Evidence dossier · candidate cand-typhoid-diarrhoea · VICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that Typhoid vaccine causes Diarrhoea, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
insufficient_data
missing: A1 A2
C2
Consistent temporal window
insufficient_data
missing: A5
C3
Epidemiologic excess risk
insufficient_data
missing: B1 B2 B3
C4
Consistency / replication
insufficient_data
missing: B5 B6
C5
Specificity (product / dose)
insufficient_data
missing: C2n
C6
Biological mechanism
insufficient_data
missing: E1
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: no established case definition (needs_human_review — not in spec §1's named-standard list) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportsno_data
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Case reports pubmed · 66189 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A2 · Series with objective confirmationno_data
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: no evidence found
Case-certainty distribution (no established case definition): 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Series with objective confirmation pubmed · 5646 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
12 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A3 · Onset histogramno_data
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: A single case report describes a woman who developed diarrhea 3-5 days after receiving both typhoid and yellow fever vaccines, but the report does not isolate typhoid vaccine as the cause, and the onset window is unclear relative to the specific vaccine.
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: No retrieved evidence addresses temporal plausibility of diarrhea following typhoid vaccination, as all retrieved studies concern hepatitis B, COVID-19, HPV, monkeypox, rubella, and other vaccines, not typhoid vaccine.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Temporal plausibility pubmed · 33 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
14 retrieved record(s)
does_not_resolve 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
does_not_resolve 23754771 · Human psychopharmacology (2013) — Quality of case reports of adverse drug reactions with psychotropic drugs: a 25-year review.
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: A single case report describes a patient who developed diarrhea 3-5 days after receiving typhoid vaccine and yellow fever vaccine, but the onset interval is recorded in the primary source.
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Differential diagnosis excluded pubmed · 429 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: A single case report describes diarrhea occurring 3-5 days after concurrent administration of typhoid and yellow fever vaccines, but no evidence addresses recurrence upon rechallenge (i.e., a subsequent dose).
A8 · Adjudicated by criteria (no established case definition)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Adjudicated by criteria pubmed · 41 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
does_not_resolve 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A9 · Natural-history consistencyno_data
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series Natural-history consistency pubmed · 105 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 42229499 · The Lancet. Infectious diseases (2026) — Global burden of enteric infectious diseases, diarrhoeal diseases, and corresponding aetiologies, 1990-2023: a systematic analysis for the Global Burden of Dise
does_not_resolve 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A10 · No confounding objectno_data
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea case report OR case series No confounding object pubmed · 21 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-09
13 retrieved record(s)
does_not_resolve 34312836 · Clinical pharmacology and therapeutics (2022) — Angiotensin-Converting Enzyme Inhibitors Used Concomitantly with Insulin Secretagogues and the Risk of Serious Hypoglycemia.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
mirror: Typhoid vaccine Diarrhoea Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Kinetics class not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea No internal contradiction coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea No internal contradiction inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Analogy to a known object coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Analogy to a known object inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 25187623 · Reproduction (Cambridge, England) (2014) — Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Latency coherence coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Latency coherence inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Pre-specification pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Pre-specification post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J2 · Contrary-evidence logno_data
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Contrary-evidence log pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea No temporality-only claim pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J4 · Passive-surveillance roleno_data
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Passive-surveillance role pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
does_not_resolve 41493293 · Journal of the American College of Cardi (2026) — Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials.
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: The retrieved evidence discusses immune-related adverse events from immune checkpoint inhibitors, not Typhoid vaccine or Diarrhoea, and provides no data on dose/lot exposure mapping for Typhoid vaccine-attributed Diarrhoea.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Dose mapping pre-specified OR adjudicated pubmed · 13561 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Dose mapping post-hoc OR hypothesis-generating only pubmed · 1712 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: The retrieved evidence does not contain any study that directly examines an association between Typhoid vaccine and Diarrhoea, or that provides a relative risk estimate for this specific pair.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Excess vs baseline pubmed · 88523 hits · run 2026-09-09
7 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 34672967 · Lancet (London, England) (2021) — Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, pha
does_not_resolve 34489307 · Gut (2022) — Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort.
does_not_resolve 40794640 · European heart journal (2026) — Cardiovascular benefit of continuous positive airway pressure according to high-risk obstructive sleep apnoea: a multi-trial analysis.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: No retrieved evidence specifically examines the association between Typhoid vaccine and Diarrhoea using an SCCS design. The available studies focus on other vaccines (e.g., Shingrix, COVID-19 mRNA, rotavirus) or methods, and none report an SCCS risk ratio for this pair.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea SCCS incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk SCCS pubmed · 88633 hits · run 2026-09-09
8 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 39795956 · International journal of molecular scien (2024) — The Potential Metalloestrogenic Effect of Aluminum on Breast Cancer Risk for Antiperspirant Users.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 39271677 · NPJ vaccines (2024) — Risk benefit analysis to evaluate risk of thromboembolic events after mRNA COVID-19 vaccination and COVID-19.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: No retrieved evidence directly examines the incidence rate ratio (IRR) for diarrhoea following typhoid vaccination in a cohort or risk-interval design. The retrieved papers describe self-controlled case series methodology for other vaccines and outcomes, but none address Typhoid vaccine or diarrhoea.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Cohort / risk-interval pubmed · 88132 hits · run 2026-09-09
7 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
ambiguous 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 37082039 · Journal of oral and maxillofacial pathol (2022) — Null genotypes of Glutathione S-transferase M1 and T1 and risk of oral cancer: A meta-analysis.
does_not_resolve 23884605 · Tumour biology : the journal of the Inte (2013) — Association between glutathione S-transferase M 1 null genotype and risk of ovarian cancer: a meta-analysis.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: No retrieved evidence provides a pooled estimate with quantified heterogeneity (I2) for the association between typhoid vaccine and diarrhoea; the retrieved studies address self-controlled case series methodology, shingles, falls, glioma, pancreatic cancer, diabetes, and Staphylococcus aureus infection, none of which are relevant to this specific vaccine-outcome pair.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Meta-analysis / pooling pubmed · 111982 hits · run 2026-09-09
9 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
ambiguous 29402646 · Journal of the American Medical Director (2018) — Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.
does_not_resolve 28230042 · Journal of cancer research and therapeut (2016) — Meta-analysis of association between mobile phone use and glioma risk.
does_not_resolve 25502106 · International journal of epidemiology (2015) — Risk factors for pancreatic cancer: a summary review of meta-analytical studies.
does_not_resolve 23296061 · Gene (2013) — Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: a meta-analysis.
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Negative-control outcomes pubmed · 88334 hits · run 2026-09-09
6 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38833248 · JAMA network open (2024) — Valproate Use During Spermatogenesis and Risk to Offspring.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Other-antigen comparison pubmed · 88096 hits · run 2026-09-09
7 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 37082039 · Journal of oral and maxillofacial pathol (2022) — Null genotypes of Glutathione S-transferase M1 and T1 and risk of oral cancer: A meta-analysis.
does_not_resolve 23884605 · Tumour biology : the journal of the Inte (2013) — Association between glutathione S-transferase M 1 null genotype and risk of ovarian cancer: a meta-analysis.
B7 · Absolute riskno_data
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: No retrieved evidence directly reports absolute risk per 100,000 of new diarrhea attributed to typhoid vaccine within a pre-specified risk window after vaccination.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Absolute risk incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Absolute risk pubmed · 111386 hits · run 2026-09-09
12 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 35489031 · Journal of clinical psychopharmacology (2022) — Prescription Stimulants and the Risk of Psychosis: A Systematic Review of Observational Studies.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
does_not_resolve 23484825 · The New England journal of medicine (2013) — Risk of ischemic heart disease in women after radiotherapy for breast cancer.
does_not_resolve 26950145 · Nutrients (2016) — An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.
B8 · Platform splitno_data
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: The retrieved evidence includes methodological reviews and studies on specific vaccines (e.g., Shingrix, COVID-19 mRNA), but none address Typhoid vaccine or Diarrhoea as an outcome, nor do they provide any risk estimates attributable to a specific platform for this adverse event pair.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Platform split incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Platform split pubmed · 88161 hits · run 2026-09-09
4 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
B9 · Host-structure stratificationno_data
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Host-structure stratification pubmed · 88094 hits · run 2026-09-09
6 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 37082039 · Journal of oral and maxillofacial pathol (2022) — Null genotypes of Glutathione S-transferase M1 and T1 and risk of oral cancer: A meta-analysis.
does_not_resolve 23884605 · Tumour biology : the journal of the Inte (2013) — Association between glutathione S-transferase M 1 null genotype and risk of ovarian cancer: a meta-analysis.
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 948 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no association OR null OR no increased risk Formulation / component change pubmed · 88256 hits · run 2026-09-09
4 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
H2 · Formulation natural experimentno_data
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Formulation natural experiment intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Policy / pause signal intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-09
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Infection coherence coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Infection coherence inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Dose strength gradient dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no dose effect OR no dose-response Dose strength gradient pubmed · 125 hits · run 2026-09-09
4 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 29851031 · The Cochrane database of systematic revi (2018) — Vaccines for preventing typhoid fever.
refutes_node 24385413 · The Cochrane database of systematic revi (2014) — Vaccines for preventing typhoid fever.
does_not_resolve 33373368 · PLoS medicine (2020) — Assessing the risk of ketoacidosis due to sodium-glucose cotransporter (SGLT)-2 inhibitors in patients with type 1 diabetes: A meta-analysis and meta-regression
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Dose number gradient dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no dose effect OR no dose-response Dose number gradient pubmed · 569 hits · run 2026-09-09
3 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 29851031 · The Cochrane database of systematic revi (2018) — Vaccines for preventing typhoid fever.
does_not_resolve 24385413 · The Cochrane database of systematic revi (2014) — Vaccines for preventing typhoid fever.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: A phase 2 trial of an attenuated oral typhoid vaccine (CVD 908-htrA) reported that high-dose recipients had more frequent diarrhea than placebo recipients in the first 7 days (PMID 10678926). A case report described a patient who received both yellow fever and typhoid vaccines and later experienced diarrhea, vomiting, and other symptoms (PMID 25789744). No retrieved evidence provides risk data ordered by measured-exposure tertile for typhoid vaccine and diarrhoea.
supporting: Typhoid vaccine Diarrhoea Measured-exposure tertiles dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no dose effect OR no dose-response Measured-exposure tertiles pubmed · 14 hits · run 2026-09-09
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 29851031 · The Cochrane database of systematic revi (2018) — Vaccines for preventing typhoid fever.
does_not_resolve 24385413 · The Cochrane database of systematic revi (2014) — Vaccines for preventing typhoid fever.
does_not_resolve 35436979 · Systematic reviews (2022) — Community-level interventions for mitigating the risk of waterborne diarrheal diseases: a systematic review.
ambiguous 1966245 · Indian journal of public health (1990) — The current status of diarrhoea related vaccines.
does_not_resolve 9522876 · Papua and New Guinea medical journal (1995) — A review of the current status of enteric vaccines.
ambiguous 22789509 · Vaccine (2012) — Safety of live, attenuated oral vaccines in HIV-infected Zambian adults: oral vaccines in HIV.
supports_node 10678926 · Infection and immunity (2000) — Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Organoid concentration curve dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no dose effect OR no dose-response Organoid concentration curve pubmed · 25 hits · run 2026-09-09
7 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 29851031 · The Cochrane database of systematic revi (2018) — Vaccines for preventing typhoid fever.
does_not_resolve 24385413 · The Cochrane database of systematic revi (2014) — Vaccines for preventing typhoid fever.
does_not_resolve 35436979 · Systematic reviews (2022) — Community-level interventions for mitigating the risk of waterborne diarrheal diseases: a systematic review.
does_not_resolve 1966245 · Indian journal of public health (1990) — The current status of diarrhoea related vaccines.
does_not_resolve 9522876 · Papua and New Guinea medical journal (1995) — A review of the current status of enteric vaccines.
ambiguous 22789509 · Vaccine (2012) — Safety of live, attenuated oral vaccines in HIV-infected Zambian adults: oral vaccines in HIV.
C5n · EC50 vs Cmax coherencemixed
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: One phase 2 trial of an oral live attenuated typhoid vaccine reported that 8% of high-dose recipients had diarrhea in the first 7 days compared with 0% of placebo recipients, suggesting that the vaccine can cause diarrhea at high exposure levels, but no study directly measured Cmax or tissue concentrations relative to in-vitro EC50 for this adverse event.
supporting: Typhoid vaccine Diarrhoea EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299405 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 14 hits · run 2026-09-09
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
refutes_node 29851031 · The Cochrane database of systematic revi (2018) — Vaccines for preventing typhoid fever.
does_not_resolve 24385413 · The Cochrane database of systematic revi (2014) — Vaccines for preventing typhoid fever.
does_not_resolve 35436979 · Systematic reviews (2022) — Community-level interventions for mitigating the risk of waterborne diarrheal diseases: a systematic review.
ambiguous 1966245 · Indian journal of public health (1990) — The current status of diarrhoea related vaccines.
does_not_resolve 9522876 · Papua and New Guinea medical journal (1995) — A review of the current status of enteric vaccines.
ambiguous 22789509 · Vaccine (2012) — Safety of live, attenuated oral vaccines in HIV-infected Zambian adults: oral vaccines in HIV.
supports_node 10678926 · Infection and immunity (2000) — Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Mediator identified in cases not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Mediator in healthy vaccinees not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: The retrieved evidence describes acute reactogenicity of Typhoid vaccines in US military personnel, but does not report on diarrhea relative to a natural-infection control group, nor does it address mediator levels after natural infection.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Infection contrast in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Infection contrast not associated mechanism pubmed · 1 hits · run 2026-09-09
1 retrieved record(s)
ambiguous 28268075 · Vaccine (2017) — Vaccination of active component US military personnel against Salmonella Typhi.
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Transfer to recipient not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: No evidence found.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Transfer specificity in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Transfer specificity not associated mechanism pubmed · 1 hits · run 2026-09-09
1 retrieved record(s)
does_not_resolve 42229499 · The Lancet. Infectious diseases (2026) — Global burden of enteric infectious diseases, diarrhoeal diseases, and corresponding aetiologies, 1990-2023: a systematic analysis for the Global Burden of Dise
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Add-back rescue in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Add-back rescue not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Neutralization in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Neutralization not associated mechanism pubmed · 1 hits · run 2026-09-09
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: The retrieved evidence does not address whether an isotype control fails to reproduce a block or activation in the context of Typhoid vaccine causing diarrhoea. The abstracts discuss vaccine development and immunogenicity studies, but not isotype control experiments.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Isotype control in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Isotype control not associated mechanism pubmed · 4 hits · run 2026-09-09
3 retrieved record(s)
does_not_resolve 1512046 · Gastroenterology clinics of North Americ (1992) — Bacterial enteric infections and vaccine development.
does_not_resolve 396051 · Bulletin of the World Health Organizatio (1979) — Intestinal immunity and vaccine development: a WHO memorandum.
does_not_resolve 15501790 · Infection and immunity (2004) — Effect of dosage on immunogenicity of a Vi conjugate vaccine injected twice into 2- to 5-year-old Vietnamese children.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Full product reproduces component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-09
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Empty vector / particle component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F3 · Antigen alone reproducesno_data
Measure: Isolated antigen reproduces the effect Comparator: Vehicle Hit rule: The isolated antigen (not the full product) reproduces the effect
Finding: No retrieved evidence addresses whether isolated Typhoid vaccine antigen reproduces diarrhoea; all retrieved articles discuss vaccine vector development, none involve Typhoid vaccine antigen or diarrhoea as an adverse event.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Antigen alone reproduces component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Irrelevant cargo component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: No retrieved evidence addresses the comparison of infection preparation vs product preparation for the adverse event of diarrhoea following typhoid vaccination.
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Infection preparation component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Infection preparation no effect component isolation pubmed · 1 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045628 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Component combination component OR antigen OR vector pubmed · 2045629 hits · run 2026-09-09
does_not_resolve 25142448 · Current gene therapy (2014) — Improving DNA vaccine performance through vector design.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea 2D human cells animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Organoid / chip animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15145596 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-09
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea mechanism Host-line dependence in vitro OR patient-derived pubmed · 29262 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Host-line dependence not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G3 · Animal, clinical routeno_data
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: In PMID 36332427, vaccination of young chickens with an avirulent Salmonella Gallinarum (SG01) strain resulted in no clinical symptom including diarrhea, indicating that the vaccine did not reproduce diarrhea via the clinical route in this animal model.
supporting: Typhoid vaccine Diarrhoea Animal, clinical route animal OR organoid OR cell model pubmed · 1819228 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Animal, clinical route not reproduced model pubmed · 2 hits · run 2026-09-09
2 retrieved record(s)
does_not_resolve 36332427 · Veterinary immunology and immunopatholog (2022) — Safety and protective effects of an avirulent Salmonella Gallinarum isolate as a vaccine candidate against Salmonella Gallinarum infections in young chickens.
does_not_resolve 24406393 · Vaccine (2014) — Generation of a safety enhanced Salmonella Gallinarum ghost using antibiotic resistance free plasmid and its potential as an effective inactivated vaccine candi
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Susceptible animal animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Susceptible animal not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Replication across labs animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Blinded scoring animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Blinded scoring not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Experimental time course animal OR organoid OR cell model pubmed · 1819226 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Experimental time course not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-09
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: Typhoid vaccine Diarrhoea Susceptibility trait coherence OR latency OR susceptibility pubmed · 870319 hits · run 2026-09-09
mirror: Typhoid vaccine Diarrhoea Susceptibility trait inconsistent OR contradicts pubmed · 27616 hits · run 2026-09-09
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.