Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA

Since the introduction of the Haemophilus influenzae type b vaccine, the incidence of invasive H. influenzae type b disease among children has fallen dramatically, but the effect on invasive H. influenzae disease among adults may be more complex. In this population-based study we examined the epidemiology and outcomes of invasive disease caused by typeable and nontypeable H. influenzae among Utah adults during 1998-2008. The overall incidence increased over the study period from 0.14/100,000 person-years in 1998 to 1.61/100,000 person-years in 2008. The average incidence in persons >65 years old was 2.74/100,000 person-years, accounting for 51% of cases and 67% of deaths. The incidence was highest for nontypeable H. influenzae (0.23/100,000 person-years), followed by H. influenzae type f (0.14/100,000 person-years). The case-fatality rate was 22%. The incidence of invasive H. influenzae in Utah adults appears to be increasing. Invasive H. influenzae infection disproportionately affected the elderly and was associated with a high mortality rate.     

吸附无细胞百白破、灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTaP．IPV／Hib联疫苗)应用技术指南

百日咳、白喉、破伤风、脊髓灰质炎(脊灰)、b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)引起的感染性疾病是常见的严重危害人类健康,特别是儿童健康的传染病.预防接种是控制这五种疾病最经济、有效的措施,通常预防儿童这五种疾病需要分别接种吸附百白破联合疫苗(DPT)、口服脊灰减毒活疫苗(OPV)和Hib疫苗,幼儿完成全程免疫累计需要接种11剂次[1,2].儿童接种疫苗剂次的增加,不但增加服务的成本,且还会增加疑似预防接种异常反应的风险.国家食品药品监督管理局已于2010年批准吸附无细胞百白破(DTaP)、灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTaP-IPV/Hib五联疫苗,简称五联疫苗)在中国上市.接种五联疫苗预防上述五种疾病,幼儿完成全程免疫累计仅需接种4剂次[3].     

Changes in Haemophilus influenzae capsule locus: possible emergence of novel variants in Brazil

A total of 28 strains of Haemophilus influenzae (Hi) a and b isolated from clinical samples before and after the introduction of the Hib conjugate vaccine in Brazil were analyzed to determine variants of the capsular gene. Our results suggest the occurrence of new variants closely related to types I and II previously described elsewhere. Eleven Hib strains belonged to type I, 8 were type II, and 3 Hia strains were type II. Six strains showed negative results after polymerase chain reaction targeting capsule locus; the variable regions were sequenced and compared with types I and II. Phylogenetic analysis showed that 5 Hib strains were actually subtypes of type I (type I-A), whereas 1 Hia strain was a subtype of type II (type II-A). Types I and II strains were present in both periods of vaccination. This study suggests that a gradual change in the capsule genes of H. influenzae is probably occurring, and novel variants might be emerging among Brazilian isolates.     

Chloramphenicol-resistant Haemophilus influenzae meningitis in young urban Nigerian children

In a developing country like Nigeria, the unusual emergence of Haemophilus influenzae type b, resistant to cost-effective antimicrobials, is of serious concern. We report three cases of H. influenzae type b meningitis in young Nigerian children in whom clinical and bacteriological features of resistance to chloramphenicol were identified. One of the cases had concomitant resistance to ampicillin (multiple-drug resistance). Significant anaemia was an associated feature in two cases, one of whom had a recent measles infection. All three cases were malnourished. The possible mechanisms of antimicrobial resistance in H. influenzae infections are highlighted while the need for periodic surveillance of antibiotic resistance profiles in resource-poor countries is emphasized. The potential value of prophylactic measures like H. influenzae type b conjugate immunization is discussed.     

H.<Emphasis Type="Italic">influenzae type b</Emphasis> (Hib) vaccine – controversies

Hib vaccine is the 8th vaccine knocking at the door to be included in the EPI the world over. However there are some controversies that need to be addressed, especially when it comes to use of this vaccine in India. It is difficult to culture Hib unless one uses sheep blood enriched media for culture. There is a lack of good community based data on Hib burden in India. This makes many feel that Hib is rare in India. However this is not true. There are many studies that have looked at this closely. Hib is a common cause of meningitis and pneumonitis in children less than 5 years old in India. There is wide spread problem of multi–drug resistance by Hib in India. Mortality of meningitis is as high as 100% if third generation cephalosporins are not used in time. Of the survivors of meningitis, 60% develop long-term sequelae. Hib vaccine is very effective and can lead to 99% reduction with mass vaccination in just 2–3 years. It is also a very safe vaccine. Of the conjugated vaccines available in India all are equally effective and safe and there is nothing to choose one over the other. There is a need to give a booster dose at 15–18 months of age. Even UK, which never gave the booster dose, is seriously thinking of changing their practice and give a booster dose. Lastly the combination vaccines of Hib with IPV, DPwT/DPaT, and Hepatitis B are safe and effective and should be encouraged to improve the compliance. The use of Hib vaccine is recommended in India, for those who can afford the vaccine.     

Humoral immunity to diphtheria,tetanus, measles,and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re‐vaccination

Objective

Loss of immunity to previous vaccination and timing of re‐vaccination in children receiving chemotherapy remains controversial. The aim of this study was to investigate the immunity to vaccine preventable diseases in children with acute lymphoblastic leukemia (ALL).

Procedure

Sixty‐one patients with ALL and 13 healthy siblings were enrolled. Three study groups included newly diagnosed patients (group 1), patients on maintenance chemotherapy (group 2), and patients that completed chemotherapy (group 3). Blood samples for baseline antibody titers were obtained from all the patients and controls. Patients in group 2 were vaccinated with diphtheria, tetanus, and hemophilus influenzae type b (Hib). Patients in group 3 and controls received the measles vaccine in addition to all the above vaccines. In groups 2 and 3, post‐vaccination antibody titers were also obtained.

Results

Patients and controls had no Hib vaccine during primary vaccination. After chemotherapy median antibody levels against diphtheria, tetanus, measles, and Hib were decreased but tetanus antibodies were still at the protective levels. Proportions of the patients with protective levels were 11.1%, 83.3%, 16.7%, and 16.7% for diphtheria, tetanus, Hib, and measles, respectively. Vaccination achieved protective antibody levels in 81%, 100%, 89.5%, and 70% of the patients for diphtheria, tetanus, Hib, and measles, respectively. Vaccine responses during maintenance were also satisfying.

Conclusion

We recommend re‐vaccination after 3 months of cessation of chemotherapy. Administration of Hib vaccine may be beneficial after the first 3 months of maintenance chemotherapy especially in children with no primary vaccination followed by a second booster dose after cessation of therapy to increase immunity. Pediatr Blood Cancer 2009;53:967–972. © 2009 Wiley‐Liss, Inc.     

Comparison of serum bactericidal and antibody titers induced by two Haemophilus influenzae type b conjugate vaccines: A phase III randomized double-blind study

Haemophilus influenzae type b (Hib) conjugate vaccines have drastically reduced disease incidence worldwide. Protection against Hib infection has relied on the serum bactericidal activity (SBA) of antibodies to the Hib capsular polysaccharide (polyribosylribitol phosphate). However, licensure usually relies on measuring induction of antibodies to PRP as a surrogate for SBA. In a phase III clinical trial we compared a PRP-conjugate vaccine using the nontoxic diphtheria toxin mutant, CRM₁₉₇, as carrier protein with the licensed tetanus toxoid conjugate when administered subcutaneously as a three dose primary series in Japanese infants. As an addition to the phase III study, we have now evaluated SBA and show PRP-CRM₁₉₇ induces higher levels of SBA than PRP-T four weeks after the primary series, with a statistically significant correlation with anti-PRP titers. This data confirms the superior immunogenicity of PRP-CRM₁₉₇ compared with PRP-T assessed as SBA following a three-dose primary series by subcutaneous administration.Clinical trial registry: Registered on ClinicalTrials.gov (NCT01379846).     

吸附无细胞百白破、灭活脊髓灰质炎和b型流感嗜血杆菌（结合）联合疫苗（DTaP-IPV/Hib五联疫苗）应用技术指南

百日咳、白喉、破伤风、脊髓灰质炎（脊灰）、b型流感嗜血杆菌（Haemophilusinfluenzaetypeb,Hib）引起的感染性疾病是常见的严重危害人类健康,特别是儿童健康的传染病。预防接种是控制这5种疾病最经济、有效的措施,通常预防儿童这5种疾病要分别接种吸附百白破联合疫苗（DPT）、口服脊灰减毒活疫苗（OPV）和Hib疫苗,幼儿完成全程免疫累计需要接种11剂次。     

Validity and reliability of a survey to identify vaccine-hesitant parents

Objective

To assess the construct validity and reliability of the Parent Attitudes about Childhood Vaccines survey.

Study Design

Cross-sectional survey of parents of 19-35 month old children in a closed model HMO. We used factor analysis to confirm survey sub-domains and Cronbach's α to determine the internal consistency reliability of sub-domain scales. Construct validity was assessed by linking parental responses to their child's immunization record.

Results

Our response rate was 46% (N = 230). Factor analysis identified 3 factors that explained 70% of the total variance for the 18 survey items. We deleted 3 items that failed to load highly (>.4) on an identified factor, correlated poorly with other items, or had a hesitant response that was not associated with increased under-immunization. Cronbach's α coefficients for the 3 sub-domain scales created by grouping the remaining 15 items were .74, .84, and .74, respectively. Children of parents with survey scores of 50-79 had 14% more days under-immunized from birth to 19 months (95% CI: 8.0, 20.5) than those with parents who scored <50. Scores of ≥80 were associated with 51% more days under-immunized (95% CI: 38.2, 63.4).

Conclusion

The revised survey is a valid and reliable instrument to identify vaccine-hesitant parents.