Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis

preprint OA: closed CC-BY-4.0
📄 Open PDF Full text JSON View at publisher

Abstract

Abstract The introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine have led to the reduction of Hib infection and emergence of non-b serotypes. We aimed to investigate the prevalence, clinical features, antimicrobial susceptibility, and molecular lineages of Hia disease in the post-Hib vaccine era. A total of 29 eligible studies published up to December 2025 were included. The pooled prevalence of invasive Hia infection was 15.12% (95% CI: 7.81–24.18%), with substantial geographic variation. Prevalence was highest in North America (28.57%) and lowest in Europe (2.16%). Reported incidence ranged from 0.01 to 20.2 cases per 100,000 population, with the greatest burden observed among infants, young children, and Indigenous populations. Meningitis and pneumonia were the most common clinical presentations, and case-fatality rates ranged from 1.9% to 20%. Most isolates remained susceptible to commonly used antibiotics, with β-lactamase–mediated ampicillin resistance less reported (2%). Molecular typing identified 17 sequence types, with ST23 and related lineages predominating across regions. These findings indicate that Hia disease shows heterogeneous geographic distribution, primarily affecting young children, and is characterised by low antimicrobial resistance and a predominance of the ST23 lineage.
Full text 13,338 characters · extracted from preprint-html · click to expand
Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis Richard Donkor Amponsah, Onyansaniba K. Ntim, Eric S Donkor This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8860456/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract The introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine have led to the reduction of Hib infection and emergence of non-b serotypes. We aimed to investigate the prevalence, clinical features, antimicrobial susceptibility, and molecular lineages of Hia disease in the post-Hib vaccine era. A total of 29 eligible studies published up to December 2025 were included. The pooled prevalence of invasive Hia infection was 15.12% (95% CI: 7.81–24.18%), with substantial geographic variation. Prevalence was highest in North America (28.57%) and lowest in Europe (2.16%). Reported incidence ranged from 0.01 to 20.2 cases per 100,000 population, with the greatest burden observed among infants, young children, and Indigenous populations. Meningitis and pneumonia were the most common clinical presentations, and case-fatality rates ranged from 1.9% to 20%. Most isolates remained susceptible to commonly used antibiotics, with β-lactamase–mediated ampicillin resistance less reported (2%). Molecular typing identified 17 sequence types, with ST23 and related lineages predominating across regions. These findings indicate that Hia disease shows heterogeneous geographic distribution, primarily affecting young children, and is characterised by low antimicrobial resistance and a predominance of the ST23 lineage. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Biological sciences/Microbiology Haemophilus influenzae serotype A Haemophilus influenzae haemophilus influenzae type b vaccine Humans Full Text Additional Declarations No competing interests reported. Supplementary Files Hiasupplementary.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 23 Mar, 2026 Reviews received at journal 22 Mar, 2026 Reviews received at journal 13 Mar, 2026 Reviews received at journal 04 Mar, 2026 Reviewers agreed at journal 02 Mar, 2026 Reviewers agreed at journal 28 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 20 Feb, 2026 Editor assigned by journal 20 Feb, 2026 Editor invited by journal 20 Feb, 2026 Submission checks completed at journal 18 Feb, 2026 First submitted to journal 18 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8860456","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":595936739,"identity":"5e539fbe-2289-4a7c-9d70-67b8a90a847f","order_by":0,"name":"Richard Donkor Amponsah","email":"","orcid":"","institution":"University of Ghana Medical School","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"Donkor","lastName":"Amponsah","suffix":""},{"id":595936740,"identity":"81c6a434-2152-4577-96c1-916afe47e925","order_by":1,"name":"Onyansaniba K. Ntim","email":"","orcid":"","institution":"University of Ghana Medical School","correspondingAuthor":false,"prefix":"","firstName":"Onyansaniba","middleName":"K.","lastName":"Ntim","suffix":""},{"id":595936741,"identity":"38a9dddb-f530-4e19-8181-e79e22664bfc","order_by":2,"name":"Eric S Donkor","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYHCDBAbGBgYGOTCbB4gNiNViTLqWxAZCWvj5Dz/dXFBzR46BPfnYwxkV99I3nF/A+OBtG4PddhxaJGekmd2eceyZMQPPs3TDDWeKczfceMBsOLeNIXlnA3YtBjcYzG7zsB1O3H8jx0zyYVsCUMsBNmleoBaDA9i12J8//u02z7/D9Q0SEC3pBjcOsP/Gp8WAIcfsNm/b4QQGkJaNbQkJBucb2JiBWuxwaZG4kVN2e2bfYcMGnmdpkjPOJBjOvMHYLDnnnEQCLi38/ce33S74dlgeFGKSPRUJ8nznDx/88KbMxh6XFhBgRrMYHDUQkkgt/BDT7fHoGAWjYBSMgpEFACb/YxCeVmbVAAAAAElFTkSuQmCC","orcid":"","institution":"University of Ghana Medical School","correspondingAuthor":true,"prefix":"","firstName":"Eric","middleName":"S","lastName":"Donkor","suffix":""}],"badges":[],"createdAt":"2026-02-12 09:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8860456/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8860456/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103373399,"identity":"972c77d9-7204-4548-aea3-9f3e91809e16","added_by":"auto","created_at":"2026-02-25 02:59:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":539956,"visible":true,"origin":"","legend":"","description":"","filename":"MolecularEpidemiologyofHiaRecovered.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8860456/v1_covered_228cd5b2-793b-4e32-adbc-6b7f02ab6898.pdf"},{"id":103373398,"identity":"4c09e88d-93df-4967-b4fb-8c4a35e758f1","added_by":"auto","created_at":"2026-02-25 02:59:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":54189,"visible":true,"origin":"","legend":"","description":"","filename":"Hiasupplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-8860456/v1/e6aff3644ec57e0217d7b617.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Haemophilus influenzae serotype A, Haemophilus influenzae, haemophilus influenzae type b vaccine, Humans","lastPublishedDoi":"10.21203/rs.3.rs-8860456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8860456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine have led to the reduction of Hib infection and emergence of non-b serotypes. We aimed to investigate the prevalence, clinical features, antimicrobial susceptibility, and molecular lineages of Hia disease in the post-Hib vaccine era. A total of 29 eligible studies published up to December 2025 were included. The pooled prevalence of invasive Hia infection was 15.12% (95% CI: 7.81–24.18%), with substantial geographic variation. Prevalence was highest in North America (28.57%) and lowest in Europe (2.16%). Reported incidence ranged from 0.01 to 20.2 cases per 100,000 population, with the greatest burden observed among infants, young children, and Indigenous populations. Meningitis and pneumonia were the most common clinical presentations, and case-fatality rates ranged from 1.9% to 20%. Most isolates remained susceptible to commonly used antibiotics, with β-lactamase–mediated ampicillin resistance less reported (2%). Molecular typing identified 17 sequence types, with ST23 and related lineages predominating across regions. These findings indicate that Hia disease shows heterogeneous geographic distribution, primarily affecting young children, and is characterised by low antimicrobial resistance and a predominance of the ST23 lineage.","manuscriptTitle":"Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-25 02:59:14","doi":"10.21203/rs.3.rs-8860456/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-23T08:55:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-22T13:36:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-13T14:59:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-04T21:29:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92969576500698702434861256533392733897","date":"2026-03-02T11:09:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189356439582734680206568159564176962352","date":"2026-03-01T02:45:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"257500737283673625103052920382167569968","date":"2026-02-26T07:11:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-20T17:35:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-20T17:32:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-20T17:10:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-18T20:27:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-18T20:21:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1719e323-8093-4ec2-8320-c0d9e8c7bce1","owner":[],"postedDate":"February 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":63411061,"name":"Health sciences/Diseases"},{"id":63411062,"name":"Health sciences/Health care"},{"id":63411063,"name":"Health sciences/Medical research"},{"id":63411064,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2026-03-23T09:10:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-25 02:59:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8860456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8860456","identity":"rs-8860456","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-4.0