RARE DISEASE
Typhoid
Typhoid
Typhoid
Synonyms: Typhoid fever, Typhoidal salmonellosis
Synonyms: Typhoid fever, Typhoidal salmonellosis
Synonyms: Typhoid fever, Typhoidal salmonellosis
Drug discovery
0
drugs
With orphan designations
Overview
Typhoid fever, caused by Salmonella enterica serotype Typhi, is a systemic illness transmitted via contaminated food/water. It presents with prolonged high fever, headache, abdominal pain, constipation/diarrhea, and rose spots. Severe cases may lead to intestinal perforation, encephalopathy, or death. Diagnosis relies on blood/stool cultures, and treatment requires antibiotics (ceftriaxone, fluoroquinolones, or azithromycin), guided by susceptibility testing due to rising antimicrobial resistance. Chronic carriers shed bacteria, necessitating prolonged antibiotic courses [1][5][9][15].
Burden
Global burden: ~9.2 million cases and 110,000 deaths annually (2019 estimates) [2][6][9].
Complications: 1–4% become chronic carriers; case fatality <1% with treatment, rising to 10–30% untreated [1][5][9].
Economic impact: Strains healthcare systems in endemic regions due to hospitalization costs and antimicrobial resistance crises [7][10][15].
Therapies
First-line antibiotics: Ceftriaxone, azithromycin, or fluoroquinolones (if susceptible) [1][5][12][16].
Resistance management: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains necessitate susceptibility testing; alternatives include high-dose azithromycin [12][16].
Carrier eradication: Prolonged antibiotic regimens (e.g., ciprofloxacin) ± cholecystectomy [1][5][9].
Categories: rare infectious diseases
Research Papers
2,634 drug discovery papers about Typhoid, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,634 drug discovery papers about Typhoid, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Direct Hospitalization Costs Associated with Resistant and Susceptible Salmonella and Shigella Infections in the United States, 2012-2019.
Antimicrobial-resistant enteric infections may be difficult to treat, associated with severe outcomes, and costly. To determine if resistant enteric infections are more costly, we described direct hospitalization costs for hospital admissions for typhoid fever, salmonellosis, and shigellosis infections by resistance status. We included all inpatient admissions with culture-confirmed infections from approximately 300 hospitals in the Premier Healthcare database during 2012-2019. We classified typhoid fever, salmonellosis, and shigellosis infections as clinically resistant if laboratory testing found resistance to ≥1 antibiotic class recommended for treatment. We examined patient demographic characteristics and underlying chronic conditions. We used the Wilcoxon rank sum test to assess the difference in median hospitalization cost for each patient admission by resistance status. We estimated adjusted cost and length of stay (LOS) using multivariable linear regression, adjusting for host and health care provider characteristics. Among 67 inpatient admissions for typhoid fever, 3421 for salmonellosis, and 619 for shigellosis, 33% of typhoid fever, 13% of salmonellosis, and 82% of shigellosis infections were clinically resistant. The unadjusted median costs for resistant salmonellosis were higher than susceptible infection-related costs ($7,753 vs. $6,909, p = 0.002). The unadjusted costs for resistant versus susceptible typhoid fever ($13,709 vs. $9,254, p = 0.111) and shigellosis were similar ($5,365 vs. $5,777, p = 0.167). For all three pathogens, the adjusted mean hospitalization costs were not statistically different for resistant and susceptible infections. Adjusted mean LOS was significantly longer for resistant typhoid fever compared with susceptible infections (6.50 days vs. 4.35 days, p = 0.001). Although adjusted cost differences for resistant infections were not significant, we observed differences by host factors including age and comorbidities, suggesting patient demographic characteristics for resistant infections are impactful on cost. These findings support the premise that public health interventions to limit the spread of resistant infections, particularly among individuals at higher risk for severe illness, could reduce hospitalization costs.
2026-08-17 | OmpW-mediated sensing of MUC2 GalNAc contributes to the ileal tropism of Salmonella Typhi.
Salmonella Typhi (STy), the causative agent of typhoid fever, preferentially infects the ileum, but the basis for this preference has remained unknown. We show that STy exploits MUC2-derived monosaccharides, such as N-acetylgalactosamine (GalNAc), to upregulate invasion and target the ileum-opposite to the response of closely related S. Typhimurium (STm), whose invasion is inhibited by MUC2. Three STy-specific extracellular residues of the outer-membrane protein OmpW (K141/T142/Q193) engage GalNAc, and a periplasmic relay through the short FepE_STy, RS12510, and TonB transmits this signal to activate the master invasion regulator HilD. Mice lacking MUC2 or gut microbiota lose STy ileal tropism, which is restored by oral GalNAc-containing monosaccharides. An OmpW triple-mutant STy strain establishes a murine oral STy infection model, identifying STy-MUC2 glycan interactions as an early step of typhoid pathogenesis and a potential target for prevention.
2026-08-11 | 8-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in children in Nepal (TyVOID): a prospective cohort follow-up study of the TyVAC Nepal randomised controlled trial.
In low-income and middle-income countries, where typhoid fever remains a major public health problem, WHO recommends the use of typhoid conjugate vaccine (TCV). Here, we report vaccine effectiveness up to 8 years following a single dose of TCV in Nepal. TyVOID was a prospective cohort study that extended the follow-up of children enrolled in a phase 3, double-blind, randomised controlled trial in Lalitpur, Nepal (TyVAC; Nov 20, 2017, to Oct 20, 2021). Children aged 9 months to 15 years were randomly assigned (1:1) to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) or a capsular group A meningococcal conjugate (MenA) vaccine. After unmasking and crossover vaccination, our study followed the trial participants until Oct 31, 2025. TyVAC participants who received Vi-TT were eligible for this study and categorised into either the 2017-18 cohort or 2020-21 cohort, depending on when they received the Vi-TT vaccine. The primary outcome, which was assessed in children who received both Vi-TT and MenA vaccines and with known TCV vaccination status during the government catch-up campaign in 2022, was the incidence of blood culture-confirmed typhoid identified through facility-based passive surveillance and medical record review. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression adjusted for age and sex. Vaccine effectiveness at 1-5 years and 4-8 years post-vaccination was estimated using a test-negative design among febrile children presenting to surveillance clinics, comparing odds of Vi-TT vaccination between culture-confirmed typhoid cases with negative controls. 16 131 TyVAC participants were enrolled at TyVOID baseline, of whom 14 850 provided information on Vi-CRM197 vaccination during the government catch-up campaign. After crossover and unmasking, the primary analysis population included 4941 participants vaccinated with Vi-TT in 2017-18 and 4856 participants vaccinated with Vi-TT in 2020-21. In 4856 participants in the 2020-21 Vi-TT cohort, 2402 (49·5%) were female, 2454 (50·5%) were male, and the median age at Vi-TT vaccination was 10·4 years (IQR 7·3-13·7). In 4941 participants in the 2017-18 Vi-TT cohort, 2482 (50·2%) were female, 2459 (49·8%) were male, and the median age at Vi-TT vaccination was 7·7 years (IQR 4·5-11·0). During a median follow-up of 3·7 years (3·7-3·8), the typhoid incidence rate was 111 per 100 000 person-years (95% CI 64-177) in the 2017-18 cohort and 46 per 100 000 person-years (18-94) in the 2020-21 cohort (adjusted IRR 2·41 [95% CI 1·00-5·80]; one-sided p=0·025). Vaccine effectiveness was 77% (95% CI 46-90; p=0·0006) in the 2020-21 Vi-TT cohort (1-5 years after vaccination), and 53% (8-76; p=0·027) in the 2017-18 Vi-TT cohort (4-8 years after vaccination). A single Vi-TT dose confers strong protection in the first 4 years among Nepali children, with evidence of waning by 8 years. These findings support consideration of a booster dose to sustain protection in school-age children who remain at high risk of typhoid fever. Gates Foundation and Wellcome Trust.
2026-08-10 | Mathematical Modelling of Typhoid Fever Transmission Dynamics Incorporating Antibiotic Resistance
Typhoid fever remains a significant public health challenge, particularly in developing countries with inadequate sanitation infrastructure. The emergence and spread of drug-resistant typhoid fever strains have complicated treatment, leading to prolonged illness, higher healthcare costs, and sustained transmission within communities. This growing resistance underscores the need for effective treatment approaches and disease control strategies. This study develops a mathematical model of typhoid fever transmission that incorporates antibiotic resistance. The model categorises infected individuals into drug-sensitive and drug-resistant typhoid fever strains. The impact of treatment modification through different therapeutic options is examined to assess its effect on the prevalence of both sensitive and resistant strains. The model is analysed qualitatively, and the basic reproduction number, R0 , is derived as the sum of two reproduction numbers, R0s and Rr0, representing the transmission contributions of the sensitive and resistant strains, respectively. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined. Sensitivity analysis is conducted to identify the key parameters that influence typhoid fever transmission and persistence. Numerical simulations were performed to validate the analytical results, which demonstrated that typhoid vaccination, the use of appropriate treatment adjustment using first-line and second-line antibiotics, and improved hygiene and sanitation practices significantly reduce the prevalence of both drug-sensitive and drug-resistant strains, as well as the overall infection burden. These findings highlight the effectiveness of integrated prevention and treatment strategies in mitigating antibiotic resistance and enhancing typhoid fever control in the community
2026-08-09 | Cost-effectiveness and budget impact analyses of introducing typhoid conjugate vaccine into Indonesia's national immunisation program.
Typhoid fever remains a health threat in endemic countries. In Indonesia, it causes an estimated 470,000 cases and 6000 deaths annually. We assessed the cost-effectiveness and budget impact of introducing the typhoid conjugate vaccine (TCV) into Indonesia's routine National Immunisation Program (NIP) at 9 months of age, with or without a catch-up campaign up to 15 years of age. A validated dynamic model of typhoid transmission was used to project health outcomes over a 30-year analytical horison for each scenario. Cost-of-illness data were drawn from the Surveillance of Typhoid Fever in Indonesia study and published literature. Incremental cost-effectiveness ratios (ICERs) were estimated from healthcare sector and societal perspectives. Uncertainty was explored using one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA). Budget impact analysis supported annual fiscal planning. Six-year budget impact costs were US$61 million (routine) and US$251 million (routine and catch-up), equivalent to 0.48%-2.95% and 2.97%-9.84% of the annual national immunisation budget, respectively. Compared to no vaccination, routine TCV yielded ICERs at US$240.6 and US$238.8 per DALY averted from the healthcare sector and societal perspectives, respectively, corresponding to 5% of GDP per capita. Compared with routine immunisation alone, adding a catch-up campaign yielded ICERs of US$521.3 and US$519.5 per DALY averted from the healthcare sector and societal perspective, respectively, corresponding to approximately 11% of GDP per capita. OWSA showed that both strategies remained very cost-effective at a willingness-to-pay threshold of 1xGDP. PSA estimated probabilities of cost-effectiveness of 99.7% (routine and catch-up vs. routine) and 99.2% (routine vs. no vaccination). The multi-strategy cost-effectiveness acceptability curve identified the combined routine and catch-up campaign as the optimal strategy. Introducing TCV into Indonesia's NIP is projected to be very cost-effective. A routine-only program requires a lower budget, but adding a catch-up campaign is an optimal strategy with greater public health impact while remaining very cost-effective. Gates Foundation grants to Murdoch Children's Research Institute in collaboration with Universitas Gadjah Mada [ref. no. INV-003867] and to TyVAC 2.0 [ref. no. INV-030857].
2026-08-17 | Direct Hospitalization Costs Associated with Resistant and Susceptible Salmonella and Shigella Infections in the United States, 2012-2019.
Antimicrobial-resistant enteric infections may be difficult to treat, associated with severe outcomes, and costly. To determine if resistant enteric infections are more costly, we described direct hospitalization costs for hospital admissions for typhoid fever, salmonellosis, and shigellosis infections by resistance status. We included all inpatient admissions with culture-confirmed infections from approximately 300 hospitals in the Premier Healthcare database during 2012-2019. We classified typhoid fever, salmonellosis, and shigellosis infections as clinically resistant if laboratory testing found resistance to ≥1 antibiotic class recommended for treatment. We examined patient demographic characteristics and underlying chronic conditions. We used the Wilcoxon rank sum test to assess the difference in median hospitalization cost for each patient admission by resistance status. We estimated adjusted cost and length of stay (LOS) using multivariable linear regression, adjusting for host and health care provider characteristics. Among 67 inpatient admissions for typhoid fever, 3421 for salmonellosis, and 619 for shigellosis, 33% of typhoid fever, 13% of salmonellosis, and 82% of shigellosis infections were clinically resistant. The unadjusted median costs for resistant salmonellosis were higher than susceptible infection-related costs ($7,753 vs. $6,909, p = 0.002). The unadjusted costs for resistant versus susceptible typhoid fever ($13,709 vs. $9,254, p = 0.111) and shigellosis were similar ($5,365 vs. $5,777, p = 0.167). For all three pathogens, the adjusted mean hospitalization costs were not statistically different for resistant and susceptible infections. Adjusted mean LOS was significantly longer for resistant typhoid fever compared with susceptible infections (6.50 days vs. 4.35 days, p = 0.001). Although adjusted cost differences for resistant infections were not significant, we observed differences by host factors including age and comorbidities, suggesting patient demographic characteristics for resistant infections are impactful on cost. These findings support the premise that public health interventions to limit the spread of resistant infections, particularly among individuals at higher risk for severe illness, could reduce hospitalization costs.
2026-08-17 | OmpW-mediated sensing of MUC2 GalNAc contributes to the ileal tropism of Salmonella Typhi.
Salmonella Typhi (STy), the causative agent of typhoid fever, preferentially infects the ileum, but the basis for this preference has remained unknown. We show that STy exploits MUC2-derived monosaccharides, such as N-acetylgalactosamine (GalNAc), to upregulate invasion and target the ileum-opposite to the response of closely related S. Typhimurium (STm), whose invasion is inhibited by MUC2. Three STy-specific extracellular residues of the outer-membrane protein OmpW (K141/T142/Q193) engage GalNAc, and a periplasmic relay through the short FepE_STy, RS12510, and TonB transmits this signal to activate the master invasion regulator HilD. Mice lacking MUC2 or gut microbiota lose STy ileal tropism, which is restored by oral GalNAc-containing monosaccharides. An OmpW triple-mutant STy strain establishes a murine oral STy infection model, identifying STy-MUC2 glycan interactions as an early step of typhoid pathogenesis and a potential target for prevention.
2026-08-11 | 8-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in children in Nepal (TyVOID): a prospective cohort follow-up study of the TyVAC Nepal randomised controlled trial.
In low-income and middle-income countries, where typhoid fever remains a major public health problem, WHO recommends the use of typhoid conjugate vaccine (TCV). Here, we report vaccine effectiveness up to 8 years following a single dose of TCV in Nepal. TyVOID was a prospective cohort study that extended the follow-up of children enrolled in a phase 3, double-blind, randomised controlled trial in Lalitpur, Nepal (TyVAC; Nov 20, 2017, to Oct 20, 2021). Children aged 9 months to 15 years were randomly assigned (1:1) to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) or a capsular group A meningococcal conjugate (MenA) vaccine. After unmasking and crossover vaccination, our study followed the trial participants until Oct 31, 2025. TyVAC participants who received Vi-TT were eligible for this study and categorised into either the 2017-18 cohort or 2020-21 cohort, depending on when they received the Vi-TT vaccine. The primary outcome, which was assessed in children who received both Vi-TT and MenA vaccines and with known TCV vaccination status during the government catch-up campaign in 2022, was the incidence of blood culture-confirmed typhoid identified through facility-based passive surveillance and medical record review. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression adjusted for age and sex. Vaccine effectiveness at 1-5 years and 4-8 years post-vaccination was estimated using a test-negative design among febrile children presenting to surveillance clinics, comparing odds of Vi-TT vaccination between culture-confirmed typhoid cases with negative controls. 16 131 TyVAC participants were enrolled at TyVOID baseline, of whom 14 850 provided information on Vi-CRM197 vaccination during the government catch-up campaign. After crossover and unmasking, the primary analysis population included 4941 participants vaccinated with Vi-TT in 2017-18 and 4856 participants vaccinated with Vi-TT in 2020-21. In 4856 participants in the 2020-21 Vi-TT cohort, 2402 (49·5%) were female, 2454 (50·5%) were male, and the median age at Vi-TT vaccination was 10·4 years (IQR 7·3-13·7). In 4941 participants in the 2017-18 Vi-TT cohort, 2482 (50·2%) were female, 2459 (49·8%) were male, and the median age at Vi-TT vaccination was 7·7 years (IQR 4·5-11·0). During a median follow-up of 3·7 years (3·7-3·8), the typhoid incidence rate was 111 per 100 000 person-years (95% CI 64-177) in the 2017-18 cohort and 46 per 100 000 person-years (18-94) in the 2020-21 cohort (adjusted IRR 2·41 [95% CI 1·00-5·80]; one-sided p=0·025). Vaccine effectiveness was 77% (95% CI 46-90; p=0·0006) in the 2020-21 Vi-TT cohort (1-5 years after vaccination), and 53% (8-76; p=0·027) in the 2017-18 Vi-TT cohort (4-8 years after vaccination). A single Vi-TT dose confers strong protection in the first 4 years among Nepali children, with evidence of waning by 8 years. These findings support consideration of a booster dose to sustain protection in school-age children who remain at high risk of typhoid fever. Gates Foundation and Wellcome Trust.
2026-08-10 | Mathematical Modelling of Typhoid Fever Transmission Dynamics Incorporating Antibiotic Resistance
Typhoid fever remains a significant public health challenge, particularly in developing countries with inadequate sanitation infrastructure. The emergence and spread of drug-resistant typhoid fever strains have complicated treatment, leading to prolonged illness, higher healthcare costs, and sustained transmission within communities. This growing resistance underscores the need for effective treatment approaches and disease control strategies. This study develops a mathematical model of typhoid fever transmission that incorporates antibiotic resistance. The model categorises infected individuals into drug-sensitive and drug-resistant typhoid fever strains. The impact of treatment modification through different therapeutic options is examined to assess its effect on the prevalence of both sensitive and resistant strains. The model is analysed qualitatively, and the basic reproduction number, R0 , is derived as the sum of two reproduction numbers, R0s and Rr0, representing the transmission contributions of the sensitive and resistant strains, respectively. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined. Sensitivity analysis is conducted to identify the key parameters that influence typhoid fever transmission and persistence. Numerical simulations were performed to validate the analytical results, which demonstrated that typhoid vaccination, the use of appropriate treatment adjustment using first-line and second-line antibiotics, and improved hygiene and sanitation practices significantly reduce the prevalence of both drug-sensitive and drug-resistant strains, as well as the overall infection burden. These findings highlight the effectiveness of integrated prevention and treatment strategies in mitigating antibiotic resistance and enhancing typhoid fever control in the community
2026-08-09 | Cost-effectiveness and budget impact analyses of introducing typhoid conjugate vaccine into Indonesia's national immunisation program.
Typhoid fever remains a health threat in endemic countries. In Indonesia, it causes an estimated 470,000 cases and 6000 deaths annually. We assessed the cost-effectiveness and budget impact of introducing the typhoid conjugate vaccine (TCV) into Indonesia's routine National Immunisation Program (NIP) at 9 months of age, with or without a catch-up campaign up to 15 years of age. A validated dynamic model of typhoid transmission was used to project health outcomes over a 30-year analytical horison for each scenario. Cost-of-illness data were drawn from the Surveillance of Typhoid Fever in Indonesia study and published literature. Incremental cost-effectiveness ratios (ICERs) were estimated from healthcare sector and societal perspectives. Uncertainty was explored using one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA). Budget impact analysis supported annual fiscal planning. Six-year budget impact costs were US$61 million (routine) and US$251 million (routine and catch-up), equivalent to 0.48%-2.95% and 2.97%-9.84% of the annual national immunisation budget, respectively. Compared to no vaccination, routine TCV yielded ICERs at US$240.6 and US$238.8 per DALY averted from the healthcare sector and societal perspectives, respectively, corresponding to 5% of GDP per capita. Compared with routine immunisation alone, adding a catch-up campaign yielded ICERs of US$521.3 and US$519.5 per DALY averted from the healthcare sector and societal perspective, respectively, corresponding to approximately 11% of GDP per capita. OWSA showed that both strategies remained very cost-effective at a willingness-to-pay threshold of 1xGDP. PSA estimated probabilities of cost-effectiveness of 99.7% (routine and catch-up vs. routine) and 99.2% (routine vs. no vaccination). The multi-strategy cost-effectiveness acceptability curve identified the combined routine and catch-up campaign as the optimal strategy. Introducing TCV into Indonesia's NIP is projected to be very cost-effective. A routine-only program requires a lower budget, but adding a catch-up campaign is an optimal strategy with greater public health impact while remaining very cost-effective. Gates Foundation grants to Murdoch Children's Research Institute in collaboration with Universitas Gadjah Mada [ref. no. INV-003867] and to TyVAC 2.0 [ref. no. INV-030857].
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