Invasive Haemophilus Influenzae Infections Research Articles

Evolution of Haemophilus influenzae infection during the vaccination period: literature review

Mass immunization with H. influenzae type b (Hib) vaccines has led to a sharp decrease in the incidence of invasive and non-invasive forms of Haemophilus influenza infection. H. influenzae causes a diverse spectrum of diseases from usually asymptomatic carriage to otitis, sinusitis, epiglottitis, pneumonia, endopericarditis, inflammation of the subcutaneous tissue, arthritis, and is one of the four main causative agents of bacterial meningitis. Materials and methods. In order to identify the significance of Hemophilus influenzae infection during the vaccination period, an analysis was carried out on the spread of Hemophilus influenzae infection, its clinical forms, as well as the antibiotic resistance of the pathogen. A review of domestic and foreign publications over the past 20 years was conducted in the search engines PubMed, Google Scholar, Cochrane Library and Elibrary. Results. Studies conducted in various countries show that after the start of mass immunization, H. influenzae type b is no longer the dominant serotype of the pathogen causing invasive infections in most countries. Everywhere in the world, the leading positions are occupied by cases of infection caused by non-typable serotypes of H. influenzae type a, f, b (Hia, Hif, Hib) predominate among the capsular forms. Unprotected aminopenicillins, second-generation cephalosporins, and sulfonamides are the leading classes of antibacterial drugs to which H. influenzae strains have developed resistance. A variety of clinical forms is still relevant for hemophilic infection. Bacteremia, meningitis, and pneumonia are the main clinical manifestations of invasive Haemophilus influenzae infection caused by typed and non-typed serotypes of the pathogen.

Genome Characterisation of Invasive Haemophilus influenzae in Pregnancy: The Noticeable Placental Tissue Tropism Is Distributed across the Species Rather Than Linked with Capsulation or Particular Clones.

Pregnancy is associated with a 5-26 times increased risk of invasive Haemophilus influenzae infection and subsequent adverse pregnancy outcomes. Incidence rate and outcome are published in some regions, but the characterisation of bacterial isolates is limited. We performed comparative genomic analyses of isolates from 12 pregnancy-associated cases, cultured from maternal bacteraemia in pregnancy (nine), postpartum bacteraemia (one), neonatal bacteraemia (one), and placental tissue (one). In two bacteraemia cases, identical isolates were also cultured from cervical swabs. Eight cases occurred early in pregnancy (gestational week 7-26), and seven of them resulted in miscarriage or neonatal death. All bacterial genomes were devoid of capsule loci, and they were evenly distributed in the major phylogenetic group I of the species. The conspicuous tropism of H. influenzae for pregnancy and placental tissue is associated with the species rather than specific clonal subtypes.

Haemophilus influenzae meningitis: A rare etiology of bacterial meningitis in adults! A case report

Invasive Haemophilus influenzae infections can occur as a sepsis, an invasive pneumonia, an epiglottitis and an acute bacterial meningitis. H. influenzae meningitis accounts for about 4% of community-acquired bacterial meningitis in adults. We report a case of Haemophilus influenzae serotype b (Hib) meningitis in a 37-year-old patient having an osteomeningeal breach as a predisposing factor. The diagnosis was established by lumbar puncture. The course was satisfactory with antibiotic treatment. The systematic search for an osteomeningeal breach as well as other risk factors is crucial in any adult patient presenting with an episode of confirmed H. influenzae meningitis. The quick performance of bacteriological samples is primordial in order to obtain an early diagnosis and to ensure a good clinical outcome.

Fetal Loss and Preterm Birth Caused by Intraamniotic Haemophilus influenzae Infection, New Zealand.

Invasive Haemophilus influenzae infection during pregnancy can cause preterm birth and fetal loss, but the mechanism is unclear. We investigated 54 cases of pregnancy-associated invasive H. influenzae disease in 52 unique pregnancies in the Auckland region of New Zealand during October 1, 2008‒September 30, 2018. Intraamniotic infection was identified in 36 (66.7%) of 54 cases. Outcome data were available for 48 pregnancies. Adverse pregnancy outcomes, defined as fetal loss, preterm birth, or the birth of an infant requiring intensive/special care unit admission, occurred in 45 (93.8%) of 48 (pregnancies. Fetal loss occurred in 17 (35.4%) of 48 pregnancies, before 24 weeks' gestation in 13 cases, and at >24 weeks' gestation in 4 cases. The overall incidence of pregnancy-associated invasive H. influenzae disease was 19.9 cases/100,000 births, which exceeded the reported incidence of pregnancy-associated listeriosis in New Zealand. We also observed higher rates in younger women and women of Māori ethnicity.

Changes in Invasive Neisseria meningitidis and Haemophilus influenzae Infections in France during the COVID-19 Pandemic.

BackgroundSince the appearance of COVID-19 in January 2020, invasive bacterial infections have decreased significantly worldwide. However, alterations in age and sex distributions, clinical forms, phenotypes, and genotypes of isolates have not been analyzed. Our goal is to present and discuss these data considering the current COVID-19 pandemic situation. Methods: The data of the national reference center for meningococci and Haemophilus influenzae in France were mined to examine the above aspects of invasive bacterial infection before (2018–2019) and after (2020–2021) the COVID-19 pandemic. Detailed epidemiological, clinical, and microbiological data were collected, and whole genome sequencing was carried out on meningococcal isolates (n = 1466). Results: In addition to the overall decline in the number of cases, various changes in age, sex, and phenotypes of isolates were also noted. As for N. meningitidis, more cases were observed in adults, as well as more invasive pneumopathies. Furthermore, fewer hyperinvasive meningococcal genotypes have circulated since COVID-19 emerged. The situation has been different for H. influenzae, as the number of invasive cases among adults decreased due to a reduction in non-typeable isolates. In contrast, cases due to serotypeable isolates, particularly serotypes a and b, increased in children <5 years-old. Conclusions: It is possible that measures implemented to stop COVID-19 may have reduced the circulation of N. meningitidis and H. influenzae isolates, but to a variable extent. This may be due to differences in circulation between these two species according to age groups. Vaccination schedules against these two species may have also influenced the evolution of these invasive bacterial infections since the emergence of the COVID-19 pandemic.

Evaluation of the adequacy of the antimicrobial therapy of invasive Haemophilus influenzae infections: A pharmacokinetic/pharmacodynamic perspective

IntroductionIn Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets. MethodsPharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population. ResultsRegardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL− and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR≤8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints. ConclusionsOur study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected.

Genomic insights of international clones of Haemophilus influenzae causing invasive infections in vaccinated and unvaccinated infants

The emergence of invasive Haemophilus influenzae infections in vaccinated patient is a public health concern. We have investigated the genomic basis of invasiveness and possible vaccine failure in H. influenzae causing invasive disease in vaccinated and unvaccinated children in Brazil. Three H. influenzae strains isolated from blood cultures of pediatric patients were sequenced. Serotype, MLST, resistome and virulome were predicted using bioinformatic tools, whereas single nucleotide polymorphisms (SNPs) analysis of cap loci and the presence of the putative virulence-enhancing IS1016-bexA partial deletion were predicted in silico. Infections were caused by H. influenzae type a (Hia), type b (Hib) and nontypeable (NTHi), belonging to international high-risk clones of sequence types ST23, ST6 and ST368, respectively, which have been identified in North American, European and Asian countries. Convergence of ampicillin resistance and virulence in Hib-ST6 was supported by blaTEM-1B and deletion in the bexA gene, whereas presence of SNPs in the cap-b locus was associated with antigenic modifications of the capsule structure. Hia-ST23 and NTHi-ST368 strains carried galU, lpsA, opsX, rfaF, iga1, lgtC and lic1/lic2 virulence genes, associated with colonization, adaptation and damage to the lung, or invasiveness. In summary, deletion in the bexA gene and presence of SNPs in the cap locus of Hib could be contributing to invasive disease and possible vaccine failure in pediatric patients, whereas serotype replacement of Hib with type “a” and NTHi strains denotes the ability of non-vaccine serotypes to re-colonize vaccinated patients. Finally, the dissemination of international high-risk clones of H. influenzae emphasizes the importance of monitoring changes in the molecular epidemiology of invasive H. influenzae disease.

Invasive Haemophilus influenzae Infections in Germany After the Introduction of Routine Childhood Immunization, 2001-2016.

Background Haemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001–2016, including serotype distribution and ampicillin resistance.MethodsNationwide data from statutory disease surveillance (2001–2016) were linked with laboratory surveillance data (2009–2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends.ResultsIn 2001–2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups <1 year (15.2) and ≥80 years (15.5). Nontypeable Hi (NTHi) caused 81% (n = 1545) of cases in 2009–2016. Of capsulated cases, 69% were serotype f and 17% serotype b. Of Hib cases eligible for vaccination, 10% (3/29) were fully vaccinated. For 2009–2016, significant increasing trends were observed for NTHi and Hif infections in the age groups <5 years and ≥60 years and for ampicillin resistance in NTHi.ConclusionsThis is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

Invasive non-typeable Haemophilus influenzae infection due to endometritis associated with adenomyosis

BackgroundThe widespread administration of the Haemophilus influenzae type b vaccine has led to the predominance of non-typable H. influenzae (NTHi). However, the occurrence of invasive NTHi infection based on gynecologic diseases is still rare.Case presentationA 51-year-old Japanese woman with a history of adenomyoma presented with fever. Blood cultures and a vaginal discharge culture were positive with NTHi. With the high uptake in the uterus with 67Ga scintigraphy, she was diagnosed with invasive NTHi infection. In addition to antibiotic administrations, a total hysterectomy was performed. The pathological analysis found microabscess formations in adenomyosis.ConclusionsAlthough NTHi bacteremia consequent to a microabscess in adenomyosis is rare, this case emphasizes the need to consider the uterus as a potential source of infection in patients with underlying gynecological diseases, including an invasive NTHi infection with no known primary focus.

Evaluation of the adequacy of the antimicrobial therapy of invasive Haemophilus influenzae infections: A pharmacokinetic/pharmacodynamic perspective

IntroductionIn Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets. MethodsPharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population. ResultsRegardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL− and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR≤8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints. ConclusionsOur study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected.

Molecular epidemiology of imipenem resistance in invasive Haemophilus influenzae infections in Germany in 2016

The carbapenems imipenem and meropenem play an important role in the empirical anti-infective treatment of critically ill patients. Carbapenem resistance in Haemophilus influenzae (Hi) has rarely been reported. We provide prevalence data for resistance to carbapenems from laboratory surveillance of invasive Hi infections in Germany in 2016. Phenotypic susceptibility testing against ampicillin, amoxicillin/clavulanate, cefotaxime and imipenem was carried out on 474 isolates from blood and CSF. The isolates were collected as part of the national laboratory surveillance programme. Imipenem-resistant strains were further tested for meropenem susceptibility. Molecular analysis was done by ftsI sequencing to detect mutations in PBP3, by acrR sequencing to detect alterations in the regulatory protein of the AcrAB-TolC efflux pump and by MLST. No resistance to meropenem was detected. Cefotaxime resistance was rare (n = 3; 0.6%). Imipenem resistance was found in 64 strains (13.5%) using gradient agar diffusion and was confirmed in 26 isolates by broth microdilution (5.5%). Imipenem resistance occurred predominantly in Hi that were β-lactamase negative but ampicillin resistant and in those that were β-lactamase positive but nevertheless amoxicillin/clavulanate resistant. This finding suggested a β-lactamase-independent mechanism. Accordingly, sequence analysis of PBP3 identified previously described mutations. MLST of the imipenem-resistant strains, which were all non-typeable Hi, revealed a high diversity. We conclude that imipenem, but not meropenem, resistance is frequent in Hi. It is likely to be supported by PBP3 mutations.

Invasive Nontypeable Haemophilus influenzae Infection Among Adults With HIV in Metropolitan Atlanta, Georgia, 2008-2018

Invasive nontypeable Haemophilus influenzae (NTHi) infection among adults is typically associated with bacteremic pneumonia. Nontypeable H influenzae is genetically diverse and clusters of infection are uncommon. To evaluate an increase in invasive NTHi infection from 2017-2018 among HIV-infected men who have sex with men in metropolitan Atlanta, Georgia. A population-based surveillance study with a cohort substudy and descriptive epidemiological analysis identified adults aged 18 years or older with invasive NTHi infection (isolation of NTHi from a normally sterile site) between January 1, 2008, and December 31, 2018 (final date of follow-up). Time period, HIV status, and genetic relatedness (ie, cluster status) of available NTHi isolates. The primary outcome was incidence of invasive NTHi infection (from 2008-2016 and 2017-2018) among persons with HIV and compared with NTHi infection from 2008-2018 among those without HIV. The secondary outcomes were assessed among those aged 18 to 55 years with invasive NTHi infection and included epidemiological, clinical, and geographic comparisons by cluster status. Among 553 adults with invasive NTHi infection (median age, 66 years [Q1-Q3, 48-78 years]; 52% male; and 38% black), 60 cases occurred among persons with HIV. Incidence of invasive NTHi infection from 2017-2018 among persons with HIV (41.7 cases per 100 000) was significantly greater than from 2008-2016 among those with HIV (9.6 per 100 000; P < .001) and from 2008-2018 among those without HIV (1.1 per 100 000; P < .001). Among adults aged 18 to 55 years with invasive NTHi infections from 2017-2018 (n = 179), persons with HIV (n = 31) were significantly more likely than those from 2008-2018 without HIV (n = 124) to be male (94% vs 49%, respectively; P < .001), black (100% vs 53%; P < .001), and have septic arthritis (35% vs 1%; P < .001). Persons with HIV who had invasive NTHi infection from 2017-2018 (n = 31) were more likely than persons with HIV who had invasive NTHi infection from 2008-2016 (n = 24) to have septic arthritis (35% vs 4%, respectively; P = .01). Pulsed-field gel electrophoresis of 174 of 179 NTHi isolates from 18- to 55-year-olds identified 2 genetically distinct clonal groups: cluster 1 (C1; n = 24) and cluster 2 (C2; n = 23). Whole-genome sequencing confirmed 2 clonal lineages of NTHi infection and revealed all C1 isolates (but none of the C2 isolates) carried IS1016 (an insertion sequence associated with H influenzae capsule genes). Persons with HIV were significantly more likely to have C1 or C2 invasive NTHi infection from 2017-2018 (28/31 [90%]) compared with from 2008-2016 among persons with HIV (10/24 [42%]; P < .001) and compared with from 2008-2018 among those without HIV (9/119 [8%]; P < .001). Among persons with C1 or C2 invasive NTHi infection who had HIV (n = 38) (median age, 34.5 years; 100% male; 100% black; 82% men who have sex with men), 32 (84%) lived in 2 urban counties and an area of significant spatial aggregation was identified compared with those without C1 or C2 invasive NTHi infection. Among persons with HIV in Atlanta, the incidence of invasive nontypeable H influenzae infection increased significantly from 2017-2018 compared with 2008-2016. Two unique but genetically related clonal strains were identified and were associated with septic arthritis among black men who have sex with men and who lived in geographic proximity.

Non-typeable Haemophilus influenzae-associated early pregnancy loss: an emerging neonatal and maternal pathogen

ObjectivesThere is increasing evidence indicating an association between invasive non-typeable Haemophilus influenzae (NTHi) infection in pregnancy and early pregnancy loss. As the diagnosis relies on microbiological investigation of post-mortem placental and foetal samples, a significant proportion of NTHi-related pregnancy loss remains unrecognised. To better characterise NTHi in septic abortion, we report NTHi cases associated with early pregnancy loss.MethodsWe reviewed all post-mortems at <24 weeks gestation with histologically proven acute chorioamnionitis on placental histology and enrolled cases with at least one matched foetal and placental sample culture positive for NTHi. The study was approved by the NHS Lothian Caldicott Guardian.ResultsIn our cohort, invasive NTHi has accounted for 20% of infections associated with early pregnancy loss prior to 24 weeks gestation. All patients were young and healthy pregnant women at < 20 weeks' gestation who presented with abdominal pain, PV bleed /discharge and were septic at the time of presentation. One patient with previous history of miscarriage who presented with cervical incompetence had more severe pathology suggestive of early intrauterine pneumonia.ConclusionThe burden of invasive NTHi disease in early pregnancy loss is likely to be much larger than currently recognised. NTHi should be considered in pregnant women presenting with abdominal pain and PV bleed/discharge in whom clinical signs of sepsis are present. Active surveillance should be considered in this patient group including septic abortion to capture the true prevalence of this emerging pathogen to inform preventative and therapeutic approaches.

Clinical characteristics of 84 children with invasive Haemophilus influenzae infection from 2014 to 2018

Objective: To investigate the clinical characteristics of invasive Haemophilus influenzae (HI) infection in children. Methods: The clinical manifestations, laboratory examinations and treatment outcomes of 84 children with HI infection confirmed by bacterial culture in 7 tertiary children's hospitals from 2014 to 2018 were analyzed retrospectively. Results: Among the 84 cases, 50 were males. The age was 1.54 years (ranged from 5 days to 13 years).Twenty cases (24%) had underlying diseases and 48 cases (57%) had not received antibiotics before collecting specimens. Eighty-two cases (98%) had fever and 75 cases (89%) had clear infection foci, among which 31 cases (37%) had meningitis and 27 cases (32%) had pneumonia. Blood culture was positive in 62 cases (74%), cerebrospinal fluid culture was positive in 10 cases (12%), blood culture and cerebrospinal fluid culture were both positive in 11 cases (13%). Antibiotics susceptibility test showed that 27% (22/82) of all HI strains produced β-lactamases and 48% (37/77) strains were resistant to ampicillin. The drug resistance rates to cefuroxime, ampicillin-sulbactam, trimethoprim-sulfamethoxazole and azithromycin were 25% (20/80) , 20% (9/45) , 71% (44/62) and 19%(11/58), respectively. All strains were sensitive to meropenem, levofloxacin and ceftriaxone. After sensitive antibiotic therapy, 83% (70/84) of all patients were cured and improved, the mortality rate and loss of follow-up rate were 13% (11/84) and 4% (3/84) respectively. Conclusions: Meningitis and pneumonia are common presentation of invasive HI infections in children. Mortality in HI meningitis children is high and the third generation of cephalosporins, such as ceftriaxone can be used as the first choice for the treatment of invasive HI infection.

2314. Invasive Haemophilus influenzae Infections in Children: A 10-Year Study

BackgroundThe rate of Haemophilus influenzae type b (HIB) infections has decreased dramatically since the use of HIB vaccines in infants and children. The current prevalence of invasive HIB infections and those due to non-type b H. influenzae is not fully known. The objective was to describe the cases of all invasive H. influenzae infections and describe the spectrum and severity of clinical disease.MethodsRetrospective study of all hospitalized patients with culture-proven invasive Haemophilus influenzae infections at Nationwide Children’s Hospital, Columbus, Ohio, from 2009 to 2018. The electronic health records were reviewed for pertinent demographic, clinical, laboratory data, and outcomes.ResultsThere were a total of 59 culture-proven H. influenzae infections of which 12 were excluded due to insufficient patient data. The remaining 47 patients (32 [68%] male; 30 [64%] white, 8 [17%] African-American) and their culture results are provided in Table:Haemophilus influenzae Infections in 47 Patients: Culture ResultsType a N = 1 (%)Type bN = 3(%)Encapsulated non-b N = 11(%)Not typeableN = 30(%)Not typedN = 2(%)TotalN = 47(%)<6 months0007(23)1(50)8(17)≥6–12 months1(100)2(67)7(64)7(23)017(36)>1–5 years01(33)4(36)6(20)1(50)12(25)>5–8 years0008(26)08(17)>8–17 years000000≥18 years0002(6)02(4)Blood only1(100)1(33)4(36)27(90)2(100)35(75)CSF only01(33)0001(2)Both Blood and CSF01(33)5(45)006(13)Both CSF and Peritoneal Fluid0001(3)01(2)Both Blood and Synovial Fluid002(18)002(4)Both Blood and Eye Discharge0002(6)02(4)Virus Coinfection1(100)3(100)3(27)14(46)1(50)22(47)Bacteria Coinfection01(33)05(16)2(100)8(17)Death0001(3)01(2)There were 14 (30%) patients with pneumonia and bacteremia, 6 (13%) with meningitis and bacteremia, 2 (4%) with only meningitis, 1 (2%) with bacteremia/meningitis and septic hip, 2 (4%) septic arthritis with bacteremia, 1 (2%) with periorbital cellulitis and bacteremia, and 21 (45%) with only bacteremia. Of the 3 cases of H. influenzae type b, 2 had not been vaccinated while 1 received only 1 dose of HIB vaccine.ConclusionInvasive H. influenzae infections were associated with substantial morbidity and a 2% case-fatality rate.Disclosures All authors: No reported disclosures.

Clinical and microbiological characteristics of adult invasive Haemophilus influenzae infections: results of a 14-year single-center experience from Hungary.

To describe the characteristics of adult invasive H. influenzae disease, 34 patients diagnosed at a single tertiary center between 2004 and 2017 were analyzed in a retrospective case series study. The annual estimated incidence was 0.1 cases/100.000 inhabitants. Dominant source of infection was pneumonia accompanied by sepsis (62%) and caused by nontypeable strains (74%) with low ampicillin resistance (14%). Survival (94%) and complication rates were high (35%). Main empirical treatments were ceftriaxone or levofloxacine.

Invasive Haemophilus influenzae infections in children in Kamikawa subprefecture, Hokkaido, Japan, 2006-2015: The effectiveness of H.influenzae type b vaccine.

We evaluated 24 children with invasive Haemophilus influenzae infections between 2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%) and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of age. Seventeen (70.8%) of the total were less than 2 years old. The incidence rate of H.influenzae infection varied from 15.1 to 36.3 per 100,000 population in the Kamikawa area during the period from 2006 through 2011. The corresponding rate decreased to 10.4 per 100,000 population in 2012, and there were no cases after 2013. Meningitis occurred in 1-2 patients annually from 2006 to 2011, showing an incidence rate of 4-10 per 100,000 population per year, while no cases were reported during or after 2012. No patients with invasive H.influenzae infection died, but sequelae were seen at discharge in 1 patient with meningitis, that had hydrocephalus and developmental delay. In Japan, introduction of the H.influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination was voluntary, resulting in a low vaccination rate. According to the national policy, and the self-pay burden for vaccination was decreased in December 2010, and the vaccination rate increased markedly to over 90%. This report provides a meaningful demonstration that introduction of the Hib vaccine markedly reduced invasive H.influenzae infections, exerting a beneficial effect in Japan, as it has in the world.

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

BackgroundInfectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands.Methods and FindingsThe average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the National Immunisation Programme. The average disease burden per individual varied from 0.2 (95% UI: 0.1–0.4) DALYs per 100 infections for giardiasis, to 5081 and 3581 (95% UI: 3540–3611) DALYs per 100 infections for rabies and variant Creutzfeldt-Jakob disease, respectively.ConclusionsFor guiding and supporting public health policy decisions regarding the prioritisation of interventions and preventive measures, estimates of disease burden and the comparison of burden between diseases can be informative. Although the collection of disease-specific parameters and estimation of incidence is a process subject to continuous improvement, the current study established a baseline for assessing the impact of future public health initiatives.

Risk of Invasive Haemophilus influenzae Infection During Pregnancy and Association With Adverse Fetal Outcomes

Collins, Sarah*; Ramsay, Mary*; Slack, Mary P. E.†; Campbell, Helen*; Flynn, Sally†; Litt, David†; Ladhani, Shamez N.‡ Author Information

Risk for Invasive Haemophilus influenzae Infection During Pregnancy and Association With Adverse Fetal Outcomes

Haemophilus influenzae is a gram-negative coccobacillus with 6 serotypes (a-f), categorized by the polysaccharide capsule. The most invasive is serotype b, and the organism can also remain unencapsulated. Routine vaccination against serotype b has decreased the incidence of the disease in all age groups. Invasive infections caused by unencapsulated H. influenzae are now relatively more common. An increased risk for invasive H. influenzae disease during pregnancy can cause serious illness in pregnant women, as well as lead to fetal death and premature delivery. This national surveillance study was undertaken to determine the epidemiology, clinical characteristics, and outcomes of invasive H. influenzae in women of reproductive age during 2009 to 2012 in England and Wales. Public Health England performs national surveillance for invasive H. influenzae disease by a combination of isolate submission, routine laboratory reporting, and clinical reporting protocols. Standardized questionnaires were sent prospectively to clinicians ∼3 months after the patients’ infections were reported. The women were aged 15 to 44 years with laboratory-confirmed invasive H. influenzae disease. From 45,215,800 woman-years of follow-up, 2568 cases of invasive infection were recorded; 1906 isolates (74.2%) were serotyped. Women of reproductive age accounted for 224 cases (8.7%) and 171 cases (9.0%) with serotyped isolates. Questionnaires were completed for all 171 cases; 144 cases (94.2%) had unencapsulated H. influenzae infection, 11 (6.4%) had serotype b, and 16 (9.4%) had other encapsulated serotypes. Sixty-five (38.4%) of the 171 women had at least 1 concurrent condition, most commonly chronic respiratory disease, malignancy, or immunosuppression; this was not associated with age at infection or serotype. Bacteremia was present in 53.8%; and pneumonia, in 29.2%, and 4% of women had meningitis. Nine women with unencapsulated H. influenzae had pelvic inflammatory disease. Four of 12 deaths were associated with H. influenzae. The case-fatality rate was 2.3%, and the strains were unencapsulated in 2 and serotype b and f in 1 each. Of the 75 women (43.9%) pregnant at diagnosis, 72 (96.0%) had unencapsulated H. influenzae; 73 (97.3%) miscarried or delivered the infant at the time of infection. The incidence rate ratio of invasive H. influenzae disease was 13 times higher in parturients compared with nonpregnant women and 17 times higher for women with unencapsulated H. influenzae (P < 0.001 for both). No women had concurrent conditions at the time of infections, and all pregnant women survived the infection. Outcomes for 75 pregnancies (77 fetuses), including 72 cases (74 fetuses) with unencapsulated disease, were recorded. Among the unencapsulated H. influenzae pregnancies, 43 (58.1%) of 74 fetuses were miscarried, 2 were stillborn (2.7%), and 29 were liveborn (39.2%), including 11 at less than 37 weeks. Unencapsulated H. influenzae infection during the first 24 weeks was associated with fetal loss (44/47; 93.6%) and extremely premature birth (3/47; 6.4%). During the second half of pregnancy, unencapsulated H. influenzae infection in 28 cases was associated with premature birth and stillbirth in 8 (28.6%) and 2 (7.1%) cases, respectively. The incidence of pregnancy loss was 61.0 of 100 pregnancies for women with invasive disease and 60.8 of 100 for those with unencapsulated H. influenzae. Crude incidence rate ratios for pregnancy loss were 2.91 and 2.90 for all serotypes and unencapsulated H. influenzae, respectively. For suspected intrapartum sepsis, intrauterine death, septic abortion, or premature rupture of membranes, vaginal and placental samples should be tested for H. influenzae. A joint medical record for mothers and their infants would assist with developing evidence-based standards to reducing maternal and neonatal morbidity and mortality resulting from H. influenzae infection.