Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

Comparability studies of hemin from two different origins porcine and bovine in the production of Haemophilus influenzae type b (Hib) polysaccharide.

Hemin is one of the critical components of medium required for growth of Haemophilus influenzae type b (Hib) organisms. It is important to have different sources of critical components to ensure continuous supply for commercial production. Regulatory bodies also recommend having multiple sources for critical components. Hemin is produced from animal blood and the main sources are porcine and bovine origin. The approved Hib vaccine of SIIPL used for immunization is produced using hemin obtained from porcine origin. The present work focuses on the comparison of the growth of organisms on a large scale using hemin from bovine or porcine origin. Purified polysaccharide obtained using bovine source is tested with respect to the set WHO specifications as recommended by regulatory bodies and compared with commercial lots of PRP obtained from using hemin of porcine source. Identical product profile and quality attributes were obtained for PRP produced using bovine hemin and the regular commercial product suggests that there is no change in the product. Hemin from bovine source can be used as a replacement for hemin from porcine source in the fermentation medium for country specific requirement of Hib conjugate vaccine as long as it meets the guidelines on TSE/BSE risk.

Association of ß-Lactam-Sensitive Haemophilus influenzae Type B with Adenoid Biofilm Formation in Patients with Adenoidectomy Surgery.

BACKGROUND: Chronic adenoid infection by ß-lactam-resistant Haemophilus influenzae type b (Hib) and biofilm formation contribute to adenoid hyperplasia. Middle ear disease consequently remains a critical issue in the pediatric population. The aim of this study was to investigate the correlation of Hib biofilm formation with middle ear effusion with adenoid hyperplasia (MEE-AH) and with pediatric obstructive sleep apnea (OSA). METHODS: A total of 384 patients with adenoidectomy from January 2008 to December 2012 were recruited in this investigation. Thirty-two patients (14 female and 18 male; age 4-13 years) who obtained routine adenoidectomy surgery had Hib-positive cultures were enrolled in a retrospective manner. By using polysomnography, 18 patients were diagnosed as having MEE-AH with chronic adenotonsillitis, and 14 patients were diagnosed as having pediatric OSA. The results of the Hib biofilm, antibiotic resistance profiles, and scanning electron microscopy observation, which correlated with the clinical diagnosis, were analyzed by the chi-square test and Fisher exact test. RESULTS: Biofilm formation by Hib was significantly present in the patients with MEE-AH rather than patients with OSA. ß-lactam-sensitive Hib were resistant to augmentin because of the adenoid biofilm formation. However, this finding was uncommon in the pediatric OSA group. CONCLUSIONS: Properly treating ß-lactam-sensitive Hib infection may be an important issue in reducing MEE-AH and adenoid vegetation in the pediatric population. Further research is warranted to elucidate the association of Hib-related biofilm formation with treatment failure and the need to consider earlier surgical intervention.

The seroepidemiology of Haemophilus influenzae type b prior to introduction of an immunization programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease.

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.

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.

Architecture and adhesive activity of the Haemophilus influenzae Hsf adhesin.

Haemophilus influenzae type b is an important cause of meningitis and other serious invasive diseases and initiates infection by colonizing the upper respiratory tract. Among the major adhesins in H. influenzae type b is a nonpilus protein called Hsf, a large protein that forms fiber-like structures on the bacterial surface and shares significant sequence similarity with the nontypeable H. influenzae Hia autotransporter. In the present study, we characterized the structure and adhesive activity of Hsf. Analysis of the predicted amino acid sequence of Hsf revealed three regions with high-level homology to the HiaBD1 and HiaBD2 binding domains in Hia. Based on examination of glutathione S-transferase fusion proteins corresponding to these regions, two of the three had adhesive activity and one was nonadhesive in assays with cultured epithelial cells. Structural modeling demonstrated that only the two regions with adhesive activity harbored an acidic binding pocket like the binding pocket identified in the crystal structure of HiaBD1. Consistent with these results, disruption of the acidic binding pockets in the adhesive regions eliminated adhesive activity. These studies advance our understanding of the architecture of Hsf and the family of trimeric autotransporters and provide insight into the structural determinants of H. influenzae type b adherence.

La exposición al tabaco como factor de riesgo de enfermedad invasora en niños / Exposure to tobacco smoke as a risk factor for invasive disease in children

La gran mayoría de niños expuestos al tabaco no eligen esta exposición. Se estima que alrededor de la mitad de los niños se encuentran en un ambiente contaminado por el humo del tabaco, particularmente en su domicilio. Los resultados obtenidos en los estudios sobre tabaco y enfermedad invasora por Haemophilus influenzae tipo B y Streptococcus pneumoniae no son consistentes; se precisan nuevas investigaciones que aporten mayor evidencia con respecto a esta posible asociación, ya que determinados hallazgos biológicos apuntan hacia ella. La exposición al tabaco en los niños aumenta el riesgo de padecer enfermedad invasora por meningococo; así lo confirman varios estudios en los que existe una importante fuerza de asociación después de haber ajustado por posibles variables de confusión. Estos hallazgos aumentan la evidencia del efecto perjudicial del tabaco en la salud infantil. Toda estrategia encaminada a la reducción de esta exposición contribuirá a mejorar la salud infantil; en este sentido, hay que hacer hincapié en la conveniencia de no fumar en presencia del niño y, fundamentalmente, en el domicilio

The great majority of children who are exposed to tobacco smoke do not choose this exposure. It is estimated that about half of all children are subjected to environments contaminated by tobacco smoke, mainly at home. The results of studies of the association between exposure to tobacco smoke and risk for invasive Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae are not consistent and further studies providing greater evidence of a relationship will be necessary since there are certain biological findings that suggest that it exists. Exposure to tobacco smoke increases the risk of invasive meningococcal disease in children, as has been shown in a number of studies that have demonstrated a strong association after adjustment for different confounding variables. These findings increase the body of evidence of the harmful effect of tobacco smoke on children's health. Any strategy aimed at reducing the exposure of children to tobacco smoke will improve their health. It is important to educate parents and the importance of avoiding smoking in the household should be stressed

[Study on Haemophilus influenzae type b: data from autopsy of community acquired pneumonia among children].

OBJECTIVE: To evaluate the status of Haemophilus influenza type b(Hib) on death cases of children from community-acquired pneumonia (CAP) and to estimate the value of direct in-situ polymerase chain reaction (ISPCR) on diagnosis of children CAP, pathogenically. METHODS: Ordinary PCR, Southern blot and direct ISPCR were applied and compared in detecting Hib in 100 paraffin-embedded lung tissues of autopsy children died of CAP. RESULTS: No major difference on the detection rate of Hib between 50-60s and 80s-2002 was found. The detection rate of Hib by direct ISPCR was higher than the other two methods. By Southern blot, Hib was identified from 8 out of 100 samples (8%), including 4 out of 56 in 1950-60s (7.1%) and 4 out of 44 (9.1%) (chi2 = 0.084, P>0.05) in 1980s-2002. By ISPCR, Hib was identified from 17 out of 100 samples (17%), including 8 out of 56 in 1950-60s (14.3%) and 9 out of 44 (20.5%) with chi2 = 0.665, P > 0.05, in 1980s-2002. Positive cases diagnosed by both Southern blot and ISPCR were 7%. CONCLUSION: Hib was one of the main bacterial pathogens causing CAP and deaths among children. Direct ISPCR was prefertable to be used in pathogenic diagnosis on children pneumonia, in terms of its sensitivity, specificity and localization.

Haemophilus influenza cellulitis. A review and case report.

Buccal cellulitis resulting from Haemophilus Influenzae type B (Hlb) is an uncommon yet potentially life-threatening illness that afflicts the facial soft tissues of the very young. Early recognition is essential for the effective treatment of this illness. A clinical case of Haemophilus Influenzae buccal cellulitis is presented, accompanied by a discussion of the presenting symptoms, diagnosis and treatment of this unusual childhood infection.

Structure and function of Hib pili from Haemophilus influenzae type b.

Pathogenic bacteria are specifically adapted to bind to their customary host. Disease is then caused by subsequent colonization and/or invasion of the local environmental niche. Initial binding of Haemophilus influenzae type b to the human nasopharynx is facilitated by Hib pili, filaments expressed on the bacterial surface. With three-dimensional reconstruction of electron micrograph images, we show that Hib pili comprise a helix 70 A in diameter with threefold symmetry. The Hib pilus filament has 3.0 subunits per turn, with each set of three subunits translated 26.9 A along and rotated 53 degrees about the helical axis. Amino acid sequence analysis of pilins from Hib pili and from P-pili expressed on uropathogenic Escherichia coli were used to predict the physical location of the highly variable and immunogenic region of the HifA pilin in the Hib pilus structure. Structural differences between Hib pili and P-pili suggest a difference in the strategies by which bacteria remain bound to their host cells: P-pili were shown to be capable of unwinding to five times their original length (E. Bullitt and L. Makowski, Nature 373:164-167, 1995), while damage to Hib pili occurs by slight shearing of subunits with respect to those further along the helical axis. This capacity to resist unwinding may be important for continued adherence of H. influenzae type b to the nasopharynx, where the three-stranded Hib pilus filaments provide a robust tether to withstand coughs and sneezes.

The numbers of leukocyte subsets in lung sections differ between intercellular adhesion molecule-1-/-, lymphocyte function-associated antigen-1-/- mice and intercellular adhesion molecule-1-/- mice after aerosol exposure to Haemophilus influenzae type-b.

In order to investigate the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in pulmonary immunological processes, leukocyte populations were stained immunohistochemically on cryostat lung sections of ICAM-1-/- and LFA-1-/- mice. A further group of ICAM-1-/- mice was exposed to Haemophilus influenzae type-b (Hib) 24 h before being sacrificed. Comparison of the numbers of leukocytes in these groups revealed different behaviors of the leukocyte subsets: granulocytes were significantly increased in all three groups. Lymphocytes were increased in ICAM-1-/- mice, while there was no significant difference in LFA-1-/- and even a decrease in ICAM-1-/- mice after Hib exposure. Neither in ICAM-1-/- nor in LFA-1-/- mice did macrophages and dendritic cells (DCs) show significant differences to control animals. After Hib exposure, a significant elevation of DCs was observed. The following conclusions can be drawn: (1) all investigated leukocyte subsets can use ICAM-1- and LFA-1-independent pathways in the lungs of mice; (2) the pathways used by the leukocytes are cell-type specific; (3) ICAM-1 plays an important role in the enhanced recruitment of lymphocytes during Hib challenge in the lung; and (4) the alternative migratory mechanisms are able to compensate for the absence of ICAM-1 or LFA-1 or even lead to increased cell numbers. This overcompensation can be seen as a result of a balance between active alternative migratory mechanisms, which takes place in the absence of ICAM-1 or LFA-1.