Published online August 1, 2006
PEDIATRICS Vol. 118 No. 2 August 2006, pp. e421-e429 (doi:10.1542/peds.2006-0287)
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ARTICLE

The Alaska Haemophilus influenzae Type b Experience: Lessons in Controlling a Vaccine-Preventable Disease

Rosalyn Singleton, MD MPHa,b, Laura Hammitt, MDa,b, Thomas Hennessy, MD, MPHa, Lisa Bulkow, MSa, Carolynn DeByle, BSa, Alan Parkinson, PhDa, Tammy E. Cottle, BAa, Helen Peters, RNa and Jay C. Butler, MDa

a Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
b Alaska Native Tribal Health Consortium, Anchorage, Alaska


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE. Before 1991, Alaska Native children experienced one of the highest rates of invasive Haemophilus influenzae type b disease. H influenzae type b vaccine has led to a near-elimination of invasive H influenzae type b disease in the United States. We describe challenges encountered in controlling H influenzae type b disease in Alaska and update the current status of H influenzae disease and carriage in Alaska as lessons to other populations.

PATIENTS AND METHODS. We reviewed data from statewide H influenzae disease surveillance conducted during 1980–2004. Vaccine coverage data were based on audits from tribal facilities and the National Immunization Survey. H influenzae type b colonization data were based on 6 carriage studies.

RESULTS. After universal infant vaccination in 1991, H influenzae type b disease among Alaska Native and non-Native children <5 years of age decreased by 94% and 96%, respectively. After a 1996 change in H influenzae type b vaccine from polyribosylribitol phosphate-outer membrane protein conjugate vaccine to H influenzae type b oligosaccharide-CRM197 vaccine, the incidence of H influenzae type b disease increased in rural Alaska Natives from 19.8 to 91.1 cases per 100000 per year <5 years of age. During 2001–2004, with use of polyribosylribitol phosphate-outer membrane protein conjugate vaccine, the rate of H influenzae type b disease in Alaska Native and non-Native children aged <5 years decreased to 5.4 and 0 per 100000 per year, respectively. In postvaccine studies, H influenzae type b carriage has decreased in Alaska Native children <5 years of age.

CONCLUSIONS. H influenzae type b vaccination has resulted in a dramatic decrease in invasive H influenzae type b disease in Alaska; however, despite high rates of H influenzae type b vaccine coverage, H influenzae type b disease rates among rural Alaska Native children <5 years of age remain higher than the rates among non-Native Alaska and other US children. Equity in disease rates may not be achieved in indigenous populations with the current vaccines unless other environmental and household factors contributing to disease transmission are addressed.

Key Words: Haemophilus influenzae type b • vaccine • Alaska Native children

Abbreviations: Hib—Haemophilus influenzae type b • CDC—Centers for Disease Control and Prevention • AIP—Arctic Investigations Program • TVF—true vaccine failure • ANTHC—Alaska Native Tribal Health Consortium • PRP—polyribosylribitol phosphate • HbOC—Haemophilus influenzae type b oligosaccharide-CRM197 vaccine • OMP—outer membrane protein conjugate vaccine • CI—confidence interval

In 2006, US physicians are unlikely to see a case of meningitis caused by Haemophilus influenzae type b (Hib).1 Yet, before infant vaccination starting in 1991, Hib was the most common cause of meningitis in children.2 Alaska Native children <5 years of age experienced rates of invasive Hib disease ≥6 times higher than other similarly aged children in the United States (400–700 vs 60–100 per 100000, respectively)3,4 with the highest rate occurring in rural southwestern Alaska. In Alaska, before introduction of pediatric conjugate vaccines, rates of invasive disease because of Hib and Streptococcus pneumoniae were 3 times higher among rural Alaska Native children compared with urban Alaska Native and non-Native children (Centers for Disease Control and Prevention [CDC], unpublished data, 1995–2000). Hib disease in Alaska Native people was characterized by a young age with 23% of disease occurring in infants <6 months of age. The young age of disease and evidence of continued Hib colonization5–7 have been critical factors affecting the choice of Hib vaccines in Alaska, favoring those providing a protective immune response after 1 dose. In this article, we describe the obstacles encountered in preventing Hib disease in Alaska and provide an update of the current status of Hib and non-b H influenzae disease and carriage as lessons for other populations.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Population Statistics
Denominators for calculating disease rates are derived from 1980, 1990, and 2000 US censuses. In 2000, there were 626932 Alaskans, of which 16.3% (102347) were <10 years old, and 119499 (19.1%) were Alaska Native people, of which 23% were <10 years old. Alaska Native people are a diverse group that includes Eskimo, Aleut, Athabascan, Tsimpsian, Haida, Tlingit, and American Indian groups. Persons were considered urban if they resided in 1 of the 3 largest municipalities: Anchorage, Fairbanks, or Juneau. All others were considered rural.

Hib Surveillance
Invasive H influenzae is defined by a compatible clinical illness with recovery of H influenzae from a normally sterile site (blood, cerebrospinal fluid, pleural fluid, or other aspirate). The Arctic Investigations Program (AIP) of the CDC in Anchorage has conducted statewide surveillance for all invasive H influenzae disease since 1980.3 The 26 microbiology laboratories around the state send invasive H influenzae isolates to AIP for confirmation of identity and serotyping. H influenzae is confirmed by Gram stain and factor V and X requirements (Differentiation Disks; Difco Laboratories, Detroit, MI). Serotyping is conducted by slide agglutination (H influenzae type a through f typing antisera, Difco). Since 2003, slide agglutination serotyping has been routinely confirmed by polymerase chain reaction. Primers specific for the bexA gene, required for capsular export, are used to differentiate nontypeable isolates from capsulated isolates. Then, 6 primer pairs specific for the capsule types a through f are used, each in a separate polymerase chain reaction to determine genotype.8 The AIP annually reconciles the list of submitted samples with culture results from participating laboratories and reviews state communicable disease surveillance data and state death certificate codes for H influenzae infection to identify possible missed cases.

To calculate Hib infection rates we included all H influenzae in children <10 years of age confirmed as serotype b at the AIP laboratory. In addition, we counted as Hib a proportion of H influenzae confirmed as Hib at a hospital laboratory but not received at AIP. For this calculation, we used the proportion of H influenzae in children <10 years of age that was serotype b during 1980–1991 (96.6%) and 1992–2004 (60.7%). The specimens that were unconfirmed at AIP represent 22% of cases identified during 1980–1991 and 5% of cases identified during 1992–2004. For the purpose of calculating disease rates and vaccine effectiveness, 1991 is included in the prevaccine period, because it was a transition year during which Hib vaccine was introduced into the vaccine schedule.

Hib Vaccine Effectiveness
To determine cases of disease prevented, we calculated the rate difference between the prevaccine and postvaccine periods and multiplied this by the postvaccine population. Vaccine effectiveness was estimated by (1 – Ir) where Ir is the rate ratio of prevaccine to postvaccine periods. Confidence intervals were calculated using the same transformation. Poisson regression was used to assess differences in rate changes.

Hib Vaccine Failures
We reviewed all of the cases of invasive Hib disease occurring from 1991 through 2004 in Alaska children aged <10 years. Cases of invasive Hib disease developing after ≥1 dose of conjugate Hib vaccine were considered as possible vaccine failures if disease developed ≥14 days after the first vaccine dose or ≥7 days after subsequent doses. True vaccine failure (TVF) is defined in Table 1. Children who had been vaccinated but did not meet the definition for TVF were considered to be partially immunized, and all others were classified as unimmunized.


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  		TABLE 1 Vaccine Algorithm for Determining TVFs

 
Vaccine Coverage
Immunization rates in Alaska Native children are based on quarterly audits of electronic immunization records for on-time immunization rates in 3- to 27-month-old children and completion of the vaccine series in 19- to 35-month-old children at tribal facilities coordinated through the Alaska Native Tribal Health Consortium (ANTHC). During 1994–1999 and 2000–2004, ANTHC reported the immunization status of ~80% and 93%, respectively, of the Alaska Native children 3 to 35 months of age who received health care from a federally funded tribal facility. We also present Alaska Native-specific Hib vaccine rates determined through the National Immunization Survey.

Hib Carriage
There have been 6 studies of Hib colonization, predominantly among Alaska Native persons, conducted in Alaska. Two studies were conducted before the introduction of Hib conjugate vaccines. The first, in 1977–1978, recruited 121 children <5 years of age from a town in the rural southwest region of Alaska.4 The second, conducted in 1982–1983, involved 354 adults and children of 132 households in 4 villages in southwest Alaska.5 Three studies were done when Hib disease had reemerged in 1996–1998. The first of these was a study of children aged 1 to 5 years in 6 southwest Alaska villages (April 1997).6 The other 2 studies included children aged 1 to 8 years attending an urban Anchorage clinic (January 1998) and children aged 1 to 16 years recruited at school in the town of Barrow (September 1998).7 A final study (2000–2001) recruited persons of all ages in 7 southwest Alaska villages.9


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Hib Vaccines and Disease Rates
Before routine infant Hib vaccination (1980–1991), the overall rates of invasive Hib disease in Alaska Native and non-Native children <5 years of age were, respectively, 309.4 and 84.8 cases per 100000 (Table 2 and Fig 1). The rate in rural Alaska Native children was 331.9 and in urban Alaska Native children it was 238.1 cases per 100000. Prevention measures against Hib in this period included the use of polyribosylribitol phosphate (PRP)10 vaccine in toddlers, PRP-diphtheria toxoid conjugate vaccine among infants enrolled in an efficacy trial that failed to show significant protection,11 and passive immunization with bacterial polysaccharide immune globulin infants in southwestern Alaska.12


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  		TABLE 2 Numbers and Annual Incidence Rates (Cases per 100 000 Persons) of Hib Invasive Disease Cases in Alaska Native and Non-Native Children Aged <5 Years Before (1980–1991) and After (1992–2004) Universal Infant Hib Vaccination

 

Figure 1
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  		FIGURE 1 Invasive Hib disease rates per 100000 in Alaska Native and non-Native children aged <5 years, 1980–2004.

 
Universal infant Hib vaccination began in January 1991 when the state of Alaska, which purchases all routine childhood vaccines, introduced Hib oligosaccharide-CRM197 vaccine (HbOC). In July 1991, the vaccine was changed to PRP-outer membrane protein conjugate vaccine (OMP) because of its unique ability to elicit protective antibody levels after 1 dose,13–15 and this vaccine was used until January 1996. After introduction of PRP-OMP infant vaccination, there was a 94% decrease in the annualized rate of Hib disease in Alaska Native children <5 years of age from 309.4 per 100000 in 1980–1991 to 18.3 per 100000 in 1992–1995 (Table 2 and Fig 1). During the same period, Hib disease declined 96% among non-Native Alaska children from 84.8 to 3.5 per 100000. Of 9 cases occurring in Alaska Native children during 1992–1995, 5 (56%) occurred in unvaccinated infants.

To reduce the number of injections per visit, HbOC, given as combined diphtheria-tetanus toxoids-pertussis/HbOC, became the statewide vaccine in January 1996. During 1996–1997, 17 Hib cases occurred in Alaska Native children <5 years of age. Sixteen of the 17 cases occurred in rural Alaska Native children, in whom the incidence increased from 19.8 to 91.1 cases per 100000 children <5 years old (P < .001), whereas the rate in urban Alaska Native children remained unchanged (Table 2 and Fig 1). Unlike the previous period, only 1 case (6%) occurred in a completely unvaccinated child, and 8 (47%) of the cases occurred in partially vaccinated infants who had received 1 or 2 doses of HbOC.6

In October 1997, the state of Alaska adopted a sequential Hib vaccination schedule using PRP-OMP for the first dose and HbOC for the subsequent 3 doses. (This sequential schedule was provided by tribal facilities for Alaska Native children as early as July 1996; however, implementation occurred in approximately half of Alaska Native children.) Between October 1997 and December 2000, 14 Hib cases occurred in Alaska Native children <5 years of age, respectively. Three of the cases occurred in children who had inadvertently received HbOC for their first and only dose. The Hib disease incidence for 1996–2000 was 65.6, 9.7, and 1.7 per 100000 in rural and urban Alaska Native children and non-Native children <5 years of age, respectively (Table 2 and Fig 1).

Since January 2001, the state of Alaska has adopted a vaccine schedule using PRP-OMP alone or combined hepatitis B/PRP-OMP vaccine. During 2001–2004, 3 Hib cases occurred in vaccinated Alaska Native children <5 years of age (5.4 of 100000 per year), whereas 0 cases occurred in non-Native children.

Cases Prevented
Since universal Hib vaccination (1992–2004) an estimate of 479 Hib cases (95% confidence interval [CI] 423–533) have been prevented in Alaska Native children <5 years (average yearly population: 12975), whereas 411 cases (95% CI: 369–453) have been prevented in non-Native Alaska children (average yearly population: 38077). The estimated Hib vaccine effectiveness during the entire Hib vaccine era (1992–2004) among children aged <5 years in Alaska was 97.9% (95% CI: 95.90%–99.0%) for non-Native and 91.7% (95% CI: 88.6%–94.1%) for Alaska Native children (P < .001). During the recent period of PRP-OMP vaccine use (2001–2004), vaccine effectiveness was 100% (95% CI lower bound: 97.1%) for non-Native and 98.2% (95% CI: 94.8%–99.6%) for Alaska Native children (P = .928). Vaccine effectiveness was 89.9% (95% CI: 85.7%–92.9%) in rural and 96.8% (95% CI: 91.5%–99.2%) in urban Alaska Native children for the entire vaccine period (P = .032). During the recent period of PRP-OMP use (2001–2004), effectiveness was similar in urban and rural Alaska Native children (P = .971), but Hib occurred only in rural Alaska Native children.

During the entire vaccine period, there was only 1 Hib infection in an Alaska Native child and 1 Hib infection in a non-Native Alaska child aged 5 to 9 years. The rate of Hib disease in children 5 to 9 years of age decreased significantly from 2.3 per 100000 in the prevaccine era to 0.3 per 100000 in the postvaccine era (P = .001). Overall, there was a significant increase in the proportion of childhood Hib cases occurring in infants <6 months of age (51%) in the postvaccine period (1992–2004) as compared with the prevaccine period (21%).

Hib Vaccine Failures
Invasive Hib disease was reported in 68 Alaska children aged <5 years and 2 children aged 5 to 9 years during 1991 through 2004. Vaccine history was available for 69 children. Of these, 28 children (40%) were classified as unimmunized (including 3 children who developed disease within 14 days of receipt of their first dose of Hib vaccine, all PRP-OMP), 18 (26%) met the criteria for TVF, and 23 (33%) were classified as partially immunized (Fig 2 and Table 3). Meningitis occurred in 52% (36 of 69) of cases.


Figure 2
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  		FIGURE 2 Cases of invasive Hib disease in children aged <10 years, Alaska, 1991–2004.

 

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  		TABLE 3 Characteristics of Children Aged <10 Years With Invasive Hib Disease After Vaccine Introduction, Alaska, 1991–2004

 
The 18 patients with TVF had received a median 3 doses of Hib vaccine (range: 2–4 doses) and had received the first and second doses at median ages of 1.5 months (range: 1.3–23.0 months) and 4.7 months (range: 3.6–29.5 months), respectively. The median time from receipt of the last dose of vaccine to onset of disease was 306 days (range: 11–2045 days). Invasive Hib disease occurred in 6 children (33%) who had associated medical conditions (4 born prematurely, 1 with metabolic disorder, and 1 with leukemia). In addition, 1 child with hip dysplasia developed septic arthritis.

Two of the 18 children with TVF developed invasive Hib disease only 11 days after receipt of vaccine. One child (aged 10.5 months) had been vaccinated with PRP-OMP at 1.4 months, HbOC at 5.4 months, and PRP-OMP 11 days before illness. The other (aged 4.6 months) received PRP-OMP at 1.5 months and again 11 days before illness.

Eight children with TVF developed invasive Hib disease despite completing the primary series and receiving a booster dose of vaccine after 1 year of age. Two of these children were born prematurely, and no risk factors were identified for the other 6 children. The 23 patients who were partially immunized had received a median of 1 dose of Hib vaccine (range: 1–2 doses). Seven (30%) were adequately immunized for age; 16 (70%) had been vaccinated at least once but were behind on their immunizations (Table 3).

Vaccine Coverage in Alaska Native People
During each year from 1994 through 1998, 88% to 95% of Alaska Native 2-year-olds received ≥3 Hib vaccines by 24 months of age. However, only 72% to 83% of urban and 51% to 75% of rural Alaska Native 2-year-olds had received their second Hib dose by 5 months of age. On December 31, 2004, 88% of Alaska Native 3- to 4-month-olds had received ≥1 Hib dose, 86% of 5- to 15-month-olds had received ≥2 doses, and 93% of 19- to 35-month-olds had received ≥3 Hib vaccines. Analysis of the 2000–2001 National Immunization Survey showed that 95.6% (95% CI: ±3.6%) of 19- to 35-month-old Alaska Native children had received ≥3 doses of Hib vaccine, which exceeded the national health objective for 2010 and equaled or exceeded the levels in United States overall (93.2%; 95% CI: ±0.4) and non-Native Alaska children (87.1%; 95% CI: ±3.5%).16

Non-b H influenzae Disease in Alaska Children
Serotyping of invasive H influenzae was incomplete before 1991. Invasive H influenzae disease due to non-b encapsulated serotypes was reported in 20 children aged <10 years during 1991–2004 (8 serotype a, 1 serotype d, 1 serotype e, and 10 serotype f), with a median of 1 case per year (range: 1–6; Fig 3). Eight children (40%) were female, and 13 (65%) were Alaska Native; the median age of children was 12 months (range: 4 months to 9 years). The primary clinical diagnosis for the 20 children with non-b invasive H influenzae disease was bacteremia without a focus in 8 (40%), meningitis in 5 (25%), pneumonia with bacteremia in 5 (25%), and septic arthritis in 2 (10%). Invasive disease due to nontypeable H influenzae was reported in 15 children during this time period. Seven (47%) were female, and 7 (47%) were Alaska Native; the median age of children with disease because of nontypeable H influenzae was 1.5 months (range: 1 day to 6 years). Clinical illness included bacteremia without a focus in 9 (60%), pneumonia with bacteremia in 5 (33%), and meningitis in 1 (7%). No children with invasive disease because of non-b encapsulated H influenzae died; however, 2 infants died because of nontypeable H influenzae invasive disease.


Figure 3
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  		FIGURE 3 Cases of invasive H influenzae non-b disease in Alaska children aged <10 years, 1991–2004.

 
Hib Carriage
In the 2 studies conducted before introduction of the Hib vaccine, carriage among infants and children <5 years old was ~5% (Table 4). In the 1983 study, carriage was also found among children 5 to 9 years old (3.7%) and adults (9.3%). During the vaccine era, colonization was studied in 1997–1998 after changing from HbOC to a sequential schedule and in 2000–2001 when PRP-OMP was routinely used. Hib colonization in southwest Alaska in 2000–2001 was 1.2% in the overall population with no colonization found among children <2 years old. Colonization in children 1 to 4 years old (1.5%) was significantly lower than in 1997 (7.1%; P < .001; Table 4). As was seen in 1997–1998, the highest carriage was among children aged 5 to 9 years (3.4%). Compared with the 2 prevaccine-era studies, data from 2000–2001 show significantly lower Hib carriage among infants, children 1 to 4 years old, and adults. Adult carriers represented 22% (17 of 74) of persons identified with Hib in this community-wide study.


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  		TABLE 4 Hib Oropharyngeal Carriage Studies in Alaska by Time Period, Region, and Age Group

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Although Alaska Native children comprised only 27% of the Alaska child population <5 years of age, Hib vaccine has prevented an equal or greater number of invasive Hib infections in Alaska Native children than in other Alaska children assuming the continuation of prevaccine rates in both groups. Hib disease has decreased >98% in Alaskan children, and nearly 900 Hib cases have been prevented. However, the rate of disease in Alaska Native children through 2004 remained 5 times the rate in US children <5 years of age1 despite exceptionally high Hib vaccination levels and high vaccine effectiveness. The suboptimal vaccine program effectiveness in rural Alaska Native children during 1996–2000 resulted from use of a Hib vaccine that did not achieve protective antibody concentrations (≥0.15 µg/mL) until the third dose plus low on-time rates of immunization.6 Since 2001, use of PRP-OMP and improved on-time immunization rates have resulted in similarly high vaccine effectiveness in Alaska Native and non-Native children; however, a small number of cases are still occurring among rural Alaska Native children.

Existing data suggest that Hib disease rates remain higher in other indigenous groups compared with nonindigenous populations. The rate of Hib invasive disease among Navajo children <2 years of age in 1992–1999 was 22 per 100000 compared with 2 per 100000 in the US general population of children <2 years of age.17 Among aboriginal Australian children <5 years of age in 1998–1999, the rate was 6.7 per 100000 compared with 1.7 per 100000 for all Australian children.18 In Canada, for the 4-year period from 2001–2004, 4 cases of Hib (28 per 100000 per year) were reported in children aged <3 years in the largely indigenous regions of Nunavut and northern Quebec (International Circumpolar Surveillance, CDC, unpublished data, 2001–2004). During this period, the reported rate was 1 per 100000 per year for all Canadian children <3 years of age.19

Although use of Hib vaccines has resulted in a dramatic reduction in the burden of disease, a small number of vaccinated children still develop invasive Hib disease because of vaccine failure. Several medical conditions have been commonly reported with vaccine failure including prematurity, immunodeficiency, malignancy, and Down syndrome.20–22 Immunodeficiency was not uniformly evaluated in the children in our series; however, the presence of an associated medical condition in 39% of our patients is similar to the 44% in the United Kingdom reported by Heath et al.21 In Canada, 78% of Hib immunization failure defined as illness onset ≥4 weeks after completion of primary vaccination occurred in children with immunodeficiency or a predisposing condition.19

Ongoing statewide surveillance enabled us to evaluate and respond to a reemergence of disease in 1996. During 1996-2000 there was an increase in vaccine failures.7 This was attributed to a change in vaccine in January 1996 to DPT/HbOC and a corresponding lower antibody response after the first dose of HbOC compared with PRP-OMP. Vaccine failures continued with the sequential schedule (PRP-OMP followed by HbOC) partly because this schedule was complex, and some children inadvertently received HbOC instead of PRP-OMP for the first dose. Anecdotal observation suggests that this was not a common occurrence. Vaccine failures decreased after the vaccine policy was revised in 2001 to use PRP-OMP for all Hib vaccine doses.

The first infant Hib immunization is often given at age 6 weeks in Alaska Native infants to coincide with the mother’s postpartum follow-up. Earlier age of vaccination could lead to lower anti-PRP levels and increase the risk of vaccine failure. However, 3 studies suggest that a first Hib vaccine dose at age 6 weeks provides comparable immunogenicity to a first dose at 2 months old. In Navajo and Apache infants vaccinated at ages 6 to 8 weeks, age at first vaccination did not significantly affect serum response until 12 months of age, at which time the antibody concentrations were slightly lower in children vaccinated at 6 weeks of age.23 An immunogenicity study in Gambian children showed that postvaccination levels after 2 doses did not differ significantly in children immunized at 1 and 3 months compared with children immunized at 2 and 4 months, although the level after 1 dose was lower in the 1-month group (0.53 µg/dL) than the 2-month group (0.82 µg/dL).24 A 1993 comparative study of Hib vaccine immunogenicity among Alaska Native children demonstrated anti-PRP levels to Hib vaccines that were generally similar to those seen in other populations despite a median age of 6 weeks at the first dose.13

We identified 3 patients who developed invasive Hib disease 2 to 10 days after receipt of the first dose of vaccine (PRP-OMP in all cases). In the early 1990s, concern was raised about a possible increase in the number of Hib cases during the period immediately after immunization because of the formation of antigen-antibody complexes with existing antibody to PRP that resulted in a transient decline in antibody concentration. Daum et al25 found that a majority of children vaccinated with PRP-OMP showed a decline in antibody after vaccination, but the decline did not reach statistical significance. Although it is possible that a brief period of increased susceptibility after Hib immunization may contribute to some cases of Hib vaccine failure, data on this topic are limited, and the potential contribution to overall Hib disease is small.

Although the relative importance of illness because of encapsulated nontype b H influenzae has increased in the Hib-vaccine era, these pathogens remain an uncommon cause of invasive disease in children. There was concern that the reduction in oropharyngeal colonization with Hib might open an ecologic niche for increased colonization with nontype b strains of H influenzae. Surveillance has not shown a significant, sustained increase in invasive disease caused by nontype b encapsulated strains.1,17,26 We previously reported an outbreak of invasive H influenzae type a disease that occurred in rural Alaska in 200327; however, continued surveillance has documented only 1 additional case (occurring in 2005) of H influenzae type a invasive disease in an Alaskan child.

The studies evaluating Hib carriage in Alaska are limited by differences in the age groups sampled and by the restricted geographic area sampled; however, some general conclusions can be drawn. First, although disease rates in the prevaccine period were much higher than in the general US population, the prevalence of Hib carriage among Alaska Native children was similar to or slightly higher than reported in other surveys.28–31 Second, during the period of disease reemergence in 1996–1998, Hib carriage was found to persist and was higher among children in the regions with Hib cases. Third, in recent years, Hib carriage seems to be substantially lower in infants and young children than during the prevaccine period. This is similar to a colonization study in Navajo children conducted in 1997–1999, which showed reduction of Hib carriage in the vaccine era to very low levels in young children.32 Presumably, this is likely a direct effect of vaccine-induced antibody at concentrations high enough to prevent colonization.13,33 Hib carriage is now highest among children 5 to 9 years old, an age cohort in whom it is likely that anticapsular antibody levels after infant vaccination have fallen low enough to permit colonization. Fourth, adult carriage seems to be lower than in the prevaccine era and coincides with the decline in invasive disease among adults after Hib vaccine introduction in Alaska.34 However, the continued presence of Hib colonization among older children and adults indicates that some Hib transmission is ongoing. Therefore, the risk of disease for young children continues through exposure to colonized older community members.

We reported previously the impact of infant Hib vaccination on rates of H influenzae disease in Alaska children and adults aged ≥10 years.34 In this article we analyzed rates of H influenzae in children <10 years of age, as well as <5 years of age, to provide a complete picture of H influenzae disease across age groups in the postvaccine era. Longitudinal comparisons of incidence and cases prevented are limited by the assumptions that disease rates would have continued at the prevaccine rate without Hib vaccine intervention and that patterns of diagnosis and isolate submission would have remained static.

Since 1991, Hib vaccination has resulted in a dramatic decrease in disease in Alaska, with nearly 1000 cases prevented. Rare Hib cases continue to occur because low-level colonization facilitates ongoing transmission to susceptible children. Hib disease for Alaska Natives is limited primarily to rural Alaska. A substantial proportion of vaccine failures occur in children with preexisting conditions, such as prematurity.20,21 Other factors, such as environmental or household factors, may be related to the higher rates of infections seen in rural Alaska Native children both prevaccine and postvaccine. Household crowding, poverty, unemployment,35 and lack of indoor plumbing (ANTHC, unpublished data, 2005) are each more prevalent among rural Alaska Native persons than persons living in urban Alaska. Equity in disease rates may not be achieved in indigenous populations with the current vaccines unless other factors contributing to disease transmission are addressed.


   ACKNOWLEDGMENTS
 
We thank Trudy Murphy and Margaret Cortese for their critical review of this article.


   FOOTNOTES
 
Accepted Mar 23, 2006.

Address correspondence to Rosalyn Singleton, MD, MPH, Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Centre Dr, Anchorage, AK 99508. E-mail: ris2{at}cdc.gov

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

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