The scale of the findings is striking. At their peak, annual prevalence estimates reached 347 cases per 100,000 population in primary care settings in 2017 and 314 per 100,000 in hospitals in 2016, figures that consistently exceed the threshold of more than 100 cases per 100,000 person-years used to define high-burden settings. Even after years of gradual decline, the most recent estimates from 2023 stood at 143 per 100,000 in primary care and 167 per 100,000 in hospitals, still well above that benchmark. Hospital admissions accounted for 47.62 percent of all typhoid-related visits, and cumulative deaths over the nine-year period included 11,991 recorded in hospitals, corresponding to an average annual hospital mortality rate of 0.57 per 100,000 population.

Methodologically, the study is a serial cross-sectional analysis built on an unweighted sample of 2,499,681 unique individual records, which, after applying BPJS Kesehatan’s stratified sampling weights, represents a national population of approximately 290 million people. Cases were identified using physician-assigned ICD-10 codes, primarily A01.0 for typhoid fever, recorded as either primary or secondary diagnoses. To avoid inflating prevalence with repeat consultations for the same illness, the researchers applied an episode-based filtering approach: encounters occurring within 30 days of a preceding record for the same individual were treated as part of a single clinical episode, a boundary chosen because typhoid’s incubation period typically ranges from 6 to 30 days and relapses most commonly occur two to three weeks after treatment ends. Only the final record within each episode was retained for analysis.

The choice of data source matters because diagnosing typhoid fever in endemic settings is notoriously difficult. The Widal agglutination test, long used in low-resource settings, has poor sensitivity and specificity because of high background seroprevalence, and rapid diagnostic tests offer only modest improvements. Blood culture remains the reference standard, but its sensitivity drops after prior antibiotic use, and laboratory capacity and cost constraints mean microbiological confirmation is rarely performed in routine Indonesian practice. In primary care, where reimbursement is capitation-based, laboratory confirmation is not routinely required at all; in hospitals, supporting investigations such as Tubex, Typhidot, or Widal testing are generally undertaken for reimbursement claims, though these do not replace culture confirmation. The study’s estimates therefore describe the burden of physician-coded typhoid requiring healthcare utilisation rather than microbiologically confirmed disease, a distinction the authors acknowledge carefully.

Demographically, the burden fell unevenly. Adults aged 19 to 64 accounted for roughly half of all typhoid-related visits, yet the highest prevalence was observed among children under five years of age in both primary care and hospital settings. Adjusted analyses using Poisson regression with robust variance estimation revealed that children aged 0 to 5 years had a modestly higher likelihood of hospitalisation compared with working-age adults, with an adjusted prevalence ratio of 1.02, while adolescents aged 6 to 18 showed a ratio of 1.03. The most pronounced elevation appeared among people aged 65 and older, whose adjusted prevalence ratio of 1.07 was the highest of any age group, despite this group having the lowest overall prevalence of typhoid-related visits. The authors suggest this may reflect comorbidities, frailty, and a lower clinical threshold for admitting older patients rather than greater disease severity per se.

Socioeconomic vulnerability emerged as another powerful determinant. Individuals enrolled in the subsidised insurance scheme, which serves low-income households, had a 7 percent higher likelihood of hospitalisation than those in the formal sector, with an adjusted prevalence ratio of 1.07. Members of Class III, the most affordable tier of care with the simplest inpatient facilities, contributed the largest share of visits across all settings. These patterns, the researchers argue, reflect underlying socioeconomic disadvantage and potential barriers to timely access to care, meaning that by the time subsidised patients reach hospital, their illness may be more advanced. The intersection of age-related vulnerability and social disadvantage, they conclude, shapes severe disease trajectories in ways that targeted interventions must address.

Geographically, the study uncovered pronounced subnational clustering that national-level statistics had long obscured. Primary care prevalence was highest in Central Java province at a mean annual 302 per 100,000, followed by Bengkulu at 289, while hospital prevalence peaked in Aceh at 496 per 100,000, followed by Gorontalo and North Sumatra. When provinces were aggregated into the INA-CBGs regional classification, the highest annual prevalence reached 2,367 visits per 100,000 population in region 1, covering Java, Indonesia’s most populous island, for primary care, and 2,213 per 100,000 in region 3, covering Sulawesi and parts of Sumatra and Kalimantan, for hospitals. Urban areas consistently showed higher prevalence than rural ones across both care settings throughout the study period.

The concentration of cases in densely populated Java is particularly revealing because it runs counter to a simple sanitation narrative. Several provinces in Java exhibited both relatively high percentages of households with access to improved sanitation and high typhoid prevalence, while provinces outside Java with better sanitation access generally showed lower prevalence. Previous research has documented widespread use of shallow, contaminated groundwater as a household drinking water source and poor sanitation management in dense and informal urban settlements on Java, and parts of Sumatra and Sulawesi where cases clustered also show WASH infrastructure access below the national figure. The eastern provinces of Papua and Papua Barat recorded the lowest prevalence, at 24 and 10 per 100,000 respectively in primary care, but the authors caution this likely reflects lower healthcare utilisation and under-ascertainment rather than genuinely low transmission.

The temporal trends carry their own lessons. A marked decline in cases occurred during 2020 and 2021, coinciding with the COVID-19 pandemic, likely reflecting the reallocation of 20 to 40 percent of general ward beds to COVID-19 care, reduced healthcare-seeking, and non-pharmaceutical interventions such as social distancing and improved hand hygiene that may have limited faecal-oral transmission. When cases rebounded in 2022, the increase was more pronounced among inpatients than outpatients, which the authors attribute to the restoration of routine inpatient services rather than a true rise in disease severity. Earlier fluctuations during 2016 and 2017 may relate to the rapid expansion of insurance membership, evolving referral policies, and maturation of coding practices during the early phase of the scheme’s implementation.

The implications extend well beyond Indonesian borders. The Global Burden of Disease 2023 study estimates that Indonesia has the highest typhoid incidence, 99 per 100,000, and mortality rate, 1.29 per 100,000, in Southeast Asia, yet those figures rely substantially on modelled extrapolation in a country lacking nationwide culture-confirmed surveillance. The new claims-based estimates, which exceed even the GBD figures, arrive as neighbouring countries move forward with typhoid conjugate vaccine introduction: Nepal and Pakistan have incorporated the vaccine into routine immunisation, and Bangladesh introduced it in 2025, following the World Health Organization’s 2018 recommendation of a single dose for children from six months of age. Indonesia, however, continues to face financing constraints and competing priorities, with policymakers citing a lack of robust contemporary epidemiological data. The authors also point to complementary environmental surveillance showing Salmonella Typhi in 13 percent of 406 wastewater samples collected from treatment plants, manholes, rivers, and public spaces, evidence of persistent community transmission. Combined with rising multidrug and extensively drug-resistant strains documented across endemic settings, and imported cases linked to travel from Indonesia reported abroad, the converging evidence strengthens the case for introducing the vaccine alongside targeted water and sanitation improvements, prioritising high-burden regions and vulnerable populations, and building serosurveillance and wastewater monitoring into the country’s surveillance architecture.

Subject of Research: Population-based epidemiology of typhoid fever in Indonesia using national health insurance claims data

Article Title: Burden of typhoid fever in primary and hospital care in Indonesia: a serial cross-sectional study using national health insurance (BPJS Kesehatan) data, 2015–2023

Article References: Oktaria, V., Ramadhani, A. D., Maula, A. W., Murni, I. K., Watts, E., Baehaqi, I. S., Dinari, R., Wiryawan, D. A., Daniel, D., Donato, C. M., & Bines, J. E. (2026). Burden of typhoid fever in primary and hospital care in Indonesia: a serial cross-sectional study using national health insurance (BPJS Kesehatan) data, 2015–2023. The Lancet Regional Health – Western Pacific, 75, Article 101994. https://doi.org/10.1016/j.lanwpc.2026.101994

Image Credits: AI Generated

DOI: 10.1016/j.lanwpc.2026.101994

Keywords: typhoid fever, Indonesia, Salmonella Typhi, BPJS Kesehatan, epidemiology, hospitalisation, typhoid conjugate vaccine, water sanitation and hygiene, antimicrobial resistance, health insurance claims, subnational disparities, wastewater surveillance

Typhoid fever remains a formidable challenge to health systems in endemic areas, primarily affecting children under 15 but also posing risks across age groups. The causative agent, Salmonella Typhi, thrives in regions with inadequate sanitation infrastructure, and the emerging threat of antimicrobial resistance exacerbates the urgent need for efficacious vaccines. Against this backdrop, EuTYPH-C Inj.® Multi-dose offers renewed hope by meeting stringent international benchmarks for safety and immunogenicity, thereby promising enhanced protection and facilitating broader vaccine coverage.

This multicenter Phase 3 trial employed a randomized, observer-blind methodology encompassing over 3,200 healthy participants aged from six months to 45 years at two African sites—Kericho in Kenya and Sandiara in Senegal. Participants were administered either EuTYPH-C Inj.® Multi-dose or the World Health Organization (WHO)-prequalified Typbar TCV®. Comprehensive safety assessments revealed a tolerability profile for EuTYPH-C that was consistent with, if not superior to, the comparator vaccine, with no vaccine-related serious adverse events observed throughout the study duration.

Critically, immunogenicity evaluations centered on infants aged 9 to 12 months demonstrated that immune responses elicited by both single-dose and multi-dose formats of EuTYPH-C were not inferior to Typbar TCV®. High seroconversion rates were documented 28 days post-vaccination and sustained at six months, indicating durable antibody-mediated protection. Furthermore, EuTYPH-C displayed compatibility with the co-administration of measles-rubella and yellow fever vaccines—a significant finding that supports integrated immunization schedules without compromising immunologic efficacy.

Dr. Patricia Njuguna, the senior medical officer and project lead from PATH, emphasized the paramount importance of safety in vaccine deployment, underscoring that EuTYPH-C’s safety profile reassures its suitability for mass immunization campaigns across diverse age groups. The absence of serious adverse events related to the vaccine is notable, especially in pediatric cohorts where tolerability often dictates programmatic success.

The successful licensure of EuTYPH-C Inj.® Multi-dose by the Korean Ministry of Food and Drug Safety, bolstered by Phase 3 data, positions the vaccine for imminent submission to the WHO for prequalification. This designation is essential for procurement by UN agencies and Gavi, the Vaccine Alliance, which play critical roles in vaccine distribution to low- and middle-income countries. Increasing the portfolio of WHO-prequalified TCVs actively contributes to fostering competitive pricing, ensuring supply resiliency, and accelerating access to lifesaving immunizations.

EuBiologics, the manufacturer based in Seoul, has a commendable track record, including WHO prequalification of their oral cholera vaccine, highlighting their expertise in vaccine development and global health contributions. The introduction of EuTYPH-C into the typhoid vaccine market is anticipated to further diversify and stabilize supply chains, a vital consideration given the escalating demand in Gavi-supported countries where seven have already integrated TCVs into national immunization programs.

Typhoid remains a major public health threat, with more than 7 million cases and over 93,000 deaths estimated globally in 2021, predominantly in Asia and sub-Saharan Africa. Given the rise in drug-resistant strains of Salmonella Typhi, vaccination emerges as an indispensable preventive tool alongside improvements in water, sanitation, and hygiene infrastructure. Over 90 million doses of TCVs have already been administered globally, yet vaccine access and affordability continue to be barriers in many high-burden regions.

The robust immune responses observed with EuTYPH-C, its safety, and ability to be co-administered with other childhood vaccines underscore its potential for seamless integration into existing immunization schedules. Such integration is critical to optimizing healthcare delivery efficiencies and increasing vaccination coverage among vulnerable populations, particularly infants and young children who bear the highest disease burden.

This trial represents a successful collaboration among international stakeholders, including PATH, EuBiologics, Kenya Medical Research Institute (KEMRI), Walter Reed Army Institute of Research (WRAIR), and the Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (IRESSEF). Funding support from EuBiologics and the RIGHT Foundation underscores the importance of public-private partnerships in driving vaccine innovation and equitable health advancements globally.

Looking ahead, WHO prequalification of EuTYPH-C will enhance the vaccine’s availability for widespread use, potentially transforming typhoid prevention strategies in endemic countries. Expanding the vaccine arsenal is pivotal to combating the persistent challenges posed by typhoid fever, ultimately reducing morbidity and mortality, and contributing to the global agenda for vaccine-preventable disease control and elimination.

EuTYPH-C Inj.® Multi-dose exemplifies cutting-edge conjugate vaccine technology that leverages the Vi polysaccharide antigen coupled with CRM197 carrier protein to evoke a strong, persistent immune response. This immunological strategy addresses the limitations of earlier polysaccharide vaccines, which were less efficacious particularly in young children, by inducing T-cell-dependent immunity and immune memory—an essential feature for durable protection and herd immunity.

The trial’s rigorous design, encompassing lot-to-lot consistency and evaluation across various age cohorts, provides comprehensive data supporting the vaccine’s quality and effectiveness. Such robust scientific evidence is instrumental in informing policy makers, immunization programs, and global health stakeholders in their decisions to scale TCV deployment and optimize typhoid control efforts.

In summary, the publication of EuTYPH-C Inj.® Multi-dose Phase 3 clinical trial data marks a significant milestone in typhoid vaccine research and public health practice. This vaccine’s demonstrated safety, immunogenicity, and operational compatibility position it as a key addition to the international fight against typhoid fever, particularly within sub-Saharan Africa and other regions grappling with endemic disease and the rising threat of antimicrobial resistance.

Subject of Research: People

Article Title: A Multi-Center, Observer-Blind, Randomized, Phase 3 Study to Evaluate Safety, Non-Inferiority of Multi-Dose and Single-Dose Vial Formulations of EuTCV (Vi-CRM197 Typhoid Conjugate Vaccine) and Lot-to-Lot Consistency of the Immune Response to Multi-Dose Vial Formulation EuTCV in Healthy Participants in Kenya and Senegal

News Publication Date: 12-Nov-2025

Image Credits: Photo courtesy of EuBiologics Co., Ltd.

Keywords: Vaccine development, Vaccine research, Clinical research, Typhoid, Bacterial infections, Vaccination, Africa, Asia, Infectious diseases, Public health, Clinical trials, Preventive medicine