Invasive Hib Disease Research Articles

P13 ‐ Vaccination against Haemophilus B as a treatment of recurrent upper respiratory tract infections

Haemophilus influenza b (Hib) conjugate vaccines are highly immunogenic in infants, as >95% develop protective antibody levels after 2 or 3 doses; hence invasive Hib disease is now uncommon in vaccinated children. The precise protective level is not clearly established, although a titre of 1 μg/mL is considered to offer long-term protection. Hib vaccination above the age of 5 is not recommended; the majority of older even unvaccinated children seem to be immune to Hib, probably from asymptomatic infections in infancy. The vaccine though is used in any age as a functional assay of the responsiveness of the immune system to capsular polysaccharide antigens, We present 3 children with recurrent upper respiratory tract infections where the test vaccine has also acted in a therapeutic manner. 1) A 6 yr old boy was referred to us for urticaria. His mother mentioned frequent “colds” requiring antibiotics several times a year. His serum Immunoglobulins and routine investigations were normal/negative except for the functional Hib antibody levels which were suboptimal at 0.22 μg/mL rising to >10 μg/mL 4 weeks post-vaccination, when the recurrent infections stopped. 2) Another 6 yr old was referred with eczema and the mother mentioned that he had been investigated inconclusively for unexplained lethargy. He was blowing green mucus from his “constantly blocked nose”; his functional Hib antibody levels were suboptimal at <0.15 rising eventually to 1.7 μg/mL after 3 vaccinations, which stopped the subclinical sinusitis and of course the lethargy. 3) A third child was seen for nut allergy. He missed his follow-up appointments for 18 months because he was constantly having respiratory infections, which caused bronchiectasis. A sputum sample at the time of the diagnosis grew Haemophilus (not typed) and started prophylactic antibiotics. A blood test a month later showed suboptimal levels of functional antibody and subsequently excellent response to the vaccination; the infections stopped, although one could argue this was an effect of the prophylactic antibiotics. Our relevant adult and paediatric data is currently being studied and processed as this is a new therapeutic aspect.

Meningitis in a School-Aged Child due to Haemophilus influenzae Type E during the Post-Conjugate Vaccine Era-Monroe County, NY, 2011.

In late October 2011, the Monroe County Department of Public Health (MCDPH) was notified of a suspected case of meningitis in a 9-year old girl from Monroe County, NY. Laboratory testing at the New York State Department of Health (NYSDOH) Wadsworth Center confirmed the identification of Haemophilus influenzae serotype e (Hie) isolated from the patient’s cerebrospinal fluid (CSF) using real-time polymerase chain reaction (RT-PCR). The universal immunization of infants with conjugate H. influenzae type b (Hib) vaccine has significantly reduced the incidence of invasive Hib disease, including meningitis, one of the most serious complications for infected children. Not surprisingly, as the epidemiology of invasive H. influenzae continues to change, non-Hib serotypes will likely become more common. The findings reported here underscore the importance for clinicians, public health officials, and laboratory staff to consider non-Hib pathogens in pediatric cases of meningitis, especially when initial investigations are inconclusive.

Estimation of the herd protection of Haemophilus influenzae type b conjugate vaccine against radiologically confirmed pneumonia in children under 2 years old in Dhaka, Bangladesh

Background Herd protection of Haemophilus influenzae type b (Hib) conjugate vaccine has been associated with excessive decrease of invasive Hib diseases, i.e., pneumonia and meningitis, with increased national or regional Hib vaccine coverage. Only a few studies have examined herd protection at the individual level and even less evidence is available from Asia. We examined Hib vaccine herd protection against radiologically confirmed pneumonia among children less than 2 years old.Methods We incorporated data from a matched case-control study and a vaccine coverage survey in Dhaka, Bangladesh. Pneumonia cases (n=343) were confirmed by radiology. For each case, two controls with conditions other than pneumonia or meningitis were selected from the same hospital. Hib vaccine coverage was calculated as percentages of children who received at least 2 doses of Hib vaccine from a survey in the neighborhood centered on each case and control. Conditional logistic regression was fit to examine the association between vaccine coverage and risk of radiologically confirmed pneumonia.Results Neighborhood Hib vaccine coverage varied from 0% to 63.5% for cases and from 8.7% to 61.5% for controls, respectively. Cases were less likely to have neighborhood coverage higher than 20% (OR=0.49, 0.52, 0.55, and 0.69 for coverage 20–29%, 30–39%, 40–49%, and ≥50%, respectively) than coverage <20%, compared to controls, although the estimates for coverage 40–49% and ≥50% were not statistically significant.Conclusions The study indicates that Hib vaccine may provide herd protection, even when the coverage is as low as 20–39%, in a low-income country. Asian countries should consider herd protection in implementing effective vaccine policy with limited resources.

Effectiveness of Haemophilus influenzae Type b Vaccines Administered According to Various Schedules

Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear. We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis. Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE>90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series. Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.

Invasive Haemophilus influenzae Type b Disease in England and Wales: Who Is at Risk After 2 Decades of Routine Childhood Vaccination?

The introduction of the Haemophilus influenzae serotype b (Hib) conjugate vaccine into national immunization has led to rapid and sustained declines in invasive Hib disease incidence across all age groups. In industrialized countries with established Hib vaccination programs, however, little is known about individuals who develop invasive Hib disease. This study describes the epidemiology of invasive Hib disease in England and Wales during 2000-2012 and the clinical characteristics of laboratory-confirmed Hib cases diagnosed during 2009-2012. Public Health England (PHE) conducts enhanced national surveillance of invasive Hib disease in England and Wales. Detailed clinical information was obtained for all laboratory-confirmed Hib cases diagnosed during 2009-2012. Invasive Hib disease in England and Wales has been declining since 2002, reaching its lowest incidence of 0.02 per 100 000 (14 cases) in 2012. In children aged <5 years of age, Hib incidence was 0.06 per 100 000 (2 cases), compared with 35.5 per 100 000 prior to routine Hib vaccination. Follow-up of all 106 case patients over the 4-year period revealed that most cases occurred in adults (73%) who often had preexisting medical conditions (77%) and presented with pneumonia (56%). The Hib-associated case fatality rate was 9.4% (10/106 cases). Control of Hib disease in England and Wales is currently the best that has been achieved since the introduction of routine Hib vaccination in 1992. Invasive Hib disease is no longer a major cause of acute bacterial meningitis in children but, instead, cases are more likely to present as pneumonia in older adults with comorbidities, similar to the less virulent nonencapsulated H. influenzae.

The Effectiveness of Conjugate Haemophilus influenzae Type B Vaccine in The Gambia 14 Years After Introduction

The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years. The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries.

Incidence of Haemophilus influenzae Type b Disease in The Gambia 14 Years after Introduction of Routine Haemophilus influenzae Type b Conjugate Vaccine Immunization

Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine. This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002. The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months. Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.

Haemophilus influenzae Type b Disease among Children in Rural Mozambique: Impact of Vaccine Introduction

Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.

Incidence of Radiologically-Confirmed Pneumonia and Haemophilus influenzae Type b Carriage before Haemophilus influenzae Type b Conjugate Vaccine Introduction in Central Vietnam

To determine the incidence of radiologically-confirmed pneumonia (RCP) and Haemophilus influenzae type b (Hib) carriage in central Vietnam as a baseline data before Hib conjugate vaccine introduction. In the context of ongoing population-based prospective, hospitalized acute respiratory infection surveillance study, a cross-sectional Hib carriage study was conducted among 1000 children < 5 years of age livingin NhaTrang, Vietnam in June 2010, 1 month before the nationwide introduction of Hib conjugate vaccine in Vietnam. The incidence of RCP hospitalizations among children < 5 years of age was 3.3 per 1000 children. The highest incidence was observed among children 12-23 month age group (8.3 per 1000). Haemophilus influenzae carriage was detected in 37% of the children and Hib carriage rate was 3%. Eighty-two percent of the Haemophilus influenzae had TEM β-lactamase resistance gene. The presence of 6 or more family members was associated with an increased rate of Hib carriage (P = .04). Incidence of RCP and Hib carriage in this cross-sectional survey are lower compared with other studies. Continued surveillance for invasive Hib disease and sequential Hib carriage surveys are needed to support future assessments of the impact of Hib conjugate vaccine in Vietnam.

Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine (HibMenCY-TT; MenHibrix®): A Review

The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6weeks-18months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the HibMenCY-TT vaccine in infants and toddlers in the phase III trial was considered to be clinically acceptable and comparable to that of the Hib conjugate vaccines received by the control group.

No evidence of increasing Haemophilus influenzae non-b infection in Australian Aboriginal children

BackgroundHigh, or increasing, rates of invasive Haemophilus influenzae (Hi) type a disease have been reported from North American native children from circumpolar regions, raising the question of serotype replacement being driven by vaccination against Hi type b (Hib). Indigenous Australians from remote areas had high rates of invasive Hib disease in the past, comparable to those in North American Indigenous populations.ObjectiveEvaluate incidence rates of invasive Hi (overall and by serotype) in Indigenous Australian children over time.DesignDescriptive study of Hi incidence rates by serotype, in the Northern Territory (NT) and South Australia (SA) from 2001 to 2011. Comparison of NT data with a study that was conducted in the NT in 1985–1988, before Hib vaccine was introduced.ResultsThe average annual rate of invasive Hi type a (Hia) disease in Indigenous children aged<5 years was 11/100,000 population. Although the incidence of Hi infection in Indigenous children in 2001–2003 was lower than during 2004–2011, this may be due to changes in surveillance. No other trend over time in individual serotypes or total invasive Hi disease, in Indigenous or non-Indigenous people, was identified. Compared to 1985–1988, rates in 2001–2011 were lower in all serotype groupings, by 98% for Hib, 75% for Hia, 79% for other serotypes and 67% for non-typeable Hi.ConclusionsThere is no evidence of increases in invasive disease due to Hia, other specific non-b types, or non-typeable Hi in Australian Indigenous children. These data suggest that the increase in Hia some time after the introduction of Hib vaccine, as seen in the North American Arctic Region, is not common to all populations with high pre-vaccine rates of invasive Hib disease. However, small case numbers and the lack of molecular subtyping and PCR confirmation of pre-vaccine results complicate comparisons with North American epidemiology.

Adapting Group Sequential Methods to Observational Postlicensure Vaccine Safety Surveillance: Results of a Pentavalent Combination DTaP-IPV-Hib Vaccine Safety Study

To address gaps in traditional postlicensure vaccine safety surveillance and to promote rapid signal identification, new prospective monitoring systems using large health-care database cohorts have been developed. We newly adapted clinical trial group sequential methods to this observational setting in an original safety study of a combination diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) conjugate vaccine (DTaP-IPV-Hib) among children within the Vaccine Safety Datalink population. For each prespecified outcome, we conducted 11 sequential Poisson-based likelihood ratio tests during September 2008-January 2011 to compare DTaP-IPV-Hib vaccinees with historical recipients of other DTaP-containing vaccines. No increased risk was detected among 149,337 DTaP-IPV-Hib vaccinees versus historical comparators for any outcome, including medically attended fever, seizure, meningitis/encephalitis/myelitis, nonanaphylactic serious allergic reaction, anaphylaxis, Guillain-Barré syndrome, or invasive Hib disease. In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94). Findings were similar in analyses with concurrent comparators who received other DTaP-containing vaccines during the study period. Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation.

Inwazyjne zakażenie Haemophilus influenzae typu b u dziecka z pełnym cyklem szczepień

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection of young children worldwide. Especially vulnerable are children in the first years of life because of immature, T-independent immune response for polysaccharide of the capsule. Introduction of Hib protein-polysaccharide conjugate vaccines into national immunization programs has resulted in the virtual elimination of invasive Hib disease in vaccinated children and their community. Here is descripted a case of 4 years boy, who developed Hib septicemia and encephalomeningitis probably the same etiology despite of vaccination (at the age of 6, 7, 18 months). The boy was evaluated for immunoglobulin and complement deficiency at Clinic Vaccination of Risk Groups in Children's Memorial Health Institute, and no immunodeficiency was found.

Haemophilus influenzae Type b Disease and Vaccine Booster Dose Deferral, United States, 1998–2009

Since the introduction of effective vaccines, the incidence of invasive Haemophilus influenzae type b (Hib) disease among children <5 years of age has decreased by 99% in the United States. In response to a limited vaccine supply that began in 2007, Hib booster doses were deferred for 18 months. We reviewed national passive and active surveillance (demographic and serotype) and vaccination status data for invasive H. influenzae disease in children aged <5 years before (1998-2007) and during (2008-2009) the vaccine shortage years to assess the impact of the vaccine deferral on Hib disease. We estimated the average annual number of Hib cases misclassified as unknown (not completed or missing) serotype. From 1998 to 2007 and 2008 to 2009, the annual average incidence of Hib disease per 100000 population was 0.2 and 0.18, respectively; no significant difference in incidence was found by age group, gender, or race. Among Hib cases in both time periods, most were unvaccinated or too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown serotype. The booster deferral did not have a significant impact on the burden of invasive Hib disease in children <5 years of age. Continued surveillance and serotype data are important to monitor changes in Hib incidence, especially during vaccine deferrals. Hib booster deferral is a reasonable short-term approach to a Hib vaccine shortage.

Naturally Acquired and Conjugate Vaccine-Induced Antibody to Haemophilus influenzae Type b (Hib) Polysaccharide in Malian Children: Serological Assessment of the Hib Immunization Program in Mali

Haemophilus influenzae type b (Hib) conjugate vaccine for infants (6, 10, and 14 weeks of age) was introduced into the Malian Expanded Program on Immunization in July 2005, to diminish invasive Hib disease in young children. Antibodies to Hib capsular polysaccharide (PRP) were measured in infants and toddlers from an area already served by the Hib immunization program (Bamako) and in unimmunized children of the same age in a district (Kangaba) where Hib immunization had not yet begun. Among vaccinated Bamako children 6-23 months of age, 77-93% exhibited PRP titers ≥ 1.0 μg/mL, indicating long-term protection, versus only 10-23% of Kangaba children of that age. High PRP antibody titers in immunized children persisted through 2 years of age. Moreover, ∼50% of Bamako children exhibited anti-PRP titers ≥ 5.0 μg/mL; a level that impedes Hib upper respiratory carriage, and may thereby diminish the Hib transmission to the unimmunized susceptible population (i.e., providing indirect protection).

Dose-specific efficacy ofHaemophilus influenzaetype b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials

SUMMARYGlobal coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine.

Cost-effectiveness of Haemophilus influenzae type b (Hib) vaccine introduction in the universal immunization schedule in Haryana State, India

In India, Haemophilus influenzae type b (Hib) vaccine introduction in the universal immunization programme requires evidence of its potential health impact and cost-effectiveness, as it is a costly vaccine. Since childhood mortality, vaccination coverage and health service utilization vary across states, the cost-effectiveness of introducing Hib vaccine was studied in Haryana state. A mathematical model was used to compare scenarios with and without Hib vaccination to estimate the cost-effectiveness of Hib vaccine in Haryana from 2010 to 2024. Demographic and National Family Health Surveys were used to estimate vaccination coverage and mortality rates among children under 5. Hib pneumonia, Hib meningitis and invasive Hib disease incidence were based on Indian studies. Vaccine and syringe prices of the UNICEF supply division were used. Cost-effectiveness from government and societal perspectives was calculated as the net incremental cost per unit of health benefit gained [disability-adjusted life years (DALYs) averted, life years saved, Hib cases averted, Hib deaths averted]. Sensitivity analysis was done using variation in parameter estimates among different states of India. The incremental cost of Hib vaccine introduction from a government and a societal perspective was estimated to be US$81.4 and US$27.5 million, respectively, from 2010 to 2024. Vaccination of 73.3, 71.6 and 67.4 million children with first, second and third dose of pentavalent vaccine, respectively, would avert 7 067 817 cases, 31 331 deaths and 994 564 DALYs. Incremental cost per DALY averted from a government (US$819) and a societal perspective (US$277) was found to be less than the per capita gross national income of India in 2009. In sensitivity analysis, Hib vaccine introduction remained cost-effective for India. Hib vaccine introduction is a cost-effective strategy in India.

Risk of Invasive Haemophilus influenzae Type b (Hib) Disease in Adults with Secondary Immunodeficiency in the Post-Hib Vaccine Era

Prior to the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, invasive Hib disease affected almost exclusively children. According to some recent studies, in the postvaccine era, adults, the elderly, and immunocompromised persons can be affected more often than children. As the production of type-specific anti-capsular polysaccharide antibodies is the major defense mechanism against Hib, individuals with defects in humoral immune responses have high susceptibility to infections caused by Hib. We hypothesized that nonvaccinated adults with chronic conditions causing immunosuppression may lack protective antibody to Hib. We assessed serum anti-Hib IgG levels and bactericidal activity in 59 patients with chronic renal failure, 30 patients with type 2 diabetes mellitus, 28 patients with chronic obstructive pulmonary disease (COPD), and 20 patients with multiple myeloma compared to 32 healthy controls of similar age. Considering antibody at >0.15 μg/ml as the protective correlate in unvaccinated individuals, we detected subprotective Hib antibody levels in 29% of chronic renal failure, 20% of diabetes, 14% of COPD, and 55% of myeloma patients compared to 3% of healthy controls. Additionally, 70% of myeloma and 58% of chronic renal failure patients did not have detectable serum bactericidal activity against Hib. Among individuals with severe diseases causing secondary immunodeficiency, patients with multiple myeloma and chronic renal failure are at an increased risk of invasive Hib disease. Considering that Hib continues to circulate in the population, this study provides a rationale for the immunization of some adult patients with secondary immunodeficiency with the pediatric Hib vaccine to achieve protective immunity.

Two Decades of Experience With the Haemophilus influenzae Serotype b Conjugate Vaccine in the United Kingdom

BackgroundThe Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced into the UK national childhood immunization program in 1992 after clinical trials reported the vaccine to be highly immunogenic in infants as young as two months of age. ObjectiveThe goal of this study was to describe and comment on the impact of routine Hib immunization on the epidemiology of invasive Hib disease in the United Kingdom. In addition, the development of Hib polysaccharide and conjugate vaccines was reviewed. MethodsA literature search was conducted of PubMed for invasive Hib disease epidemiology in the United Kingdom. The UK Health Protection Agency Web site was also searched for relevant publications. ResultsThe incidence of invasive Hib incidence in children aged <5 years fell from 21/100,000 to 44/100,000 in the prevaccine era to 0.63/100,000 in 1998, with an estimated vaccine failure rate of 2.2/100,000 vaccinees. After 1999, however, invasive Hib disease increased, particularly in toddlers, and peaked in 2003. Potential reasons for the resurgence included a greater-than-expected decline in Hib antibodies after primary immunization, waning of herd immunity offered by the initial catch-up campaign, and use of a less immunogenic Hib combination vaccine containing acellular pertussis in 2000–2001. In response to the resurgence, a Hib combination vaccine containing whole-cell pertussis was reintroduced in 2002, followed by a childhood Hib booster campaign in 2003. In 2004, the recommended infant vaccine was changed to a different Hib/acellular pertussis combination vaccine containing inactivated polio, which had a satisfactory Hib response, was less reactogenic, and eliminated the risk of vaccine-associated paralytic poliomyelitis. This action was followed by introduction of a routine 12-month Hib booster in 2006. Together, these measures led to a decline in invasive Hib disease across all age groups. In 2010, there were only 30 invasive Hib cases, with 6 reported in children aged <5 years and no deaths in this age group since 2007. ConclusionsControl of Hib disease is currently the best that has been achieved since the introduction of the routine Hib vaccination almost 20 years ago.

Modeling Insights intoHaemophilus influenzaeType 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.