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"Haemophilus Infections - epidemiology"
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Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease-United States, 2009-2015
2018
Invasive Haemophilus 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 American Indian and Alaska Native children.
Abstract
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.
Journal Article
Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis
by
de Winter-de Groot, Karin M.
,
de Steenhuijsen Piters, Wouter A. A.
,
van der Ent, Cornelis K.
in
Anti-Bacterial Agents - therapeutic use
,
Burkholderia - genetics
,
Burkholderia Infections - drug therapy
2016
Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens.
To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life.
We conducted a prospective cohort study, from the time of diagnosis onward, in which we collected questionnaires and 324 nasopharynx samples from 20 infants with CF and 45 age-matched healthy control subjects. Microbiota profiles were characterized by 16S ribosomal RNA-based sequencing.
We observed significant differences in microbial community composition (P < 0.0002 by permutational multivariate analysis of variance) and development between groups. In infants with CF, early Staphylococcus aureus and, to a lesser extent, Corynebacterium spp. and Moraxella spp. dominance were followed by a switch to Streptococcus mitis predominance after 3 months of age. In control subjects, Moraxella spp. enrichment occurred throughout the first 6 months of life. In a multivariate analysis, S. aureus, S. mitis, Corynebacterium accolens, and bacilli were significantly more abundant in infants with CF, whereas Moraxella spp., Corynebacterium pseudodiphtericum and Corynebacterium propinquum and Haemophilus influenzae were significantly more abundant in control subjects, after correction for age, antibiotic use, and respiratory symptoms. Antibiotic use was independently associated with increased colonization of gram-negative bacteria such as Burkholderia spp. and members of the Enterobacteriaceae bacteria family and reduced colonization of potential beneficial commensals.
From diagnosis onward, we observed distinct patterns of nasopharyngeal microbiota development in infants with CF under 6 months of age compared with control subjects and a marked effect of antibiotic therapy leading toward a gram-negative microbial composition.
Journal Article
Non-typeable Haemophilus influenzae, an under-recognised pathogen
by
Van Eldere, Johan
,
Cripps, Allan W
,
Slack, Mary P E
in
Bacterial diseases
,
Bacterial diseases of the respiratory system
,
Bacterial Typing Techniques
2014
Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk. Individuals with underlying comorbidities are most susceptible and infection is associated with high mortality. β-lactamase production is the predominant mechanism of resistance. However, the emergence and spread of β-lactamase-negative ampicillin-resistant strains in many regions of the world is of substantial concern, potentially necessitating changes to antibiotic treatment guidelines for community-acquired infections of the upper and lower respiratory tract and potentially increasing morbidity associated with invasive NTHi infections. Standardised surveillance protocols and typing methodologies to monitor this emerging pathogen should be implemented. International scientific organisations need to raise the profile of NTHi and to document the pathobiology of this microbe.
Journal Article
Molecular epidemiology of invasive Haemophilus influenzae disease in Portugal: an update of the post-vaccine period, 2011–2018
by
Bajanca-Lavado Maria Paula
,
Heliodoro Catarina Isabel Moreira
,
Bettencourt, Célia Rodrigues
in
Ampicillin
,
Children
,
Encapsulation
2020
Haemophilus influenzae reference laboratory from Portugal characterized the entire collection of 260 H. influenzae invasive isolates received between 2011 and 2018, with the purpose of updating the last published data (2002–2010). Capsular serotypes and antimicrobial susceptibility patterns were determined. The ftsI gene encoding the transpeptidase domain of PBP3 was sequenced for β-lactamase-negative ampicillin-resistant (BLNAR) isolates. Multilocus sequence typing (MLST) was performed to examine genetic relatedness among isolates. The majority of H. influenzae invasive isolates are nonencapsulated (NTHi-79.2%). Among encapsulated isolates (20.8%), the most characterized serotype was serotype b (13.5%), followed by serotype f (3.1%), serotype a (2.7%), and serotype e (1.5%). In contrast to NTHi that mainly affected the elderly (64.0%; ≥ 65 years old), most encapsulated isolates were characterized in preschool children (55.6%). Comparing the two periods, β-lactamase production increased from 10.4 to 13.5% (p = 0.032) and low-BLNAR (MIC ≥ 1 mg/L) isolates from 7.7 to 10.5% (p = 0.017). NTHi showed high genetic diversity (60.7%), in opposition to encapsulated isolates that were clonal within each serotype. Interestingly, ST103 and ST57 were the predominant STs among NTHi, with ST103 being associated with β-lactamase-producers and ST57 with non-β-lactamase-producers. In Portugal, susceptible and genetically diverse NTHi H. influenzae continues to be responsible for invasive disease, mainly in the elderly. Nevertheless, we are now concerned with Hib circulating in children we believe to have been vaccinated. Our data reiterates the need for continued surveillance, which will be useful in the development of public health prevention strategies.
Journal Article
Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates
by
Cherian, Thomas
,
Deloria-Knoll, Maria
,
Hajjeh, Rana
in
Bacterial Capsules
,
Child Mortality
,
Child, Preschool
2009
Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities.
We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years.
We calculated that Hib caused about 8·13 million serious illnesses worldwide in 2000 (uncertainty range 7·33–13·2 million). We estimated that Hib caused 371 000 deaths (247 000–527 000) in children aged 1–59 months, of which 8100 (5600–10 000) were in HIV-positive and 363 000 (242 000–517 000) in HIV-negative children.
Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality.
Gavi Alliance and the Vaccine Fund.
Journal Article
Haemophilus influenzae serotype a as a cause of serious invasive infections
by
Ulanova, Marina
,
Tsang, Raymond S W
in
Bacterial Capsules - metabolism
,
Biological and medical sciences
,
Epidemiology
2014
Haemophilus influenzae, particularly H influenzae serotype b (Hib), is an important pathogen that causes serious diseases like meningitis and septicaemia. Since the introduction of Hib conjugate vaccines in the 1990s, the epidemiology of invasive H influenzae disease has changed substantially, with most infections now caused by non-Hib strains. We discuss the importance of H influenzae serotype a (Hia) as a cause of serious morbidity and mortality and its global epidemiology, clinical presentation, microbiology, immunology, prevention, and control. Much like Hib, the capsule of Hia is an important virulence factor contributing to the development of invasive disease. Molecular typing of Hia has identified distinct clonal groups, with some linked to severe disease and high case-fatality rates. Similarities between Hia and Hib capsules, their clinical presentation, and immunology of infection suggest that a bivalent Hia–Hib capsular polysaccharide-protein conjugate vaccine could offer protection against these two important serotypes of H influenzae.
Journal Article
The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study
by
Murdoch, David R.
,
Levine, Orin S.
,
Kotloff, Karen L.
in
Child development
,
Child Welfare
,
Child, Hospitalized
2012
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.
Journal Article
Impact of the COVID-19 pandemic on Haemophilus influenzae infections in pediatric patients hospitalized with community acquired pneumonia
2024
The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare
Haemophilus influenzae
(
H. influenzae
) infections in pediatric CAP patients hospitalized before (2018–2019) and during (2020–2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of
H. influenzae
from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with
H. influenzae
-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients’ age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of
H. influenzae
isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients,
H. influenzae
infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of
H. influenzae
in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.
Journal Article
Increase in invasive Haemophilus influenzae type b disease in young children despite high vaccination coverage, France, 2018–2024
by
Deghmane, Ala-Eddine
,
Marie, Cécile
,
Taha, Muhamed-Kheir
in
Age groups
,
Allergy and Immunology
,
Child, Preschool
2025
The introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in France led to low invasive Hib disease incidence for two decades. In 2013, the vaccination schedule changed from 3+1 to 2+1 ((2, 4, and 11 months). Hib vaccination has been mandatory for children born since 2018. Despite vaccination coverage exceeding 95%, invasive Hib disease has increased since 2018. This study reports trends and characteristics of cases in mainland France from 2018 to 2024.
Cases were children under five years old with invasive Hib disease confirmed by culture or PCR by the National Reference Center for Haemophilus influenzae. Vaccination status was reported by biologists/clinicians or by regional investigation teams. Cases were described by age and vaccination status (unvaccinated, partially vaccinated, correctly vaccinated). Vaccine failure was defined as invasive Hib disease despite completion of the three-dose series. Vaccine effectiveness (VE) for three doses was estimated using the screening method in children aged 2-4 years.
The incidence of invasive Hib disease among children under 5 years old increased during the 2018-2024 period, peaking in 2021 with 46 cases (1.4/100,000 children). From 2018 to 2024, 181 cases of invasive Hib disease were reported. Among those aged 6-11 months (n=60), 76.7% were correctly vaccinated with two doses. In children ≥12 months (n=65), 67.7% were correctly vaccinated with three doses and there were 44 vaccine failures. The estimated VE for three doses was 91.2% [95% confidence interval: 76.3-96.8%].
Invasive Hib disease increased among children under 5 years old in France during 2018-2024, and most cases were correctly vaccinated. VE estimate do not suggest waning immunity. The reasons that may explain the increase in invasive Hib cases remain uncertain. Our results call for further studies on the VE following the two primary doses and the impact of vaccination on carriage.
•Invasive Hib cases increased among children <5 years old in France in 2018–2024.•77 % of children aged 6–11 months were correctly vaccinated with 2 primary doses.•44 vaccine failures were reported among children ≥12 months vaccinated with 3 doses.•Vaccine effectiveness for 3 doses was estimated at 91.2 % using the screening method.
Journal Article
Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil
by
Brandileone, Maria-Cristina de C.
,
Brandao, Angela P.
,
da Glória Carvalho, Maria
in
Allergy and Immunology
,
Brazil
,
Brazil - epidemiology
2016
•Vaccine-type pneumococcal carriage declined by >90% after PCV10 introduction.•Effectiveness of 4 PCV10 doses against carriage of vaccine serotypes was 97.3%.•No protection against carriage of vaccine-related serotypes (including 6A and 19A) was observed.•Colonization by non-typeable H. influenzae increased from 26.0% at baseline to 43.6% post-PCV10.
In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12–23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio×100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8–21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8–11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7–99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.
Journal Article