Effectiveness of the TYPHIBEV® (Vi-CRM197 conjugate) vaccine introduction in Nepal: a test-negative, case-control study

Tamrakar, Dipesh1 ; Bikram Shahi, Sabin2; Jung, Esther 3 ; Naga, Shivram1; Shrestha, Basudha4; Bista Roka, Pratibha5; Sharma Pokharel, Rabin6; Hari Chapagain, Ram7; Tamrakhar, Akhil8; Mahoto, Manoj9; Kumar Madhup, Surendra2; Shrestha, Rajeev1 2; Doyle, Kate10; Bogoch, Isaac11; Luby, Stephen3; Garrett, Denise10; Cheirakul, Wirongrong12; Andrews, Jason3

Published May 06, 2026 on Dryad. https://doi.org/10.5061/dryad.dr7sqvbcn

Data files

May 06, 2026 version files 52.99 KB

README.md

21.19 KB
TND_DATA_disidentified.csv

31.79 KB

Abstract

Objectives

We aimed to evaluate the effectiveness of TYPHIBEV®, which was introduced through a catch-up campaign and routine immunization in Nepal, in preventing blood culture-confirmed typhoid fever among children.

Methods

We conducted a test-negative, case-control study where typhoid test-positive cases were defined as vaccine-eligible pediatric patients who tested positive for Salmonella Typhi by blood culture at participating health facilities and test-negative controls were vaccine-eligible patients who tested negative for S. Typhi on blood cultures. We matched by age, location, date of blood culture, and surveillance site. We used conditional logistic regression to calculate odds ratios(OR), and vaccine effectiveness was calculated as 1-OR.

Results

Between October 1, 2022 and December 31, 2024, 40 typhoid cases and 113 matched, test-negative controls were enrolled. Both cases and controls were similar in sociodemographic characteristics and water, sanitation and hygiene-related living conditions. Among 39 cases and 108 controls with known vaccine status, 20 cases(51%) and 91 controls(84%) had received TCV. Vaccine effectiveness was 89% (95% CI: 65-97%) and was lower among children <5 years (72%, 95% CI: -203-97%) compared with those 5-15 years (98%, 95% CI: 80-100%). Vaccine effectiveness estimates did not significantly differ when restricted to participants with documented vaccination status.

Conclusions

The findings indicate that TYPHIBEV® was highly effective in preventing typhoid fever up to 30 months following a national introduction, with effectiveness estimates comparable to those observed for Typbar-TCV®.

This document describes the structure and variables of the disidentified dataset (TND_DATA_disidentified.csv) used in the Nepal Typhoid Vaccine Effectiveness study.

Dataset Overview

File Name: TND_DATA_disidentified.csv
Format: Comma-separated values (CSV)
Population: Children and adolescents aged 15 months to 15 years enrolled in the Test-Negative Design study.
Geography: Nepal

Missing Data and Skip Logic

Empty cells (null values) in this dataset are intentionally left blank to ensure compatibility with statistical analysis scripts and software. These empty cells primarily represent two scenarios:

Skip Logic (Conditional Branching): Many variables are only applicable and thus only populated if a previous "gatekeeper" variable met a certain condition. For example:
- vacc_date_unc and vacc_type are only populated if vacc_yn (TCV Vaccination status) is 1 (Yes).
- travel_timing is only populated if travel is 1 (Yes).
- abx_type and abx_length are only populated if abx_hx (Recent antibiotic use) is 1 (Yes).
- house_purify_method is only populated if house_purify is 1 (Always) or 2 (Sometimes).
Unavailable Information: In cases where a question was applicable but the participant chose not to answer, or the data was otherwise unavailable, the cell remains empty.

Users should refer to the "Coding / Values" and "Description" columns in the tables below to understand the context of each variable and the likely reasons for any missing values.

1. Core Study Variables

Variable Name	Description	Coding / Values
`record_id`	Unique participant identifier	Integer
`status`	Participant enrollment status	1 = Not yet contacted (culture pending), 2 = Not yet contacted (control pending match), 3 = Attempting to contact, 4 = Not able to contact, 5 = Contacted (refused or ineligible), 6 = Contacted (visit pending), 7 = Visit completed
`gender`	Participant gender	1 = Male, 2 = Female
`ethnicity`	Ethnic group	Categorical (key suppressed for de-identification)
`agecalc`	Age at enrollment	Generalized age values (rounded to nearest whole year)
`region`	Study region / municipality	Categorical (key suppressed for de-identification)
`culture_neg_oth`	Specific blood culture finding	Text (pathogen name if not typhoid)
`assignment`	Study group (Case/Control)	1 = Case (positive for typhoid), 2 = Control (negative for typhoid)
`control_id_match`	Matching identifier for controls	ID of the case participant this control is matched to
`case_match1`	Matching identifier for cases (Control 1)	ID of the first control matched to this case
`case_match2`	Matching identifier for cases (Control 2)	ID of the second control matched to this case
`case_match3`	Matching identifier for cases (Control 3)	ID of the third control matched to this case
`remove`	Internal exclusion flag	0 = Keep in analysis, 1 = Exclude

2. Contact & Screening Variables

Variable Name	Description	Coding / Values
`outcome_att1`	Outcome of first contact attempt	1 = Reached participant, 2 = Did not reach participant
`outcome_att2`	Outcome of second contact attempt	1 = Reached participant, 2 = Did not reach participant
`outcome_att3`	Outcome of third contact attempt	1 = Reached participant, 2 = Did not reach participant
`outcome_att4`	Outcome of fourth contact attempt	1 = Reached participant, 2 = Did not reach participant
`outcome_att5`	Outcome of fifth contact attempt	1 = Reached participant, 2 = Did not reach participant
`screen_agree`	Willingness to participate in home visit	1 = Yes, 0 = No
`screen_residency`	Lived in Nepal during April 2022 campaign	1 = Yes, 0 = No
`screen_address`	Address confirmation	1 = Yes (lives at listed address), 0 = No
`consent`	Formal consent provided by parent/guardian	1 = Yes, 0 = No

3. Vaccination Information

Variable Name	Description	Coding / Values
`vacc_yn`	TCV Vaccination status	1 = Yes, 0 = No, 77 = Don't Know
`vacc_card_yn`	Vaccine card availability	1 = Yes, 0 = No
`vacc_yes_confirm___1`	Confirmation Source: Parent/guardian	1 = Yes, 0 = No
`vacc_yes_confirm___2`	Confirmation Source: School records	1 = Yes, 0 = No
`vacc_yes_confirm___99`	Confirmation Source: Other	1 = Yes, 0 = No
`vacc_date_unc`	Approximate vaccination date flag	1 = Yes (date is approximate), 0 = No
`vacc_type`	Type of vaccine received	1 = TyphiBEV (Bio-E), 2 = TypbarTCV (Bharat), 3 = Polysaccharide (ViPS), 4 = Oral live attenuated (Ty21a), 99 = Other, 77 = Unknown
`vacc_loc`	Location of vaccination	1 = School, 2 = Hospital/Clinic, 3 = Pharmacy, 4 = Mass campaign, 99 = Other

4. Socioeconomic & Environmental Variables (SES/WASH)

Variable Name	Description	Coding / Values
`ed_pat`	Education level: Male head of household	0 = None, 1 = Primary, 2 = Secondary, 3 = Post-secondary, 99 = Other, 77 = N/A
`ed_mat`	Education level: Female head of household	0 = None, 1 = Primary, 2 = Secondary, 3 = Post-secondary, 99 = Other
`house_num`	Number of residents in the house	Integer (Range: 1–40)
`house_bedrooms`	Number of bedrooms in the house	Integer (Range: 0–100)
`house_material`	Primary house construction material	1 = Cement/Brick/Stone, 2 = Mud/Brick/Stone, 3 = Tin, 4 = Wood, 5 = Wood/Mud, 99 = Other
`house_toilets`	Number of toilets in the house	Integer (Range: 0–100)
`house_toilets_type___1`	Toilet Type: Commode with flush	1 = Yes, 0 = No
`house_toilets_type___2`	Toilet Type: Pit hole with flush	1 = Yes, 0 = No
`house_toilets_type___3`	Toilet Type: Pithole without flush	1 = Yes, 0 = No
`house_toilets_type___4`	Toilet Type: Open defecation	1 = Yes, 0 = No
`house_toilets_type___99`	Toilet Type: Other	1 = Yes, 0 = No
`house_sewage`	Sewage disposal method	1 = Municipal pipeline (closed), 2 = Open sewer, 3 = Septic tank, 99 = Other
`house_sewage_oth`	Specific other sewage disposal	Text
`house_garbage___1`	Garbage: Thrown on street	1 = Yes, 0 = No
`house_garbage___2`	Garbage: Carried away by Metropolitan	1 = Yes, 0 = No
`house_garbage___3`	Garbage: Deposited in garbage bin	1 = Yes, 0 = No
`house_garbage___4`	Garbage: Decomposed for compost	1 = Yes, 0 = No
`house_garbage___99`	Garbage: Other method	1 = Yes, 0 = No
`house_water___1`	Water Source: Municipal supply (running)	1 = Yes, 0 = No
`house_water___2`	Water Source: Tanker	1 = Yes, 0 = No
`house_water___3`	Water Source: Community tap	1 = Yes, 0 = No
`house_water___4`	Water Source: Open well	1 = Yes, 0 = No
`house_water___5`	Water Source: Covered well	1 = Yes, 0 = No
`house_water___6`	Water Source: Spring water	1 = Yes, 0 = No
`house_water___7`	Water Source: Underground boring	1 = Yes, 0 = No
`house_water___8`	Water Source: Jar (mineral water)	1 = Yes, 0 = No
`house_water___99`	Water Source: Other	1 = Yes, 0 = No
`house_purify`	Frequency of water purification	1 = All of the time, 2 = Some of the time, 3 = None of the time
`house_purify_method`	Main purification method	1 = Filtration, 2 = Boiling, 3 = Alum, 4 = Chlorination, 5 = Tablets, 99 = Other
`house_water_boil`	Time water is boiled after boiling starts	1 = <1 min, 2 = 1–3 mins, 3 = 3–5 mins, 4 = >5 mins

5. Food & Water Exposure Matrices

Note on Frequency Coding (Variables w... and f...):

0 = Never / did not go to this place
1 = Every day
2 = A few times a week
3 = 1–3 times in the four weeks
77 = Don't know / not sure

Unboiled/Untreated Water Exposure (Last 4 weeks)

Variable Name	Location
`wwork`	Workplace
`wschool`	School
`wresto`	Restaurant
`whotel`	Hotel
`wvend`	Roadside vendors
`wtap`	Community tap
`whouse`	Someone else's house
`woth`	Another place

Food Exposure (Last 4 weeks)

Variable Name	Location
`fwork`	Workplace
`fschool`	School
`fresto`	Restaurant
`fhotel`	Hotel
`fvend`	Roadside vendors
`fhouse`	Someone else's house
`fparty`	Party or wedding
`foth`	Another place
`foth_spec`	Specific other place for food

6. Clinical & Travel History

Variable Name	Description	Coding / Values
`prep_who`	Main person who prepares food	1 = Family member, 2 = Servant, 3 = Hired help, 99 = Other
`prep_oth`	Specific other food preparer	Text
`prep_hands`	Handwashing frequency of food preparer	1 = All of the time, 2 = Some of the time, 3 = None, 77 = Don't know
`prep_typh`	Food preparer history of typhoid	1 = Yes, 2 = No, 77 = Don't know
`prep_typh_when`	Timing of food preparer's typhoid	1 = <1 month ago, 2 = 1–3 months, 3 = 3–6 months, 4 = >6 months, 77 = Don't know
`prep_typh_test`	Food preparer had blood test for typhoid	1 = Yes, 0 = No, 77 = Don't know
`food_store`	Location of cooked food storage	1 = Refrigerator, 2 = Kitchen, 3 = Somewhere else
`food_outside`	Frequency of child eating outside house	1 = >1 meal/day, 2 = 1 meal/day, 3 = Several/week, 4 = 1/week, 5 = 1–3/month, 6 = Rarely/never
`handwash_food`	Child handwashing before eating	1 = All of the time, 2 = Some of the time, 3 = Rarely or never
`handwash_latrine`	Child handwashing after latrine use	1 = All of the time, 2 = Some of the time, 3 = Rarely or never
`school_lunch`	Frequency of school lunch money	88 = N/A (no school), 1 = Every day, 2 = Some time, 3 = Never
`school_lunch_where`	Where child spends lunch money	1 = School canteen, 2 = Restaurant, 3 = Roadside vendors, 77 = Don't know, 99 = Other
`school_share`	Frequency of sharing food at school	1 = All of the time, 2 = Some of the time, 3 = None, 77 = Don't know
`contact_yn`	Known contact with typhoid patient	1 = Yes, 0 = No, 77 = Don't Know
`travel`	Recent travel history outside city/village	1 = Yes, 0 = No, 77 = Don't Know
`travel_timing`	Timing of illness after travel	1 = During travel, 2 = 1–3 days after, 3 = 4–6 days after, 4 = 7–13 days after, 5 = >2 weeks after
`abx_hx`	Recent antibiotic use before illness	1 = Yes, 2 = No, 77 = Don't know / not sure
`abx_type`	Type of antibiotic(s) taken	Text
`abx_length`	Duration of antibiotic use (days)	Text/Integer

7. Form Completion Status

Variable Name	Description	Coding / Values
`preenrollment_form_complete`	Pre-enrollment form status	0 = Incomplete, 1 = Unverified, 2 = Complete
`contact_form_complete`	Contact form status	0 = Incomplete, 1 = Unverified, 2 = Complete
`survey_complete`	Main survey form status	0 = Incomplete, 1 = Unverified, 2 = Complete
`risk_factor_questionnaire_complete`	Risk factor questionnaire status	0 = Incomplete, 1 = Unverified, 2 = Complete

Data Usage Note

This dataset has been disidentified for publication. Personal identifiable information (PII) such as specific addresses and full dates of birth have been removed or transformed into age values.

Human subjects data

We have received consent to publish the de-identified data in the public domain, and we are following the Open Access Policy for Gates-funded studes: https://openaccess.gatesfoundation.org/how-to-comply/data-sharing-requirements/. All personal health identifiers and dates were removed.