Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease-United States, 2009-2015.

Background: Following Haemophilus influenzae serotype b (Hib) conjugate vaccine introduction in the 1980s, Hib disease in young children dramatically decreased, and epidemiology of invasive H. influenzae changed. Methods: Active surveillance for invasive H. influenzae disease was conducted through Active Bacterial Core surveillance sites. Incidence rates were directly standardized to the age and race distribution of the US population. Results: During 2009-2015, the estimated mean annual incidence of invasive H. influenzae disease was 1.70 cases per 100000 population. Incidence was highest among adults aged ≥65 years (6.30) and children aged <1 year (8.45); many cases in infants aged <1 year occurred during the first month of life in preterm or low-birth-weight infants. Among children aged <5 years (incidence: 2.84), incidence was substantially higher in American Indian and Alaska Natives AI/AN (15.19) than in all other races (2.62). Overall, 14.5% of cases were fatal; case fatality was highest among adults aged ≥65 years (20%). Nontypeable H. influenzae had the highest incidence (1.22) and case fatality (16%), as compared with Hib (0.03; 4%) and non-b encapsulated serotypes (0.45; 11%). Compared with 2002-2008, the estimated incidence of invasive H. influenzae disease increased by 16%, driven by increases in disease caused by serotype a and nontypeable strains. Conclusions: Invasive H. influenzae disease has increased, particularly due to nontypeable strains and serotype a. A considerable burden of invasive H. influenzae disease affects the oldest and youngest age groups, particularly AI/AN children. These data can inform prevention strategies, including vaccine development.

A Population-Based Assessment of the Impact of 7- and 13-Valent Pneumococcal Conjugate Vaccines on Macrolide-Resistant Invasive Pneumococcal Disease: Emergence and Decline of Streptococcus pneumoniae Serotype 19A (CC320) With Dual Macrolide Resistance Mechanisms.

BACKGROUND: Macrolide efflux encoded by mef(E)/mel and ribosomal methylation encoded by erm(B) confer most macrolide resistance in Streptococcus pneumoniae. Introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) in 2000 reduced macrolide-resistant invasive pneumococcal disease (MR-IPD) due to PCV7 serotypes (6B, 9V, 14, 19F, and 23F). METHODS: In this study, the impact of PCV7 and PCV13 on MR-IPD was prospectively assessed. A 20-year study of IPD performed in metropolitan Atlanta, Georgia, using active, population-based surveillance formed the basis for this study. Genetic determinants of macrolide resistance were evaluated using established techniques. RESULTS: During the decade of PCV7 use (2000-2009), MR-IPD decreased rapidly until 2002 and subsequently stabilized until the introduction of PCV13 in 2010 when MR-IPD incidence decreased further from 3.71 to 2.45/100000 population. In 2003, serotype 19A CC320 isolates containing both mef(E)/mel and erm(B) were observed and rapidly expanded in 2005-2009, peaking in 2010 (incidence 1.38/100000 population), accounting for 36.1% of MR-IPD and 11.7% of all IPD isolates. Following PCV13 introduction, dual macrolide-resistant IPD decreased 74.1% (incidence 0.32/100000 in 2013). However, other macrolide-resistant serotypes (eg, 15A and 35B) not currently represented in PCV formulations increased modestly. CONCLUSIONS: The selective pressures of widespread macrolide use and PCV7 and PCV13 introductions on S. pneumoniae were associated with changes in macrolide resistance and the molecular basis over time in our population. Durable surveillance and programs that emphasize the judicious use of antibiotics need to continue to be a focus of public health strategies directed at S. pneumoniae.

Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA.

OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted.

Socioeconomic and racial disparities of pediatric invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine.

BACKGROUND: Racial differences have been well described for invasive pneumococcal disease (IPD), but little information exists on how race interacts with community socioeconomic factors. METHODS: The Active Bacterial Core surveillance/Emerging Infections Program performed active surveillance for IPD in the 20-county Metropolitan Atlanta area. All IPD cases among children younger than 5 years from 2001 to 2009 were geocoded and linked to census tract-level socioeconomic measures from the 2000 US Census. Race- and socioeconomic-specific average annual incidence rates per 100,000 population were calculated. Trends in IPD incidence were determined by χ² tests for trend. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS: IPD incidence among the total population of children increased as percentage of household poverty increased (P = 0.002), as median household income decreased (P < 0.001), as wealth decreased (P = 0.018) and as percentage of individuals with less than a high school education increased (P = 0.023). After stratifying by race, there was no significant linear trend between socioeconomic characteristics and IPD incidence among white children; among black children, however, IPD incidence decreased as socioeconomic conditions worsened. Despite adjusting for sex and socioeconomic factors, the IPD rate remained higher among black children compared with white children (RR = 1.60; 95% CI: 1.39-1.84). Differences in RR of IPD associated with highest poverty and lowest wealth noted in 2001 [RR = 2.71 (95% CI: 2.17-3.39) and 1.80 (95% CI: 1.09-2.96), respectively] declined in 2009 [RR = 1.33 (95% CI: 0.90-1.96) and 0.76 (95% CI: 0.48-1.19), respectively]. CONCLUSIONS: Although socioeconomic disparities in IPD incidence exist among children, the association between socioeconomic characteristics and IPD rates may differ by race and may change over time. Community-level socioeconomic factors did not account for racial differences in IPD incidence.

An assessment of the screening method to evaluate vaccine effectiveness: the case of 7-valent pneumococcal conjugate vaccine in the United States.

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ≥1 dose increased from 38% to 97%. Case-control VE for ≥1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ≥1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs.

Socioeconomic and racial/ethnic disparities in the incidence of bacteremic pneumonia among US adults.

OBJECTIVES: We examined associations between the socioeconomic characteristics of census tracts and racial/ethnic disparities in the incidence of bacteremic community-acquired pneumonia among US adults. METHODS: We analyzed data on 4870 adults aged 18 years or older with community-acquired bacteremic pneumonia identified through active, population-based surveillance in 9 states and geocoded to census tract of residence. We used data from the 2000 US Census to calculate incidence by age, race/ethnicity, and census tract characteristics and Poisson regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: During 2003 to 2004, the average annual incidence of bacteremic pneumonia was 24.2 episodes per 100 000 Black adults versus 10.1 per 100 000 White adults (RR = 2.40; 95% CI = 2.24, 2.57). Incidence among Black residents of census tracts with 20% or more of persons in poverty (most impoverished) was 4.4 times the incidence among White residents of census tracts with less than 5% of persons in poverty (least impoverished). Racial disparities in incidence were reduced but remained significant in models that controlled for age, census tract poverty level, and state. CONCLUSIONS: Adults living in impoverished census tracts are at increased risk of bacteremic pneumonia and should be targeted for prevention efforts.

Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment.

BACKGROUND: The prevalence of macrolide resistance in Streptococcus pneumoniae has risen in recent years after the introduction of new macrolides and their increased use. We assessed emergence of macrolide-resistant invasive S pneumoniae disease in Atlanta, GA, USA, before and after the licensing, in February 2000, of the heptavalent pneumococcal conjugate vaccine for young children. METHODS: Prospective population-based surveillance was used to obtain pneumococcal isolates and demographic data from patients with invasive pneumococcal disease. We calculated cumulative incidence rates for invasive pneumococcal disease for 1994-2002 using population estimates and census data from the US Census Bureau. FINDINGS: The incidence of invasive pneumococcal disease in Atlanta fell from 30.2 per 100,000 population (mean annual incidence 1994-99) to 13.1 per 100,000 in 2002 (p<0.0001). Striking reductions were seen in children younger than 2 years (82% decrease) and in those 2-4 years (71% decrease), age-groups targeted to receive pneumococcal conjugate vaccine. Significant declines were also noted in adults aged 20-39 (54%), 40-64 (25%), and 65 years and older (39%). Macrolide resistance in invasive S pneumoniae disease in Atlanta, after increasing steadily from 4.5 per 100,000 in 1994 to 9.3 per 100,000 in 1999, fell to 2.9 per 100,000 by 2002. Reductions in disease caused by mefE-mediated and erm-mediated macrolide-resistant isolates of conjugate-vaccine serotypes 6B, 9V, 19F, and 23F, and the vaccine-associated serotype 6A were also recorded. INTERPRETATION: Vaccines can be a powerful strategy for reducing antibiotic resistance in a community.

FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States.

To determine the burden of Salmonella infections in the United States, Foodborne Diseases Active Surveillance Network (FoodNet) investigators conducted population-based active surveillance for culture-confirmed Salmonella infections during 1996-1999 at FoodNet laboratories. In addition, all clinical microbiology FoodNet laboratories were surveyed to determine their practices for isolating Salmonella. Telephone interviews were also conducted among residents of the FoodNet sites to determine the proportion of persons with diarrheal illness who sought medical care and the proportion who submitted stool specimens for bacterial culture. Using our model, we estimated that there were 1.4 million nontyphoidal Salmonella infections in the United States, resulting in 168,000 physician office visits per year during 1996-1999. Including both culture-confirmed infections and those not confirmed by culture, we estimated that Salmonella infections resulted in 15,000 hospitalizations and 400 deaths annually. These estimates indicate that salmonellosis presents a major ongoing burden to public health.

Hospitalizations and deaths due to Salmonella infections, FoodNet, 1996-1999.

Nontyphoidal Salmonella causes a higher proportion of food-related deaths annually than any other bacterial pathogen in the United States. We reviewed 4 years (1996-1999) of population-based active surveillance data on laboratory-confirmed Salmonella infections from the Emerging Infections Program's Foodborne Diseases Active Surveillance Network (FoodNet), to determine the rates of hospitalization and death associated with Salmonella infection. Overall, 22% of infected persons were hospitalized, with the highest rate (47%) among persons aged >60 years. Fifty-eight deaths occurred, for an estimated annual incidence of 0.08 deaths/100,000 population. These deaths accounted for 38% of all deaths reported through FoodNet from 1996 through 1999, and they occurred primarily among adults with serious underlying disease. Although Salmonella infection was seldom listed as a cause of death on hospital charts and death certificates, our chart review suggests that Salmonella infection contributed to these deaths.

Recurrent invasive pneumococcal disease: a population-based assessment.

We sought to define the risk of recurrence of invasive pneumococcal disease (IPD) and to define the characteristics of persons experiencing recurrent IPD through population-based surveillance. Cases of IPD were identified through the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Recurrent episodes were defined as isolation of Streptococcus pneumoniae from any normally sterile site > or =30 days after initial positive culture. Among 13,924 persons who survived their initial episode of IPD, 318 (2.3%) experienced > or =1 subsequent episode, for 376 total recurrences. The recurrence rate was 1294 episodes per 100,000 person-years, or 50 times the annual incidence of IPD. In multivariable analysis, a higher risk of recurrence was seen in persons infected with human immunodeficiency virus and in children <5 years old with chronic illness. Most (92%) persons with recurrence had a vaccine indication. The risk of recurrence among certain persons with IPD is extremely high.

Association between antimicrobial resistance among pneumococcal isolates and burden of invasive pneumococcal disease in the community.

Treatment of infections with drug-resistant strains of Streptococcus pneumoniae (pneumococcus) may fail; whether drug resistance is associated with an increase in the number of serious infections in the community is unknown. We evaluated the relationship between the proportion of antimicrobial-resistant S. pneumoniae isolates and the number of cases of invasive pneumococcal disease. Linear regression models included 1996 county-level data from 38 counties participating in the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Separate models evaluated hospitalized children aged <5 years, nonhospitalized children aged <5 years, adults aged 18-64 years, and adults aged >64 years. The proportion of isolates resistant to > or =3 drug classes was associated with invasive disease in both hospitalized (P=.06) and nonhospitalized (P=.001) children. The proportion of multidrug-resistant pneumococcal isolates did not predict invasive cases among adults. The increasing prevalence of multidrug-resistant pneumococci among children may be leading to an increase in invasive disease.