Fever is not considered a typical presentation of pertussis. We characterized fever among 7840 pertussis cases from the Centers for Disease Control and Prevention's Enhanced Pertussis Surveillance with cough onset from 2015 to 2022. Ten percent of cases had a reported fever. The presence of fever should not rule out pertussis as a cause of cough illness.

Evolving technology and the development of new devices that can aerosolize water present a risk for new sources of Legionella bacteria growth and spread within industrial settings. We investigated a cluster of legionellosis among employees of a manufacturing facility in South Carolina, USA, and found 2 unique equipment sources of Legionella bacteria. The cluster of cases took place during August-November 2022; a total of 34 cases of legionellosis, including 15 hospitalizations and 2 deaths, were reported. Legionella pneumophila was isolated from 3 devices: 2 water jet cutters and 1 floor scrubber. L. pneumophila sequence type 36 was identified in environmental isolates and 1 patient specimen, indicating that those devices were the likely source of infection. Remediation was ultimately achieved through the development and implementation of a device-specific water management program. Manufacturing facilities that use aerosol-generating devices should consider maintaining updated Legionella water management programs to prevent Legionella bacterial infections.

BACKGROUND: In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying PCR-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in seven sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. METHODS: We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. RESULTS: Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6,124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. CONCLUSIONS: Despite a substantial decrease in reported pertussis cases in the setting of COVID-19, our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts.

Few data exist on asymptomatic carriage of Bordetella species among populations receiving acellular pertussis vaccine. We conducted a cross-sectional study among acellular-vaccinated children presenting to an emergency department. B. pertussis carriage prevalence was <1% in this population, a lower prevalence than that found in recent studies among whole-cell pertussis-vaccinated participants.

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.

Respiratory diphtheria is a serious infection caused by toxigenic Corynebacterium diphtheriae, and disease transmission mainly occurs through respiratory droplets. Between 2017 and 2019, a large diphtheria outbreak among forcibly displaced Myanmar nationals densely settled in Bangladesh was investigated. Here we utilized whole-genome sequencing (WGS) to characterize recovered isolates of C. diphtheriae and two co-circulating non-diphtheritic Corynebacterium (NDC) species - C. pseudodiphtheriticum and C. propinquum. C. diphtheriae isolates recovered from all 53 positive cases in this study were identified as toxigenic biovar mitis, exhibiting intermediate resistance to penicillin, and formed four phylogenetic clusters circulating among multiple refugee camps. Additional sequenced isolates collected from two patients showed co-colonization with non-toxigenic C. diphtheriae biovar gravis, one of which exhibited decreased susceptibility to the first-line antibiotics and harboured a novel 23-kb multidrug resistance plasmid. Results of phylogenetic reconstruction and virulence-related gene contents of the recovered NDC isolates indicated they were likely commensal organisms, though 80.4 %(45/56) were not susceptible to erythromycin, and most showed high minimum inhibition concentrations against azithromycin. These results demonstrate the high resolution with which WGS can aid molecular investigation of diphtheria outbreaks, through the quantification of bacterial genetic relatedness, as well as the detection of virulence factors and antibiotic resistance markers among case isolates.

We report a toxigenic strain of Corynebacterium diphtheriae isolated from an oozing dermal wound in a pet cat in Texas, USA. We also describe the epidemiologic public health efforts conducted to identify potential sources of infection and mitigate its spread and the molecular and genetic studies performed to identify the bacterium.

In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen.

IMPORTANCE: Racial and ethnic minority groups are disproportionately affected by COVID-19. OBJECTIVES: To evaluate whether rates of severe COVID-19, defined as hospitalization, intensive care unit (ICU) admission, or in-hospital death, are higher among racial and ethnic minority groups compared with non-Hispanic White persons. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included 99 counties within 14 US states participating in the COVID-19-Associated Hospitalization Surveillance Network. Participants were persons of all ages hospitalized with COVID-19 from March 1, 2020, to February 28, 2021. EXPOSURES: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test within 14 days prior to or during hospitalization. MAIN OUTCOMES AND MEASURES: Cumulative age-adjusted rates (per 100 000 population) of hospitalization, ICU admission, and death by race and ethnicity. Rate ratios (RR) were calculated for each racial and ethnic group compared with White persons. RESULTS: Among 153 692 patients with COVID-19-associated hospitalizations, 143 342 (93.3%) with information on race and ethnicity were included in the analysis. Of these, 105 421 (73.5%) were 50 years or older, 72 159 (50.3%) were male, 28 762 (20.1%) were Hispanic or Latino, 2056 (1.4%) were non-Hispanic American Indian or Alaska Native, 7737 (5.4%) were non-Hispanic Asian or Pacific Islander, 40 806 (28.5%) were non-Hispanic Black, and 63 981 (44.6%) were White. Compared with White persons, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely to have higher cumulative age-adjusted rates of hospitalization, ICU admission, and death as follows: American Indian or Alaska Native (hospitalization: RR, 3.70; 95% CI, 3.54-3.87; ICU admission: RR, 6.49; 95% CI, 6.01-7.01; death: RR, 7.19; 95% CI, 6.47-7.99); Latino (hospitalization: RR, 3.06; 95% CI, 3.01-3.10; ICU admission: RR, 4.20; 95% CI, 4.08-4.33; death: RR, 3.85; 95% CI, 3.68-4.01); Black (hospitalization: RR, 2.85; 95% CI, 2.81-2.89; ICU admission: RR, 3.17; 95% CI, 3.09-3.26; death: RR, 2.58; 95% CI, 2.48-2.69); and Asian or Pacific Islander (hospitalization: RR, 1.03; 95% CI, 1.01-1.06; ICU admission: RR, 1.91; 95% CI, 1.83-1.98; death: RR, 1.64; 95% CI, 1.55-1.74). CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely than White persons to have a COVID-19-associated hospitalization, ICU admission, or in-hospital death during the first year of the US COVID-19 pandemic. Equitable access to COVID-19 preventive measures, including vaccination, is needed to minimize the gap in racial and ethnic disparities of severe COVID-19.

We read with interest the analysis by Eisenberg and colleagues [1] on diphtheria antitoxin (DAT) use during the diphtheria outbreak in Bangladesh, especially with regard to product safety. Eisenberg et al found that administration of a DAT product manufactured by Premium Serum and Vaccines Pvt Ltd (India) was associated with adverse events (AEs) in 170 of 790 (24%) recipients. However, most events were mild, and anaphylaxis occurred in only 3% [1]. Here we provide further evidence on the safety of DAT, administered in a high-resource, non-outbreak setting in the United States.

Carriage evaluations were conducted during 2015 to 2016 at two U.S. universities in conjunction with the response to disease outbreaks caused by Neisseria meningitidis serogroup B and at a university where outbreak and response activities had not occurred. All eligible students at the two universities received the serogroup B meningococcal factor H binding protein vaccine (MenB-FHbp); 5.2% of students (181/3,509) at one university received MenB-4C. A total of 1,514 meningococcal carriage isolates were obtained from 8,905 oropharyngeal swabs from 7,001 unique participants. Whole-genome sequencing data were analyzed to understand MenB-FHbp's impact on carriage and antigen genetic diversity and distribution. Of 1,422 isolates from carriers with known vaccination status (726 [51.0%] from MenB-FHbp-vaccinated, 42 [3.0%] from MenB-4C-vaccinated, and 654 [46.0%] from unvaccinated participants), 1,406 (98.9%) had intact fHbp alleles (716 from MenB-FHbp-vaccinated participants). Of 726 isolates from MenB-FHbp-vaccinated participants, 250 (34.4%) harbored FHbp peptides that may be covered by MenB-FHbp. Genogroup B was detected in 122/1,422 (8.6%) and 112/1,422 (7.9%) isolates from MenB-FHbp-vaccinated and unvaccinated participants, respectively. FHbp subfamily and peptide distributions between MenB-FHbp-vaccinated and unvaccinated participants were not statistically different. Eighteen of 161 MenB-FHbp-vaccinated repeat carriers (11.2%) acquired a new strain containing one or more new vaccine antigen peptides during multiple rounds of sample collection, which was not statistically different (P = 0.3176) from the unvaccinated repeat carriers (1/30; 3.3%). Our findings suggest that lack of MenB vaccine impact on carriage was not due to missing the intact fHbp gene; MenB-FHbp did not affect antigen genetic diversity and distribution during the study period.IMPORTANCE The impact of serogroup B meningococcal (MenB) vaccines on carriage is not completely understood. Using whole-genome sequencing data, we assessed the diversity and distribution of MenB vaccine antigens (particularly FHbp) among 1,514 meningococcal carriage isolates recovered from vaccinated and unvaccinated students at three U.S. universities, two of which underwent MenB-FHbp mass vaccination campaigns following meningococcal disease outbreaks. The majority of carriage isolates recovered from participants harbored intact fHbp genes, about half of which were recovered from MenB-FHbp-vaccinated participants. The distribution of vaccine antigen peptides was similar among carriage isolates recovered from vaccinated and unvaccinated participants, and almost all strains recovered from repeat carriers retained the same vaccine antigen profile, suggesting insignificant vaccine selective pressure on the carriage population in these universities.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

On March 13, 2020, the United States declared a national emergency concerning the novel coronavirus disease 2019 (COVID-19) outbreak (1). In response, many state and local governments issued shelter-in-place or stay-at-home orders, restricting nonessential activities outside residents' homes (2). CDC initially issued guidance recommending postponing routine adult vaccinations, which was later revised to recommend continuing to administer routine adult vaccines (3). In addition, factors such as disrupted operations of health care facilities and safety concerns regarding exposure to SARS-CoV-2, the virus that causes COVID-19, resulted in delay or avoidance of routine medical care (4), likely further affecting delivery of routine adult vaccinations. Medicare enrollment and claims data of Parts A (hospital insurance), B (medical insurance), and D (prescription drug insurance) were examined to assess the change in receipt of routine adult vaccines during the pandemic. Weekly receipt of four vaccines (13-valent pneumococcal conjugate vaccine [PCV13], 23-valent pneumococcal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]) by Medicare beneficiaries aged ≥65 years during January 5-July 18, 2020, was compared with that during January 6-July 20, 2019, for the total study sample and by race and ethnicity. Overall, weekly administration rates of the four examined vaccines declined by up to 89% after the national emergency declaration in mid-March (1) compared with those during the corresponding period in 2019. During the first week following the national emergency declaration, the weekly vaccination rates were 25%-62% lower than those during the corresponding week in 2019. After reaching their nadirs of 70%-89% below 2019 rates in the second to third week of April 2020, weekly vaccination rates gradually began to recover through mid-July, but by the last study week were still lower than were those during the corresponding period in 2019, with the exception of PPSV23. Vaccination declined sharply for all vaccines studied, overall and across all racial and ethnic groups. While the pandemic continues, vaccination providers should emphasize to patients the importance of continuing to receive routine vaccinations and provide reassurance by explaining the procedures in place to ensure patient safety (3).

Using a coronavirus disease 2019 (COVID-19)-associated hospitalization surveillance network, we found that 42.5% of hospitalized COVID-19 cases with available data from March 1-June 30, 2020, received ≥1 COVID-19 investigational treatment. Hydroxychloroquine, azithromycin, and remdesivir were used frequently; however, hydroxychloroquine and azithromycin use declined over time, while use of remdesivir increased.

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.

Between July 2018 and May 2019, Corynebacterium diphtheriae was isolated from eight patients with non-respiratory infections, seven of whom experienced homelessness and had stayed at shelters in King County, WA, USA. All isolates were microbiologically identified as nontoxigenic C. diphtheriae biovar mitis. Whole-genome sequencing confirmed that all case isolates were genetically related, associated with sequence type 445 and differing by fewer than 24 single-nucleotide polymorphisms (SNPs). Compared to publicly available C. diphtheriae genomic data, these WA isolates formed a discrete cluster with SNP variation consistent with previously reported outbreaks. Virulence-related gene content variation within the highly related WA cluster isolates was also observed. These results indicated that genome characterization can readily support epidemiology of nontoxigenic C. diphtheriae.

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: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSION: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in U.S. waters in March 2020.

In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population.IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.

Currently, the Advisory Committee on Immunization Practices recommends one-time tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination for all adults 19 years and older. This study is designed to evaluate the cost-effectiveness of Tdap vaccination for Tdap-eligible adults aged 19 through 85 in the United States. A cost-effectiveness model was developed to compute costs and health outcomes associated with pertussis among 100,000 Tdap-eligible persons of each age cohort. From the societal perspective, the cost per quality-adjusted life-year (QALY) saved was evaluated under the vaccination scenarios. Sensitivity analyses were also conducted to evaluate the impacts of changes in key variables. All costs were adjusted to 2018 US$ with an annual discount rate of 3% applied to costs and outcomes. The incremental cost-effectiveness ratios (ICERs) for vaccinating US adults aged 19 to 85 with Tdap ranged from $248,000/QALY to $900,000/QALY. The lowest cost per QALY was found to be $248,000 for the age 65 cohort, followed by $332,000 for the cohort of age 19, and followed by $477,000 for the age 50 cohort. Sensitivity analysis showed the most dramatic changes in ICER occurred when changing the underreporting factor, vaccine effectiveness and vaccination costs. While Tdap vaccination may not be as cost effective as predicted earlier, it remains the best available preventive measure against pertussis. Further investigation of the true burden of pertussis disease among adults and the effectiveness of Tdap vaccination in this population is needed to better estimate the impact of Tdap vaccination.

Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouelessebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

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.

From September 2015 to March 2018, CDC confirmed four cases of cutaneous diphtheria caused by toxin-producing Corynebacterium diphtheriae in patients from Minnesota (two), Washington (one), and New Mexico (one). All patients had recently returned to the United States after travel to countries where diphtheria is endemic. C. diphtheriae infection was not clinically suspected in any of the patients; treating institutions detected the organism through matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) testing of wound-derived coryneform isolates. MALDI-TOF is a rapid screening platform that uses mass spectrometry to identify bacterial pathogens. State public health laboratories confirmed C. diphtheriae through culture and sent isolates to CDC's Pertussis and Diphtheria Laboratory for biotyping, polymerase chain reaction (PCR) testing, and toxin production testing. All isolates were identified as toxin-producing C. diphtheriae. The recommended public health response for cutaneous diphtheria is similar to that for respiratory diphtheria and includes treating the index patient with antibiotics, identifying close contacts and observing them for development of diphtheria, providing chemoprophylaxis to close contacts, testing patients and close contacts for C. diphtheriae carriage in the nose and throat, and providing diphtheria toxoid-containing vaccine to incompletely immunized patients and close contacts. This report summarizes the patient clinical information and response efforts conducted by the Minnesota, Washington, and New Mexico state health departments and CDC and emphasizes that health care providers should consider cutaneous diphtheria as a diagnosis in travelers with wound infections who have returned from countries with endemic diphtheria.

BACKGROUND: In 2011, Argentina experienced the highest pertussis incidence and mortality rates in the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at >/=20 weeks of gestation. Although recent studies suggest maternal Tdap vaccination is effective at preventing infant disease, no data have come from low or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization. METHODS: We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case-patients identified from September 2012 to March 2016 at six hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case-patient by hospital site and mother's health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 - OR) x 100%. RESULTS: Seventy-one case-patients and 300 controls were included in the analysis. Forty-nine percent of case-patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence intervals: 52.1%-92.2%). We found similar VE whether Tdap was administered during the second or third trimester. CONCLUSIONS: Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.

The Latin American Pertussis Project (LAPP), established in 2009, is a collaboration between the Centers for Disease Control and Prevention, Pan American Health Organization, Sabin Vaccine Institute, and the ministries of health of 6 countries in Latin America. The project goal is to expand understanding of pertussis epidemiology in Latin America to inform strategies for control and prevention. Here we describe LAPP structure and activities. After an initial surveillance evaluation, LAPP activities are tailored to individual country needs. LAPP activities align with Global Health Security Agenda priorities and have focused on expanding laboratory diagnostic capacity, implementing a laboratory quality control and quality assurance program, and providing epidemiologic support to strengthen reporting of pertussis surveillance data. Lessons learned include that ongoing mentoring is key to the successful adoption of new technologies and that sustainability of laboratory diagnostics requires a regional commitment to procure reagents and related supplies.

BACKGROUND: In the United States, the proportion of Bordetella pertussis isolates lacking pertactin, a component of acellular pertussis vaccines, increased from 14% in 2010 to 85% in 2012. The impact on vaccine effectiveness (VE) is unknown. METHODS: We conducted 2 matched case-control evaluations in Vermont to assess VE of the 5-dose diphtheria, tetanus, and acellular pertussis vaccine (DTaP) series among 4- to 10-year-olds, and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) among 11- to 19-year-olds. Cases reported during 2011 to 2013 were included. Three controls were matched to each case by medical home, and additionally by birth year for the Tdap evaluation. Vaccination history was obtained from medical records and parent interviews. Odds ratios (OR) were calculated by using conditional logistic regression; VE was estimated as (1-OR) x 100%. Pertactin status was determined for cases with available isolates. RESULTS: Overall DTaP VE was 84% (95% confidence interval [CI] 58%-94%). VE within 12 months of dose 5 was 90% (95% CI 71%-97%), declining to 68% (95% CI 10%-88%) by 5-7 years post-vaccination. Overall Tdap VE was 70% (95% CI 54%-81%). Within 12 months of Tdap vaccination, VE was 76% (95% CI 60%-85%), declining to 56% (95% CI 16%-77%) by 2-4 years post-vaccination. Of cases with available isolates, >90% were pertactin-deficient. CONCLUSIONS: Our DTaP and Tdap VE estimates remain similar to those found in other settings, despite high prevalence of pertactin deficiency in Vermont, suggesting these vaccines continue to be protective against reported pertussis disease.

BACKGROUND: Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited. METHODS: To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993-2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993-1997) or all acellular vaccines (1998-2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls. RESULTS: Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: -0.03% to 58%). CONCLUSIONS: Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents.