BACKGROUND: Diagnostic methods for detecting infections caused by Bordetella species include culture, polymerase chain reaction (PCR), and serology. As the epidemiology of pertussis continues to evolve in the United States, we aimed to assess recent trends in provider testing practices and positivity for both B. pertussis and B. parapertussis. METHODS: Using deidentified data from a large U.S. commercial laboratory, we identified Bordetella tests from 2019 through 2023. We described monthly trends in number of tests ordered by test type for culture, PCR (both non-panel B. pertussis and B. parapertussis tests and those included as part of a respiratory panel), and serology, as well as percent positivity for serology and PCR. We also examined orders and positivity by patient age group and geographic region of the ordering provider. RESULTS: Among 527,206 tests, we identified 316,428 (60.1%) PCR tests, 204,480 (38.8%) serologic tests, and 5,840 (1.1%) cultures. While most PCR tests were ordered as part of a respiratory panel (83.5%), only 215 (0.08%) were positive for B. pertussis. Non-panel PCR positivity for B. pertussis was substantially higher but variable over the study period, ranging from 3% to 16%. We also observed a notable increase in B. parapertussis positivity on non-panel PCR tests in the first half of 2023. CONCLUSIONS: Both PCR and serology remain preferred diagnostic methods for providers. Despite their increasing popularity, B. pertussis positivity remained low for respiratory panels. Data from commercial laboratories can provide crucial insights into pertussis diagnostic trends over time.

BACKGROUND: To protect infants aged <2 months against pertussis, the United States recommends Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during each pregnancy. Data are limited on the strategy's effectiveness against pertussis in infants aged ≥2 months. METHODS: Pertussis case infants aged 2 to <6 months with cough onset between 1 January 2011 and 31 December 2014 were identified in 6 US states. Controls were 2 to <6 months of age, hospital matched, and selected by birth certificate. Mothers were interviewed to collect demographic and healthcare information. Provider-verified vaccination history was obtained for infants and mothers. Adjusted odds ratios (aORs) were calculated using conditional logistic regression; overall vaccine effectiveness (VE) was estimated as (1 - aOR)×100. To describe maternal Tdap VE modified by infant DTaP (diphtheria and tetanus toxoids and acellular pertussis) doses, case-control sets were unmatched, and a time-to-event analysis was conducted through a generalized linear mixed model. RESULTS: A total of 335 cases and 927 controls were enrolled. The overall adjusted VE estimate for Tdap during pregnancy was 45.6% (95% confidence interval [CI], 5.8%-68.5%) and increased slightly, but not significantly, against infant hospitalization (55.7% [-116.8% to 90.9%]). Although point estimates were not significant, VE was modified by infant DTaP doses (58.8% [95% CI, -6.0% to 84.0%] for 0 DTaP doses, 30.5% [-21.4% to 60.2%] for 1 dose, and 3.2% [-170.8% to 65.4%] for 2 doses). CONCLUSIONS: Our study suggests that there is some benefit of maternal Tdap vaccination beyond the first 2 months of life, however, on-time vaccination of infants remains critical to maintain protection from pertussis.

BACKGROUND: College students are at increased risk for invasive meningococcal disease, but which students are most at risk is unclear. METHODS: US meningococcal disease cases in persons aged 18-24 years during 2014-2017 were included. Patients were classified as undergraduate students or other persons. Incidence in different student and non-student populations was compared. RESULTS: During 2014-2017, 229 meningococcal disease cases were reported in persons aged 18-24 years; 120 were in undergraduate students. Serogroup B accounted for 74% of cases in students. Serogroup B disease incidence was 4-fold higher in undergraduate students, 11.8-fold higher among first-year undergraduate students, and 8.6-fold higher among residence hall residents versus non-undergraduates. During outbreaks, students affiliated with Greek life had a 9.8-fold higher risk of disease compared to other students. A significantly higher party school ranking was observed for schools with sporadic or outbreak cases when compared to schools with no cases. CONCLUSIONS: The findings of increased disease risk among first-year students and those living on campus or affiliated with Greek life can inform shared clinical decision-making for serogroup B vaccines to prevent this rare but serious disease. These data also can inform school serogroup B vaccination policies and outbreak response measures.

INTRODUCTION: Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine during pregnancy is highly effective against Bordetella pertussis in young infants. We aimed to evaluate the uptake of maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination during the recommended gestation period of 27 through 36 weeks among women enrolled in a public medical insurance plan in the U.S. 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 live-born infant from 2016 through 2019. We identified claims for tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination to calculate the proportion of women who were vaccinated during Weeks 27 through 36 of gestation in each calendar year. We also assessed the average annual maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis 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 4-year national average for tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination was 26%, improving from 22% in 2016 to 31% in 2019 (p<0.001). Within subgroups, the lowest 4-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%); those enrolled in a Children's Health Insurance Program plan (22%); and those covered by a fee-for-service plan (19%). Coverage increased across all subgroups from 2016 through 2019. CONCLUSIONS: Although maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis coverage among publicly insured women in the U.S. increased from 2016 through 2019, it remained considerably lower than estimated national coverage, with notable differences by race and ethnicity.

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.

Haemophilus influenzae (Hi) can cause meningitis and other serious invasive disease. Encapsulated Hi is classified into six serotypes (a-f) based on chemical composition of the polysaccharide capsule; unencapsulated strains are termed nontypeable Hi (NTHi). Hi serotype b (Hib) was the most common cause of bacterial meningitis in children in the pre-Hib vaccine era, and secondary transmission of Hi among children (e.g., to household contacts and in child care facilities) (1,2) led to the Advisory Committee on Immunization Practices (ACIP) recommendation for antibiotic chemoprophylaxis to prevent Hib disease in certain circumstances.* High Hib vaccination coverage since the 1990s has substantially reduced Hib disease, and other serotypes now account for most Hi-associated invasive disease in the United States (3). Nevertheless, CDC does not currently recommend chemoprophylaxis for contacts of persons with invasive disease caused by serotypes other than Hib and by NTHi (non-b Hi). Given this changing epidemiology, U.S. surveillance data were reviewed to investigate secondary cases of invasive disease caused by Hi. The estimated prevalence of secondary transmission was 0.32% among persons with encapsulated Hi disease (≤60 days of one another) and 0.12% among persons with NTHi disease (≤14 days of one another). Isolates from all Hi case pairs were genetically closely related, and all patients with potential secondary infection had underlying medical conditions. These results strongly suggest that secondary transmission of non-b Hi occurs. Expansion of Hi chemoprophylaxis recommendations might be warranted to control invasive Hi disease in certain populations in the United States, but further analysis is needed to evaluate the potential benefits against the risks, such as increased antibiotic use.

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.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States. We evaluated the epidemiology of invasive NTHi disease in the United States, including among pregnant women, infants, and people with HIV (PWH). METHODS: We used data from population- and laboratory-based surveillance for invasive H. influenzae disease conducted in 10 sites to estimate national incidence of NTHi, and to describe epidemiology in women of childbearing age, infants aged ≤30 days (neonates), and PWH living in the surveillance catchment areas. H. influenzae isolates were sent to the Centers for Disease Control and Prevention for species confirmation, serotyping, and whole genome sequencing of select isolates. RESULTS: During 2008-⁠2019, average annual NTHi incidence in the United States was 1.3/100,000 population overall, 5.8/100,000 among children aged <1 year and 10.2/100,000 among adults aged ≥80 years. Among 225 reported neonates with NTHi, 92% had a positive culture within the first week of life and 72% were preterm. NTHi risk was 23 times higher among preterm compared to term neonates, and 5.6 times higher in pregnant/postpartum compared to non-pregnant women. Over half of pregnant women with invasive NTHi had loss of pregnancy post-infection. Incidence among PWH aged ≥13 years was 9.5 cases per 100,000, compared to 1.1 cases per 100,000 for non-PWH (RR=8.3; 95% CI=7.1-9.7; p<0.0001). CONCLUSION: NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and evaluation of targeted interventions to prevent perinatal NTHi infections may be warranted.

BACKGROUND: Recently, several invasive meningococcal disease (IMD) outbreaks caused by Neisseria meningitidis have occurred among people experiencing homelessness (PEH). However, overall IMD risk among PEH is not well described. We compared incidence and characteristics of IMD among PEH and persons not known to be experiencing homelessness (non-PEH) in the United States. METHODS: We analyzed 2016-2019 IMD data from the National Notifiable Diseases Surveillance System (NNDSS) and enhanced meningococcal disease surveillance. Incidence was calculated using U.S. census data and Point-in-Time counts from the U.S. Department of Housing and Urban Development. RESULTS: Of cases from states participating in enhanced surveillance during 2016-2019 (n = 1409), 45 (3.2%) cases occurred among PEH. Annual incidence was higher among PEH (2.12 cases/100,000) than non-PEH (0.11 cases/100,000; relative risk: 19.8, 95% CI: 14.8-26.7). Excluding outbreak-associated cases (PEH n = 18, 40%; non-PEH n = 98, 7.2%), incidence among PEH remained elevated compared to incidence in non-PEH (relative risk: 12.8, 95% CI: 8.8-18.8). Serogroup C was identified in 68.2% of PEH cases compared to 26.4% in non-PEH (p < 0.0001). CONCLUSIONS: PEH are at increased risk for IMD. Further assessment is needed to determine the feasibility and potential impact of meningococcal vaccination for PEH in the United States.

BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness.

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: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

BACKGROUND: Declining antimicrobial susceptibility to current gonorrhoea antibiotic treatment and inadequate treatment options have raised the possibility of untreatable gonorrhoea. New prevention approaches, such as vaccination, are needed. Outer membrane vesicle meningococcal serogroup B vaccines might be protective against gonorrhoea. We evaluated the effectiveness of a serogroup B meningococcal outer membrane vesicle vaccine (MenB-4C) against gonorrhoea in individuals aged 16-23 years in two US cities. METHODS: We identified laboratory-confirmed gonorrhoea and chlamydia infections among individuals aged 16-23 years from sexually transmitted infection surveillance records in New York City and Philadelphia from 2016 to 2018. We linked gonorrhoea and chlamydia case records to immunisation registry records to determine MenB-4C vaccination status at infection, defined as complete vaccination (two MenB-4C doses administered 30-180 days apart), partial vaccination (single MenB-4C vaccine dose), or no vaccination (serogroup B meningococcal vaccine naive). Using log-binomial regression with generalised estimating equations to account for correlations between multiple infections per patient, we calculated adjusted prevalence ratios (APR) and 95% CIs to determine if vaccination was protective against gonorrhoea. We used individual-level data for descriptive analyses and infection-level data for regression analyses. FINDINGS: Between Jan 1, 2016, and Dec 31, 2018, we identified 167 706 infections (18 099 gonococcal infections, 124 876 chlamydial infections, and 24 731 gonococcal and chlamydial co-infections) among 109 737 individuals linked to the immunisation registries. 7692 individuals were vaccinated, of whom 4032 (52·4%) had received one dose, 3596 (46·7%) two doses, and 64 (<1·0%) at least three doses. Compared with no vaccination, complete vaccination series (APR 0·60, 95% CI 0·47-0·77; p<0·0001) and partial vaccination series (0·74, 0·63-0·88; p=0·0012) were protective against gonorrhoea. Complete MenB-4C vaccination series was 40% (95% CI 23-53) effective against gonorrhoea and partial MenB-4C vaccination series was 26% (12-37) effective. INTERPRETATION: MenB-4C vaccination was associated with a reduced gonorrhoea prevalence. MenB-4C could offer cross-protection against Neisseria gonorrhoeae. Development of an effective gonococcal vaccine might be feasible with implications for gonorrhoea prevention and control. FUNDING: None.

We describe cases of invasive meningococcal disease caused by nongroupable Neisseria meningitidis belonging to a novel phylogenetic clade associated with urethritis. Seven cases were identified, comprising 0.6% of sequenced invasive meningococcal disease isolates from 2013 to 2017. Five patients had a known or likely immunocompromising condition, including 2 with a complement deficiency.

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.

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: 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.

Declining gonococcal susceptibility to ceftriaxone and azithromycin has raised the possibility of untreatable gonorrhea in the future and re-ignited interest in gonococcal vaccine development. Despite decades of research, previous gonococcal vaccine candidates have been ineffective. A growing body of data suggest that meningococcal group B outer membrane vaccines (MenB OMV) may be cross-protective against Neisseria gonorrhoeae. Clinical trials of a licensed vaccine against N. meningitidis serogroup B containing an OMV component are underway to determine its efficacy against N. gonorrhoeae. Other experimental gonococcal vaccine candidates are in the preclinical phases. Population impact of future gonococcal vaccines with different levels of efficacy and duration of protection in various populations are being evaluated using modeling studies. Despite recent progress, gaps in gonococcal vaccine research remain. Research is needed to evaluate vaccine efficacy in preventing gonococcal infections acquired via various anatomic routes and among patients co-infected with other sexually transmitted infections. Studies that model the impact of a future vaccine on high-burden populations such as men who have sex with men and estimate both vaccine cost-effectiveness and the incremental cost-effectiveness ratio of vaccination to antimicrobial resistance and treatment costs are warranted. This narrative review examines the current state of gonococcal vaccine research, the possible impact of a gonococcal vaccine on gonorrhea rates based on modeling studies, gaps in the gonococcal vaccine literature, and public health implications of a future gonococcal vaccine on reducing the gonorrhea burden in the United States.

This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines. 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 with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16-23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.

Respiratory illness caused by Corynebacterium diphtheriae and C. ulcerans, and use of diphtheria anti-toxin in the United States, 1996-2018. BACKGROUND: Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by C. ulcerans, a zoonotic bacterium that can also produce diphtheria toxin. In the United States, respiratory diphtheria is nationally notifiable: specimens from suspected cases are submitted to the Centers for Disease Control (CDC) for species and toxin confirmation, and diphtheria antitoxin (DAT) is obtained from CDC for treatment. We summarize the epidemiology of respiratory diphtheria and diphtheria-like illness and describe DAT use during 1996-2018 in the United States. METHODS: We described respiratory diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and C. ulcerans-related diphtheria-like illness identified through specimen submissions to CDC during 1996-2018. We reviewed DAT requests from 1997-2018. RESULTS: From 1996-2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were non-toxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but PCR-positive for diphtheria toxin gene, 1 was culture-positive without further testing, and the remaining 3 were either not tested or tested negative. Five cases of respiratory diphtheria-like illness caused by toxigenic C. ulcerans were identified. DAT was requested by healthcare providers for 151 suspected diphtheria cases between 1997-2018, with an average of 11 requests per year from 1997-2007, and 3 per year from 2008-2018. CONCLUSIONS: Respiratory diphtheria remains rare in the United States, and requests for DAT have declined. Incidental identification of C. ulcerans-related diphtheria-like illness suggests surveillance of this condition might be warranted.

BACKGROUND: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used CDC's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and non-pregnant women of childbearing age. METHODS: Pertussis cases in women aged 18-44 years with cough onset between 1/1/2012-12/31/2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interview and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. RESULTS: 1,582 pertussis cases were identified among women aged 18-44 years; 5.1% (76/1499) of patients with known pregnancy status were pregnant at cough onset. Of pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median age of pregnant and non-pregnant patients was 29.0 and 33.0 years, respectively. Most pregnant and non-pregnant patients were white (78.3% vs. 86.4%, p=0.09) and non-Hispanic (72.6% vs. 77.3%, p=0.35). Average annual pertussis incidence was 5.7/100,000 among pregnant and 7.3/100,000 among non-pregnant women. Compared to non-pregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%), post-tussive vomiting (58.1% vs. 47.9%) and apnea (37.3% vs. 29.0%); however, differences were not statistically significant (p>0.05 for all). A similar proportion of pregnant and non-pregnant patients reported ever having received Tdap (31.6% vs. 32.7%, p=0.84). CONCLUSIONS: Our analysis suggests that pertussis incidence and clinical characteristics of disease are similar among pregnant and non-pregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women.

IMPORTANCE: In 2005, the US Advisory Committee on Immunization Practices recommended routine quadrivalent meningococcal conjugate (MenACWY) vaccine for all adolescents aged 11 to 12 years, and in 2010, a booster dose for adolescents aged 16 years. Measuring the association between MenACWY vaccination and the incidence of meningococcal disease in adolescents is critical for evaluating the adolescent vaccination program and informing future vaccine policy. OBJECTIVE: To describe the association between MenACWY vaccination and the incidence of meningococcal disease in US adolescents. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of surveillance data included all confirmed and probable cases of Neisseria meningitidis reported to the National Notifiable Diseases Surveillance System from January 1, 2000, to December 31, 2017. Statistical analysis was conducted from October 1, 2018, to August 31, 2019. EXPOSURES: Routine MenACWY vaccination among US adolescents. MAIN OUTCOMES AND MEASURES: Poisson segmented regression analysis was used to model the annual incidence of meningococcal disease among adolescents aged 11 to 15 years and 16 to 22 years before the introduction of the MenACWY vaccine (2000-2005), after the primary dose recommendation (2006-2010), and after the booster dose recommendation (2011-2017); 95% CIs were used to determine significant differences between time periods. RESULTS: The national incidence of meningococcal disease declined from 0.61 cases per 100 000 population during the prevaccine period (2000-2005) to 0.15 cases per 100 000 population during the post-booster dose period (2011-2017). The greatest percentage decline was observed for serogroup C, W, and Y combined (CWY) among adolescents aged 11 to 15 years and 16 to 22 years in the periods after vaccine introduction. Incidence of serogroup CWY meningococcal disease among adolescents aged 11 to 15 years decreased by 16.3% (95% CI, 12.1%-20.3%) annually during the prevaccine period and 27.8% (95% CI, 20.6%-34.4%) during the post-primary dose period (P = .02); among adolescents aged 16 to 22 years, the incidence decreased by 10.6% (95% CI, 6.8%-14.3%) annually in the post-primary dose period and 35.6% (95% CI, 29.3%-41.0%) annually in the post-booster dose period (P < .001). An estimated 222 cases of meningococcal disease due to serogroup CWY among adolescents were averted through vaccination during the evaluation period. CONCLUSIONS AND RELEVANCE: After introduction of a primary and booster MenACWY dose, the rates of decline in incidence of meningococcal disease due to serogroup C, W, or Y accelerated nearly 2-fold to 3-fold in vaccinated adolescent age groups. Although the MenACWY vaccine alone cannot explain the decline of meningococcal disease in the United States, these data suggest that MenACWY vaccination is associated with reduced disease rates in adolescents.

Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations.

Since 2005, a single dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents and adults (1,2). After receipt of Tdap, booster doses of tetanus and diphtheria toxoids (Td) vaccine are recommended every 10 years or when indicated for wound management. During the October 2019 meeting of ACIP, the organization updated its recommendations to allow use of either Td or Tdap where previously only Td was recommended. These situations include decennial Td booster doses, tetanus prophylaxis when indicated for wound management in persons who had previously received Tdap, and for multiple doses in the catch-up immunization schedule for persons aged >/=7 years with incomplete or unknown vaccination history. Allowing either Tdap or Td to be used in situations where Td only was previously recommended increases provider point-of-care flexibility. This report updates ACIP recommendations and guidance regarding the use of Tdap vaccines (3).

Objective: Quadrivalent meningococcal conjugate vaccines (MenACWY) have been recommended routinely for adolescents since 2005; in 2015, serogroup B meningococcal (MenB) vaccines were recommended for persons aged 16-23 years based on individual clinical decision making. We surveyed college health providers or administrators to understand current meningococcal vaccine policies. Methods/Participants: In January 2017, we distributed a survey to 985 institutions in partnership with the American College Health Association to assess vaccination policies and outbreak response plans. Results: Overall, 352 (36%) institutions completed the survey. Most either required (N = 186, 53%) or recommended (N = 148, 42%) a meningococcal vaccine; only half (N = 167) had a policy specifically addressing MenB vaccines. Few institutions with a MenB vaccine policy required vaccination (N = 7, 4%); most recommended vaccination (N = 160, 96%). Conclusion: Most institutions have a meningococcal vaccination policy; however, there is substantial diversity in policies. Fewer schools have policies specifically addressing MenB vaccines.

BACKGROUND: In the United States, persons >/=11 years are recommended to receive one dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, followed by decennial tetanus- and diphtheria-toxoid (Td) boosters. Many providers use Tdap instead of Td. We evaluated epidemiologic and economic impacts of replacing Td boosters with Tdap. METHODS: We used a static cohort model to examine replacing Td with Tdap over the lifetime of 4,386,854 adults >/=21 years. Because pertussis is underdiagnosed and true incidence is unknown, we varied incidence from 2.5 cases/100,000 person-years to 500 cases/100,000 person-years. We calculated vaccine and medical costs from claims data. We estimated cost per case prevented and per quality-adjusted life year (QALY) saved; sensitivity analyses were conducted on vaccine effectiveness (VE), protection duration, vaccine cost, disease duration, hospitalization rates, productivity loss and missed work. We did not include programmatic advantages resulting from use of a single tetanus-toxoid containing vaccine. RESULTS: At lowest incidence estimates, administering Tdap resulted in high costs per averted case ($111,540) and QALY saved ($8,972,848). As incidence increased, cases averted increased and cost per QALY saved decreased rapidly. With incidence estimates of 250 cases/100,000 person-years, cost per averted case and QALY saved were $984 and $81,678 respectively; at 500 cases/100,000 person-years, these values were $427 and $35,474. In multivariate sensitivity analyses, assuming 250 cases/100,000 person-years, estimated cost per QALY saved ranged from $971 (most favorable) to $217,370 (least favorable). CONCLUSIONS: Our findings suggest that replacing Td with Tdap for the decennial booster would result in high cost per QALY saved based on reported cases. However, programmatic considerations were not accounted for, and if pertussis incidence, which is incompletely measured, is assumed to be higher than reported through national surveillance, substituting Tdap for Td may lead to moderate decreases in pertussis cases and cost per QALY.

AIMS: To examine the cost-effectiveness of hepatitis C (HCV) treatment of people who inject drugs (PWID), combined with medication-assisted treatment (MAT) and syringe-service programs (SSP), to tackle the increasing HCV epidemic in the United States. DESIGN: HCV-transmission and disease progression models with cost-effectiveness analysis using a health care perspective. SETTING: Rural Perry County, Kentucky (PC), and urban San Francisco, California (SF),USA. Compared with PC, SF has a greater proportion of PWID with access to MAT or SSP. HCV treatment of PWID is negligible in both settings. PARTICIPANTS: PWID, data collected between 1998 and 2015 from Social Networks Among Appalachian People, U Find Out, Urban Health Study, and National HIV Behavioral Surveillance System studies. INTERVENTIONS AND COMPARATOR: Three intervention scenarios modeled: baseline-existing SSP and MAT coverage with HCV screening and treatment with direct-acting antiviral for ex-injectors only as per standard of care; Intervention 1-scale-up of SSP and MAT without changes to treatment; and Intervention 2-scale-up as Intervention 1 combined with HCV screening and treatment for current PWID. MEASUREMENTS: Incremental cost-effectiveness ratios (ICERs) and uncertainty using cost-effectiveness acceptability curves. Benefits were measured in quality-adjusted life-years (QALYs). FINDINGS: For both settings, Intervention 2 is preferred to Intervention 1 and the appropriate comparator for Intervention 2 is the baseline scenario. Relative to baseline, for PC Intervention 2 averts 1,852 more HCV infections, increases QALYS by 3,095, costs $21.6 million more, and has an ICER of $6,975/QALY. For SF, Intervention 2 averts 36,473 more HCV infections, increases QALYs by 78,93, costs $ 872 million more, and has an ICER of $11,044/QALY. The cost-effectiveness of Intervention 2 was robust to several sensitivity analysis. CONCLUSIONS: Hepatitis C screening and treatment for people who inject drugs, combined with medication-assisted treatment and syringe-service programs, is a cost-effective strategy for reducing hepatitis C burden in the United States.

On December 12, 2018, an immunocompromised man with non-Hodgkin’s lymphoma, aged 73 years, was evaluated by an ophthalmologist for left eyelid redness, swelling, and eye discharge and received a diagnosis of ligneous (pseudomembranous) conjunctivitis. The pseudomembrane was debrided and sent for culture, and the patient was prescribed oral amoxicillin clavulanate and moxifloxacin eye drops, with topical loteprednol and cyclosporine to decrease the robust inflammatory response. Corynebacterium ulcerans, one of three species of Corynebacterium (in addition to C. diphtheriae and C. psuedotuberculosis) that can harbor the diphtheria toxin–producing gene was initially identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry performed on an isolate obtained from culture of the pseudomembrane at a Missouri hospital on December 13. The Missouri Department of Health and Senior Services (MDHSS) laboratory-confirmed C. ulcerans by culture and forwarded the isolate to CDC for toxin testing. On December 28, CDC confirmed toxin-producing C. ulcerans. The patient had no systemic symptoms, was not hospitalized, and did not receive diphtheria antitoxin. On January 11, 2019, following multiple membrane removals and no residual membrane; cultures of conjunctival swabs tested by the hospital were negative for C. ulcerans. The patient was not up-to-date for tetanus-diphtheria (Td) vaccine and had postponed vaccination because of his ongoing cancer treatment.

In the U.S. Hepatitis C virus (HCV) transmission is increasing among people who inject drugs (PWID). Many regions have insufficient prevention intervention coverage. Using modelling, we investigate the impact of scaling-up prevention and treatment interventions on HCV transmission among PWID in Perry County, Kentucky (PC), and San Francisco, California (SF), where HCV sero-prevalence among PWID is >50%. A greater proportion of PWID access medication-assisted treatment (MAT) or syringe service programs (SSP) in urban SF (established community) than rural PC (young, expanding community). We model the proportion of HCV-infected PWID needing HCV-treatment annually to reduce HCV-incidence by 90% by 2030, with and without MAT scale-up (50% coverage, both settings) and SSP scale-up (PC only) from 2017. With current MAT&SSP coverage during 2017-2030, HCV-incidence will increase in PC (21.3 to 22.6 per 100 person-years (/100pyrs)) and decrease in SF (12.9 to 11.9/100pyrs). With concurrent MAT&SSP scale-up, 5%/year of HCV-infected PWID need HCV-treatment in PC to achieve incidence targets; 13%/year without MAT&SSP scale-up. In SF, a similar proportion need HCV-treatment (10%/year) irrespective of MAT scale-up. Reaching the same impact by 2025 requires increases in treatment rates of 45-82%. Achievable provision of HCV-treatment, alongside MAT&SSP scale-up (PC) and MAT scale-up (SF), could reduce HCV-incidence.

Background: The country of Georgia launched the world's first Hepatitis C Virus (HCV) Elimination Program in 2015 and set a 90% prevalence reduction goal for 2020. We conducted a nationally representative HCV seroprevalence survey to establish baseline prevalence to measure progress toward elimination over time. Methods: A cross-sectional seroprevalence survey was conducted in 2015 among adults aged ≥18 years using a stratified, multi-stage cluster design (n = 7000). Questionnaire variables included demographic, medical, and behavioral risk characteristics and HCV-related knowledge. Blood specimens were tested for antibodies to HCV (anti-HCV) and HCV RNA. Frequencies were computed for HCV prevalence, risk factors, and HCV-related knowledge. Associations between anti-HCV status and potential risk factors were calculated using logistic regression. Results: National anti-HCV seroprevalence in Georgia was 7.7% (95% confidence interval (CI) = 6.7, 8.9); HCV RNA prevalence was 5.4% (95% CI = 4.6, 6.4). Testing anti-HCV+ was significantly associated with male sex, unemployment, urban residence, history of injection drug use (IDU), incarceration, blood transfusion, tattoos, frequent dental cleanings, medical injections, dialysis, and multiple lifetime sexual partners. History of IDU (adjusted odds ratio (AOR) = 21.4, 95% CI = 12.3, 37.4) and blood transfusion (AOR = 4.5, 95% CI = 2.8, 7.2) were independently, significantly associated with testing anti-HCV+ after controlling for sex, age, urban vs. rural residence, and history of incarceration. Among anti-HCV+ participants, 64.0% were unaware of their HCV status, and 46.7% did not report IDU or blood transfusion as a risk factor. Conclusions: Georgia has a high HCV burden, and a majority of infected persons are unaware of their status. Ensuring a safe blood supply, implementing innovative screening strategies beyond a risk-based approach, and intensifying prevention efforts among persons who inject drugs are necessary steps to reach Georgia's HCV elimination goal.