Amanda C. Cohn

Changes in Neisseria meningitidis Disease Epidemiology in the United States, 1998–2007: Implications for Prevention of Meningococcal Disease

BACKGROUND In January 2005, a quadrivalent (serogroups A, C , Y, and W-135) meningococcal conjugate vaccine was licensed for use in adolescents. This report describes the epidemiologic features of meningococcal disease in the United States from January 1998 through December 2007, before and during implementation of adolescent quadrivalent meningococcal conjugate vaccination. METHODS Data were collected from active surveillance for invasive Neisseria meningitidis conducted through the Active Bacterial Core surveillance (ABCs) sites during 1998-2007. Isolates from cases were serogrouped at the ABCs site and confirmed at the Centers for Disease Control and Prevention. Estimates of the incidence and number of cases in the 50 states were calculated, standardizing for race and age group. RESULTS In the period 1998-2007, a total of 2262 cases of meningococcal disease were reported from ABCs sites; 11.3% of these cases were fatal. The estimated United States average annual incidence of meningococcal disease was 0.53 cases per 100,000 population (95% confidence interval, 0.51-0.55), and an estimated 1525 (95% confidence interval, 1470-1598) cases occurred annually. The annual incidence decreased 64.1%, from 0.92 cases per 100,000 population in 1998 to 0.33 cases per 100,000 population in 2007. Infants aged <1 year have the highest incidence of meningococcal disease (5.38 cases per 100,000 population). After introduction of the quadrivalent meningococcal conjugate vaccine, no significant decrease in serogroup C or Y meningococcal disease was seen among those aged 11-19 years in 2006-2007, compared with 2004-2005. CONCLUSIONS Before the introduction of the quadrivalent meningococcal conjugate vaccine, the incidence of meningococcal disease in the United States decreased to a historic low. However, meningococcal disease still causes a substantial burden of disease among all age groups. Future vaccination strategies may include targeting infants and preventing serogroup B meningococcal disease.

Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America.

We report on three cases of meningococcal disease caused by ciprofloxacin-resistant Neisseria meningitidis, one in North Dakota and two in Minnesota. The cases were caused by the same serogroup B strain. To assess local carriage of resistant N. meningitidis, we conducted a pharyngeal-carriage survey and isolated the resistant strain from one asymptomatic carrier. Sequencing of the gene encoding subunit A of DNA gyrase (gyrA) revealed a mutation associated with fluoroquinolone resistance and suggests that the resistance was acquired by means of horizontal gene transfer with the commensal N. lactamica. In susceptibility testing of invasive N. meningitidis isolates from the Active Bacterial Core surveillance system between January 2007 and January 2008, an additional ciprofloxacin-resistant isolate was found, in this case from California. Ciprofloxacin-resistant N. meningitidis has emerged in North America.

Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease—United States, 1989–2008

BACKGROUND With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. METHODS Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. RESULTS During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. CONCLUSIONS Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States.

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure — United States, 2016

CDC has updated its interim guidance for U.S. health care providers caring for women of reproductive age with possible Zika virus exposure to include recommendations on counseling women and men with possible Zika virus exposure who are interested in conceiving. This guidance is based on limited available data on persistence of Zika virus RNA in blood and semen. Women who have Zika virus disease should wait at least 8 weeks after symptom onset to attempt conception, and men with Zika virus disease should wait at least 6 months after symptom onset to attempt conception. Women and men with possible exposure to Zika virus but without clinical illness consistent with Zika virus disease should wait at least 8 weeks after exposure to attempt conception. Possible exposure to Zika virus is defined as travel to or residence in an area of active Zika virus transmission ( http://www.cdc.gov/zika/geo/active-countries.html), or sex (vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who traveled to or resided in an area of active transmission. Women and men who reside in areas of active Zika virus transmission should talk with their health care provider about attempting conception. This guidance also provides updated recommendations on testing of pregnant women with possible Zika virus exposure. These recommendations will be updated when additional data become available.

Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States

Neisseria meningitidis (Nm) serogroups B, C and Y are the major causes of meningococcal diseases in the United States. NmB accounts for ∼1/3 of the disease but no licensed vaccine is yet available. Two candidate vaccines are being developed specifically to target NmB, but may also provide protection against other serogroups. To assess the potential impact of these vaccines on NmB and other serogroups causing disease in the US, we determined the prevalence, genetic diversity and epidemiological characteristics of three candidate antigen genes in Nm isolates collected through Active Bacterial Core surveillance (ABCs), a population-based active surveillance program. fHbp was detected in all NmB, NmY and NmW135 isolates. Eleven NmC isolates contain fHbp with a single base-pair deletion creating a frame shift in the C-terminal region. Among NmB, 59% were FHbp subfamily/variant B/v1 and 41% A/v2-3. Among NmC and NmY, 39% and 3% were B/v1, respectively. nadA was detected in 39% of NmB, 61% of NmC and 4% of NmY. Among isolates tested, nhbA was present in all NmB and 96% of non-B. For the subset of strains sequenced for NadA and NhbA, pairwise identity was greater than 93% and 78%, respectively. The proportion of FHbp subfamily/variant was different between ABCs site and year, but no linear temporal trend was observed. Although assessment of the vaccine coverage also requires understanding of the antigen expression and the ability to induce bactericidal activity, our finding that all isolates contain one or more antigen genes suggests these candidate vaccines may protect against multiple Nm serogroups.

Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae.

Since the implementation of Haemophilus influenzae (Hi) serotype b vaccine, other serotypes and non-typeable strains have taken on greater importance as a cause of Hi diseases. A rapid and accurate method is needed to detect all Hi regardless of the encapsulation status. We developed 2 real-time PCR (rt-PCR) assays to detect specific regions of the protein D gene (hpd). Both hpd assays are very specific and sensitive for detection of Hi. Of the 63 non-Hi isolates representing 21 bacterial species, none was detected by the hpd #1 assay, and only one of 2 H. aphrophilus isolates was detected by the hpd #3 assay. The hpd #1 and #3 assays detected 97% (229/237) and 99% (234/237) of Hi isolates, respectively, and were superior for detection of both typeable and non-typeable Hi isolates, as compared to previously developed rt-PCR targeting ompP2 or bexA. The diagnostic sensitivity and specificity of these rt-PCR assays were assessed on cerebrospinal fluid specimens collected as part of meningitis surveillance in Ulaanbaatar, Mongolia. The etiology (Neisseria meningitidis, Hi, and Streptococcus pneumoniae) of 111 suspected meningitis cases was determined by conventional methods (culture and latex agglutination), previously developed rt-PCR assays, and the new hpd assays. The rt-PCR assays were more sensitive for detection of meningitis pathogens than other classical methods and improved detection from 50% (56/111) to 75% (83/111). The hpd #3 assay identified a non-b Hi that was missed by the bexA assay and other methods. A sensitive rt-PCR assay to detect both typeable and non-typeable Hi is a useful tool for improving Hi disease surveillance especially after Hib vaccine introduction.

Early Impact of the US Tdap Vaccination Program on Pertussis Trends

OBJECTIVE To evaluate the impact of the adolescent Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine) vaccination program on pertussis trends in the United States. DESIGN Retrospective analysis of nationally reported pertussis cases, January 1, 1990, through December 31, 2009. SETTING United States. PARTICIPANTS Confirmed and probable pertussis cases. Intervention The US Tdap vaccination program. MAIN OUTCOME MEASURE Rate ratios of reported pertussis incidence (defined as incidence among 11- to 18-year-olds divided by the combined incidence in all other age groups) modeled through segmented regression analysis and age-specific trends in reported pertussis incidence over time. RESULTS A total of 200 401 pertussis cases were reported in the United States from 1990 to 2009. Overall incidence ranged from 1.0 to 8.8 per 100,000 persons (1991 and 2004, respectively). Slope coefficients (estimated annual rate of change in rate ratios) from segmented regression showed a steady increase in pertussis incidence among adolescents 11 to 18 years old compared with all other age groups before Tdap introduction (slope = 0.22; P < .001), and a steep decreasing trend post introduction (slope = -0.48; P < .001), suggesting a direct impact of vaccination among adolescents. Indirect effects of adolescent vaccination were not observed among infants younger than 1 year. CONCLUSIONS Changes in pertussis incidence in the United States from 2005 to 2009 revealed a divergence between 11- to 18-year-olds and other age groups, suggesting that targeted use of Tdap among adolescents reduced disease preferentially in this age group. Increased Tdap coverage in adolescents and adults is needed to realize the full direct and indirect benefits of vaccination.

Adolescent Immunizations and Other Clinical Preventive Services: A Needle and a Hook?

Advances in technology have led to development of new vaccines for adolescents, but these vaccines will be added to a crowded schedule of recommended adolescent clinical preventive services. We reviewed adolescent clinical preventive health care guidelines and patterns of adolescent clinical preventive service delivery and assessed how new adolescent vaccines might affect health care visits and the delivery of other clinical preventive services. Our analysis suggests that new adolescent immunization recommendations are likely to improve adolescent health, both as a “needle” and a “hook.” As a needle, the immunization will enhance an adolescents health by preventing vaccine-preventable diseases during adolescence and adulthood. It also will likely be a hook to bring adolescents (and their parents) into the clinic for adolescent health care visits, during which other clinical preventive services can be provided. We also speculate that new adolescent immunization recommendations might increase the proportion and quality of other clinical preventive services delivered during health care visits. The factor most likely to diminish the positive influence of immunizations on delivery of other clinical preventive services is the additional visit time required for vaccine counseling and administration. Immunizations may “crowd out” delivery of other clinical preventive services during visits or reduce the quality of the clinical preventive service delivery. Complementary strategies to mitigate these effects might include prioritizing clinical preventive services with a strong evidence base for effectiveness, spreading clinical preventive services out over several visits, and withholding selected clinical preventive services during a visit if the prevention activity is effectively covered at the community level. Studies are needed to evaluate the effect of new immunizations on adolescent preventive health care visits, delivery of clinical preventive services, and health outcomes.

First Use of a Serogroup B Meningococcal Vaccine in the US in Response to a University Outbreak

BACKGROUND: In 2013–2014, an outbreak of serogroup B meningococcal disease occurred among persons linked to a New Jersey university (University A). In the absence of a licensed serogroup B meningococcal (MenB) vaccine in the United States, the Food and Drug Administration authorized use of an investigational MenB vaccine to control the outbreak. An investigation of the outbreak and response was undertaken to determine the population at risk and assess vaccination coverage. METHODS: The epidemiologic investigation relied on compilation and review of case and population data, laboratory typing of meningococcal isolates, and unstructured interviews with university staff. Vaccination coverage data were collected during the vaccination campaign held under an expanded-access Investigational New Drug protocol. RESULTS: Between March 25, 2013, and March 10, 2014, 9 cases of serogroup B meningococcal disease occurred in persons linked to University A. Laboratory typing results were identical for all 8 isolates available. Through May 14, 2014, 89.1% coverage with the 2-dose vaccination series was achieved in the target population. From the initiation of MenB vaccination through February 1, 2015, no additional cases of serogroup B meningococcal disease occurred in University A students. However, the ninth case occurred in March 2014 in an unvaccinated close contact of University A students. CONCLUSIONS: No serogroup B meningococcal disease cases occurred in persons who received 1 or more doses of 4CMenB vaccine, suggesting 4CMenB may have protected vaccinated individuals from disease. However, the ninth case demonstrates that carriage of serogroup B Neisseria meningitidis among vaccinated persons was not eliminated.

Adolescent Vaccination-Coverage Levels in the United States: 2006–2009

BACKGROUND: From 2005 through 2007, 3 vaccines were added to the adolescent vaccination schedule: tetanus-diphtheria-acellular pertussis (TdaP); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) for girls. OBJECTIVE: To assess implementation of new adolescent vaccination recommendations. METHODS: Data from the 2006–2009 National Immunization Survey–Teen, an annual provider-verified random-digit-dial survey of vaccination coverage in US adolescents aged 13 to 17 years, were analyzed. Main outcome measures included percentage of adolescents who received each vaccine according to survey year; potential coverage if all vaccines were administered during the same vaccination visit; and, among unvaccinated adolescents, the reasons for not receiving vaccine. RESULTS: Between 2006 and 2009, ≥1 TdaP and ≥1 MenACWY coverage increased from 11% to 56% and 12% to 54%, respectively. Between 2007 and 2009, ≥1 HPV coverage among girls increased from 25% to 44%; between 2008 and 2009, ≥3 HPV coverage increased from 18% to 27%. In 2009, vaccination coverage could have been >80% for Td/TdaP and MenACWY and as high as 74% for the first HPV dose if providers had administered all recommended vaccines during the same vaccination visit. For all years, the top reported reasons for not vaccinating were no knowledge about the vaccine, provider did not recommend, and vaccine is not needed/necessary (for TdaP and MenACWY) and adolescent is not sexually active, no knowledge about the vaccine, and vaccine is not needed/necessary (for HPV). CONCLUSIONS: Adolescent vaccination coverage is increasing but could be improved. Strategies are needed to increase parental knowledge about adolescent vaccines and improve provider recommendation and administration of all vaccines during the same visit.