1. Basic Information
Disease Overview
- Typhoid Fever: Systemic infection caused by Salmonella enterica serovar Typhi, transmitted via contaminated food and water. Causes prolonged high fever, abdominal pain, and can lead to intestinal perforation or death. Case-fatality is 10–20% untreated, <1% with prompt antibiotics. WHO estimates ~9 million cases and ~110,000 deaths annually, concentrated in South Asia and sub-Saharan Africa.
- Antimicrobial resistance: Extensively drug-resistant (XDR) typhoid strains, first identified in Pakistan in 2016, have accelerated vaccine introduction in some endemic countries.
Vaccine Options
| Vaccine | Type | Schedule | Booster |
|---|---|---|---|
| ViCPS (Typhim Vi) | Injectable Vi capsular polysaccharide | Single IM dose, ≥2 years old | Every 2 years if continued exposure |
| Ty21a (Vivotif) | Oral live-attenuated | 4 capsules over 1 week, ≥6 years old | Every 5 years |
| TCV (e.g. Typbar-TCV) | Vi polysaccharide conjugated to protein carrier | Single IM dose, usable from 6 months of age; used in endemic-country programs (e.g. Pakistan EPI, Gavi-supported campaigns) | Not yet established; not licensed for routine use in the U.S. |
Source: CDC Yellow Book; WHO Typhoid position paper (2018).
Recommended For
- Travelers to regions with endemic or epidemic typhoid, especially South Asia, and those visiting friends/relatives with prolonged rural/local-food exposure.
- Laboratory workers who routinely handle S. Typhi.
- In endemic countries, TCV is increasingly offered as part of routine national infant/childhood immunization programs.
Ingredients (Package Insert)
Structured composition for 2 branded products covered on this page, taken from FDA-approved package inserts (DailyMed / manufacturer prescribing information). Lists are per product — formulations differ by manufacturer and presentation. Click an ingredient name to open its safety-context page when available.
Vivotif Bavarian Nordic / Emergent · Live attenuated
Delivery
Route: Oral
Form: Enteric-coated capsule
Dose volume: 1 capsule × 4 doses (days 1, 3, 5, 7)
Presentation: blister of 4 capsules
Encapsulation / delivery vehicle
None (no nanoparticle/VLP encapsulation system) — Enteric-coated capsule for gastric acid protection (not a nanoparticle system).
Antigens
| Antigen | Type | Amount / dose |
|---|---|---|
| Salmonella typhi Ty21a (live attenuated) | Live attenuated bacteria | 2–10 × 10^9 CFU viable organisms per capsule |
Adjuvants
None listed on the package insert for this product (common for live attenuated and some inactivated whole-virus vaccines).
Preservatives
- None — Single-dose presentation; label states no preservative.
Excipients & residuals
| Ingredient | Category | Amount | Role |
|---|---|---|---|
| Sucrose | Stabilizer | label quantity | stabilizer |
| Ascorbic acid | Stabilizer | label quantity | antioxidant |
| Amino acids | Stabilizer | label quantity | stabilizer |
| Lactose / magnesium stearate / capsule shell | Other | label quantity | capsule formulation |
Source: FDA package insert · Verified 2026-07-09
Typhim Vi Sanofi Pasteur · Subunit
Delivery
Route: Intramuscular (IM)
Form: Solution for injection
Dose volume: 0.5 mL
Presentation: single-dose syringe
Encapsulation / delivery vehicle
None (no nanoparticle/VLP encapsulation system)
Antigens
| Antigen | Type | Amount / dose |
|---|---|---|
| Salmonella typhi Vi capsular polysaccharide | Polysaccharide | 25 mcg |
Adjuvants
None listed on the package insert for this product (common for live attenuated and some inactivated whole-virus vaccines).
Preservatives
- Phenol — ≤1.25 mgPhenol used as preservative in Typhim Vi.
Excipients & residuals
| Ingredient | Category | Amount | Role |
|---|---|---|---|
| Sodium chloride | Buffer | label quantity | tonicity |
| Sodium phosphate buffer | Buffer | label quantity | buffer |
| Water for injection | Diluent | q.s. | vehicle |
Source: FDA package insert · Verified 2026-07-09
ⓘ How to read this section
Ingredient lists are sourced from official package inserts for the specific brands named above. Formulations can change between lots and over time — verify against the current label before any clinical decision. Presence of a substance does not by itself indicate harm; toxicology is dose-, route-, and context-dependent. Browse the full ingredient database: Vaccine Ingredients index.
Causality assessment & potential mechanisms
Conditions below combine WHO-style causality levels with potential biological mechanisms from the site mechanism catalog (ae_mechanisms_catalog.json). HRSA VICP table listing (where shown) indicates a compensable temporal association under U.S. program rules — not automatic proof of causation for every case. Mechanisms are hypothesis-level pathways with graded evidence.
| Condition | Time window | Causality | Potential mechanism(s) |
|---|---|---|---|
| Anaphylaxis (injectable) | 0–1 days |
Possible
Evidence: Moderate |
IgE-mediated hypersensitivity (anaphylaxis) (primary · hypersensitivity) Pre-existing or newly formed IgE against vaccine antigens or excipients (e.g., gelatin, egg proteins, PEG, polysorbate) triggers mast-cell and basophil degranulation with systemic mediator release. |
| GI reactogenicity (oral live Ty21a) | 0–3 days |
Very likely / Probable
Evidence: High |
Uncontrolled live attenuated vaccine replication (contributing · live_replication) In immunocompromised or otherwise susceptible hosts, live attenuated vaccine strains can replicate beyond the intended limited infection, causing disseminated disease or organ-specific infection. Adjuvant-driven local and systemic reactogenicity (primary · innate_inflammation) Aluminum or other adjuvants (e.g., AS01B) amplify innate immune signaling, producing injection-site inflammation and transient systemic symptoms (fever, myalgia, fatigue). |
| SIRVA (injectable) | 0–2 days |
Very likely / Probable
Evidence: High |
SIRVA — incorrect injection into shoulder structures (primary · procedural) Needle placement into the subdeltoid/subacromial bursa or joint rather than deltoid muscle causes prolonged local inflammation and restricted range of motion (procedural, not antigen-specific). |
Framework: WHO causality + HRSA VICP (where applicable) + AE mechanism catalog.
Last updated: 2026-07-18.
Schema: schemas/vaccine_injury_table.schema.json
· Mechanisms: schemas/ae_mechanism.schema.json.
Not medical or legal advice.
2. Pre-Licensure Clinical Trial Data
Licensure trial design (ICAN / OpenVAERS)
This vaccine is not listed in ICAN’s childhood-schedule No Placebo Table (which covers CDC routine pediatric injectable products). Pre-licensure trial comparators for travel, adult, or specialty vaccines should be taken from FDA review documents and product labels in the sections below.
Source: OpenVAERS — No Placebo Table · ICAN original PDF · Attribution: Informed Consent Action Network (ICAN) via OpenVAERS · Last fetched: 2026-07-16. For many trials listing '6 months' safety review, ICAN notes review was typically ~30 days post-injection with a phone call at 6 months.
Efficacy has been evaluated in large field trials conducted primarily in endemic settings (Nepal, Bangladesh, South Africa) rather than U.S. pre-licensure trials.
| Vaccine | Efficacy Data | Evidence Strength |
|---|---|---|
| ViCPS | ~50–80% efficacy over 2–3 years across field trials (Nepal, South Africa) | Moderate |
| Ty21a | ~50–80% efficacy with full 4-dose oral course over multiple years, though real-world adherence to the full oral course is a limiting factor | Moderate |
| TCV (Typbar-TCV) | ~79–85% efficacy in a randomized controlled human challenge trial and in a large cluster-randomized field trial in Nepal; longer duration and usable in infants, an advantage over older vaccines | Strong |
Key Limitations
- Ty21a is a live vaccine: Contraindicated in immunocompromised individuals; requires refrigeration and completion of all 4 doses, which can reduce real-world effectiveness versus trial conditions.
- ViCPS does not protect young children well: Polysaccharide (non-conjugate) vaccines are poorly immunogenic in children <2 years, which is part of why TCV (a conjugate vaccine) was developed for infant use.
- TCV real-world U.S. data are sparse: Most TCV effectiveness evidence comes from South Asian and sub-Saharan African immunization programs, not U.S. travelers.
3. Post-Licensure Safety Data
Post-Licensure Safety Monitoring
Both older vaccines have decades of post-marketing use. TCV has been monitored through Gavi-supported introduction campaigns and WHO-coordinated pharmacovigilance in Pakistan, Nepal, Zimbabwe, and Liberia.
| Vaccine | Key Post-Licensure Finding |
|---|---|
| ViCPS | No unusual safety signals identified over decades of use; injection site and mild systemic reactions are the dominant reported events |
| Ty21a | Well tolerated; GI symptoms are the main reported events; rare reports of urticaria/rash |
| TCV | Large-scale campaign pharmacovigilance in Pakistan (>10 million doses) and Nepal field trial found no unexpected serious adverse event signal |
⚠ Critical Caveat
No typhoid vaccine is 100% effective and none protects against paratyphoid fever (caused by Salmonella Paratyphi); safe food and water practices remain necessary for travelers even after vaccination.
Passive Surveillance: AE Type Breakdown (Multi-System)
Side-by-side view of U.S. VAERS, Health Canada Canada Vigilance, Japan JADER (PMDA), EU EudraVigilance, and live-scraped international systems via SurVigilance (VigiAccess, Lareb, DAEN, DMA, Medsafe). SurVigilance panels show MedDRA PT mention totals (not individual-case counts). Category assignment uses keyword matching — approximate, not official SOC coding. VAERS ZIP CAPTCHA downloads use this site’s vaers_pipeline.py; FAERS is bulk quarterly ZIP via SurVigilance (not product search).
VAERS (United States)
Canada Vigilance (Canada)
JADER (PMDA, Japan)
No matching vaccine reports in the current JADER public extract.
EudraVigilance (EU)
3,383
individual cases · adrreports.eu DAP export (up to 28/06/2026)
Reaction SOC breakdown not included in this workbook export.
SurVigilance: VigiAccess · Lareb · DAEN · DMA · Medsafe
VigiAccess (WHO)
Lareb (Netherlands)
DAEN (Australia)
No DAEN (Australia) data yet — run python scrape_survigilance_one.py daen <vaccine-id> or python survigilance_pipeline.py --system daen (SurVigilance + direct scrapers: GitHub).
DMA (Denmark)
Denmark DMA interactive ADR search is currently offline (Danish Medicines Agency IT transition; public overviews frozen at 12 Mar 2024). Live product PT tables cannot be retrieved until DKMA restores the search. See DKMA notice. Denmark continues to report into EU EudraVigilance (panel above).
Medsafe (New Zealand)
4. Documented Adverse Events — Evidence of Association
Rank-aggregated VAERS signal detection (rankv)
The table below lists vaccine–event pairs that were detected as disproportionality signals by all four base methods used in rankv (GPS, PRR, ROR, BCPNN) on multi-decade VAERS data, then ordered by rank aggregation (Borda average rank; related to the Spearman/GA top-list approach in the rankv paper).
| Agg. rank | VAERS product | Preferred term (event) | N | Method ranks (GPS / PRR / ROR / BCPNN) |
|---|---|---|---|---|
| 146 | TYPHOID LIVE ORAL TY21A (VIVOTIF) |
Abdominal pain
clinical-coded PT
|
225 | GPS rank 114 (EBGM=12.69); PRR rank 193 (PRR=16.9137); ROR rank 189 (ROR=17.569); BCPNN rank 96 (IC_LB=3.749) |
| 150 | TYPHOID LIVE ORAL TY21A (VIVOTIF) |
Oral administration complication
clinical-coded PT
|
10 | GPS rank 15 (EBGM=57.04); PRR rank 145 (PRR=40.6031); ROR rank 147 (ROR=40.6728); BCPNN rank 294 (IC_LB=2.1578) |
| 217 | TYPHOID LIVE ORAL TY21A (VIVOTIF) |
Abdominal pain upper
clinical-coded PT
|
110 | GPS rank 161 (EBGM=8.34); PRR rank 240 (PRR=12.7094); ROR rank 238 (ROR=12.9403); BCPNN rank 179 (IC_LB=3.2171) |
| 272 | TYPHOID LIVE ORAL TY21A (VIVOTIF) |
Diarrhoea
clinical-coded PT
|
286 | GPS rank 189 (EBGM=7.06); PRR rank 284 (PRR=6.6301); ROR rank 284 (ROR=6.9281); BCPNN rank 274 (IC_LB=2.5131) |
Showing up to 15 pairs for this page (clinical-coded terms listed first).
Full processed tables: rankv_signals.json.
- Methods combined: BCPNN (IC), GPS/EBGM, PRR, ROR — then rank aggregation.
- Data: ~30 years of public VAERS (rankv processed tables).
- Origin: precisionFDA “Gaining New Insights by Detecting Adverse Event Anomalies” challenge solution.
- Caveat: Disproportionality signals are statistical associations in spontaneous reports. They do not establish causality, incidence, or product defect. Many top pairs reflect administration/product-use coding rather than clinical injury.
Source: nanx.me/rankv · Code: github.com/nanxstats/rankv (MIT) · Built: 2026-07-30.
▶ Strong Evidence of Causal Association
- Injection site pain/redness (ViCPS, TCV): Common, ~10–20%. Self-limited. Strong
- Fever/headache (ViCPS, TCV): ~1–5%. Self-limited. Strong
- GI upset, nausea, abdominal discomfort (Ty21a, oral live vaccine): ~1–5%. Self-limited. Strong
▶ Moderate or Preliminary Evidence
- Urticaria/rash (Ty21a): Rare, isolated case reports; not consistently replicated across large series. Limited
5. Disease Prevention Benefits
Program Impact
| Setting | Outcome |
|---|---|
| Pakistan TCV introduction (2019–present) | Rolled out amid XDR typhoid outbreak; large-scale campaigns and routine EPI introduction associated with substantial declines in pediatric typhoid incidence in vaccinated districts |
| Nepal cluster-randomized trial (2018) | ~79% efficacy against blood-culture-confirmed typhoid over 2 years of follow-up |
| Traveler use (ViCPS/Ty21a) | Reduces but does not eliminate risk; typhoid remains one of the most common vaccine-preventable causes of fever in travelers returning from South Asia |
Source: WHO SAGE typhoid position paper (2018); Nepal TyVAC trial (Lancet, 2021 follow-up).
6. Evidence Summary
Typhoid vaccines provide moderate, time-limited protection; the newer conjugate vaccine (TCV) offers the strongest and longest-lasting efficacy data and is increasingly the preferred option in endemic-country programs. For U.S. travelers, ViCPS and Ty21a remain the standard options, each requiring periodic revaccination for continued protection. All formulations are well tolerated with adverse events limited mainly to mild, self-resolving local and systemic reactions.
| Domain | Evidence Grade | Key Finding |
|---|---|---|
| ViCPS/Ty21a efficacy | Moderate | ~50–80% over 2–5 years depending on vaccine |
| TCV efficacy | Strong | ~79–85%, usable in infants, longer duration |
| Common reactogenicity | Strong | Mild, self-limited local/systemic reactions |
| Serious adverse events | No Association | No unusual safety signal identified across decades/large campaigns |
7. International Surveillance & Global Data
Quick links to public pharmacovigilance databases and trial registries relevant to Typhoid Vaccine. Reporting counts do not establish causality.
8. Curated Adverse Event Literature
Curated peer-reviewed literature linking specific adverse events to Typhoid Vaccine. Each entry is a case report, case series, or related safety publication identified via PubMed. Expand Search PubMed for additional literature below to run custom queries.
9. Key References
- WHO. Typhoid vaccines: WHO position paper. Wkly Epidemiol Rec. 2018;93(13):153–172.
- CDC. Typhoid Fever & Paratyphoid Fever. CDC Yellow Book, Travelers’ Health. cdc.gov/yellowbook
- Meiring JE, et al. Typhoid conjugate vaccine effectiveness (TyVAC Nepal). Lancet. 2023 follow-up analyses.
- Shakya M, et al. Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal. N Engl J Med. 2019;381:2209–2218.
- Gavi. Typhoid Conjugate Vaccine Support. gavi.org