine, and after its implementation, there was a significant decrease in the incidence difference between the 2 groups ( P < 0.001). These results suggest an association between the maternal Tdap vaccination and trends of pertussis incidence in infants younger than 2 months. This also indicates a possible reduction in disease burden attributable to maternal Tdap vaccination before delivery. Limitations of this study include limited availability of individual maternal vaccination status, as well as an inability to identify if any infants were vaccinated before the age of 2 months. Further research should focus on clinical impact of the Tdap vaccination in context with the later DTaP vaccination and on analyzing the trends in disease associated with both vaccinations. Clinical guidelines should also be examined to ensure that public health trends and individual health trends are in alignment.

Maternal Tdap vaccination during pregnancy is recommended to protect infants from pertussis, pre-vaccination. However, it is unclear whether maternal immune responses improve following Tdap booster. We present analysis of immune responses pre- and post-Tdap booster, of pregnant women (Pw) primed by whole cell vaccines, who received Tdap booster during pregnancy, compared to Tdap boosted non-pregnant women (NPw). Tdap antigen specific serum antibody reactivity and avidity increased following booster in both groups. Reactivity and avidity were higher in NPw compared to Pw. Activation-induced marker assay of peripheral blood revealed that pertussis specific Tmem cells increased following Tdap booster in Pw and NPw. After Tdap booster, the percentage of CD4+CD25+OX40+ T cells was approximately 2.5-fold higher in NPw. In contrast, the proportion of CD4+CD25+PDL1+ T cells post-booster were 3-fold higher in Pw compared to NPw, suggesting that Tdap booster may elevate Tregs in Pw. Interim analysis suggests that booster vaccination increases immune responses, although the magnitude and phenotype differ between Pw and NPW. Antibody function, race related immune profiles, and detailed phenotyping of T cell responses are in progress.

Importance: Infants younger than 1 year have the highest burden of pertussis morbidity and mortality. In 2011, the US introduced tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy to protect infants before vaccinations begin. Objective: To assess the association of maternal Tdap vaccination during pregnancy with the incidence of pertussis among infants in the US. Design, setting, and participants: In this ecologic study, a time-trend analysis was performed of infant pertussis cases reported through the National Notifiable Diseases Surveillance System between January 1, 2000, and December 31, 2019, in the US. Statistical analysis was performed from April 1, 2020, to October 31, 2022. Exposures: Maternal Tdap vaccination during pregnancy. Main outcomes and measures: Pertussis incidence rates were calculated and compared between 2 periods-the pre-maternal Tdap vaccination period (2000-2010) and the post-maternal Tdap vaccination period (2012-2019)-for 2 age groups: infants younger than 2 months (target group of maternal vaccination) and infants aged 6 months to less than 12 months (comparison group). Incidence rate differences between the 2 age groups were modeled using weighted segmented linear regression. The slope difference between the 2 periods was estimated to assess the association of maternal Tdap vaccination with pertussis incidence among infants. Results: A total of 57 460 pertussis cases were reported in infants younger than 1 year between 2000 and 2019; 19 322 cases (33.6%) were in infants younger than 2 months. During the pre-maternal Tdap vaccination period, annual pertussis incidence did not change among infants younger than 2 months (slope, 3.29 per 100 000 infants per year; P = .28) but increased slightly among infants aged 6 months to less than 12 months (slope, 2.10 per 100 000 infants per year; P = .01). There was no change in the difference in incidence between the 2 age groups (slope, 0.08 per 100 000 infants per year; P = .97) during the pre-maternal Tdap vaccination period overall. However, in the post-maternal Tdap vaccination period, incidence decreased among infants younger than 2 months (slope, -14.53 per 100 000 infants per year; P = .001) while remaining unchanged among infants aged 6 months to less than 12 months (slope, 1.42 per 100 000 infants per year; P = .29). The incidence rate difference between the 2 age groups significantly decreased during the post-maternal Tdap vaccination period (slope, -14.43 per 100 000 infants per year; P < .001). Pertussis incidence rate differences were significantly different between the pre-maternal and post-maternal Tdap vaccination periods (slope difference, -14.51 per 100 000 infants per year; P = .01). Conclusions and relevance: In this study, following maternal Tdap vaccine introduction, a sustained decrease in pertussis incidence was observed among infants younger than 2 months, narrowing the incidence gap with infants aged 6 months to less than 12 months. These findings suggest that maternal Tdap vaccination is associated with a reduction in pertussis burden in the target age group (<2 months) and that further increases in coverage may be associated with additional reductions in infant disease.

Introduction Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) during pregnancy is highly effective against Bordetella pertussis in young infants. We aimed to evaluate uptake of maternal Tdap vaccination during the recommended gestation period of 27 through 36 weeks among women enrolled in a public medical insurance plan in the United States. Methods In this analysis using Centers for Medicare and Medicaid Services insurance claims data, we identified women aged 15 through 49 years who delivered a liveborn infant from 2016 through 2019. We identified claims for Tdap vaccination to calculate the proportion of women who were vaccinated during weeks 27 through 36 of gestation in each calendar year. We also assessed average annual maternal Tdap coverage by age group, race and ethnicity, U.S. Census region of residence, and plan type. Data were analyzed in 2021. Results Among 4,318,823 deliveries, the four-year national average for Tdap vaccination was 26%, improving from 22% in 2016 to 31% in 2019 (p<0.001). Within subgroups, the lowest four-year average coverage was among women aged 15 through 18 years (22%), black, non-Hispanic (23%) and Hispanic women (24%), those residing in the South (18%), enrolled in a Children's Health Insurance Program plan (22%), and covered by a fee-for-service plan (19%). Coverage increased across all subgroups from 2016 through 2019. Conclusion Although maternal Tdap coverage among publicly insured women in the United States increased from 2016 through 2019, it remained considerably lower than estimated national coverage, with notable differences by race and ethnicity.

Background Acellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the U.S. childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy may be impacted. Methods Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMC) of pertussis-specific IgG antibodies (IU/mL) 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 < 0.01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed versus wP-primed women (PT: 17.3 vs. 36.4, GMC ratio 0.475 (95% Confidence Interval [CI], 0.408–0.552); FHA: 104.6 vs. 121.4, GMC ratio 0.861 (95% CI, 0.776–0.958)). 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 woman received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP- vs. wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in young infants born to aP-primed than those born to wP-primed women.

Background: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. Methods: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. Results: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. Conclusions: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.

Background Acellular pertussis (aP) vaccines replaced whole cell pertussis (wP) vaccines for the recommended childhood primary series in the United States in 1997. As women primed with aP vaccines in childhood enter reproductive age, it is unknown how maternal aP-priming will impact pertussis protection conferred to infants through Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination during pregnancy. Methods Infants born at term to women who had been vaccinated with Tdap at 27-36 weeks’ gestation and ≥ 14 days prior to delivery were included. Geometric mean concentrations (GMC) of pertussis-specific antibodies (measured in IU/mL) in umbilical cord blood of infants born to women born after 1997 (aP vaccine primed) were compared with those born to women born before 1992 (wP vaccine primed). Results 253 and 506 neonates born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger (19.3 v. 24.5 years), more likely to be Hispanic or non-Hispanic black and to have infants with lower birthweight (3264 v. 3392 grams, p< 0.01 for all). Gestation at Tdap receipt, gestational age at delivery, and interval between Tdap administration and delivery were not statistically different. Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were significantly lower among neonates born to aP-primed versus wP-primed mothers (PT: 17.3 v. 36.4, GMC ratio 0.475 (0.408 – 0.552) (Figure); FHA: 104.6 v. 121.4, GMC ratio 0.861 (0.776 – 0.958)). No significant differences were observed between the aP and wP-primed groups for anti- fimbriae (FIM) or anti-pertactin (PRN) antibodies ((FIM: 469.6 v. 577.2, GMC ratio 0.81 (CI 0.65 – 1.01); PRN 338.8 v. 292.6, GMC ratio 1.16 (CI 0.99 – 1.35)). Figure. Distribution of anti-PT antibody levels in cord blood in infants born to women who were primed with whole cell pertussis compared with acellular pertussis vaccines in childhood.* Conclusion The type of pertussis vaccine a woman received during childhood significantly impacted her response to Tdap vaccination during pregnancy; the largest reduction was in anti-PT antibodies thought to be most important in preventing severe infection in infants. These findings suggest that infants born to aP-primed women who received Tdap during pregnancy may have less passive protection against pertussis during the first months of life than those born to wP-primed women. Disclosures All Authors: No reported disclosures

We confirmed a large diphtheria outbreak among the Forcibly Displaced Myanmar Nationals in Bangladesh and identified frequent co-circulation with azithromycin-resistant C. pseudodiphtheriticum among cases. Our investigation highlights the need to better understand the role of C. pseudodiphtheriticum as a pathogen. ABSTRACT Background: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin

Background Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. Methods Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. Results Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. Conclusions We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.