Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage
Identifieur interne : 001F92 ( Main/Corpus ); précédent : 001F91; suivant : 001F93Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage
Auteurs : Rosalyn Singleton ; Lisa R. Bulkow ; Orin S. Levine ; Jay C. Butler ; Thomas W. Hennessy ; Alan ParkinsonSource :
- The Journal of Pediatrics [ 0022-3476 ] ; 2000.
English descriptors
Abstract
Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)
Url:
DOI: 10.1067/mpd.2000.107843
Links to Exploration step
ISTEX:EA6228BBABA89477B41134505E3A7382A96CAFB0Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title><author><name sortKey="Singleton, Rosalyn" sort="Singleton, Rosalyn" uniqKey="Singleton R" first="Rosalyn" last="Singleton">Rosalyn Singleton</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Bulkow, Lisa R" sort="Bulkow, Lisa R" uniqKey="Bulkow L" first="Lisa R." last="Bulkow">Lisa R. Bulkow</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Levine, Orin S" sort="Levine, Orin S" uniqKey="Levine O" first="Orin S." last="Levine">Orin S. Levine</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Butler, Jay C" sort="Butler, Jay C" uniqKey="Butler J" first="Jay C." last="Butler">Jay C. Butler</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Hennessy, Thomas W" sort="Hennessy, Thomas W" uniqKey="Hennessy T" first="Thomas W." last="Hennessy">Thomas W. Hennessy</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Parkinson, Alan" sort="Parkinson, Alan" uniqKey="Parkinson A" first="Alan" last="Parkinson">Alan Parkinson</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:EA6228BBABA89477B41134505E3A7382A96CAFB0</idno><date when="2000" year="2000">2000</date><idno type="doi">10.1067/mpd.2000.107843</idno><idno type="url">https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001F92</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title><author><name sortKey="Singleton, Rosalyn" sort="Singleton, Rosalyn" uniqKey="Singleton R" first="Rosalyn" last="Singleton">Rosalyn Singleton</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Bulkow, Lisa R" sort="Bulkow, Lisa R" uniqKey="Bulkow L" first="Lisa R." last="Bulkow">Lisa R. Bulkow</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Levine, Orin S" sort="Levine, Orin S" uniqKey="Levine O" first="Orin S." last="Levine">Orin S. Levine</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Butler, Jay C" sort="Butler, Jay C" uniqKey="Butler J" first="Jay C." last="Butler">Jay C. Butler</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Hennessy, Thomas W" sort="Hennessy, Thomas W" uniqKey="Hennessy T" first="Thomas W." last="Hennessy">Thomas W. Hennessy</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Parkinson, Alan" sort="Parkinson, Alan" uniqKey="Parkinson A" first="Alan" last="Parkinson">Alan Parkinson</name><affiliation><mods:affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">The Journal of Pediatrics</title><title level="j" type="abbrev">YMPD</title><idno type="ISSN">0022-3476</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">137</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="313">313</biblScope><biblScope unit="page" to="320">320</biblScope></imprint><idno type="ISSN">0022-3476</idno></series><idno type="istex">EA6228BBABA89477B41134505E3A7382A96CAFB0</idno><idno type="DOI">10.1067/mpd.2000.107843</idno><idno type="PII">S0022-3476(00)12972-5</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AIP</term><term>HbOC</term><term>Hib</term><term>IgG</term><term>PRP</term><term>PRP-OMP</term><term>YK</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Rosalyn Singleton MD, MPH</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Lisa R. Bulkow MS</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Orin S. Levine PhD</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Jay C. Butler MD</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Thomas W. Hennessy MD, MPH</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Alan Parkinson PhD</name><affiliations><json:string>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>AIP : Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>HbOC : Hib oligosaccharide-CRM197 vaccine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Hib : Haemophilus influenzae type b</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>IgG : Immunoglobulin G</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PRP : Polyribosylribitol phosphate</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PRP-OMP : PRP–outer-membrane protein conjugate vaccine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>YK : Yukon Kuskokwim [Delta]</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children >5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was >1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants >6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)</abstract><qualityIndicators><score>7.776</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>7</keywordCount><abstractCharCount>1533</abstractCharCount><pdfWordCount>4468</pdfWordCount><pdfCharCount>28843</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>234</abstractWordCount></qualityIndicators><title>Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title><pii><json:string>S0022-3476(00)12972-5</json:string></pii><genre><json:string>research-article</json:string></genre><serie><pages><last>386</last><first>337</first></pages><genre></genre><language><json:string>unknown</json:string></language><title>Vaccines</title></serie><host><volume>137</volume><pii><json:string>S0022-3476(00)X0003-0</json:string></pii><pages><last>320</last><first>313</first></pages><issn><json:string>0022-3476</json:string></issn><issue>3</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>The Journal of Pediatrics</title><publicationDate>2000</publicationDate></host><categories><wos><json:string>PEDIATRICS</json:string></wos></categories><publicationDate>2000</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1067/mpd.2000.107843</json:string></doi><id>EA6228BBABA89477B41134505E3A7382A96CAFB0</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>2000</date></publicationStmt><notesStmt><note>The opinions expressed in the article are those of the authors and do not necessarily reflect the views of the Alaska Native Tribal Health Consortium or the Indian Health Service.</note><note>The results of the Yukon Kuskokwim Delta Carriage study were published previously by Galil et al (J Infect Dis 1999;179:101-65).</note><note>Reprint requests: Rosalyn Singleton, MD, CDC Arctic Investigations Program, 4055 Tudor Centre Dr, Anchorage, AK 99508.</note><note type="content">Section title: Original Articles</note><note type="content">Table I: Invasive Hib disease in Alaskans <5 years of age, 1980-1999, by ethnic group (Native vs non-Native) and vaccine era (1980-1991 vs 1992-1995, 1996-1997, and 1998-1999)</note><note type="content">Table II: Comparison of the populations studied for Hib carriage in children aged 1 to 4 years, in the YK Delta, Anchorage, and Barrow</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title><author><persName><forename type="first">Rosalyn</forename><surname>Singleton</surname></persName><roleName type="degree">MD, MPH</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Lisa R.</forename><surname>Bulkow</surname></persName><roleName type="degree">MS</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Orin S.</forename><surname>Levine</surname></persName><roleName type="degree">PhD</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Jay C.</forename><surname>Butler</surname></persName><roleName type="degree">MD</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Thomas W.</forename><surname>Hennessy</surname></persName><roleName type="degree">MD, MPH</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author><author><persName><forename type="first">Alan</forename><surname>Parkinson</surname></persName><roleName type="degree">PhD</roleName><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation></author></analytic><monogr><title level="j">The Journal of Pediatrics</title><title level="j" type="abbrev">YMPD</title><idno type="pISSN">0022-3476</idno><idno type="PII">S0022-3476(00)X0003-0</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">137</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="313">313</biblScope><biblScope unit="page" to="320">320</biblScope></imprint></monogr><idno type="istex">EA6228BBABA89477B41134505E3A7382A96CAFB0</idno><idno type="DOI">10.1067/mpd.2000.107843</idno><idno type="PII">S0022-3476(00)12972-5</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>AIP</term><term>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention</term></item><item><term>HbOC</term><term>Hib oligosaccharide-CRM197 vaccine</term></item><item><term>Hib</term><term>Haemophilus influenzae type b</term></item><item><term>IgG</term><term>Immunoglobulin G</term></item><item><term>PRP</term><term>Polyribosylribitol phosphate</term></item><item><term>PRP-OMP</term><term>PRP–outer-membrane protein conjugate vaccine</term></item><item><term>YK</term><term>Yukon Kuskokwim [Delta]</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2000-04-05">Registration</change><change when="2000-03-06">Modified</change><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity></istex:docType><istex:document><article docsubtype="fla" xml:lang="en"><item-info><jid>YMPD</jid><aid>12972</aid><ce:pii>S0022-3476(00)12972-5</ce:pii><ce:doi>10.1067/mpd.2000.107843</ce:doi><ce:document-thread><ce:refers-to-document><ce:pii>S0022-3476(00)90119-7</ce:pii></ce:refers-to-document></ce:document-thread><ce:copyright type="full-transfer" year="2000">Mosby, Inc.</ce:copyright></item-info><ce:floats><ce:table id="tab1" colsep="0" rowsep="0" frame="topbot"><ce:label>Table I</ce:label><ce:caption><ce:simple-para id="sp0010">Invasive Hib disease in Alaskans <5 years of age, 1980-1999, by ethnic group (Native vs non-Native) and vaccine era (1980-1991 vs 1992-1995, 1996-1997, and 1998-1999)</ce:simple-para></ce:caption><tgroup cols="9"><colspec colname="col1" colsep="0"></colspec><colspec colname="col2" colsep="0"></colspec><colspec colname="col3" colsep="0"></colspec><colspec colname="col4" colsep="0"></colspec><colspec colname="col5" colsep="0"></colspec><colspec colname="col6" colsep="0"></colspec><colspec colname="col7" colsep="0"></colspec><colspec colname="col8" colsep="0"></colspec><colspec colname="col9" colsep="0"></colspec><thead><row><entry morerows="2"></entry><entry namest="col2" nameend="col5" align="center">Native</entry><entry namest="col6" nameend="col9" align="center">Non-Native</entry></row><row><entry colname="col2" align="center">Before vaccine</entry><entry namest="col3" nameend="col5" align="center">After vaccine<ce:sup>†</ce:sup></entry><entry colname="col6" align="center">Before vaccine</entry><entry namest="col7" nameend="col9" align="center">After vaccine<ce:sup>†</ce:sup></entry></row><row><entry colname="col2" align="center">1980-91</entry><entry align="center">1992-95</entry><entry align="center">1996-97</entry><entry align="center">1998-99</entry><entry align="center">1980-91</entry><entry align="center">1992-95</entry><entry align="center">1996-97</entry><entry align="center">1998-99</entry></row></thead><tbody><row><entry>Cases (annual rate per 100,000 for children <5 y of age)</entry><entry align="center">396 (331.7)</entry><entry align="center">9 (16.9)</entry><entry align="center">16 (57.9)</entry><entry align="center">9 (32.5)</entry><entry align="center">396 (86.4)</entry><entry align="center">6 (3.5)</entry><entry align="center">0 (0.0)</entry><entry align="center">1 (1.2)</entry></row><row><entry>Cases (annual rate per 100,000 for children <1 y of age)</entry><entry align="center">265 (1014.1)</entry><entry align="center">7 (60.2)</entry><entry align="center">10 (165.7)</entry><entry align="center">8 (132.5)</entry><entry align="center">204 (205.0)</entry><entry align="center">3 (8.7)</entry><entry align="center">0 (0.0)</entry><entry align="center">0 (0.0)</entry></row><row><entry>Age <6 mo</entry><entry align="center">94 (23.7%)</entry><entry align="center">5 (55.6%)</entry><entry align="center">5 (31.6%)</entry><entry align="center">3 (33.3%)</entry><entry align="center">65 (16.4%)</entry><entry align="center">1 (16.7%)</entry><entry align="center">0</entry><entry align="center">0</entry></row><row><entry><1 y</entry><entry align="center">265 (66.9%)</entry><entry align="center">7 (77.8%)</entry><entry align="center">10 (62.5%)</entry><entry align="center">8 (88.9%)</entry><entry align="center">204 (51.5%)</entry><entry align="center">3 (50%)</entry><entry align="center">0</entry><entry align="center">0</entry></row><row><entry>Annual rate per 100,000 for children <5 y of age</entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry></row><row><entry>Urban areas</entry><entry align="center">225.0</entry><entry align="center">11.0</entry><entry align="center">7.1</entry><entry align="center">0.0</entry><entry align="center">87.3</entry><entry align="center">3.6</entry><entry align="center">0</entry><entry align="center">1</entry></row><row><entry>Rural areas</entry><entry align="center">447.9</entry><entry align="center">23.1</entry><entry align="center">111.0</entry><entry align="center">66.6</entry><entry align="center">NC*</entry><entry align="center">NC*</entry><entry align="center">NC*</entry><entry align="center">NC*</entry></row><row><entry namest="col1" nameend="col9">*Not calculated because of small population base. <ce:sup>†</ce:sup>Regimen used for universal immunization recommendations: PRP-OMP, 1992-95; HbOC (as part of DTP/HbOC combination vaccine), 1996-97; PRP-OMP for first dose followed by HbOC monovalent for additional doses, 1998-99.</entry></row></tbody></tgroup><ce:legend><ce:simple-para id="sp0015"><ce:italic>DTP,</ce:italic> Diphtheria-tetanus-pertussis vaccine.</ce:simple-para></ce:legend></ce:table><ce:table id="tab2" colsep="0" rowsep="0" frame="topbot"><ce:label>Table II</ce:label><ce:caption><ce:simple-para id="sp0020">Comparison of the populations studied for Hib carriage in children aged 1 to 4 years, in the YK Delta, Anchorage, and Barrow</ce:simple-para></ce:caption><tgroup cols="5"><colspec colname="col1" colsep="0"></colspec><colspec colname="col2" colsep="0"></colspec><colspec colname="col3" colsep="0"></colspec><colspec colname="col4" colsep="0"></colspec><colspec colname="col5" colsep="0"></colspec><thead><row><entry morerows="1">Characteristic</entry><entry morerows="1" align="center">YK Delta (n = 365)</entry><entry morerows="1" align="center">Anchorage (n = 383)</entry><entry namest="col4" nameend="col5" align="center">Barrow</entry></row><row><entry colname="col4" align="center">Alaska Natives (n = 98)</entry><entry align="center">Non-Natives (n = 26)</entry></row></thead><tbody><row><entry>Type of study</entry><entry align="center">Cross-sectional</entry><entry align="center">Clinic-based</entry><entry namest="col4" nameend="col5" align="center">School- and clinic-based</entry></row><row><entry>Study period</entry><entry align="center">April-May</entry><entry align="center">January-February</entry><entry namest="col4" nameend="col5" align="center">September</entry></row><row><entry></entry><entry align="center">1997</entry><entry align="center">1998</entry><entry namest="col4" nameend="col5" align="center">1998</entry></row><row><entry>Age-adjusted Hib prevalence rate in 1- to 4-year-olds (%)</entry><entry align="center">6.6</entry><entry align="center">1.1</entry><entry align="center">0</entry><entry align="center">6.3</entry></row><row><entry>Vaccination history</entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>≥2 Hib shots by age 6 mo (%)</entry><entry align="center">79.1</entry><entry align="center">88.9</entry><entry align="center">82.8</entry><entry align="center">85.7</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>≥3 Hib shots by age 18 mo (%)</entry><entry align="center">89.0</entry><entry align="center">94.6</entry><entry align="center">94.6</entry><entry align="center">73.7</entry></row><row><entry>Vaccination status at time of swabbing</entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>≥3 PRP-OMP vaccine (%)</entry><entry align="center">65.7</entry><entry align="center">36.7</entry><entry align="center">34.8</entry><entry align="center">19.0</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>≥3 HbOC or DTP/HbOC vaccine (%)</entry><entry align="center">11.8</entry><entry align="center">39.4</entry><entry align="center">44.9</entry><entry align="center">33.3</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>≥3 Hib vaccines, any type (%)</entry><entry align="center">97.5</entry><entry align="center">93.5</entry><entry align="center">95.9</entry><entry align="center">81.0</entry></row><row><entry>Household/demographic characteristics</entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry><entry align="center"></entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>Household size (average)</entry><entry align="center">6.1</entry><entry align="center">4.7</entry><entry align="center">5.7</entry><entry align="center">5.3</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>No. <13 y old in household (average)</entry><entry align="center">3.3</entry><entry align="center">2.4</entry><entry align="center">3.2</entry><entry align="center">2.7</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>Currently in day care (%)</entry><entry align="center">24.0</entry><entry align="center">32.7</entry><entry align="center">79.6</entry><entry align="center">84.6</entry></row><row><entry><ce:hsp sp="1.0"></ce:hsp>Recent antibiotic administration* (%)</entry><entry align="center">28.8</entry><entry align="center">23.2</entry><entry align="center">33.0</entry><entry align="center">7.7</entry></row><row><entry namest="col1" nameend="col5">*According to chart.</entry></row></tbody></tgroup></ce:table></ce:floats><head><ce:article-footnote><ce:label>☆</ce:label><ce:note-para>The opinions expressed in the article are those of the authors and do not necessarily reflect the views of the Alaska Native Tribal Health Consortium or the Indian Health Service.</ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>☆☆</ce:label><ce:note-para>The results of the Yukon Kuskokwim Delta Carriage study were published previously by Galil et al (J Infect Dis 1999;179:101-65).</ce:note-para></ce:article-footnote><ce:article-footnote><ce:label>★</ce:label><ce:note-para>Reprint requests: Rosalyn Singleton, MD, CDC Arctic Investigations Program, 4055 Tudor Centre Dr, Anchorage, AK 99508.</ce:note-para></ce:article-footnote><ce:dochead><ce:textfn>Original Articles</ce:textfn></ce:dochead><ce:title>Experience with the prevention of invasive <ce:italic>Haemophilus influenzae</ce:italic> type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</ce:title><ce:author-group><ce:author><ce:given-name>Rosalyn</ce:given-name><ce:surname>Singleton</ce:surname><ce:degrees>MD, MPH</ce:degrees></ce:author><ce:author><ce:given-name>Lisa R.</ce:given-name><ce:surname>Bulkow</ce:surname><ce:degrees>MS</ce:degrees></ce:author><ce:author><ce:given-name>Orin S.</ce:given-name><ce:surname>Levine</ce:surname><ce:degrees>PhD</ce:degrees></ce:author><ce:author><ce:given-name>Jay C.</ce:given-name><ce:surname>Butler</ce:surname><ce:degrees>MD</ce:degrees></ce:author><ce:author><ce:given-name>Thomas W.</ce:given-name><ce:surname>Hennessy</ce:surname><ce:degrees>MD, MPH</ce:degrees></ce:author><ce:author><ce:given-name>Alan</ce:given-name><ce:surname>Parkinson</ce:surname><ce:degrees>PhD</ce:degrees></ce:author><ce:affiliation><ce:textfn>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</ce:textfn></ce:affiliation></ce:author-group><ce:date-received day="27" month="10" year="1999"></ce:date-received><ce:date-revised day="6" month="3" year="2000"></ce:date-revised><ce:date-accepted day="5" month="4" year="2000"></ce:date-accepted><ce:abstract><ce:section-title id="st0010">Abstract</ce:section-title><ce:abstract-sec><ce:simple-para id="sp0025"><ce:bold>Objectives:</ce:bold> To report the epidemiology of invasive <ce:italic>Haemophilus influenzae</ce:italic> type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. <ce:bold>Study design:</ce:bold> Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. <ce:bold>Results:</ce:bold> The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. <ce:bold>Conclusions:</ce:bold> Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="abr"><ce:section-title id="st0015">Abbreviations</ce:section-title><ce:keyword><ce:text>AIP</ce:text><ce:keyword><ce:text>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>HbOC</ce:text><ce:keyword><ce:text>Hib oligosaccharide-CRM<ce:inf>197</ce:inf> vaccine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>Hib</ce:text><ce:keyword><ce:text><ce:italic>Haemophilus influenzae</ce:italic> type b</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>IgG</ce:text><ce:keyword><ce:text>Immunoglobulin G</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PRP</ce:text><ce:keyword><ce:text>Polyribosylribitol phosphate</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>PRP-OMP</ce:text><ce:keyword><ce:text>PRP–outer-membrane protein conjugate vaccine</ce:text></ce:keyword></ce:keyword><ce:keyword><ce:text>YK</ce:text><ce:keyword><ce:text>Yukon Kuskokwim [Delta]</ce:text></ce:keyword></ce:keyword></ce:keywords></head><body><ce:sections><ce:para id="p0010"><ce:bold>See editorial, p. 295.</ce:bold></ce:para><ce:para id="p0015">Before <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccines were licensed for infants in 1990, Alaska Natives <5 years of age experienced some of the highest reported Hib invasive disease rates anywhere, 400 to 600 per 100,000 children<ce:cross-refs refid="bib1 bib2"><ce:sup>1,2</ce:sup></ce:cross-refs> with the highest rate, 700 per 100,000, in Eskimos from southwestern Alaska. By comparison, the rate of invasive Hib disease in the general population of the United States was 60 to 100 per 100,000 children <5 years old.<ce:cross-refs refid="bib3 bib4"><ce:sup>3,4</ce:sup></ce:cross-refs></ce:para><ce:para id="p0020">Prevention of Hib disease in Alaska Native populations is complicated by several other unique features of the local epidemiology of the disease. Among Alaska Natives, 25% of invasive Hib disease in children occurred before the age of 6 months, whereas <15% occurred by the same age in the general US population.<ce:cross-ref refid="bib4"><ce:sup>4</ce:sup></ce:cross-ref> Before vaccination, the prevalence of Hib carriage in young Alaska Native children<ce:cross-ref refid="bib5"><ce:sup>5</ce:sup></ce:cross-ref> was somewhat higher (~5%-7%) than that observed in other US children (2%-5%).<ce:cross-refs refid="bib6 bib7"><ce:sup>6,7</ce:sup></ce:cross-refs> Also, living conditions in rural Alaska Native villages tend to be very crowded, similar to those in developing countries. Strategies for prevention of Hib by vaccination in Alaska have taken these characteristics into account.</ce:para><ce:para id="p0025">In this article we review the experience with prevention of Hib disease in Alaska Native and Alaska non-Native children. We present data on surveillance for invasive Hib disease, Hib vaccination coverage, and results from 3 cross-sectional studies of oropharyngeal Hib carriage. Lessons from the experience in Alaska provide information that can help define optimal strategies for Hib control and elimination in both developing and industrialized populations.</ce:para><ce:section id="s0010"><ce:section-title id="st0020">METHODS</ce:section-title><ce:section id="s0015"><ce:section-title id="st0025">Population Statistics</ce:section-title><ce:para id="p0030">Demographic information was obtained from the 1980 and 1990 US Census, the Alaska Department of Labor, and the Alaska Area Native Health Service. Sixteen percent of the Alaska population is Alaska Native, a diverse group that includes Eskimo, Aleut, Athabascan, Tsimpsian, Haida, Tlingit, and American Indian groups. More than half of Alaska Natives are Eskimos, who traditionally lived as subsistence harvesters along the northern and western coasts. Aleuts live in the Aleutian and Pribilof Islands. Athabascan Indians inhabit central and south-central Alaska, whereas the Tsimpsians, Haidas, and Tlingits inhabit southeast Alaska. Although the majority of Alaska Natives still live in these regions, many live in urban areas of the state (Fig 1).<ce:display><ce:figure id="fig1"><ce:label>Fig. 1</ce:label><ce:caption><ce:simple-para id="sp0030">Population estimates for 1996 in Alaska by service unit and ethnicity. Area of each circle is proportional to population size.</ce:simple-para></ce:caption> <ce:link locator="gr1"></ce:link></ce:figure></ce:display></ce:para><ce:para id="p0035">In 1996 an estimated 100,105 Alaska Natives lived in the state; 25,088 (25.1%) of these were <10 years of age. This compares with 507,695 other Alaska residents, of whom 83,513 (16.5%) were <10 years of age. Forty-three percent of Alaska Natives live in areas where Natives make up more than half of the population (<ce:cross-ref refid="fig1">Fig 1</ce:cross-ref>). These 5 regions are grouped and referred to as <ce:italic>rural</ce:italic> , and the remaining 3 regions are combined and referred to as <ce:italic>urban</ce:italic>.</ce:para></ce:section><ce:section id="s0020"><ce:section-title id="st0030">Case Definition</ce:section-title><ce:para id="p0040">Invasive <ce:italic>H influenzae</ce:italic> was defined by recovery of <ce:italic>H influenzae</ce:italic> from a normally sterile site (blood, cerebrospinal fluid, pleural fluid, or other aspirate).</ce:para></ce:section><ce:section id="s0025"><ce:section-title id="st0035">Surveillance Data</ce:section-title><ce:para id="p0045">The Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska, has conducted statewide surveillance for all invasive <ce:italic>H influenzae</ce:italic> disease since 1980. The 26 microbiology laboratories in the state send all <ce:italic>H influenzae</ce:italic> isolates recovered from normally sterile sites to AIP for confirmation of identity and serotyping. 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 <ce:italic>H influenzae</ce:italic> infection to identify possible missed cases.</ce:para></ce:section><ce:section id="s0030"><ce:section-title id="st0040">Laboratory Methods (Surveillance)</ce:section-title><ce:para id="p0050">Subcultures of each isolate were reestablished at the AIP on chocolate agar. <ce:italic>H influenzae</ce:italic> was confirmed by Gram stain and factor V and X requirements (Differentiation Disks; Difco Laboratories, Detroit, Mich), and 2 reference samples of each specimen were banked at –70°C for future testing. Serotyping was conducted by slide agglutination (<ce:italic>H influenzae</ce:italic> type a-f typing antisera, Difco). Isolates with discrepancies in serotype between the submitting and AIP laboratories were re-analyzed by Centers for Disease Control and Prevention in Atlanta, Georgia; the latter results took precedence.</ce:para></ce:section><ce:section id="s0035"><ce:section-title id="st0045">Carriage Surveys</ce:section-title><ce:para id="p0055">We conducted 3 cross-sectional Hib carriage studies between April 1997 and September 1998 to evaluate the role of Hib colonization in re-emergence of Hib invasive disease in 1996. After obtaining informed consent, we collected oropharyngeal swabs from 496 Alaska Native children aged 1 to 5 years in 5 villages (70%-90% of eligible children in each village) and one town in the Yukon Kuskokwim Delta in April 1997. Results of this study were previously published.<ce:cross-ref refid="bib8"><ce:sup>8</ce:sup></ce:cross-ref> In January 1998, we collected oropharyngeal swab specimens from 417 Alaska Native children aged 1 to 8 years (<20% of eligible children) in an urban Anchorage clinic and, in September 1998, from 541 Alaska Native and 160 non-Native children aged 1 to 16 years (<50% of eligible children) in the northern town of Barrow.</ce:para><ce:para id="p0060">Oropharyngeal swab specimens were inoculated immediately onto 60-mm Levinthal’s agar plates with burro Hib antiserum added (provided by Dr John Robbins, National Institutes of Health, Bethesda, Md).<ce:cross-ref refid="bib9"><ce:sup>9</ce:sup></ce:cross-ref> Antiserum agar plates were streaked for isolation in the field, placed in portable incubators at 35°C in a carbon dioxide–enhanced environment, and shipped to the AIP laboratory within 48 hours of inoculation. Presumptive identification of Hib was based on the appearance of an antigen-antibody precipitate (halo), which was then confirmed as Hib by Gram stain, X and V growth factor dependency, and serotyping.</ce:para><ce:para id="p0065">Questionnaires were completed by the parent or guardian of each subject. Information included household size, number of rooms in the house (in the YK Delta study only), number and ages of siblings, day-care attendance (cared for with 5 or more children at least 3 times per week within the past 30 days), place of residence, and antibiotic use. Vaccination data, clinic visit data, and information on antibiotic prescriptions in the previous 30 days were obtained from medical records in the village clinic and regional hospital.</ce:para></ce:section><ce:section id="s0040"><ce:section-title id="st0050">Vaccine Coverage</ce:section-title><ce:para id="p0070">Immunization rates in Alaska Natives are based on 34 immunization audits of 24- to 35-month-old children in 12 Alaska Native service areas, conducted by the Alaska Native Health Service and the State of Alaska Division of Epidemiology between 1994 and 1998. By year, an average of 90% to 95% of urban Alaska Native and 88% to 91% of rural Alaska Native 2-year-olds had received at least 3 Hib vaccine doses by 24 months. An average of only 72% to 83% of urban Alaska Native and 51% to 75% of rural Alaska Native 2-year-olds had received their first 2 Hib doses by 5 months of age.</ce:para></ce:section></ce:section><ce:section id="s0045"><ce:section-title id="st0055">RESULTS</ce:section-title><ce:section id="s0050"><ce:section-title id="st0060">Epidemiology of Hib Disease and Effectiveness of Hib Vaccination</ce:section-title><ce:para id="p0075">Before routine infant Hib vaccination, the overall rate of invasive Hib disease was 332 cases per 100,000 children <5 years old per year (Table I).<ce:float-anchor refid="tab1"></ce:float-anchor>The rate in rural Alaska Native children, however, was nearly twofold higher than that observed in urban Alaska Native children (448 vs 225 cases per 100,000; <ce:italic>P</ce:italic> <.001). Furthermore, the rate in Alaska non-Native children living in the state’s urban areas was lower than the rate in urban Alaska Native children (87 vs 225 cases per 100,000; <ce:italic>P</ce:italic> <.001).</ce:para><ce:para id="p0080">Prevention measures against Hib in the 1980s included the use of the polyribosylribitol phosphate vaccine and PRP–diphtheria toxoid conjugate vaccine in toddlers, the use of PRP-diphtheria toxoid conjugate vaccine in infants in an efficacy trial that failed to prove significant protective efficacy,<ce:cross-ref refid="bib10"><ce:sup>10</ce:sup></ce:cross-ref> and the use of bacterial polysaccharide immune globulin as passive protection in 1989 and 1990 for Alaska Native infants in southwestern Alaska.<ce:cross-ref refid="bib11"><ce:sup>11</ce:sup></ce:cross-ref>Between January and June 1991, Hib oligosaccharide-CRM<ce:inf>197</ce:inf> vaccine (HibTITER) was purchased by the State of Alaska, which purchases all routine childhood vaccines, for universal vaccination of Alaska infants. In July 1991, the state switched to PRP–outer-membrane protein conjugate vaccine (PedvaxHIB) because of its unique ability to protect infants after a single dose, a characteristic that is important for the Alaska Native population, which has a high risk for early Hib disease.<ce:cross-refs refid="bib12 bib13 bib14 bib15"><ce:sup>12-15</ce:sup></ce:cross-refs> From July 1991 to December 1995, all Alaska children received PRP-OMP.</ce:para><ce:para id="p0085">After the introduction of routine PRP-OMP vaccination, there was a rapid decrease in the rate of Hib disease in Alaska Native children (Fig 2) from 332 per 100,000 in 1980-1991 to a rate of 16.9 per 100,000 in 1992-1995, corresponding to a prevention effectiveness of 94.9% (95% CI: 90.2% to 97.7%; <ce:italic>P</ce:italic> <.001) (<ce:cross-ref refid="tab1">Table I</ce:cross-ref>).<ce:display><ce:figure id="fig2"><ce:label>Fig. 2</ce:label><ce:caption><ce:simple-para id="sp0035">Culture-confirmed invasive Hib disease in Alaska children <5 years of age, 1980-1999. <ce:italic>BPIG</ce:italic> , Bacterial polysaccharide immune globulin; <ce:italic>DTP</ce:italic> , diphtheria-tetanus-pertussis vaccine.</ce:simple-para></ce:caption> <ce:link locator="gr2"></ce:link></ce:figure></ce:display>Vaccination was similarly effective in both rural and urban Alaska Native populations. Over the same period, the rate of disease in Alaska non-Natives <5 years of age declined from 86 per 100,000 in 1980-1991 to 3.5 per 100,000 in 1992-1995, corresponding to a prevention effectiveness of 96% (95% <ce:bold>CI:</ce:bold> 91.1% to 98.5%; <ce:italic>P</ce:italic> <.001).</ce:para><ce:para id="p0090">During the period from 1992 to 1995, when PRP-OMP was routinely used, there were 9 cases of invasive Hib disease in Alaska Native children <5 years old. Of the 9 cases, the majority, 5 (56%), occurred in unvaccinated infants, and <1 case per year occurred in infants who were partially vaccinated with PRP-OMP.</ce:para><ce:para id="p0095">In January 1996, Alaska changed from routine PRP-OMP to HbOC (given as Tetramune) vaccination to decrease the number of shots given at each visit. However, during May 1996, there were 4 cases of Hib invasive disease in rural Alaska Native infants, and during 1996 and 1997, a total of 16 Hib cases occurred in children <5 years of age (<ce:cross-ref refid="fig2">Fig 2</ce:cross-ref>), an increase in annual Hib disease rate from 16.9 cases per 100,000 in 1992-1995 to 57.9 cases per 100,000 in 1996-1997. The increase in cases was uniquely confined to rural Alaska Native children, in whom the incidence increased from 23.1 to 111.0 cases per 100,000 children <5 years old (<ce:italic>P</ce:italic> =.001). The rate in urban Alaska Native children continued to decline during the same period, from 11.0 to 7.1 cases per 100,000 children <5 years old. Unlike the previous period (1992-1995), 8 (50%) of the cases occurred in partially vaccinated children who had received 1 or 2 doses of HbOC, and only one (6%) case occurred in a completely unvaccinated child. The remaining cases were breakthroughs that occurred in children >1 year old who were fully or partially vaccinated.</ce:para><ce:para id="p0100">Concern that the change to use of HbOC vaccine left some partially vaccinated children susceptible in an environment with continued transmission of Hib organisms led to a recommendation for Alaska Native providers to switch the first Hib dose back to PRP-OMP in July 1996. This policy was expanded to all Alaska infants in October 1997, when Alaska adopted an official sequential Hib vaccination schedule with PRP-OMP for the first dose and HbOC for the following doses. Even so, some children received HbOC for the first dose. Between October 1997 and December 1999, a total of 9 Hib cases occurred in Alaska Native children <5 years of age. Six cases were in partially immunized children <1 year of age. Of these, 3 had inadvertently received HbOC for their first dose. Two cases occurred in unvaccinated children.</ce:para></ce:section><ce:section id="s0055"><ce:section-title id="st0065">Carriage Surveys</ce:section-title><ce:para id="p0105">We conducted 3 surveys to estimate the prevalence of Hib carriage in Alaska Native populations (Table II).<ce:float-anchor refid="tab2"></ce:float-anchor>The YK Delta study (previously published<ce:cross-ref refid="bib8"><ce:sup>8</ce:sup></ce:cross-ref>) was a cross-sectional population-based study in April 1997, whereas the Anchorage study (January 1998) was clinic-based, and the Barrow study (September 1998) was school- and clinic-based. Children were sequentially enrolled as they became available in each setting. Although Hib vaccine coverage rates in participants varied little by study site, the vaccine regimens did vary by site, reflecting changes in the Hib vaccine schedules in Alaska and the period during which the different surveys were performed (<ce:cross-ref refid="tab2">Table II</ce:cross-ref>). Changes in Hib vaccine regimen from PRP-OMP to HbOC and then to sequential PRP-OMP/HbOC affected whole age cohorts in the state. Because carriage is directly related to age, this interferes with our ability to evaluate the independent effect of vaccine regimen on carriage. There was not significant heterogeneity in Hib vaccine types by age cohorts to allow for a comparison of carriage between different vaccine regimens.</ce:para><ce:para id="p0110">Prevalence of Hib carriage varied by age and geographic area. Carriage increased significantly with age for children (Alaska Natives and nonNatives) 1 to 5 years of age in YK Delta and Barrow (Fig 3).<ce:display><ce:figure id="f0010"><ce:label>Fig. 3</ce:label><ce:caption><ce:simple-para id="sp0040">Rates of carriage by year of age for children 1 to 5 years of age in YK Delta, 1 to 8 years of age in Anchorage, and 1 to 16 years of age in Barrow.</ce:simple-para></ce:caption> <ce:link locator="gr3"></ce:link></ce:figure></ce:display>In the Barrow study, which enrolled children up to 16 years of age, 24 (4.4%) of 541 Alaska Natives and 7 (4.4%) of 160 non-Natives were colonized with Hib. Carriage rate peaked at 7.8% (9 positive results in 116 enrolled subjects) among 6- to 7-year-old children, then decreased in subsequent ages to 0% (0 positive results in 57 subjects) among 14- to 16-year-old children. Of non-Natives enrolled in Barrow, 68 were of known Asian descent, and 4 (5.9%) of these children were colonized. Among the Alaska Native children 1 to 4 years old, age-adjusted Hib carriage was 6.6% in the YK Delta, 1.1% in Anchorage, and 0% in Barrow (<ce:cross-ref refid="tab2">Table II</ce:cross-ref>). Age-adequate vaccination was documented in 98% of carriers and 97% of non-carriers in YK Delta, 100% of carriers and 88% of non-carriers in Anchorage, and 96% of carriers and 87% of non-carriers in Barrow (<10 years of age (<ce:italic>P</ce:italic> >.05 for all regions).</ce:para><ce:para id="p0115">The average household size and mean number of children <13 years old were higher in the YK Delta and Barrow compared with the Anchorage survey, reflecting regional differences in household size. The proportion of children currently in day care was similar in the YK Delta and Anchorage surveys. The higher proportion of children in day care in the Barrow study most likely reflected the school- and clinic-based recruitment strategy used. The prevalence of recent antibiotic use was similar in each survey. In the YK Delta, other factors associated with carriage in univariate analysis included day-care attendance in the regional town (odds ratio = 6.2, 95% CI: = 1.7-22.2) and the largest village (odds ratio = 5.2, 95% CI: 1.3-20.0) and more persons per room in a household. In stepwise regression analysis, an increasing number of persons per room in household (odds ratio = l.3, 95% CI: 1.1-1.5) was independently associated with an increased risk of Hib carriage. In the Anchorage study, in which only 4 carriers were identified, no factors could be associated with carriage, and in none of the studies was the rate of carriage associated with use of antibiotics in the previous month, recent illness, or chronic medical conditions.</ce:para></ce:section></ce:section><ce:section id="s0060"><ce:section-title id="st0070">DISCUSSION</ce:section-title><ce:para id="p0120">The incidence of invasive Hib disease declined dramatically in Alaskan children after universal Hib vaccination. However, although the 1998-1999 incidence in non-Native children (1 case per 100,000 children <5 years old per year) and urban Native children (0.0 per 100,000) is similar to the rate reported by the Centers for Disease Control and Prevention for the lower 48 states (~1 per 100,000),<ce:cross-ref refid="bib16"><ce:sup>16</ce:sup></ce:cross-ref> the incidence among Alaska Native children in rural Alaska is many-fold higher (66.6 per 100,000). Factors that may contribute to continued higher rates of disease include environmental conditions (household crowding, poor house ventilation, lack of access to running water and flush toilets), persistent Hib carriage in children from these communities, and modest rates of on-time immunization in the first 6 months of life.</ce:para><ce:para id="p0125">The observation of high rates of Hib colonization and continued Hib transmission among some rural Alaska Native children contrasts with near elimination of Hib colonization<ce:cross-refs refid="bib17 bib18 bib19 bib20"><ce:sup>17-20</ce:sup></ce:cross-refs> and Hib disease<ce:cross-refs refid="bib16 bib21"><ce:sup>16,21</ce:sup></ce:cross-refs> in infants and young children by Hib conjugate vaccination in the United States and developed countries. The persistence of Hib carriage despite widespread vaccination is likely explained by several factors, but determining the contribution of each individual factor is difficult. The same environmental conditions that contributed to high rates of invasive Hib disease in rural Alaska Natives before routine vaccination may cause continued transmission of Hib carriage and attenuate the effectiveness of vaccination against Hib colonization. Substantial reservoirs of Hib colonization may remain in infants (in part because of the modest levels of on-time immunization) or among older children and adults who are not currently reached by the immunization program. Data from the carriage study in Barrow suggest that school-aged children may be an important reservoir of Hib in rural Alaska. The annual rate of invasive Hib disease among Alaska Natives aged 10 years and older fell from 2.1/100,000 in the 1980s to 0.2/100,000 in the 1990s,<ce:cross-ref refid="bib22"><ce:sup>22</ce:sup></ce:cross-ref> but there are currently no data on Hib colonization in adults in Alaska. If the reservoir of Hib colonization is large and the vaccine effect against colonization is short-lived, Hib transmission in this setting may not be eliminated simply by vaccination of infants and young children.</ce:para><ce:para id="p0130">It is unclear whether the choice of vaccine regimen may have also contributed to continued carriage despite vaccination. Some investigators have hypothesized that prevention of Hib carriage is related to the development of high levels of serum anti-PRP immunoglobulin G (~7 μg/mL) and that these antibodies then exude to the mucosal surface and prevent colonization.<ce:cross-ref refid="bib23"><ce:sup>23</ce:sup></ce:cross-ref> Although PRP-OMP protects against invasive disease after the first dose, anti-PRP IgG levels after a complete regimen with PRP-OMP are significantly lower than those after vaccination with HbOC or PRP-tetanus toxoid vaccine (ACTHib).<ce:cross-refs refid="bib12 bib13 bib14"><ce:sup>12-14</ce:sup></ce:cross-refs> The only study of the effectiveness of PRP-OMP vaccine against carriage showed a decrease in, but not elimination of, Hib carriage after vaccination.<ce:cross-ref refid="bib24"><ce:sup>24</ce:sup></ce:cross-ref> However, the dynamics of Hib carriage are probably more complicated than a relationship to antibody levels. In the carriage studies reported here, the comparative efficacy of the various vaccine regimens used against carriage cannot be determined because different age cohorts received different vaccines and age itself was a major determinant of carriage rate.</ce:para><ce:para id="p0135">According to the 1996 and 1997 National Immunization Survey, 92% of US children aged 18 to 35 months and 87% of Alaska children (all races) had received at least 3 Hib vaccine doses.<ce:cross-ref refid="bib25"><ce:sup>25</ce:sup></ce:cross-ref> Immunization rates for 2-year-old children among Alaska Natives are comparable to the US rate and higher than the Alaska rate for all races, based on the National Immunization Survey. On-time immunization rates are much lower than rates among 2-year-olds in several rural Alaska Native regions but not necessarily lower than on-time rates reported in other US populations.<ce:cross-ref refid="bib26"><ce:sup>26</ce:sup></ce:cross-ref> Factors that contribute to low on-time immunization rates include isolated villages linked only by air travel, with immunizations provided mainly by itinerant public health nurses. Lack of on-time immunization and the use of HbOC for the first dose in 1996-1997 contributed to the pool of children susceptible to Hib disease. Because of the high risk of Hib disease in Alaska Native infants <6 months of age, improving on-time vaccination coverage is essential in regions where cases are still occurring.</ce:para><ce:para id="p0140">The re-emergence of invasive Hib disease in 1996-1997 occurred after the Hib vaccine used for universal immunization was changed from PRP-OMP to HbOC combined with diphtheria, tetanus, and whole-cell pertussis. The cases of invasive disease occurring among infants inadvertently given monovalent HbOC vaccine for the first Hib vaccination during 1998-1999 provide anecdotal evidence that the 1996-1997 re-emergence was caused by use of an Hib vaccine that produced inadequate antibody levels after 1 to 2 doses, rather than by use of a combination vaccine. Our experience demonstrates that it is critical that PRP-OMP be used for the first dose in Alaska to provide optimal protection early, because this is the only Hib vaccine that provides significant protection after the first dose, and substitution of other Hib vaccines has resulted in breakthrough Hib cases. The current Alaska sequential schedule in which PRP-OMP is used for the first dose, followed by HbOC for subsequent doses, harnesses the best properties of each vaccine, that is, higher anti-PRP IgG concentrations after the first dose than with HbOC alone and higher concentrations after the third dose than with PRP-OMP alone.<ce:cross-refs refid="bib27 bib28 bib29"><ce:sup>27-29</ce:sup></ce:cross-refs></ce:para><ce:para id="p0145">The experience with Hib conjugate vaccination in Alaska demonstrates the robust ability of these vaccines to prevent Hib invasive disease in high-incidence settings. It also shows that the ability of current immunization strategies to eliminate Hib transmission and carriage may be limited in high-risk populations. The observation of higher rates of Hib carriage and disease among rural Alaska Native children highlights the need to maintain surveillance in the era of widespread vaccination and the need for further research to elaborate more effective strategies to eliminate Hib colonization in these populations. Repeating evaluations of carriage in the same populations after use of the sequential Hib schedule and evaluations of carriage before and after a booster dose of Hib vaccine may help to assess the relationship of anti-PRP concentrations to Hib carriage. The experience in rural Alaska may provide useful background for identifying the optimal strategies for prevention of Hib disease in rural areas of the developing world and in indigenous populations of Canada, Australia, New Zealand, and elsewhere.</ce:para></ce:section></ce:sections><ce:acknowledgment><ce:section-title id="st0075">Acknowledgements</ce:section-title><ce:para id="p0150"><ce:italic>We thank Helen Peters, Debby Hurlburt, Irma DeSmet, Carolyn Zanis, Susan Seidel, Debra Parks, Carolynn DeByle, Jane Moore, Alice Yates, Alisa Reasonover, and Lynne Lucher for their contributions in Hib surveillance and carriage studies; Tanja Popovic and Gloria Ajello for their preparation of Hib antiserum agar plates; and Kenneth Petersen for his comments on the manuscript.</ce:italic></ce:para></ce:acknowledgment></body><tail><ce:bibliography id="bi0010"><ce:section-title id="st0080">References</ce:section-title><ce:bibliography-sec id="bs0010"><ce:bib-reference id="bib1"><ce:label>1</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>JI</ce:given-name><ce:surname>Ward</ce:surname></sb:author><sb:author><ce:given-name>HS</ce:given-name><ce:surname>Margolis</ce:surname></sb:author><sb:author><ce:given-name>MK</ce:given-name><ce:surname>Lum</ce:surname></sb:author><sb:author><ce:given-name>DW</ce:given-name><ce:surname>Fraser</ce:surname></sb:author><sb:author><ce:given-name>TR</ce:given-name><ce:surname>Bender</ce:surname></sb:author><sb:author><ce:given-name>P.</ce:given-name><ce:surname>Anderson</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle><ce:italic>Haemophilus influenzae</ce:italic> disease in Alaskan Eskimos: characteristics of a population with an unusual incidence of invasive disease</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Lancet</sb:maintitle></sb:title><sb:volume-nr>1</sb:volume-nr></sb:series><sb:date>1981</sb:date></sb:issue><sb:pages><sb:first-page>1281</sb:first-page><sb:last-page>1285</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib2"><ce:label>2</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>JI</ce:given-name><ce:surname>Ward</ce:surname></sb:author><sb:author><ce:given-name>MK</ce:given-name><ce:surname>Lum</ce:surname></sb:author><sb:author><ce:given-name>DB</ce:given-name><ce:surname>Hall</ce:surname></sb:author><sb:author><ce:given-name>DR</ce:given-name><ce:surname>Silimperi</ce:surname></sb:author><sb:author><ce:given-name>TR.</ce:given-name><ce:surname>Bender</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Invasive <ce:italic>Haemophilus influenzae</ce:italic> type b disease in Alaska: background epidemiology for a vaccine efficacy trial</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Infect Dis</sb:maintitle></sb:title><sb:volume-nr>153</sb:volume-nr></sb:series><sb:date>1986</sb:date></sb:issue><sb:pages><sb:first-page>17</sb:first-page><sb:last-page>26</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib3"><ce:label>3</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>CV.</ce:given-name><ce:surname>Broome</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Epidemiology of <ce:italic>Haemophilus influenzae</ce:italic> type b infections in the United States</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>6</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>779</sb:first-page><sb:last-page>782</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib4"><ce:label>4</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>J</ce:given-name><ce:surname>Ward</ce:surname></sb:author><sb:author><ce:given-name>JM</ce:given-name><ce:surname>Leiberman</ce:surname></sb:author><sb:author><ce:given-name>SL.</ce:given-name><ce:surname>Cochi</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle><ce:italic>Haemophilus influenzae</ce:italic> vaccines</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:edition>2nd ed</sb:edition><sb:book-series><sb:editors><sb:editor><ce:given-name>SA</ce:given-name><ce:surname>Plotkin</ce:surname></sb:editor><sb:editor><ce:given-name>EA</ce:given-name><ce:surname>Mortimer</ce:surname></sb:editor></sb:editors><sb:series><sb:title><sb:maintitle>Vaccines</sb:maintitle></sb:title></sb:series></sb:book-series><sb:date>1994</sb:date><sb:publisher><sb:name>WB Saunders Co</sb:name><sb:location>Philadelphia</sb:location></sb:publisher></sb:edited-book><sb:pages><sb:first-page>337</sb:first-page><sb:last-page>386</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib5"><ce:label>5</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>DB</ce:given-name><ce:surname>Hall</ce:surname></sb:author><sb:author><ce:given-name>MK</ce:given-name><ce:surname>Lum</ce:surname></sb:author><sb:author><ce:given-name>LR</ce:given-name><ce:surname>Knutson</ce:surname></sb:author><sb:author><ce:given-name>WL</ce:given-name><ce:surname>Heyward</ce:surname></sb:author><sb:author><ce:given-name>JI.</ce:given-name><ce:surname>Ward</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Pharyngeal carriage and acquisition of anticapsular antibody to <ce:italic>Haemophilus influenzae</ce:italic> type b in a high-risk population in southwestern Alaska</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Am J Epidemiol</sb:maintitle></sb:title><sb:volume-nr>126</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>1190</sb:first-page><sb:last-page>1197</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib6"><ce:label>6</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>DC.</ce:given-name><ce:surname>Turk</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Nasopharyngeal carriage of <ce:italic>Haemophilus influenzae</ce:italic> type b</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Hygiene</sb:maintitle></sb:title><sb:volume-nr>61</sb:volume-nr></sb:series><sb:date>1963</sb:date></sb:issue><sb:pages><sb:first-page>247</sb:first-page><sb:last-page>256</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib7"><ce:label>7</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>RH</ce:given-name><ce:surname>Michaels</ce:surname></sb:author><sb:author><ce:given-name>CS</ce:given-name><ce:surname>Poziviak</ce:surname></sb:author><sb:author><ce:given-name>FE</ce:given-name><ce:surname>Stonebraker</ce:surname></sb:author><sb:author><ce:given-name>CW.</ce:given-name><ce:surname>Norden</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Factors affecting pharyngeal <ce:italic>Haemophilus influenzae</ce:italic> type b colonization rates in children</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Clin Microbiol</sb:maintitle></sb:title><sb:volume-nr>4</sb:volume-nr></sb:series><sb:date>1976</sb:date></sb:issue><sb:pages><sb:first-page>413</sb:first-page><sb:last-page>417</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib8"><ce:label>8</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>K</ce:given-name><ce:surname>Galil</ce:surname></sb:author><sb:author><ce:given-name>R</ce:given-name><ce:surname>Singleton</ce:surname></sb:author><sb:author><ce:given-name>OS</ce:given-name><ce:surname>Levine</ce:surname></sb:author><sb:author><ce:given-name>MA</ce:given-name><ce:surname>Fitzgerald</ce:surname></sb:author><sb:author><ce:given-name>L</ce:given-name><ce:surname>Bulkow</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Getty</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Re-emergence of invasive <ce:italic>Haemophilus influenzae</ce:italic> type b disease in a well-vaccinated population in remote Alaska</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Infect Dis</sb:maintitle></sb:title><sb:volume-nr>179</sb:volume-nr></sb:series><sb:date>1999</sb:date></sb:issue><sb:pages><sb:first-page>101</sb:first-page><sb:last-page>106</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib9"><ce:label>9</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>RH</ce:given-name><ce:surname>Michaels</ce:surname></sb:author><sb:author><ce:given-name>FE</ce:given-name><ce:surname>Stonebraker</ce:surname></sb:author><sb:author><ce:given-name>JB.</ce:given-name><ce:surname>Robbins</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Use of antiserum agar for detection of <ce:italic>Haemophilus influenzae</ce:italic> type b in the pharynx</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Res</sb:maintitle></sb:title><sb:volume-nr>9</sb:volume-nr></sb:series><sb:date>1975</sb:date></sb:issue><sb:pages><sb:first-page>513</sb:first-page><sb:last-page>516</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib10"><ce:label>10</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>JI</ce:given-name><ce:surname>Ward</ce:surname></sb:author><sb:author><ce:given-name>G</ce:given-name><ce:surname>Brenneman</ce:surname></sb:author><sb:author><ce:given-name>GW</ce:given-name><ce:surname>Letson</ce:surname></sb:author><sb:author><ce:given-name>WL</ce:given-name><ce:surname>Heyward</ce:surname></sb:author><sb:author><ce:surname>the Alaska Haemophilus influenzae Vaccine Study Group</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Limited efficacy of a <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccine in Alaska Native infants</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>323</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>1393</sb:first-page><sb:last-page>1401</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib11"><ce:label>11</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>RJ</ce:given-name><ce:surname>Singleton</ce:surname></sb:author><sb:author><ce:given-name>NM</ce:given-name><ce:surname>Davidson</ce:surname></sb:author><sb:author><ce:given-name>IJ</ce:given-name><ce:surname>DeSmet</ce:surname></sb:author><sb:author><ce:given-name>JE</ce:given-name><ce:surname>Berner</ce:surname></sb:author><sb:author><ce:given-name>RB</ce:given-name><ce:surname>Wainwright</ce:surname></sb:author><sb:author><ce:given-name>LR</ce:given-name><ce:surname>Bulkow</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Decline of <ce:italic>Haemophilus influenzae</ce:italic> type b disease in a region of high risk: impact of passive and active immunization</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>13</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>362</sb:first-page><sb:last-page>367</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib12"><ce:label>12</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>LR</ce:given-name><ce:surname>Bulkow</ce:surname></sb:author><sb:author><ce:given-name>RB</ce:given-name><ce:surname>Wainwright</ce:surname></sb:author><sb:author><ce:given-name>GW</ce:given-name><ce:surname>Letson</ce:surname></sb:author><sb:author><ce:given-name>SJ</ce:given-name><ce:surname>Chang</ce:surname></sb:author><sb:author><ce:given-name>JI.</ce:given-name><ce:surname>Ward</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Comparative immunogenicity of four <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccines in Alaska Native infants</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>12</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>484</sb:first-page><sb:last-page>492</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib13"><ce:label>13</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>MC</ce:given-name><ce:surname>Decker</ce:surname></sb:author><sb:author><ce:given-name>KM</ce:given-name><ce:surname>Edwards</ce:surname></sb:author><sb:author><ce:given-name>R</ce:given-name><ce:surname>Bradley</ce:surname></sb:author><sb:author><ce:given-name>P.</ce:given-name><ce:surname>Palmer</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Comparative trial in infants of four conjugate <ce:italic>Haemophilus influenzae</ce:italic> type b vaccines</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Pediatr</sb:maintitle></sb:title><sb:volume-nr>120</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>184</sb:first-page><sb:last-page>189</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib14"><ce:label>14</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>DM</ce:given-name><ce:surname>Granoff</ce:surname></sb:author><sb:author><ce:given-name>BI</ce:given-name><ce:surname>Anderson</ce:surname></sb:author><sb:author><ce:given-name>MT</ce:given-name><ce:surname>Osterholm</ce:surname></sb:author><sb:author><ce:given-name>SJ</ce:given-name><ce:surname>Holmes</ce:surname></sb:author><sb:author><ce:given-name>JE</ce:given-name><ce:surname>McHugh</ce:surname></sb:author><sb:author><ce:given-name>RB</ce:given-name><ce:surname>Belshe</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Differences in the immunogenicity of three <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccines in infants</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Pediatr</sb:maintitle></sb:title><sb:volume-nr>121</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>187</sb:first-page><sb:last-page>194</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib15"><ce:label>15</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M</ce:given-name><ce:surname>Santosham</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Wolff</ce:surname></sb:author><sb:author><ce:given-name>R</ce:given-name><ce:surname>Reid</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Hohenboken</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Bateman</ce:surname></sb:author><sb:author><ce:given-name>J</ce:given-name><ce:surname>Goepp</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>The efficacy in Navajo infants of a conjugate vaccine consisting of <ce:italic>Haemophilus influenzae</ce:italic> type b polysaccharide and <ce:italic>Neisseria meningitidis</ce:italic> outer membrane protein complex</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>N Engl J Med</sb:maintitle></sb:title><sb:volume-nr>324</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>1767</sb:first-page><sb:last-page>1772</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib16"><ce:label>16</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:surname>Centers for Disease Control and Prevention</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Progress toward eliminating <ce:italic>Haemophilus influenzae</ce:italic> type b disease among infants and children—United States, 1987-1997</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>MMWR</sb:maintitle></sb:title><sb:volume-nr>47</sb:volume-nr></sb:series><sb:date>1998</sb:date></sb:issue><sb:pages><sb:first-page>993</sb:first-page><sb:last-page>998</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib17"><ce:label>17</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>MI</ce:given-name><ce:surname>Barbour</ce:surname></sb:author><sb:author><ce:given-name>RT</ce:given-name><ce:surname>Mayon-White</ce:surname></sb:author><sb:author><ce:given-name>C</ce:given-name><ce:surname>Coles</ce:surname></sb:author><sb:author><ce:given-name>DW</ce:given-name><ce:surname>Crook</ce:surname></sb:author><sb:author><ce:given-name>ER.</ce:given-name><ce:surname>Moxon</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>The impact of conjugate vaccine on carriage of <ce:italic>Haemophilus influenzae</ce:italic> type b</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Infect Dis</sb:maintitle></sb:title><sb:volume-nr>171</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>93</sb:first-page><sb:last-page>98</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib18"><ce:label>18</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>JC</ce:given-name><ce:surname>Mohle-Boetani</ce:surname></sb:author><sb:author><ce:given-name>G</ce:given-name><ce:surname>Ajello</ce:surname></sb:author><sb:author><ce:given-name>E</ce:given-name><ce:surname>Breneman</ce:surname></sb:author><sb:author><ce:given-name>KA</ce:given-name><ce:surname>Deaver</ce:surname></sb:author><sb:author><ce:given-name>C</ce:given-name><ce:surname>Harvey</ce:surname></sb:author><sb:author><ce:given-name>BD</ce:given-name><ce:surname>Plikaytis</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Carriage of <ce:italic>Haemophilus influenzae</ce:italic> type b in children after widespread vaccination with conjugate <ce:italic>Haemophilus influenzae</ce:italic> type b vaccines</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>12</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>589</sb:first-page><sb:last-page>593</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib19"><ce:label>19</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>TV</ce:given-name><ce:surname>Murphy</ce:surname></sb:author><sb:author><ce:given-name>P</ce:given-name><ce:surname>Pastor</ce:surname></sb:author><sb:author><ce:given-name>F</ce:given-name><ce:surname>Medley</ce:surname></sb:author><sb:author><ce:given-name>MT</ce:given-name><ce:surname>Osterholm</ce:surname></sb:author><sb:author><ce:given-name>DM.</ce:given-name><ce:surname>Granoff</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Decreased <ce:italic>Haemophilus influenzae</ce:italic> colonization in children vaccinated with <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccine</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Pediatr</sb:maintitle></sb:title><sb:volume-nr>122</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>517</sb:first-page><sb:last-page>523</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib20"><ce:label>20</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>AK</ce:given-name><ce:surname>Takala</ce:surname></sb:author><sb:author><ce:given-name>J</ce:given-name><ce:surname>Eskola</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Leinonen</ce:surname></sb:author><sb:author><ce:given-name>H</ce:given-name><ce:surname>Kayhty</ce:surname></sb:author><sb:author><ce:given-name>A</ce:given-name><ce:surname>Nissinen</ce:surname></sb:author><sb:author><ce:given-name>E</ce:given-name><ce:surname>Pekkanen</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Reduction of oropharyngeal carriage of <ce:italic>Haemophilus influenzae</ce:italic> type b (Hib) in children immunized with an Hib conjugate vaccine</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J Infect Dis</sb:maintitle></sb:title><sb:volume-nr>164</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>982</sb:first-page><sb:last-page>986</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib21"><ce:label>21</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>WG</ce:given-name><ce:surname>Adams</ce:surname></sb:author><sb:author><ce:given-name>KA</ce:given-name><ce:surname>Deaver</ce:surname></sb:author><sb:author><ce:given-name>SL</ce:given-name><ce:surname>Cochi</ce:surname></sb:author><sb:author><ce:given-name>BD</ce:given-name><ce:surname>Plikaytis</ce:surname></sb:author><sb:author><ce:given-name>ER</ce:given-name><ce:surname>Zell</ce:surname></sb:author><sb:author><ce:given-name>CV</ce:given-name><ce:surname>Broome</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Decline of childhood <ce:italic>Haemophilus influenzae</ce:italic> type b (Hib) disease in the Hib vaccine era</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>JAMA</sb:maintitle></sb:title><sb:volume-nr>269</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>221</sb:first-page><sb:last-page>226</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib22"><ce:label>22</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>DG</ce:given-name><ce:surname>Perdue</ce:surname></sb:author><sb:author><ce:given-name>LR</ce:given-name><ce:surname>Bulkow</ce:surname></sb:author><sb:author><ce:given-name>BG</ce:given-name><ce:surname>Gellin</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Davidson</ce:surname></sb:author><sb:author><ce:given-name>KM</ce:given-name><ce:surname>Petersen</ce:surname></sb:author><sb:author><ce:given-name>RJ</ce:given-name><ce:surname>Singleton</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Invasive <ce:italic>Haemophilus influenzae</ce:italic> disease in Alaskan residents aged 10 years and older before and after infant vaccination programs</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>JAMA</sb:maintitle></sb:title><sb:volume-nr>283</sb:volume-nr></sb:series><sb:date>2000</sb:date></sb:issue><sb:pages><sb:first-page>3089</sb:first-page><sb:last-page>3094</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib23"><ce:label>23</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M</ce:given-name><ce:surname>Kauppi</ce:surname></sb:author><sb:author><ce:given-name>J</ce:given-name><ce:surname>Eskola</ce:surname></sb:author><sb:author><ce:given-name>H.</ce:given-name><ce:surname>Kayhty</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Anti-capsular polysaccharide antibody concentrations in saliva after immunization with <ce:italic>Haemophilus influenzae</ce:italic> type b conjugate vaccines</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>14</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>286</sb:first-page><sb:last-page>294</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib24"><ce:label>24</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>AK</ce:given-name><ce:surname>Takala</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Santosham</ce:surname></sb:author><sb:author><ce:given-name>J</ce:given-name><ce:surname>Almeido-Hill</ce:surname></sb:author><sb:author><ce:given-name>M</ce:given-name><ce:surname>Wolff</ce:surname></sb:author><sb:author><ce:given-name>W</ce:given-name><ce:surname>Newcomer</ce:surname></sb:author><sb:author><ce:given-name>R</ce:given-name><ce:surname>Reid</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Vaccination with <ce:italic>Haemophilus influenzae</ce:italic> type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of <ce:italic>Haemophilus influenzae</ce:italic> type b among American Indian children</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>12</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>593</sb:first-page><sb:last-page>599</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib25"><ce:label>25</ce:label><sb:reference><sb:host><sb:issue><sb:title><sb:maintitle>National, state, and urban area vaccination coverage levels among Children aged 18-35 Months—United States, July 1996- June 1997</sb:maintitle></sb:title><sb:series><sb:title><sb:maintitle>MMWR</sb:maintitle></sb:title><sb:volume-nr>47</sb:volume-nr></sb:series><sb:date>1998</sb:date></sb:issue><sb:pages><sb:first-page>108</sb:first-page><sb:last-page>116</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib26"><ce:label>26</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>RL</ce:given-name><ce:surname>Davis</ce:surname></sb:author><sb:author><ce:given-name>D</ce:given-name><ce:surname>Rubanowice</ce:surname></sb:author><sb:author><ce:given-name>HR</ce:given-name><ce:surname>Shinefield</ce:surname></sb:author><sb:author><ce:given-name>N</ce:given-name><ce:surname>Lewis</ce:surname></sb:author><sb:author><ce:given-name>D</ce:given-name><ce:surname>Gu</ce:surname></sb:author><sb:author><ce:given-name>SB</ce:given-name><ce:surname>Black</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>JAMA</sb:maintitle></sb:title><sb:volume-nr>282</sb:volume-nr></sb:series><sb:date>1999</sb:date></sb:issue><sb:pages><sb:first-page>547</sb:first-page><sb:last-page>553</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib27"><ce:label>27</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>LR</ce:given-name><ce:surname>Bulkow</ce:surname></sb:author><sb:author><ce:given-name>R</ce:given-name><ce:surname>Singleton</ce:surname></sb:author><sb:author><ce:given-name>OS.</ce:given-name><ce:surname>Levine</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Enhanced immunogenicity of a sequential <ce:italic>Haemophilus influenzae</ce:italic> type b vaccine schedule in Alaska Native infants</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatr Infect Dis J</sb:maintitle></sb:title><sb:volume-nr>18</sb:volume-nr></sb:series><sb:date>1999</sb:date></sb:issue><sb:pages><sb:first-page>1023</sb:first-page><sb:last-page>1024</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib28"><ce:label>28</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>DP</ce:given-name><ce:surname>Greenberg</ce:surname></sb:author><sb:author><ce:given-name>JM</ce:given-name><ce:surname>Lieberman</ce:surname></sb:author><sb:author><ce:given-name>SM</ce:given-name><ce:surname>Marcy</ce:surname></sb:author><sb:author><ce:given-name>VK</ce:given-name><ce:surname>Wong</ce:surname></sb:author><sb:author><ce:given-name>S</ce:given-name><ce:surname>Partridge</ce:surname></sb:author><sb:author><ce:given-name>SJ</ce:given-name><ce:surname>Chang</ce:surname></sb:author><sb:et-al></sb:et-al></sb:authors><sb:title><sb:maintitle>Enhanced antibody responses in infants given different sequences of heterogeneous <ce:italic>Haemophilus influenzae</ce:italic> type b vaccines in the primary series: evaluation of a two-dose mixed regimen</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatrics</sb:maintitle></sb:title><sb:volume-nr>126</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>206</sb:first-page><sb:last-page>211</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib29"><ce:label>29</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>MK</ce:given-name><ce:surname>Bewley</ce:surname></sb:author><sb:author><ce:given-name>JG</ce:given-name><ce:surname>Schwab</ce:surname></sb:author><sb:author><ce:given-name>GA</ce:given-name><ce:surname>Ballanco</ce:surname></sb:author><sb:author><ce:given-name>RS.</ce:given-name><ce:surname>Daum</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Interchangeability of <ce:italic>Haemophilus influenzae</ce:italic> type b vaccines in the primary series; evaluation of a two-dose mixed regimen</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Pediatrics</sb:maintitle></sb:title><sb:volume-nr>98</sb:volume-nr></sb:series><sb:date>1996</sb:date></sb:issue><sb:pages><sb:first-page>898</sb:first-page><sb:last-page>904</sb:last-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Experience with the prevention of invasive</title></titleInfo><name type="personal"><namePart type="given">Rosalyn</namePart><namePart type="family">Singleton</namePart><namePart type="termsOfAddress">MD, MPH</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lisa R.</namePart><namePart type="family">Bulkow</namePart><namePart type="termsOfAddress">MS</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Orin S.</namePart><namePart type="family">Levine</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jay C.</namePart><namePart type="family">Butler</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas W.</namePart><namePart type="family">Hennessy</namePart><namePart type="termsOfAddress">MD, MPH</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alan</namePart><namePart type="family">Parkinson</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska; Alaska Native Tribal Health Consortium, Anchorage, Alaska; and Respiratory Diseases Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><dateValid encoding="w3cdtf">2000-04-05</dateValid><dateModified encoding="w3cdtf">2000-03-06</dateModified><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Objectives: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. Study design: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. Results: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. Conclusions: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate–outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib. (J Pediatr 2000;137:313-20)</abstract><note>The opinions expressed in the article are those of the authors and do not necessarily reflect the views of the Alaska Native Tribal Health Consortium or the Indian Health Service.</note><note>The results of the Yukon Kuskokwim Delta Carriage study were published previously by Galil et al (J Infect Dis 1999;179:101-65).</note><note>Reprint requests: Rosalyn Singleton, MD, CDC Arctic Investigations Program, 4055 Tudor Centre Dr, Anchorage, AK 99508.</note><note type="content">Section title: Original Articles</note><note type="content">Table I: Invasive Hib disease in Alaskans <5 years of age, 1980-1999, by ethnic group (Native vs non-Native) and vaccine era (1980-1991 vs 1992-1995, 1996-1997, and 1998-1999)</note><note type="content">Table II: Comparison of the populations studied for Hib carriage in children aged 1 to 4 years, in the YK Delta, Anchorage, and Barrow</note><subject lang="en"><genre>Abbreviations</genre><topic>AIP : Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention</topic><topic>HbOC : Hib oligosaccharide-CRM197 vaccine</topic><topic>Hib : Haemophilus influenzae type b</topic><topic>IgG : Immunoglobulin G</topic><topic>PRP : Polyribosylribitol phosphate</topic><topic>PRP-OMP : PRP–outer-membrane protein conjugate vaccine</topic><topic>YK : Yukon Kuskokwim [Delta]</topic></subject><relatedItem type="host"><titleInfo><title>The Journal of Pediatrics</title></titleInfo><titleInfo type="abbreviated"><title>YMPD</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">200009</dateIssued></originInfo><identifier type="ISSN">0022-3476</identifier><identifier type="PII">S0022-3476(00)X0003-0</identifier><part><date>200009</date><detail type="volume"><number>137</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="issue pages"><start>291</start><end>442</end></extent><extent unit="pages"><start>313</start><end>320</end></extent></part></relatedItem><identifier type="istex">EA6228BBABA89477B41134505E3A7382A96CAFB0</identifier><identifier type="DOI">10.1067/mpd.2000.107843</identifier><identifier type="PII">S0022-3476(00)12972-5</identifier><accessCondition type="use and reproduction" contentType="">© 2000Mosby, Inc.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Mosby, Inc., ©2000</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/EA6228BBABA89477B41134505E3A7382A96CAFB0/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">PEDIATRICS</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001F92 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001F92 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:EA6228BBABA89477B41134505E3A7382A96CAFB0
|texte= Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: The impact of persistent oropharyngeal carriage
}}
| This area was generated with Dilib version V0.6.23. |  |