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Background Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States (US). We evaluated the epidemiology of invasive NTHi disease in the US, including among pregnant women, infants, and people with human immunodeficiency virus (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 US 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 nonpregnant women. More than half of pregnant women with invasive NTHi had loss of pregnancy postinfection. Incidence among PWH aged ≥13 years was 9.5 cases per 100 000, compared to 1.1 cases per 100 000 for non-PWH (rate ratio, 8.3 [95% confidence interval, 7.1–9.7]; P <.0001). Conclusions 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. [ABSTRACT FROM AUTHOR]

Introduction: Since 2009, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has been assessing in vitro antibiotic resistance for bacterial isolates sourced from ocular infections in the US. The main goal of this systematic review was to compare in vitro resistance data for ocular pathogens from published US studies with the most recently published data from the ARMOR study (2009–2018) and, where possible, to evaluate trends in bacterial resistance over time over all studies. Methods: A literature search was conducted using MEDLINE®, BIOSIS Previews®, and EMBASE® databases (1/1/1995–6/30/2021). Data were extracted from relevant studies and antibiotic susceptibility rates for common ocular pathogens (Staphylococcus aureus, coagulase-negative staphylococci [CoNS], Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae), longitudinal changes in susceptibility, and multidrug resistance (MDR) were compared descriptively. Results: Thirty-two relevant studies were identified. High in vitro resistance was found among S. aureus and CoNS to fluoroquinolones, macrolides, and methicillin/oxacillin across studies, with high rates of MDR noted, specifically among methicillin-resistant staphylococci. Data from studies pre-dating or overlapping the early years of ARMOR reflected increasing rates of S. aureus resistance to fluoroquinolones, macrolides, methicillin/oxacillin, and aminoglycosides, while the ARMOR data suggested slight decreases in resistance to these classes between 2009 and 2018. Overall, methicillin-resistant S. aureus (MRSA) prevalence peaked from 2005 to 2015 with a possible decreasing trend in more recent years. Discussion and Conclusions: Data from local and regional US datasets were generally consistent with data from the national ARMOR surveillance study. Continued surveillance of ocular bacterial pathogens is needed to track trends such as methicillin resistance and MDR prevalence and any new emerging antibiotic resistance phenotypes. Susceptibility data from ARMOR can inform initial choice of therapy, especially in practice areas where local antibiograms are unavailable. [ABSTRACT FROM AUTHOR]

Background Incidence of invasive disease due to Haemophilus influenzae serotype a (Hia) increased an average of 13% annually from 2002 through 2015. We describe clinical characteristics and adverse clinical outcomes of US invasive Hia cases detected through multistate surveillance during 2011–2015. Methods Medical record data were abstracted for cases reported in 8 jurisdictions conducting active population- and laboratory-based surveillance for invasive Hia disease across the United States. Isolates from sterile sites were serotyped using real-time polymerase chain reaction. Adverse clinical outcomes were defined as any possible complication of meningitis, bacteremic pneumonia, or bacteremia (including hearing loss and developmental delay, but excluding death) and were assessed at hospital discharge and one-year post-disease onset. Results During 2011–2015, 190 Hia cases were reported to the 8 participating sites; 169 (88.9%) had data abstracted. Many patients were aged <5 years (42.6%). Meningitis was the most common clinical presentation among those aged <1 year (71.4%); bacteremic pneumonia was the most common presentation among persons aged ≥50 years (78.7%). Overall, 95.9% of patients were hospitalized. Among those hospitalized, 47.5% were admitted to an intensive care unit and 6.2% died during hospitalization. At hospital discharge and one-year post-disease onset, adverse outcomes were identified in 17.7% and 17.8% of patients overall and in 43.9% and 48.5% of patients with meningitis (primarily children). Conclusions Hia infection can cause severe disease that requires hospitalization and may also cause short- and long-term adverse clinical outcomes, especially among children. Novel vaccines could prevent morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background Since the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease epidemiology has changed, and racial disparities have not been recently described. Methods Active population- and laboratory-based surveillance for H. influenzae was conducted through Active Bacterial Core surveillance at 10 US sites. Data from 2008–2017 were used to estimate projected nationwide annual incidence, as cases per 100 000. Results During 2008–2017, Active Bacterial Core surveillance identified 7379 H. influenzae cases. Of 6705 patients (90.9%) with reported race, 76.2% were White, 18.6% were Black, 2.8% were Asian/Pacific Islander, and 2.4% were American Indian or Alaska Native (AI/AN). The nationwide annual incidence was 1.8 cases/100 000. By race, incidence was highest among AI/AN populations (3.1) and lowest among Asian/Pacific Islander populations (0.8). Nontypeable H. influenzae caused the largest incidence within all races (1.3), with no striking disparities identified. Among AI/AN children aged <5 years, incidence of H. influenzae serotype a (Hia) was 16.7 times higher and Hib incidence was 22.4 times higher than among White children. Although Hia incidence was lower among White and Black populations than among AI/AN populations, Hia incidence increased 13.6% annually among White children and 40.4% annually among Black children aged <5 years. Conclusions While nontypeable H. influenzae causes the largest H. influenzae burden overall, AI/AN populations experience disproportionately high rates of Hia and Hib, with the greatest disparity among AI/AN children aged <5 years. Prevention tools are needed to reduce disparities affecting AI/AN children and address increasing Hia incidence in other communities. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae serotype b (Hib) is an important cause of serious, invasive infections, particularly in young children. Since 1985, a series of vaccines composed of the type b capsular polysaccharide polyribosylribitol phosphate (PRP), followed by PRP conjugated to various proteins, have been licensed for use in the United States and worldwide. The conjugated vaccines offer increased immunogenicity and prolonged durability of immune protection compared to the plain PRP vaccine and increasingly are combined with other childhood vaccines for decreased cost and increased ease of vaccination. Hib vaccines have a very favorable safety profile, have been found to be either cost-saving or cost-effective by many public health agencies, and, in most countries, are initiated during early infancy as part of routine childhood immunization programs. As a result of widespread use of the vaccines, the incidence of Hib infections, and their associated morbidity and mortality, has fallen dramatically across the globe. Yet, many children remain unimmunized or underimmunized against Hib, particularly in limited-resource countries. Future efforts to further reduce the disease burden of Hib infections remain a high priority. [ABSTRACT FROM AUTHOR]

Background Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008–2017. Methods Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. Results From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. Conclusions Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development. [ABSTRACT FROM AUTHOR]

Myopericarditis after vaccination has been sporadically reported in the medical literature. Here, we present a thorough descriptive analysis of reports to a national passive vaccine safety surveillance system (VAERS) of myopericarditis after vaccines licensed for use in the United States. We identified U.S. reports of myopericarditis received by VAERS during 1990–2018 that met a published case definition for myopericarditis or were physician-diagnosed. We stratified analysis by age group (<19, 19–49, ≥50 years), describing reports by serious/non-serious status, sex, time to symptom onset after vaccination, vaccine(s) administered, and exposure to other known causes of myopericarditis. We used Empirical Bayesian data mining to detect disproportionate reporting of myopericarditis after vaccination. VAERS received 620,195 reports during 1990–2018: 708 (0.1%) met the case definition or were physician-diagnosed as myopericarditis. Most (79%) myopericarditis reports described males; 69% were serious; 72% had symptom onset ≤ 2 weeks postvaccination. Overall, smallpox (59%) and anthrax (23%) vaccines were most commonly reported. By age, among persons aged < 19 years, Haemophilus influenzae type b (22, 22%) and hepatitis B (18, 18%); among persons aged 19–49 years smallpox (387, 79%); among persons aged ≥ 50 years inactivated influenza (31, 36%) and live attenuated zoster (19, 22%) vaccines were most commonly reported. The vaccines most commonly reported remained unchanged when excluding 138 reports describing other known causes of myopericarditis. Data mining revealed disproportionate reporting of myopericarditis only after smallpox vaccine. Despite the introduction of new vaccines over the years, myopericarditis remains rarely reported after vaccines licensed for use in the United States. In this analysis, myopericarditis was most commonly reported after smallpox vaccine, and less commonly after other vaccines. [ABSTRACT FROM AUTHOR]

An editorial is presented on the Invasive Haemophilus influenzae Serotype a Disease in the H. influenzae Serotype b Conjugate Vaccine Era. The article discusses that Encapsulated strains of the gram-negative pathogen Haemophilus influenzae are categorized into 6 serotypes on the basis of antigenically distinct polysaccharide capsules; and it is also important to consider that Indigenous populations experience environmental factors.

Introduction A common practice in the management of patients with chronic rhinosinusitis (CRS), the empirical use of antibiotics may contribute to treatment failure and to the development of antimicrobial resistance. Objective To determine the antibiotic sensitivity pattern of aerobic and anaerobic bacteria associated with CRS. Methods This was a prospective cross-sectional study in which endoscopically guided middle meatal swabs (IBM Spss, version 16.0, Chicago, IL, USA) were aseptically taken from patients diagnosed with CRS after obtaining informed consent and ethical clearance. The samples were sent to the laboratory for qualitative and semiquantitative analysis via gram stain, aerobic, anaerobic cultures and antibacterial sensitivity tests. The collected data was analyzed using SPSS for Windows, version 16 (SPSS Inc, Chicago, IL, USA). Simple statistical parameters and paired sample t-test were used, as appropriate. Results There were 74 (56.92%) bacterial growths, out of which 55 (74.32%) were aerobic and 19 (25.68%) were anaerobic isolates, from a total of 130 patients. About 13 (17.5%–18%) of these bacterial growths yielded a mixed growth of aerobic and anaerobic isolates. The most common bacterial isolates were 26 (35.14%) Staphylococcus aureus, Haemophilus influenzae 9 (12.16%), Streptococcus viridians 8 (10.81%), and Streptococcus pneumoniae 5 (6.76%). Augmentin, ciprofloxacin, and Peflacine were found to be most effective, followed by levofloxacin, Rocephin, erythromycin and Zinat in that order. Conclusion Augmentin, ciprofloxacin and Peflacine have a sensitivity of 100%, while most of the organisms show resistance to Ampiclox, amoxicillin, and Septrin. [ABSTRACT FROM AUTHOR]

The article reports on the 2019 recommended childhood and adolescent immunization schedules approved by the American Academy of Pediatrics, the Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists. Topics include purpose of revising the schedules, recommended immunization schedule from birth through 18 years old, and changes to individual footnotes.

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. [ABSTRACT FROM AUTHOR]

Investigators postulated that early-life exposure to organic mercury (Hg) significantly increases the risk of childhood neurodevelopmental disorders (NDs). The Vaccine Adverse Event Reporting System database was utilized to conduct a hypothesis testing case-control study by evaluating 3486 total adverse event reports reported following Haemophilus influenza type b (Hib) vaccination. Exposed subjects received a Thimerosal-containing formulation (HIBTITER™, Wyeth-Lederle), while unexposed subjects received a Thimerosal-free formulation (PEDVAXHIB™, Merck). Subjects were included if they received either of these two Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse event reports with a reported outcome of autism, developmental delay, psychomotor delay, or NDs in general. Cases with reported outcomes of febrile convulsions, pyrexia, or injection site pain, all of which have no biologically plausible relation to Hg exposure, were also examined. Controls were defined as adverse event reports without any mention of the specific case outcome examined. Cases of reported autism (odds ratio (OR) = 2.75, p < 0.02), developmental delay (OR = 5.39, p < 0.01), psychomotor disorder (OR = 2.38, p < 0.03), and neurodevelopmental disorder in general (OR = 2.70, p < 0.001) were each significantly more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. Significant effects for neurodevelopmental disorder in general were observed for males (OR = 2.52, p < 0.005), but not females when separated by gender. For the outcomes that had no biologically plausible relation to Hg exposure, the cases were no more likely than their respective controls to receive Thimerosal-containing Hib vaccine than Thimerosal-free Hib vaccine. This study provides suggestive evidence of an association between Thimerosal and neurodevelopmental outcomes and provides support for carrying out additional well-designed studies examining the association between Thimerosal-containing vaccines and a wide range of neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35 months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed. [ABSTRACT FROM AUTHOR]

Background: Seasonal variations are often observed for respiratory tract infections; however, limited information is available regarding seasonal patterns of acquisition of common cystic fibrosis (CF)-related respiratory pathogens. We previously reported differential seasonal acquisition of Pseudomonas aeruginosa in young children with CF and no such variation for methicillin-susceptible Staphylococcus aureus acquisition. The purpose of this study was to describe and compare the seasonal incidence of acquisition of other respiratory bacterial pathogens in young children with CF.Methods: We conducted a retrospective study to describe and compare the seasonal incidence of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Haemophilus influenzae acquisition in young CF patients residing in the U.S. using the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. Log-linear overdispersed Poisson regression was used to evaluate seasonal acquisition of each of these pathogens.Results: A total of 4552 children met inclusion criteria. During follow-up 910 (20%), 1161 (26%), 228 (5%), and 2148 (47%) children acquired MRSA, S. maltophilia, A. xylosoxidans and H. influenzae, respectively. Compared to winter season, MRSA was less frequently acquired in spring (Incidence Rate Ratio [IRR]: 0.79; 95% Confidence Interval [CI]: 0.65, 0.96) and summer (IRR: 0.69; 95% CI: 0.57, 0.84) seasons. Similarly, a lower rate of A. xylosoxidans acquisition was observed in spring (IRR: 0.59; 95% CI: 0.39, 0.89). For H. influenzae, summer (IRR: 0.88; 95% CI: 0.78, 0.99) and autumn (IRR: 0.78; 95% CI: 0.69, 0.88) seasons were associated with lower acquisition rates compared to winter. No seasonal variation was observed for S. maltophilia acquisition.Conclusion: Acquisition of CF-related respiratory pathogens displays seasonal variation in young children with CF, with the highest rate of acquisition for most pathogens occurring in the winter. Investigation of factors underlying these observed associations may contribute to our understanding of the aetiology of these infections and guide future infection control strategies. [ABSTRACT FROM AUTHOR]

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Lee H. Harrison reports reimbursement for travel to attend meetings from Merck and Pfizer, and participation on a Merck data safety monitoring board. Ruth Lynfield reports receiving payment for work as an associate editor for the American Academy of Pediatrics’ (AAP) Red Book, which was donated to the Minnesota Department of Health, support from the Council of State and Territorial Epidemiologists for travel to meetings as president and vice president, travel support to ID Week by the Infectious Diseases Society of America, and support from AAP for travel to a committee meeting on infectious diseases, in her role as associate editor. No other potential conflicts of interest were disclosed.

Background: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the coronavirus disease 2019 (COVID-19) pandemic in the United States are limited., Methods: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as 1 March to 31 December 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014 to February 2020 trends. We conducted secondary analysis of a health care database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic., Results: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated nonpharmaceutical interventions (NPIs). Significant declines were observed across all age and race groups, and surveillance sites for S. pneumoniae and H. influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years., Conclusions: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing., Competing Interests: Presented in part: 12th International Symposium on Pneumococci and Pneumococcal Diseases, Toronto, Canada, 19-23 June., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

The article discusses initiatives by U.S. government agencies to consider the role of vaccines in preventing and responding to the spread of antibiotic resistance. Topics covered include vaccines' role in antibiotic stewardship, highlights of the September 2014 President's National Strategy to Combat Antibiotic-Resistant Bacteria, and the uses of vaccines such as the Haemophilus influenzae type b (Hib) conjugate vaccines, pneumococcal conjugate vaccines, and influenza vaccines.

Purpose Haemophilus influenzae type b bacteria has been responsible for recent increase in invasive disease in the adult population of the United States. This increase in H. influenzae infections is greatest in individuals above 65 years of age. A plausible explanation for this increase may be the changes observed in the epidemiology of invasive H. influenzae type b (Hib) disease and the susceptibility of aggregate hosts. Data sources A comprehensive literature review was conducted from multiple data sources, such as PubMed, MEDLINE, CDC, journal articles, reference texts, and Internet websites. Conclusions The increase in infectious disease caused by H. influenzae type b bacteria is affecting individuals 65 years and older and is preventable. However, Hib vaccines are currently approved for the pediatric population and susceptible adults with certain immune deficiencies. New trends in this invasive disease require reevaluation of current guidelines to include individuals 65 years and older as target population for the polysaccharide Hib vaccine. Implications for practice The changing epidemiology of H. influenzae type b bacteria requires reevaluation of current immunization guidelines regarding Hib vaccination so that it is included in the immunization schedule for adults aged 65 and above. [ABSTRACT FROM AUTHOR]

BACKGROUND: Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States. METHODS: Data sources included PubMed, Advisory Committee on Immunization Practices statements, package inserts, existing reviews, manufacturer information packets, and the 2011 Institute of Medicine consensus report on vaccine safety. We augmented the Institute of Medicine report with more recent studies and increased the scope to include more vaccines. Only studies that used active surveillance and had a control mechanism were included. Formulations not used in the United States were excluded. Adverse events and patient and vaccine characteristics were abstracted. Adverse event collection and reporting was evaluated by using the McHarm scale. We were unable to pool results. Strength of evidence was rated as high, moderate, low, or insufficient. RESULTS: Of 20 478 titles identified, 67 were included. Strength of evidence was high for measles/mumps/rubella (MMR) vaccine and febrile seizures; the varicella vaccine was associated with complications in immunodeficient individuals. There is strong evidence that MMR vaccine is not associated with autism. There is moderate evidence that rotavirus vaccines are associated with intussusception. Limitations of the study include that the majority of studies did not investigate or identify risk factors for AEs; and the severity of AEs was inconsistently reported. CONCLUSIONS: We found evidence that some vaccines are associated with serious AEs; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide. [ABSTRACT FROM AUTHOR]

We explored market factors that affect pediatric combination vaccine uptake in the US public-sector pediatric vaccine market. We specifically examined how Pediarix and Pentacel earned a place in the 2009-2012 lowest overall cost formulary. Direct competition between Pediarix and Pentacel is driven by the indirect presence of the Merck Haemophilus influenzae type b vaccine and the Recommended Childhood Immunization Schedule requirement for a hepatitis B birth dose. The resulting analysis suggests that Pentacel would never have earned a place in the lowest overall cost formulary for 2009-2012 federal contract prices for any cost of an injection unless the Merck H influenzae type b advantage was ignored and the hepatitis B birth dose administration cost was recognized by health care providers in designing the lowest overall cost formularies. [ABSTRACT FROM AUTHOR]

Objectives. We assessed how nonmedical exemption (NME) laws and annual uptake of vaccines required for school or daycare entry affect annual incidence rates for 5 vaccine-targeted diseases: pertussis, measles, mumps, Haemophilus influenzae type B, and hepatitis B. Methods. We employed longitudinal mixed-effects models to examine 2001- 2008 vaccine-targeted disease data obtained from the National Notifiable Disease Surveillance System. Key explanatory variables were state-level vaccine-specific uptake rates from the National Immunization Survey and a state NME law restrictiveness level. Results. NME law restrictiveness and vaccine uptake were not associated with disease incidence rate for hepatitis B, Haemophilus influenzae type B, measles, or mumps. Pertussis incidence rate, however, was negatively associated with NME law restrictiveness (b = -0.20; P = .03) and diphtheria-pertussis-tetanus vaccine uptake (b = -0.01; P = .05). Conclusions. State NME laws and vaccine uptake rates did not appear to influence lower-incidence diseases but may influence reported disease rates for higher-incidence diseases. If all states increased their NME law restrictiveness by 1 level and diphtheria-pertussis-tetanus uptake by 1%, national annual pertussis cases could decrease by 1.14% (171 cases) and 0.04% (5 cases), respectively. [ABSTRACT FROM AUTHOR]

The article reports on the reduction of the alarming mortality of bacterial meningitis in adults in the U.S. It states that several healthcare providers promotes cost-effective and noninvasive methods in treating bacterial meningitis. It offers several signs of having a bacterial meningitis which include neck mobility, Brudzinski sign and Kernig sign. INSETS: Getting inside the meninges;Sizing up the signs.

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska's indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during 1983-2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002-2011 (p<0.001). Median age of case-patients was 0.7 years; 3 infants died. Incidence of Hia infection (2002-2011) among children <5 years was 5.4/100,000; 27 cases occurred in Alaska Native children (18/100,000) versus 2 cases in non-Native children (0.5/100,000) (risk ratio = 36, p<0.001). From 12/2009 to 12/2011, 15 cases of Hia disease occurred in southwestern Alaska (in children <5 years, rate = 204/100,000). Since introduction of the Hib conjugate vaccine, Hia infection has become a major invasive bacterial disease in Alaska Native children. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine has resulted in a dramatic reduction of Hib disease in the U.S. and an increase in the relative importance of infections caused by nontypeable strains. The current project describes the characteristics and clinical outcomes of pediatric and adult patients with invasive H. influenzae (HI) and, through multivariable analysis, identifies risk factors for in-hospital mortality. Methods: HI cases were identified during 1999–2008 through active surveillance as part of Active Bacterial Core surveillance (ABCs). Multivariable analysis was performed with logistic regression to identify factors predictive of in-hospital death. Results: 4839 cases of HI were identified from 1999–2008. Children accounted for 17.1% of cases and adults 82.9%. Underlying conditions were present in 20.7% of children and 74.8% of adults. In-hospital mortality was highest in cases ≥65 years (21.9%) and <3 months (16.2%). The risk of in-hospital death in children <1 year was higher among those who were prematurely-born (<28 weeks, OR 7.1, 95% CI 3.2–15.6; 28–36 weeks OR 2.1, 95% CI 0.9–4.8) and, among children aged 1–17 years, higher in those with healthcare-associated onset and dialysis (OR 5.66, 95% CI 1.84–17.39; OR 18.11, 95% CI 2.77–118.65). In adults, age ≥40 was associated with death in nontypeable, but not encapsulated, infections. Infections with nontypeable strains increased the risk of death in cases ≥65 years (OR 1.81, 95% CI 1.31–2.52). Healthcare-associated HI, bacteremia without identifiable focus, bacteremic pneumonia, associated cirrhosis, cerebrovascular accident, dialysis, heart failure, and non-hematologic malignancy also increased the risk of death in adults. Conclusion: Prematurity in infants, advanced age and certain chronic diseases in adults were associated with an increased risk of in-hospital death. Nontypeable HI was associated with higher mortality in the elderly. [Copyright &y& Elsevier]

BACKGROUND: Since the introduction of effective vaccines, the incidence of invasive Haemophilus influenzae type b (Hib) disease among children <5 years of age has decreased by 99% in the United States. In response to a limited vaccine supply that began in 2007, Hib booster doses were deferred for 18 months. METHODS: We reviewed national passive and active surveillance (demographic and serotype) and vaccination status data for invasive H. influenzae disease in children aged <5 years before (1998-2007) and during (2008-2009) the vaccine shortage years to assess the impact of the vaccine deferral on Hib disease. We estimated the average annual number of Hib cases misclassified as unknown (not completed or missing) serotype. RESULTS: From 1998 to 2007 and 2008 to 2009, the annual average incidence of Hib disease per 100 000 population was 0.2 and 0.18, respectively; no significant difference in incidence was found by age group, gender, or race. Among Hib cases in both time periods, most were unvaccinated or too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown serotype. CONCLUSIONS: The booster deferral did not have a significant impact on the burden of invasive Hib disease in children <5 years of age. Continued surveillance and serotype data are important to monitor changes in Hib incidence, especially during vaccine deferrals. Hib booster deferral is a reasonable short-term approach to a Hib vaccine shortage. [ABSTRACT FROM AUTHOR]

Abstract: Background: A shortage of Haemophilus influenzae type b (Hib) vaccine that occurred in the United States during December 2007 to September 2009 resulted in an interim recommendation to defer the booster dose, but to continue to vaccinate as recommended with the primary series during the first year of life. Objectives: To quantify effects of the Hib shortage on vaccination coverage and to determine if any demographic subgroups were disproportionately affected. Methods: Data from the 2009 National Immunization Survey (NIS) were divided based on child''s age at the onset of the shortage. Comparisons were made in primary series coverage by 9 months between children <7 months versus ≥7 months at the start of the shortage. Comparisons in primary series plus booster dose completion by 19 months were made between children who were <12 months versus ≥12 months at the start of the shortage. Results: Nationally, there was a difference in Hib primary series completion by 9 months among children age <7 months versus ≥7 months at the start of the shortage (73.9% versus 81.2%, P <0.001). There was a large difference in the percentage of children fully vaccinated with the primary series plus booster dose by 19 months among children age <12 months versus ≥12 months at the start of the shortage (39.5% versus 66.0%, P<0.001). There were differential effects of the shortage on primary series coverage among states and for some demographic characteristics. Conclusions: As expected booster dose coverage was reduced consistent with interim recommendations, but primary series coverage was also reduced by 7 percentage points nationally. [Copyright &y& Elsevier]

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is a serious problem in pediatric clinics and, therefore, needs urgent and empirical chemotherapy. We investigated 1,116 cases of empirical chemotherapy of patients aged older than 4 months from 1997 through 2008 by sending questionnaires. A single antibiotic treatment was carried out in less than 30% of the cases throughout the years, whereas the combination of two antibiotics had been practiced in more than 70% of the cases. The main antibiotics used were cephalosporins, carbapenems, and ampicillin. Combinatory use of ampicillin and cephalosporin was carried out in 74.7-82.7% of cases in 1997-2000, but sharply declined thereafter to 0-13.8% in 2004-2008. However, the combination of carbapenem and cephalosporin compensated for the decline, increasing from 3.8-6.6% in 1998-1999 to 79.5-89.9% in 2005-2008. The breakdown in the use of cephalosporins, carbapenems, and ampicillin in two-drug combinatory therapy was as follows. (i) Use of cefotaxime was 61.8-75.3% in 1997-2001, but decreased to nearly 50%, equivalent to the level of ceftriaxone use in 2003-2008. (ii) Use of ampicillin dropped from 74.7-92.3% in 1997-2000 to 4.6% in 2008, and this decreased level was compensated for by the use of carbapenems. Overall, combinatory chemotherapy of the third-generation cephalosporins and carbapenems seems to be practical. The discussion in this report includes the difference between Japan and the United States in the prevalence of the causative agents and the use of antibiotics. These studies provide information on trends in the treatment of children's meningitis in Japan and will be useful for the design of future empirical chemotherapy. [ABSTRACT FROM AUTHOR]

The article focuses on the results of a 2009 National Immunization Survey (NIS) in the U.S. related to changes in measuring Haemophilus influenzae serotype b (Hib) vaccination coverage. It recalls that a new approach for measuring Hib vaccination coverage has been proposed which required vaccination providers to disclose data on Hib vaccine product types. A comparison of new measures shows that under the old method, 82.9% of children received full vaccination while under the new measurement, 92.9% received primary series and 56.9% were fully vaccinated.

The article presents changes to the U.S. Centers for Disease Control and Prevention (CDC) immunization schedule for children and adolescents. It includes age changes for the first dose of rotavirus vaccine and variances for its schedule, minimal interval changes for viruses and a recommendation that children receive an annual flu vaccination. Information about Haemophilus influenzae type b vaccine and how to catch up the schedule for human papillomavirus is also given. It discusses changes in abbreviations and where to get patient information statements and details of CDC recommendations.

OBJECTIVE. Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP[sub5]-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP[sub5] Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP[sub5] dose. SUBJECTS AND METHODS. In this randomized, muiticenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP[sub5] coadministered with IPV and Hib vaccines or 1 lot of DTaP[sub5]-IPV-Hib combination vaccine. Subsequently, 849 of these study participants were given a fourth dose of DTaP[sub5] and Hib vaccines or a fourth dose of DTaP[sub5]-IPV-Hib at I to 16 months of age. Safety was monitored throughout the study, and blood specimens were obtained to assess antibody responses. RESULTS. DTaP[sub5]-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP[sub5], tPV, and Hib vaccines. Seroresponse and seroprotection rates elicited by DTaP[sub5]-IPV-Hib were noninferior to US-licensed equivalent vaccines after the infant series and after the fourth dose. Children immunized with DTaP[sub5]-IPV-Hib had higher antibody geometric mean concentrations to pertussis toxoid and filamentous hemagglutinin; children immunized with the separate vaccines had higher responses to pertactin. Hib antibody responses to Hib polysaccharide were nearly identical in the DTaP[sub5]IPV-Hib and separate-vaccine groups. Persistence of antibodies to the fifth (preschool) dose was also similar between groups. CONCLUSIONS. DTaP[sub5]-IPV-Hib combination vaccine was shown to be immunogenic and well tolerated. No clinically important differences in the safety or immunologic profiles were noted for DTaP[sub5]-IPV-Hib versus the separately administered, USlicensed equivalent vaccines. DTaP[sub5]-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines. [ABSTRACT FROM AUTHOR]

The article focuses on the status of surveillance for Haemophilus influenzae type b (Hib) and the continued shortage of Hib vaccines in the U.S. in 2008. The shortage came after Merck & Co., Inc. announced a voluntary recall of certainn hib conjugate vaccines and the suspension of the vaccines' production. The expected date of restoration of such vaccines was also delayed to mid-2009. In its review, the U.S. Centers for Disease Control and Prevention (CDC) noted that there are 4,657 cases of Hib infection reported between Janaury 2007 and October 2008.

Vaccines against Haemophilus influenzae type B (HI) and Streptococcus pneumomae (SP) have dramatically reduced the incidence of bacterial meningitis (due to both HI and SP) and epiglottitis (due to HI) in childhood. The effects of these vaccines on other conditions, however, are less clear. We report an analysis of the effect of serial deployment of various HI and SP vaccines over a 25-year period, involving an examination of over half a million pediatric hospitalizations occurring in Army hospitals worldwide. We show that, in marked contrast to the reduction in the number of meningitis and epiglottitis cases, the disease burden of orbital and facial cellulitis--conditions oft attributed to HI and SP--did not diminish. [ABSTRACT FROM AUTHOR]

The authors review the progress to date in Hib vaccine introduction, the lessons learned, and the remaining challenges. [ABSTRACT FROM AUTHOR]

Abstract: Background:: Many causes can be proposed for achange in the microbiologic makeup of a specific disease state. However, when viewed through the scope of recent events, only one is likely to be the true cause of a change in the microbiology of acute otitis media (AOM): the release and widespread use of heptavalent pneumococcal conjugate vaccine (PCV-7). Objective:: The aim of this report was to review themicrobiology and prevalence of AOM before and after the release and widespread use of PCV-7. Methods:: For this brief review, we used a MEDLINEsearch to identify English-language literature related to the microbiology of AOM before and after the release of PCV-7 in 2000 in the United States (key terms: acute otitis media, AOM, Haemophilus influenzae, H influenzae, Streptococcus pneumoniae, and S pneumoniae; years: 1980–2005). Studies using tympanocentesis to identify the pathogen in recurrent or persistent AOM were examined; US studies reporting AOM microbiology before and after the release of PCV-7 in the same population were considered for the post-PCV-7 analysis. Results:: Following the release of PCV-7, a decreasein the overall rates of AOM was noted. This decrease brings into question the resultant effect on the microbiology of AOM. Our literature search revealed 2 studies that examined the microbiology of AOM before and after the release of PCV-7 in the United States. These 2 studies, conducted in dispersed geographic regions (rural Kentucky and Rochester, New York), illustrated a change in the predominant causative pathogen in AOM, from S pneumoniae to H influenzae in the population of children 7 to 24 months of age with recurrent AOM. Given the time period of the change, these shifts could be related to the release and widespread use of PCV-7. Conclusions:: Since the 1990s, the predominantcausative pathogen in recurrent AOM changed from S pneumoniae to H influenzae, possibly as a result of the release and widespread use of PCV 7. Although PCV-7 use was slowed from August 2001 to May 2003 and again from February to September 2004 by nationwide shortages, those shortages have now been resolved, and compliance with the full vaccine schedule is expected to increase. [Copyright &y& Elsevier]

Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal carriage continue in rural Alaska despite widespread vaccination. This study investigated whether invasivedisease reemergence during 1996-1997 could be attributed to strains distinguishable from strains carried by vaccinated children. Twenty-four invasive and 42 carriage Hib isolates, collected during 1992-1997, were characterized by pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis, and biotyping. This Hib population was highly clonal, since only 2 strains, electrophoretic type (ET) 55/PFGE 1 and ET 56/PFGE 3, accounted for 62% of all isolates. The ET 55/PFGE 1 and ET 56/PFGE 3 strains were found in 74% of the carriers and caused 80% of the invasive Hib disease that occurred during April 1996-March 1997. Strains causing invasive disease could not be distinguished from strains carried by vaccinated children. Continued monitoring of Hib carriage may provide insights into the epidemiology of continued transmission in an era of widespread vaccination. [ABSTRACT FROM AUTHOR]

Presents surveillance data on Haemophilus influenzae Type b (Hib) invasive disease in children in the United States from 1998 to 2000. Discussion on reports submitted to the Center for Disease Control; Prevalence of invasive disease cases; Summary of race and ethnicity data; Vaccination profile of patients; Implication of the findings.

Antibiotics are important for the treatment and prevention of invasive Haemophilus influenzae disease. Reduced susceptibility to clinically relevant drugs, except ampicillin, has been uncommon in the United States. Susceptibility of 700 invasive H. influenzae isolates, collected through population-based surveillance during 2016, was assessed for 15 antibiotics using broth microdilution, according to the CLSI guidelines; a subset of 104 isolates were also assessed for rifampin susceptibility using Etest. Genomes were sequenced to identify genes and mutations known to be associated with reduced susceptibility to clinically relevant drugs. A total of 508 (72.6%) had reduced susceptibility to at least one antibiotic and more than half of the isolates exhibited reduced susceptibility to only one (33.6%) or two (21.6%) antibiotic classes. All tested isolates were susceptible to rifampin, a chemoprophylaxis agent, and <1% ( n  = 3) of isolates had reduced susceptibility to third generation cephalosporins, which are recommended for invasive disease treatment. In contrast, ampicillin resistance was more common (28.1%) and predominantly associated with the detection of a β-lactamase gene; 26.2% of isolates in the collection contained either a TEM-1 or ROB-1 β-lactamase gene, including 88.8% of ampicillin-resistant isolates. β-lactamase negative ampicillin-resistant (BLNAR) isolates were less common and associated with ftsI mutations; resistance to amoxicillin-clavulanate was detected in <2% ( n  = 13) of isolates. The proportion of reduced susceptibility observed was higher among nontypeable H. influenzae and serotype e than other serotypes. US invasive H. influenzae isolates remain predominantly susceptible to clinically relevant antibiotics except ampicillin, and BLNAR isolates remain uncommon. IMPORTANCE Antibiotics play an important role for the treatment and prevention of invasive Haemophilus influenzae disease. Antimicrobial resistance survey of invasive H. influenzae isolates collected in 2016 showed that the US H. influenzae population remained susceptible to clinically relevant antibiotics, except for ampicillin. Detection of approximately a quarter ampicillin-resistant and β-lactamase containing strains demonstrates that resistance mechanisms can be acquired and sustained within the H. influenzae population, highlighting the continued importance of antimicrobial resistance surveillance for H. influenzae to monitor susceptibility trends and mechanisms of resistance.

Background: Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children., Methods: We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI., Findings: Between Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months., Interpretation: These findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis., Funding: US National Institutes of Health and CZ Biohub., Competing Interests: Declaration of interests JK reports support from Genentech, outside the submitted work. LA reports funding from Pfizer, outside the submitted work. ABM reports grants from the Francis Family Foundation and the US National Institutes of Health (NIH) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), outside the submitted work. EAFS reports grants from the US NIH during the conduct of the study. EAFS reports grants, personal fees, and non-financial support from AstraZeneca, Merck, Regeneron, Pfizer, and Roche; personal fees, non-financial support, and other support from AbbVie; personal fees from Alere; other support from GSK; grants from Johnson and Johnson; and grants and non-financial support from Novavax, outside the submitted work. MWH reports grants from NIH NICHD, during the conduct of the study; and personal fees from La Jolla Pharmaceuticals, outside the submitted work. AFZ received NICHD funding through the Collaborative Pediatric Critical Care Research Network during the conduct of the study. KLM reports grants from NIH, during the conduct of the study. AS reports grants from NIH, outside the submitted work. MMP reports grants from NIH, during the conduct of the study. PSM reports grants from NIH NICHD, during the conduct of the study. JMD reports grants from NIH, during the conduct of the study. MSZ reports grants from National Heart, Lung, and Blood Institute (NHLBI; K23HL146936), outside the submitted work. PMM reports grants from NIH, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives. The purpose of this study was to evaluate the effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccines among children aged 2 to 18 months and to determine risk factors for invasive Hib disease during a period of declining incidence (1991-1994). Methods. A prospective population-based case-control study was conducted in a multistate US population of 15.5 million. A laboratory-based active surveillance system was used for case detection. Results. in a multivariate analysis, having a single-parent mother (odds ratio [OR] =4.3, 95% confidence interval [CI] = 1.2, 14.8) and household crowding (OR = 3.5, 95% CI = 1.03, 11.7) were risk factors for Hib disease independent of vaccination status. After adjustment for these risk factors, the protective efficacy of 2 or more Hib vaccine doses was 86% (95% CI 16%, 98%). Among undervaccinated subjects, living with a smoker (P = .02) and several indicators of lower socioeconomic status were risk factors for Hib disease. Conclusions. Hib disease still occurs at low levels in the United States, predominantly in socioeconomically disadvantaged populations. Low immunization coverage may facilitate continuing transmission of Hib. Special efforts to achieve complete and timely immunization in disadvantaged populations are needed. [ABSTRACT FROM AUTHOR]

Investigates the prevalence and risk factors for oropharyngeal Haemophilus influenza type b (Hib) carriage among native children aged one to five years in remote southwestern Alaska. Epidemiology of Hib disease; Surveillance for invasive Hib disease and characterization of the cases; Hib carriage rates across village.

A national antimicrobial resistance surveillance study was conducted from December 1997 to May 1998 to determine the prevalence of antimicrobial resistance in 6620 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In this centralized study, which involved 163 institutions located in 43 states, we determined MICs for representatives of five antimicrobial classes: β-lactams (penicillin, co-amoxiclav, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), co-trimoxazole, glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). In most S. pneumoniae isolates, all antimicrobials were to be found active, but amongst penicillin-resistant isolates (MICs ≥ 2 mg/L), resistance to other β-lactams, macrolides and co-trimoxazole was common. For vancomycin and levofloxacin, however, activity was not associated with penicillin resistance. The prevalence of penicillin-nonsusceptible (intermediate and resistant) pneumococci was highest in the South Atlantic (44%) and East South Central (43%) regions and lowest in the Mid-Atlantic (28%) and New England (28%) regions. Resistance to β-lactams, macrolides and co-trimoxazole was more commonly found amongst respiratory isolates than blood isolates and in strains from patients ≤ 12 years old than from older patients. β-lactamase, which was detected in 33% of H. influenzae and 92% of M. catarrhalis strains, did not affect the activity of the β-lactams under study other than ampicillin. Certain agents, such as vancomycin and the fluoroquinolones, remain highly active, and well-designed surveillance systems that monitor MIC distributions would be needed to detect a potential for reduced susceptibility. In addition, surveillance programmes should be designed to collect information about associated resistance as well as differences in prevalence associated with region, specimen source and patient age. [ABSTRACT FROM PUBLISHER]

Reveals the interchangeability of conjugated Haemophilus influenzae type b (Hib) vaccines in infants. Safety and immunogenicity of Hib; Increase in antibody following immunization; Adverse reactions.

Focuses on a study which examined the occurrence of hemophilus influenzae b meningitis in children at the Children's Hospital Medical Center in Boston, Massachusetts from 1958 to 1973. Methodology of the study; Results and discussion.

Summarizes provisional data about invasive Haemophilus influenzae (Hi) disease among infants and children in the United States during 1993 and 1994 based on information from three surveillance systems. Data from the National Notifiable Disease Surveillance System (NNDS), the National Bacterial Meningitis and Bacteremia Reporting System (NBMRS), and a multistate laboratory-based surveillance system.

Reports on the Haemophilus influenzae (Hi) invasive disease among the United States population in 1994-1995. Reference to the analysis of the national Hi surveillance data from 1994 and 1995; Availability of serotype data; Description of Hi isolates.

Evaluates the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. Postvaccination geometric mean titers; Effect of exposure to Haemophilus b oligosaccharide conjugate vaccine.