Presence of Antibodies Against Haemophilus influenzae Serotype a in Alaska Before and After the Emergence of Invasive Infections.

BACKGROUND: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. Haemophilus influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska. METHODS: We quantified immunoglobulin G antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades before (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race. RESULTS: The anti-Hia was >0.1 µg/mL in 88.1% (348 of 395) and 91.0% (404 of 444) of samples from the decades prior and after the emergence of Hia, respectively (P = .17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 vs 2.08 µg/mL, P = .91 for age ≥5) or between AN and non-AN people (2.50 vs 2.60 µg/mL, P = .26). CONCLUSIONS: Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease.

[Vaccination against Haemophilus influenzaetype b; why and how?] / Vaccinatie tegenHaemophilus influenzaetype b.

After a development period of around 13 years, in 1993 the vaccination against infections caused by Haemophilus influenzae type b (Hib) was introduced into the Dutch National Immunisation Programme. Before the introduction of the vaccination, the burden of disease was high; every year around 700 children acquired an invasive Hib infection, half of whom developed meningitis. Of those children with Hib-related meningitis, 2% died and more than 8% were left with severe residual symptoms. Furthermore, at least one-third of those who recovered developed learning and concentration problems. Hib also caused other infections such as epiglottitis, osteomyelitis and arthritis. Initially, the conjugated Hib vaccine PRP-T was given as a separate injection. From 2005 onwards PRP-T was included in the combination DTaP-IPV-Hib vaccine, and since 2011 PRP-T has been part of the DTaP-IPV-Hib-HepB vaccine. Although H. influenzae is still around, invasive Hib infections in children now occur only very rarely.

Hospitalization rates and outcome of invasive bacterial vaccine-preventable diseases in Tuscany: a historical cohort study of the 2000-2016 period.

BACKGROUND: Invasive bacterial diseases (IBD) are a serious cause of hospitalization, sequelae and mortality. Albeit a low incidence, an increase in cases due to H. influenzae was registered in the past 4 years and, in the Tuscany region, an excess of cases due to N. meningitidis since 2015 is alarming. The purpose of this study is to deepen the knowledge of IBD epidemiology in Tuscany with particular attention to temporal trends. METHODS: Tuscan residents hospitalized for IBD from January 1st 2000 to March 18th 2016 were selected from the regional hospital discharge database based on ICD-9-CM codes. Age-specific and standardized hospitalization rates were calculated together with case-fatality rates (CFRs). A time-trend analysis was performed; whereas, prognostic factors of death were investigated through univariable and multivariable analyses. RESULTS: The average standardized hospitalization rates for invasive meningococcal diseases (IMD), invasive pneumococcal diseases and invasive diseases due to H. influenzae from 2000 to 2016 were 0.6, 1.8, and 0.2 per 100,000, respectively. The average CFRs were 10.5%, 14.5% and 11.5% respectively with higher values in the elderly. Older age was significantly associated with higher risk of death from all IBD. A significant reduction in hospitalization rates for IMD was observed after meningococcal C conjugate vaccine introduction. The Annual Percentage Change (APC) was -13.5 (95% confidence interval (CI) -22.3; -3.5) in 2005-2013 but has risen since that period. Furthermore, a significant increasing trend of invasive diseases due to H. influenzae was observed from 2005 onwards in children 1-4 years old (APC 13.3; 95% CI 0; 28.3). CONCLUSIONS: This study confirms changes in the epidemiology of invasive diseases due to H. influenzae and IMD. Furthermore, attention is called to the prevention of IBD in the elderly because of the age group's significantly higher rate of hospitalizations and deaths for all types of IBD.

Clinical and Molecular Epidemiology of Childhood Invasive Nontypeable Haemophilus influenzae Disease in England and Wales.

INTRODUCTION: In countries with established Haemophilus influenzae type b (Hib) immunization programs, nontypeable H. influenzae (NTHi) is now responsible for nearly all invasive H. influenzae cases across all age groups. METHODS: Public Health England (PHE) conducts enhanced national surveillance of invasive H. influenzae disease in England and Wales. Invasive NTHi isolates submitted to Public Health England from children of ages 1 month to 10 years during 2003-2010 were characterized by multilocus sequence typing (MLST). Detailed clinical information was obtained for all laboratory-confirmed cases of invasive NTHi disease in children during 2009-2013. RESULTS: In England and Wales, there were 7797 cases of invasive H. influenzae disease diagnosed during 2000-2013 and 1585 (20%) occurred in children aged 1 month to 10 years, where NTHi was responsible for 31-51 cases (incidence, 0.53-0.92/100,000) annually. Detailed clinical follow-up of 214 confirmed NTHi cases diagnosed in this age-group during 2009-2013 revealed that 52% (n = 111) occurred in <2-year-old and 52% (n=110) had comorbidity. Bacteremic pneumonia was the most common clinical presentation (n = 99, 46%), 16% (n = 34) required intensive care and 11% (n = 23) died. Characterization by biotyping and MLST of 316 NTHi strains from children with invasive disease during 2003-2010 revealed a genetically heterogeneous population (155 MLSTs) with diverse biotypes and no association with comorbidity status, clinical disease or outcome. CONCLUSIONS: The high level of genetic diversity in invasive NTHi strains highlights the difficulties in developing an effective vaccine against this pathogen.

Past, present and future of macrolide therapy for chronic rhinosinusitis in Japan.

In 1984, the effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after implementation of macrolide therapy. The usefulness of this treatment has since been demonstrated in patients with other chronic airway diseases, such as chronic bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and roxithromycin and the 15-membered macrolide azithromycin are also effective for treating these inflammatory diseases. The mechanism of action of the 14- and 15-membered macrolides may involve anti-inflammatory rather than anti-bacterial activities. Macrolide therapy is now widely used for the treatment of CRS in Japan; it is particularly effective for treating neutrophil-associated CRS and is useful for suppressing mucus hypersecretion. However, macrolide therapy is not effective for eosinophil-predominant CRS, which is characterized by serum and tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial asthma. Recent reports have described the clinical efficacy of macrolides in treating other inflammatory diseases and new biological activities (e.g., anti-viral). New macrolide derivatives exhibiting anti-inflammatory but not anti-bacterial activity thus have therapeutic potential as immunomodulatory drugs. The history, current state, and future perspectives of macrolide therapy for treating CRS in Japan will be discussed in this review.

Levofloxacin-resistant haemophilus influenzae, Taiwan, 2004-2010.

Levofloxacin resistance in Haemophilus influenzae has increased significantly in Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular investigations of 182 levofloxacin-resistant isolates revealed that the increase was mainly the result of the spread of several clones in the elderly population in different regions.

Leaning in to the power of the possible: the crucial role of women scientists on preventing Haemophilus influenzae type b disease.

Beginning in an era when female scientists were a lonely minority, women have made major contributions to our understanding of Haemophilus influenzae type b (Hib) as a pathogen, its treatment and its prevention. The individual scientific and public health contributions, and their collective impact, are reviewed in the context of the development and successful implementation of highly efficacious Hib vaccines that are now being deployed to nearly every country worldwide for the prevention of life-threatening pediatric Hib disease.

Haemophilus influenzae serotype a invasive disease, Alaska, USA, 1983-2011.

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.

The state of science, microbiology, and vaccines circa 1918.

The influenza pandemic of 1918-1919 dramatically altered biomedical knowledge of the disease. At its onset, the foundation of scientific knowledge was information collected during the previous major pandemic of 1889-1890. The work of Otto Leichtenstern, first published in 1896, described the major epidemiological and pathological features of pandemic influenza and was cited extensively over the next two decades. Richard Pfeiffer announced in 1892 and 1893 that he had discovered influenza's cause. Pfeiffer's bacillus (Bacillus influenzae) was a major focus of attention and some controversy between 1892 and 1920. The role this organism or these organisms played in influenza dominated medical discussion during the great pandemic. Many vaccines were developed and used during the 1918-1919 pandemic. The medical literature was full of contradictory claims of their success; there was apparently no consensus on how to judge the reported results of these vaccine trials. The result of the vaccine controversy was both a further waning of confidence in Pfeiffer's bacillus as the agent of influenza and the emergence of an early set of criteria for valid vaccine trials.

Emergence and disappearance of a virulent clone of Haemophilus influenzae biogroup aegyptius, cause of Brazilian purpuric fever.

SUMMARY: In 1984, children presented to the emergency department of a hospital in the small town of Promissão, São Paulo State, Brazil, with an acute febrile illness that rapidly progressed to death. Local clinicians and public health officials recognized that these children had an unusual illness, which led to outbreak investigations conducted by Brazilian health officials in collaboration with the U.S. Centers for Disease Control and Prevention. The studies that followed are an excellent example of the coordinated and parallel studies that are used to investigate outbreaks of a new disease, which became known as Brazilian purpuric fever (BPF). In the first outbreak investigation, a case-control study confirmed an association between BPF and antecedent conjunctivitis but the etiology of the disease could not be determined. In a subsequent outbreak, children with BPF were found to have bacteremia caused by Haemophilus influenzae biogroup aegyptius (H. aegyptius), an organism previously known mainly to cause self-limited purulent conjunctivitis. Molecular characterization of blood and other isolates demonstrated the clonal nature of the H. aegyptius strains that caused BPF, which were genetically distant from the diverse strains that cause only conjunctivitis. This led to an intense effort to identify the factors causing the unusual invasiveness of the BPF clone, which has yet to definitively identify the virulence factor or factors involved. After a series of outbreaks and sporadic cases through 1993, no additional cases of BPF have been reported.

Molecular characterization of a pre-Columbian mummy and in situ coprolite.

The history of Homo sapiens dispersal around the world and inherent interpopulation contacts and conflicts has given rise to several transitions in his relationships with the natural world, with the final result of changes in the patterns of infectious disease (McMichael [2001] Ecosystem Health 7:107-115). Of particular interest, in this context, is the contact between Amerindians and Europeans that started at the end of the 15th century, and the resulting exchange of microbes. We successfully recovered ancient DNA from a pre-Columbian mummy from Cuzco (Peru), radiocarbon-dated to 980-1170 AD, for which consistent mtDNA amplifications and sequences were obtained. The analysis of mtDNA revealed that the mummy's haplogroup was characteristic of Native American populations. We also investigated a sample of feces directly isolated from the intestines of the mummy, using a polymerase chain reaction system designed to detect the broadest spectrum of bacterial DNAs. The analysis of results, following a criterion of "paleoecological consistency" (Rollo and Marota [1998] Philos. Trans. R. Soc. Lond. [Biol.] 354: 111-119), demonstrated that some vestiges of the original microbial flora of the feces were preserved. In particular, we were able to identify the DNA of Haemophylus parainfluenzae, thus suggesting that this recently recognized pathogen was present in precontact Native Americans.

Haemophilus influenzae: then and now.

Haemophilus influenzae has long been recognised as a major cause of serious infection and mortality in children less than 5 years old. Prior to the introduction of Haemophilus influenzae type b (Hib) immunisation, the incidence of a child suffering an invasive Haemophilus infection was 20-50/100,000 in industrialised countries and up to ten times higher in developing regions. The introduction of a Hib vaccine programme results in a rapid and dramatic decline in the incidence of Hib infection in the susceptible childhood population. For example, within two years of the introduction of routine Hib vaccination of infants in the UK, the risk of serious Hib infection had fallen from 1:600 to 1:30,000 by 5 years of age. Many other European countries have introduced, or are in the process of introducing, a routine Hib immunisation programme. Because the epidemiology of Haemophilus influenzae infection is changing so dramatically, it is opportune to review Haemophilus influenzae as it was perceived in the pre-vaccine era (the past) and during vaccine implementation (the present), and how its role may change in the post-vaccination era (the future). This review will summarise the historical landmarks that have led to our present-day understanding of Haemophilus influenzae pathogenicity, the concerns about antibiotic resistance, the features of the host immune response to Haemophilus influenzae, and the introduction of the Hib vaccine. Furthermore, the possible importance of this organism in the future will be discussed.