Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use.

Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged <5 years. Its major virulence factor is the polyribosyl ribitol phosphate (PRP) polysaccharide capsule. In the 1980s, PRP-protein conjugate Hib vaccines were developed and are now included in almost all national immunization programs, achieving a sustained decline in invasive Hib infections. However, invasive Hib disease has not yet been eliminated in countries with low vaccine coverage, and sporadic outbreaks of Hib infection still occur occasionally in countries with high vaccine coverage. Over the past 2 decades, other capsulated serotypes have been recognized increasingly as causing invasive infections. H. influenzae serotype a (Hia) is now a major cause of invasive infection in Indigenous communities of North America, prompting a possible requirement for an Hia conjugate vaccine. H. influenzae serotypes e and f are now more common than serotype b in Europe. Significant year-to-year increases in nontypeable H. influenzae invasive infections have occurred in many regions of the world. Invasive H. influenzae infections are now seen predominantly in patients at the extremes of life and those with underlying comorbidities. This review provides a comprehensive and critical overview of the current global epidemiology of invasive H. influenzae infections in different geographic regions of the world. It discusses those now at risk of invasive Hib disease, describes the emergence of other severe invasive H. influenzae infections, and emphasizes the importance of long-term, comprehensive, clinical and microbiologic surveillance to monitor a vaccine's impact.

An explosive outbreak of Streptococcus pneumoniae serotype-8 infection in a highly vaccinated residential care home, England, summer 2012.

In August 2012, an explosive outbreak of severe lower respiratory tract infection (LRTI) due to Streptococcus pneumoniae serotype-8 occurred in a highly vaccinated elderly institutionalized population in England. Fifteen of 23 residents developed LRTI over 4 days (attack rate 65%); 11 had confirmed S. pneumoniae serotype-8 disease, and two died. Following amoxicillin chemoprophylaxis and pneumococcal polysaccharide vaccine (PPV) re-vaccination no further cases occurred in the following 2 months. No association was found between being an outbreak-associated case and age (P = 0.36), underlying comorbidities [relative risk (RR) 0.84 95% confidence interval (CI) 0.34-2.09], or prior receipt of PPV (RR 1.4, 95% CI 0.60-3.33). However, the median number of years since PPV was significantly higher for cases (n = 15, 10.2 years, range 7.3-17.9 years) than non-cases (n = 8, 7.2 years, range 6.8-12.8 years) (P = 0.045), provided evidence of waning immunity. Alternative vaccination strategies should be considered to prevent future S. pneumoniae outbreaks in institutionalized elderly populations.

Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines.

We report an enhanced prospective survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b (Hib) vaccination program. During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b; most (89%) of these infections occurred in children <5 years of age and the most common presentation was meningitis. Since the introduction of routine immunization of infants with conjugate Hib vaccine, there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children <5 years of age. This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs. The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period, emphasizing the need for continued surveillance. There was no increase in the number of infections caused by other serotypes. Diagnostic category varied with both age and serotype but was not affected by vaccine introduction; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates.

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

Comparison of the epidemiology and cost of Haemophilus influenzae type b disease in five western countries.

To determine and compare the cost of Haemophilus influenzae type b (Hib) disease in Australia, Finland, Israel, Switzerland and the United Kingdom a collaborative study was undertaken. The incidence of Hib disease varies in these 5 countries from 34 to 58.5 cases per 100,000 children less than 5 years of age. Although the incidence of meningitis in this age group is similar (between 18 and 26/100,000) in these countries, the incidence of epiglottitis varies from 0 to 22.7/100,000. The cost of hospitalization and the frequency of sequelae are similar for 4 of the 5 countries; however, the break even cost of a vaccination program to prevent 90% of Hib disease is estimated to vary from $22 to $84 per child (US$). Because of a lower incidence of Hib disease and lower cost for hospitalization, these costs are considerably less than those for the United States ($301.64 using similar calculations).

Clinical and microbiological features of Haemophilus influenzae vulvovaginitis in young girls.

AIMS: To define the clinical and microbiological features of vulvovaginitis in prepubertal girls whose genital swabs yielded Haemophilus influenzae. METHODS: Laboratory based study and retrospective collection of clinical data from the requesting doctors. RESULTS: Thirty eight isolates of non-capsulate Haemophilus influenzae and one of H parainfluenzae were isolated from 32 girls aged 18 months to 11 years. No other pathogens, such as beta haemolytic streptococci or yeasts, were present with H influenzae. The most common biotype was biotype II, comprising 57% of the 26 isolates biotyped. Six children had more than one episode of vulvovaginitis caused by H influenzae and a total of 14 children had recurrent vaginal symptoms. CONCLUSION: Children who have H influenzae vulvovaginitis are at risk of recurrent symptoms. Biotype II is the one most commonly associated with this condition.

The Fluoretec system for rapid diagnosis of bacteroides infections by direct immunofluorescence of clinical specimens.

Fluoretec, a commercial kit for the rapid diagnosis by immunofluorescence of infections caused by Bacteroides spp was compared with a standard culture method. A total of 1010 specimens were tested for the presence of B fragilis group by Fluoretec F and B melaninogenicus-oralis and asaccharolytic groups by Fluoretec M. Fluoretec F was positive in 123/152 specimens culturing B fragilis group strains. Seventeen specimens were positive by Fluoretec F but negative on culture. Fluoretec M was positive in 21 of 22 specimens from which B melaninogenicus was cultured. The Fluoretec system was convenient in use, results being obtained within one hour of receipt of the specimen.

A simple and safe volumetric alternative to the method of Miles, Misra and Irwin for counting viable bacteria.

A rapid and simple method for counting viable bacteria is described. The technique involves the use of a semi-automatic micropipette and disposable glass-capillary tubes. Viable counts obtained by this method were not significantly different from those obtained by the Miles, Misra and Irwin method or by a pour-plate method. The micropipette procedure is less hazardous than techniques involving the use of calibrated dropping pipettes.

Synovial fluid lactate and the diagnosis of septic arthritis.

To assess the value of synovial fluid lactate estimation in the diagnosis of septic arthritis, 238 specimens received for routine culture and 75 reference samples were examined using a rapid enzyme technique. Samples were collected without special treatment and the effect of delay in transport to the laboratory investigated. Raised levels were found in all cases of untreated septic arthritis, in six out of ten partially treated patients and in 19 out of 219 non-septic fluids. Special treatment of the sample was unnecessary if it was examined within six hours of aspiration. The predictive value of a negative result was 98 per cent and the value of the test appeared to be in the rapid exclusion of sepsis in untreated patients.

Hepatobiliary infections due to non-capsulated Haemophilus influenzae.

We present two cases of non-capsulated Haemophilus influenzae hepatobiliary infection and review the literature. Such cases are rare, and prior to routine immunization against H. influenzae serotype b invasive Haemophilus disease was largely caused by capsulated strains. The epidemiology of invasive Haemophilus infections has changed and the number of cases of intra-abdominal and hepatobiliary infection may be underestimated due to current microbiological processing practices.

Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes.

The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

Genetic characteristics of pneumococcal disease in elderly patients before introducing the pneumococcal conjugate vaccine.

Streptococcus pneumoniae strains causing invasive pneumococcal disease (IPD) in the elderly population of England and Wales during the winter of 2003/2004 (1 November 2003 to 30 April 2004) were characterized by serotyping and genotyping in order to determine their population structure in the elderly. Serotyping and multilocus sequence typing (MLST) were carried out on 542 invasive isolates referred to the Respiratory and Systemic Infection Laboratory. Pneumococci were distributed among 32 serotypes and 144 MLST sequence types. A high genetic diversity was observed within the major serotypes. Genetic relatedness varied with regard to serotype. Isolates within serotypes 3, 7F and 8 were the most genetically related whereas serotypes 6A and 19F comprised isolates originating from unrelated ancestors. There was indirect evidence that some pneumococci were derived from clones that had undergone capsular switching in the past. Interestingly one case of IPD was caused by a pneumococcus originating from a clone that had undergone capsular switching from serotype 18C, a serotype included in 7-valent pneumococcal conjugate vaccine (PCV) to serotype 1 (serotype not included in PCV) suggesting that virulent clones with the potential ability to evade PCV existed in the pneumococcal population prior to the routine introduction of this vaccine. Isolates from 28 cases of apparent 23-valent pneumococcal polysaccharide vaccine (PPV) failure were included but there was no evidence of the emergence of particular clones associated with vaccine failures. Longitudinal studies based on serotypic and genetic characterization of pneumococci are fundamental to understanding the impact of both PPV and PCV on the genetic structure of pneumococcal populations.