{
  "abstract": "IntroductionExtrapulmonary tuberculosis (EPTB) is rising in India and carries higher case fatality than pulmonary tuberculosis (PTB). A Phase III trial of VPM1002 missed its primary composite endpoint, but secondary endpoints showed a stronger EPTB signal (vaccine efficacy 42{middle dot}3%, 95% CI -9{middle dot}1 to 69{middle dot}4). We identified no published model resolving tuberculosis by disease type, nutritional and socioeconomic status, and dose event against a dynamic baseline.\n\nMethodsWe built a deterministic model with 1,152 population compartments (72 strata by age, HIV status, body-mass index and socioeconomic status), calibrated to WHO India incidence and mortality for 2015-2024. Separate PTB and EPTB effectiveness posteriors, derived by Bayesian evidence synthesis of the trials per-protocol and modified intention-to-treat estimates, were propagated through 1,000 Monte Carlo iterations. Three doses were modeled at 10-year intervals assuming 3 or 10 years of protection. Economic analysis used societal and health-system perspectives with 3% discounting.\n\nResultsPosterior median effectiveness was higher against EPTB (42{middle dot}9%, 95% credible interval [CrI] -5{middle dot}6 to 69{middle dot}1) than PTB (14{middle dot}0%, -19{middle dot}0 to 37{middle dot}9). Per 1,000,000 targeted under 10-year protection, three doses averted 5,218 cases (95% uncertainty interval 153-10,157), 682 deaths (24-1,255) and 9,463 disability-adjusted life-years (DALYs; 328-17,404); under 3-year protection, 1,961 cases and 3,708 DALYs. EPTB accounted for about two-thirds of averted deaths and DALYs but about half of averted cases. Under 10-year protection, the first booster added 46% more cases and 34% more DALYs at an incremental benefit-cost ratio of 19{middle dot}1 (initial dose 20{middle dot}7); the second booster added 8% more cases and 4{middle dot}5% more DALYs at 6{middle dot}8. Median gross incremental cost-effectiveness ratios were US$329 (10-year) and US$832 (3-year) per DALY averted.\n\nConclusionComposite-endpoint models cannot show this dissociation. A booster a decade later was nearly as economically efficient but averted less disease. This is an adolescent and adult booster program, not a replacement for infant BCG.\n\nWhat is already known on this topicO_LITB vaccine modeling studies for India and other high burden settings have relied on aggregate single efficacy estimates that combine pulmonary and extrapulmonary disease into a single endpoint. C_LIO_LIPublished models have evaluated vaccines against static programmatic baselines and a single course intervention, so the marginal value of revaccination has rarely been quantified. C_LI\n\nWhat this study addsO_LIThis 1,152 population compartment model tracks pulmonary and extrapulmonary TB as separate compartments with independently calibrated natural history and separately propagated Bayesian effectiveness posteriors. C_LIO_LIVaccination history is preserved through disease treatment and recovery, so people infected after vaccination remain correctly identified as previously vaccinated and eligible for later doses; this becomes relevant only once boosting is modeled C_LIO_LIExtrapulmonary disease accounts for approximately 2/3 of averted deaths and DALYs against roughly half of averted cases, a dissociation that a composite endpoint model cannot provide. C_LIO_LISeed-matched paired Monte Carlo makes each dose events marginal contribution directly estimable rather than inferential. C_LI\n\nHow this study might affect research, practice or policyO_LIPolicy assessments anchored to composite endpoints, or assuming a single lifetime dose, may underestimate this vaccines population value. C_LIO_LIA single booster a decade after the initial dose is close to as economically efficient as the initial dose; a second booster is materially less so within a horizon to 2050. C_LIO_LIThe framework is country- and candidate-agnostic and can be recalibrated for other high-burden settings and other vaccine candidates, including those evaluated in other Phase III trials. C_LIO_LIThe schedule evaluated here is an adolescent and adult booster program and does not bear on infant BCG policy. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "Aseesa Inc., and UCSF"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "M. Revathy"
    },
    {
      "name": "V. Niranjan"
    },
    {
      "name": "A. Uttarkar"
    },
    {
      "name": "V. Swaminathan"
    },
    {
      "name": "A. Carrese"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Bhargava"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ea5dw71rts839.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.07.31.26359434",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.07.31.26359434v2.full",
  "id": "ea5dw71rts839",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.07.31.26359434v2",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
    ]
  ],
  "openalex": "W7172295008",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.07.31.26359434v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ea5dw71rts839.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:55Z",
      "native_id": "10.64898/2026.07.31.26359434",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.07.31.26359434v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "A disaggregated dynamic model of pulmonary and extrapulmonary tuberculosis for vaccine and booster-schedule evaluation: VPM1002 in India as a case study",
  "title_text": "A disaggregated dynamic model of pulmonary and extrapulmonary tuberculosis for vaccine and booster-schedule evaluation: VPM1002 in India as a case study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:55Z",
  "url": "https://research.draconitic.com/paper/ea5dw71rts839",
  "venue": "medRxiv",
  "versions": []
}