Paratyphoid fever is an enteric fever syndrome caused by human-adapted Salmonella enterica serovars Paratyphi A, B, and C.
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name: Paratyphoid Fever
creation_date: '2026-05-08T13:18:55Z'
updated_date: '2026-05-08T14:35:00Z'
category: Infectious Disease
description: >-
Paratyphoid fever is an enteric fever syndrome caused by human-adapted
Salmonella enterica serovars Paratyphi A, B, and C.
disease_term:
preferred_term: paratyphoid fever
term:
id: MONDO:0018626
label: paratyphoid fever
parents:
- Bacterial Infection
- Enteric fever
synonyms:
- Paratyphoid
- Enteric fever due to Salmonella Paratyphi
infectious_agent:
- name: Salmonella enterica serovar Paratyphi
description: >-
Salmonella enterica serovars Paratyphi A, B, and C are Gram-negative
typhoidal Salmonella that cause paratyphoid enteric fever.
has_subtypes:
- name: Salmonella enterica subsp. enterica serovar Paratyphi A
- name: Salmonella enterica subsp. enterica serovar Paratyphi B
- name: Salmonella enterica subsp. enterica serovar Paratyphi C
evidence:
- reference: DOI:10.25259/ijmr_1382_2024
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Enteric fever is caused by the infection of Gram-negative bacteria, Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B and C, through contaminated food and water."
explanation: The review identifies S. Paratyphi A, B, and C as causal agents of enteric fever transmitted through contaminated food and water.
transmission:
- name: Fecal-oral food and water transmission
description: >-
Transmission occurs through ingestion of food or water contaminated with
typhoidal Salmonella from human sources.
evidence:
- reference: DOI:10.25259/ijmr_1382_2024
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Enteric fever is caused by the infection of Gram-negative bacteria, Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B and C, through contaminated food and water."
explanation: The citation directly supports contaminated food and water as the route of paratyphoid transmission.
environmental:
- name: Contaminated food and water exposure
description: >-
Exposure to contaminated food and water is the core environmental risk
context for paratyphoid fever.
presence: Present
evidence:
- reference: DOI:10.25259/ijmr_1382_2024
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Enteric fever is caused by the infection of Gram-negative bacteria, Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B and C, through contaminated food and water."
explanation: The reference ties enteric fever due to S. Paratyphi to contaminated food and water exposure.
pathophysiology:
- name: Salmonella epithelial invasion
description: >-
Salmonella pathogenicity island virulence factors support adhesion and
invasion of the intestinal mucosa after fecal-oral exposure.
cell_types:
- preferred_term: intestinal epithelial cell
term:
id: CL:0002563
label: intestinal epithelial cell
locations:
- preferred_term: small intestine
term:
id: UBERON:0002108
label: small intestine
biological_processes:
- preferred_term: symbiont entry into host cell
term:
id: GO:0046718
label: symbiont entry into host cell
evidence:
- reference: DOI:10.1128/ecosalplus.esp-0001-2023
supports: SUPPORT
evidence_source: OTHER
snippet: "Salmonella pathogenicity islands (SPIs), which are scattered throughout different Salmonella genomes and encode factors essential for adhesion, invasion, survival, and replication within the host."
explanation: The Salmonella infection biology review supports SPI-associated adhesion and invasion as an early host-entry mechanism.
downstream:
- target: Salmonella-containing vacuole survival and replication
description: After host-cell entry, Salmonella can persist and replicate intracellularly.
- name: Salmonella-containing vacuole survival and replication
description: >-
After invasion, Salmonella virulence systems support intracellular survival
and replication within host cells, including macrophage-associated niches.
cell_types:
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
cellular_components:
- preferred_term: Salmonella-containing vacuole
term:
id: GO:0020003
label: symbiont-containing vacuole
biological_processes:
- preferred_term: development of symbiont in host
term:
id: GO:0044114
label: development of symbiont in host
evidence:
- reference: DOI:10.1128/ecosalplus.esp-0001-2023
supports: SUPPORT
evidence_source: OTHER
snippet: "Salmonella pathogenicity islands (SPIs), which are scattered throughout different Salmonella genomes and encode factors essential for adhesion, invasion, survival, and replication within the host."
explanation: The same EcoSal Plus abstract explicitly supports Salmonella survival and replication within the host; the SCV label captures the established intracellular niche without adding unsupported wording to the quote.
downstream:
- target: Salmonella immune evasion
description: Intracellular persistence is reinforced by virulence factors that evade host immune responses.
- target: Typhoidal Salmonella bacteremia
description: Intracellular survival and replication support invasive disease and blood culture-positive enteric fever.
- name: Salmonella immune evasion
description: >-
Salmonella virulence determinants include genes that contribute to immune
system evasion during pathogenesis.
biological_processes:
- preferred_term: symbiont-mediated evasion of host immune response
term:
id: GO:0042783
label: symbiont-mediated evasion of host immune response
evidence:
- reference: DOI:10.1128/ecosalplus.esp-0001-2023
supports: SUPPORT
evidence_source: OTHER
snippet: "Plasmids can also carry various genes that contribute to Salmonella pathogenicity. For example, strains from several serovars associated with significant human disease, including Choleraesuis, Dublin, Enteritidis, Newport, and Typhimurium, can carry virulence plasmids with genes contributing to attachment, immune system evasion, and other roles."
explanation: The cached abstract supports Salmonella immune-system evasion generally; it does not provide exact abstract text for Vi capsule, complement, NF-kB, MAPK, or JNK mechanisms, so this node is limited to the supported language.
downstream:
- target: Typhoidal Salmonella bacteremia
description: Immune evasion can facilitate invasive Salmonella infection and systemic bacteremia.
- name: Typhoidal Salmonella bacteremia
description: >-
After invasive infection, S. Paratyphi can be recovered from blood cultures,
producing bacteremia as part of enteric fever.
cell_types:
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
locations:
- preferred_term: blood
term:
id: UBERON:0000178
label: blood
biological_processes:
- preferred_term: response to bacterium
term:
id: GO:0009617
label: response to bacterium
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The main objective of this study is to determine the prevalence and clinical presentation of Salmonella Typhi and Paratyphi bacteremia in cases of suspected enteric fever, and their antimicrobial-resistance pattern."
explanation: The clinical cohort frames S. Paratyphi bacteremia as a central manifestation of suspected enteric fever.
downstream:
- target: Multidrug and extensively drug-resistant Paratyphi B
description: Blood culture-positive isolates can be assessed for clinically relevant antimicrobial-resistance mechanisms.
- name: Multidrug and extensively drug-resistant Paratyphi B
description: >-
Mobile resistance elements can drive treatment-modifying antimicrobial
resistance in S. Paratyphi B, including ramAp-mediated AcrAB-TolC efflux
activation in XDR strains.
biological_processes:
- preferred_term: response to antibiotic
term:
id: GO:0046677
label: response to antibiotic
evidence:
- reference: DOI:10.3390/antibiotics13060519
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Notably, these four plasmids carried the ramAp gene responsible for multiple antibiotic resistance by regulating the AcrAB-TolC pump, predominantly originating from China."
explanation: The genomic analysis supports plasmid-borne ramAp and efflux regulation as a mechanism for resistance in XDR S. Paratyphi B.
phenotypes:
- name: Fever
category: Constitutional
frequency: VERY_FREQUENT
description: Fever is a predominant manifestation in culture-confirmed enteric fever caused by typhoidal Salmonella.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Predominant clinical features included fever 100% (n = 424), vomiting/nausea 66.98% (n = 284), abdominal pain 68.86% (n = 291), and diarrhea 67.92% (n = 288)."
explanation: The cohort reports fever in all confirmed typhoidal Salmonella cases, including S. Paratyphi A and B isolates.
- name: Nausea and vomiting
category: Gastrointestinal
frequency: FREQUENT
description: Nausea or vomiting commonly accompanies enteric fever.
phenotype_term:
preferred_term: Nausea and vomiting
term:
id: HP:0002017
label: Nausea and vomiting
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Predominant clinical features included fever 100% (n = 424), vomiting/nausea 66.98% (n = 284), abdominal pain 68.86% (n = 291), and diarrhea 67.92% (n = 288)."
explanation: The clinical cohort reports vomiting/nausea among predominant features in confirmed typhoidal Salmonella infection.
- name: Abdominal pain
category: Gastrointestinal
frequency: FREQUENT
description: Abdominal pain is a common gastrointestinal manifestation.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Predominant clinical features included fever 100% (n = 424), vomiting/nausea 66.98% (n = 284), abdominal pain 68.86% (n = 291), and diarrhea 67.92% (n = 288)."
explanation: The cohort reports abdominal pain among predominant clinical features.
- name: Diarrhea
category: Gastrointestinal
frequency: FREQUENT
description: Diarrhea is a frequent gastrointestinal manifestation.
phenotype_term:
preferred_term: Diarrhea
term:
id: HP:0002014
label: Diarrhea
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Predominant clinical features included fever 100% (n = 424), vomiting/nausea 66.98% (n = 284), abdominal pain 68.86% (n = 291), and diarrhea 67.92% (n = 288)."
explanation: The cohort reports diarrhea among predominant clinical features.
- name: Bacteremia
category: Infectious
description: Viable Salmonella Paratyphi in blood is the microbiologic syndrome captured by blood culture-positive enteric fever.
phenotype_term:
preferred_term: Bacteremia
term:
id: HP:0031864
label: Bacteremia
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The main objective of this study is to determine the prevalence and clinical presentation of Salmonella Typhi and Paratyphi bacteremia in cases of suspected enteric fever, and their antimicrobial-resistance pattern."
explanation: The reference explicitly identifies Salmonella Paratyphi bacteremia in suspected enteric fever cases.
- name: Coated tongue
category: Gastrointestinal
frequency: FREQUENT
description: Coated tongue was reported in over one-third of patients with culture-confirmed typhoidal Salmonella enteric fever.
phenotype_term:
preferred_term: Coated tongue
term:
id: HP:0000157
label: Abnormality of the tongue
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Typical features, i.e., rash, were noticed in only 2.59% (n = 11) of cases, whereas coated tongue was observed in 37.73% (n = 160) of patients."
explanation: HPO lacks a specific coated-tongue term in the local adapter search, so the phenotype uses the conservative parent term Abnormality of the tongue while preserving the more specific preferred_term and exact clinical quote.
diagnosis:
- name: Blood culture and serotyping
description: >-
Blood culture with organism identification and serotyping is important for
confirming suspected enteric fever and distinguishing S. Paratyphi from S.
Typhi.
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Among the total bacteremia cases, almost half were due to typhoidal Salmonella, which highlights the importance of blood culture for all suspected enteric fever cases."
explanation: The study conclusion supports blood culture for suspected enteric fever diagnosis.
- name: Blood qPCR for Salmonella virulence genes
description: >-
qPCR assays targeting Salmonella virulence genes such as Inv A and ttr can
supplement culture-based diagnosis, especially when culture sensitivity is
limited.
evidence:
- reference: DOI:10.1186/s12866-025-04127-9
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The enriched blood-based ttr and Inv A qPCR method is a promising rapid tool for diagnosing typhoid fever, offering high sensitivity, specificity, accuracy and unaffected by antibiotic intake."
explanation: Although evaluated for typhoid fever, the assay targets S. enterica genes and supports molecular diagnosis of typhoidal Salmonella infections.
treatments:
- name: Antibiotic therapy guided by susceptibility testing
description: >-
Antibiotic therapy is required for paratyphoid fever, but empiric choices
should account for local resistance patterns and susceptibility results.
treatment_term:
preferred_term: antibiotic therapy
term:
id: NCIT:C15620
label: Antibiotic Therapy
target_mechanisms:
- target: Multidrug and extensively drug-resistant Paratyphi B
treatment_effect: MODULATES
description: Susceptibility-guided antibiotic selection accounts for resistance mechanisms that modify effective therapy.
evidence:
- reference: DOI:10.3390/tropicalmed10040108
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Empiric ciprofloxacin should be avoided due to persistently high resistance rates."
explanation: The typhoidal Salmonella bacteremia cohort supports avoiding empiric ciprofloxacin where resistance is high.
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "No resistance was observed for ceftriaxone or carbapenems."
explanation: The clinical cohort supports preserved activity of ceftriaxone and carbapenems in that setting.
- name: Fluid replacement therapy
description: >-
Fluid replacement may be needed as supportive care when diarrhea, vomiting,
or poor intake cause dehydration risk.
treatment_term:
preferred_term: fluid replacement therapy
term:
id: MAXO:0000618
label: fluid replacement therapy
target_phenotypes:
- preferred_term: Diarrhea
term:
id: HP:0002014
label: Diarrhea
evidence:
- reference: PMID:41939541
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "Predominant clinical features included fever 100% (n = 424), vomiting/nausea 66.98% (n = 284), abdominal pain 68.86% (n = 291), and diarrhea 67.92% (n = 288)."
explanation: The citation supports common fluid-loss symptoms; the supportive treatment inference is standard but not directly tested in this study.
- name: Paratyphi A vaccine development
description: >-
No licensed S. Paratyphi A vaccine exists yet, but bivalent and conjugate
vaccine candidates are under active evaluation.
treatment_term:
preferred_term: vaccination
term:
id: MAXO:0001017
label: vaccination
evidence:
- reference: PMID:42044495
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Salmonella Paratyphi A is a major cause of paratyphoid fever. Despite growing global concern, knowledge of S. Paratyphi A immunity remains limited, and no licensed vaccine exists."
explanation: The human immunology study supports the current lack of a licensed Paratyphi A vaccine.
- reference: DOI:10.3390/vaccines12111272
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: "The serovar-specific O-antigen (O:2) was linked to the CRM197 carrier protein (O:2–CRM197) and a panel of conjugates differing for structural characteristics were compared in mice and rabbits."
explanation: The vaccine design paper supports preclinical development of an O:2-CRM197 conjugate vaccine candidate.
prevalence:
- population: South Delhi suspected enteric fever patients
percentage: 16.74% of typhoidal Salmonella isolates were S. Paratyphi A and B in this cohort
evidence:
- reference: PMID:41939541
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Of these, 83.25% (n = 353) isolates were S. Typhi and 16.74% (n = 71) were S. Paratyphi A and B."
explanation: The cohort provides a local proportion of Paratyphi A/B among culture-confirmed typhoidal Salmonella isolates.
notes: >-
Falcon deep research found no human Mendelian genetic etiology for paratyphoid
fever; pathogen genotype and antimicrobial resistance determinants are modeled
under pathophysiology rather than the human genetic section. Falcon reported
no licensed Paratyphi A vaccine and no clinical trial NCT identifiers suitable
for direct inclusion in this entry.
datasets:
Paratyphoid fever is part of “enteric fever,” a clinically similar syndrome to typhoid fever, but caused by Salmonella enterica serovars Paratyphi A, Paratyphi B, or Paratyphi C (as opposed to typhoid fever caused by S. Typhi) (rahman2025comparativeepidemiologyof pages 1-2, chakraborty2024typhoid¶typhoid pages 1-2). A GBD-based analysis states that paratyphoid “shares similar clinical characteristics with typhoid fever but is usually milder with a shorter incubation period” (liu2025theglobalburden pages 1-2).
Commonly used terms include enteric fever (broader umbrella including typhoid + paratyphoid), and serovar-specific labels (e.g., “paratyphoid fever due to S. Paratyphi A”) (rahman2025comparativeepidemiologyof pages 1-2, chakraborty2024typhoid¶typhoid pages 1-2).
The evidence base combines (i) aggregated global burden modeling (GBD 1990–2021), (ii) prospective or surveillance cohorts (Dhaka 2018–2020 incidence), and (iii) hospital-based microbiology datasets and genomic surveillance (North Delhi pediatric isolates; Jiangsu genomic AMR study) (liu2025theglobalburden pages 1-2, rahman2025comparativeepidemiologyof pages 1-2, kumar2024antimicrobialsusceptibilityof pages 2-3, peng2024emergenceofrarely pages 1-2).
Paratyphoid fever is caused by infection with Salmonella enterica serovars Paratyphi A/B/C via contaminated food and water (fecal–oral transmission) (chakraborty2024typhoid¶typhoid pages 1-2, rahman2025comparativeepidemiologyof pages 1-2).
WASH-related exposures: Lack of safe drinking water and private toilets were associated with enteric fever risk in Dhaka surveillance (rahman2025comparativeepidemiologyof pages 1-2).
Travel exposure: In British Columbia (Fraser Health, 2018–2024), 96% of typhoidal Salmonella bacteremias were travel-associated, predominantly to South Asia (lo2025currentantimicrobialsusceptibility pages 2-4).
Host factors (broader Salmonella/enteric fever literature in retrieved corpus): Dose-dependence and host susceptibility factors such as gastric hypochlorhydria, age, and immunosuppression are highlighted in a 2024 prevention-focused review, relevant as modifiers of infection risk and severity (zizza2024foodborneinfectionsand pages 6-8).
Direct protective-factor evidence specific to paratyphoid (e.g., immune correlates conferring reduced acquisition risk) was not identified in the retrieved 2023–2025 corpus. Indirectly, prevention strategies (WASH and vaccination against S. Typhi) reduce overall enteric fever burden but typhoid vaccines do not reliably protect against paratyphoid (lo2025currentantimicrobialsusceptibility pages 7-8, jamil2025emergingantimicrobialresistance pages 7-9).
No robust human germline gene–environment interaction evidence specific to paratyphoid fever was identified in the retrieved sources.
Clinical presentation overlaps strongly with typhoid fever, requiring laboratory confirmation (rahman2025comparativeepidemiologyof pages 1-2). In a large Canadian cohort of typhoidal Salmonella bacteremia cases, fever (97.8%) and gastrointestinal symptoms (73.5%) were common, illustrating the nonspecific febrile–GI syndrome relevant to paratyphoid (lo2025currentantimicrobialsusceptibility pages 4-5).
Suggested HPO terms (examples) are provided in artifact-01; core concepts include fever and diarrhea, with broader systemic manifestations consistent with enteric fever.
Specific paratyphoid-focused lab abnormality frequencies were not extracted from the retrieved corpus. The general enteric fever literature and clinical series emphasize the need for microbiological confirmation and susceptibility testing (rahman2025comparativeepidemiologyof pages 1-2, lo2025currentantimicrobialsusceptibility pages 4-5).
Direct QoL instruments (EQ-5D/SF-36) data specific to paratyphoid were not identified in the retrieved sources.
Paratyphoid fever is an infectious disease; there are no human “causal genes” in the Mendelian sense.
Paratyphi A (Taiwan, 2001–2024 surveillance): 223 cases were reported; among 88 sequenced isolates, 76.1% were resistant to nalidixic acid and non-susceptible to ciprofloxacin, attributed to gyrA codon 83 mutations (S83F/S83Y). Domestically acquired infections became predominant after 2022, with genomic relatedness suggesting introduction from Indonesia (liao2025paratyphoidfeverand pages 1-7).
Paratyphi B (Jiangsu, China, 2013–2022): Among 27 isolates, predominant STs were ST42 (11), ST86 (10), and ST2814 (5). Four of five ST2814 isolates were XDR (peng2024emergenceofrarely pages 1-2). XDR was strongly linked to an IncHI2A plasmid carrying ramAp, which increased expression of AcrAB-TolC efflux genes and elevated MICs across multiple antibiotic classes (peng2024emergenceofrarely pages 11-12).
Transmission is strongly linked to contaminated food and water and poor sanitation (chakraborty2024typhoid¶typhoid pages 1-2, rahman2025comparativeepidemiologyof pages 1-2). Food safety and safe handling of foods/water are repeatedly highlighted as primary prevention measures, including in travel medicine contexts (lo2025currentantimicrobialsusceptibility pages 7-8, lo2025currentantimicrobialsusceptibility pages 4-5).
Pathogens: Salmonella enterica serovars Paratyphi A, B, C (rahman2025comparativeepidemiologyof pages 1-2, chakraborty2024typhoid¶typhoid pages 1-2).
1) Ingestion and intestinal entry: Contaminated food/water leads to intestinal exposure; invasion proceeds via epithelial interactions, including M-cell routes (jamil2025emergingantimicrobialresistance pages 3-5, ranjan2026salmonellainfectionsglobal pages 7-8). 2) Epithelial invasion (upstream): SPI-1–encoded Type III secretion system (T3SS-1) mediates “trigger” invasion by manipulating host actin (SipA/SipC/SopB/SopE/SopE2) (ranjan2026salmonellainfectionsglobal pages 7-8). 3) Intracellular survival and systemic spread (downstream): Following uptake, Salmonella establishes a Salmonella-containing vacuole (SCV) and uses SPI-2/T3SS-2 for intracellular survival/replication and dissemination (ranjan2026salmonellainfectionsglobal pages 7-8, jamil2025emergingantimicrobialresistance pages 3-5). 4) Immune modulation/evasion: Typhoidal Salmonella immune-evasion features include the Vi capsule (for certain serovars) that reduces complement/neutrophil recruitment and can target macrophages via DC-SIGN, plus SPI-encoded effectors that modulate NF-κB/MAPK/JNK and antigen presentation (han2024infectionbiologyof pages 32-34, ranjan2026salmonellainfectionsglobal pages 7-8). 5) AMR as a treatment-modifying mechanism: Plasmids and mobile elements drive acquisition of AMR; in XDR Paratyphi B, ramAp-mediated efflux upregulation is a key contributor to multi-class resistance (peng2024emergenceofrarely pages 11-12, punchihewagedon2024defensemechanismsof pages 1-2).
Suggested GO biological process concepts and relevant immune/epithelial cell types are summarized in artifact-01; key process themes include bacterial invasion, type III secretion, intracellular survival, and immune evasion (ranjan2026salmonellainfectionsglobal pages 7-8, jamil2025emergingantimicrobialresistance pages 3-5, han2024infectionbiologyof pages 32-34).
Primary involvement is gastrointestinal with systemic dissemination (liver, spleen, blood) implied by invasion and macrophage-associated spread; gallbladder involvement is relevant for chronic carriage (jamil2025emergingantimicrobialresistance pages 3-5, jamil2025emergingantimicrobialresistance pages 9-11). Suggested UBERON mappings are provided in artifact-01.
Paratyphoid typically presents as an acute febrile illness; relative to typhoid, paratyphoid is described as often milder with shorter incubation (liu2025theglobalburden pages 1-2). Detailed stage models specific to paratyphoid were not identified in the retrieved sources.
Urban Dhaka, Bangladesh (2018–2020): incidence for paratyphoid was 27/100,000 person-years (95% CI 23–32), compared with typhoid 216/100,000 person-years (95% CI 198–236), with highest incidence in children age 2–4 (rahman2025comparativeepidemiologyof pages 1-2).
GBD 1990–2021 trend: global paratyphoid new cases decreased 73.15% and deaths decreased 65.44% (liu2025theglobalburden pages 1-2).
The burden remains concentrated in South Asia (including Pakistan, India, Nepal for paratyphoid mortality/DALYs in GBD) (liu2025theglobalburden pages 1-2).
Culture remains the diagnostic gold standard but sensitivity is limited and performance varies by specimen type and timing (sam2024diagnosticperformanceof pages 1-2, sam2024diagnosticperformanceof pages 2-4). In Ghana (2022–2023 sampling; published 2024), recovery from stool (14.7%) greatly exceeded blood (1.6%) in a clinically suspected cohort, consistent with shedding dynamics (sam2024diagnosticperformanceof pages 1-2).
In Egypt (published 2025), blood-based qPCR targeting ttr and invA showed far higher positivity than routine cultures: enriched blood qPCR positivity 90% (ttr) and 85% (invA) vs blood culture 48% and stool culture 32% (elaskary2025validationofstool pages 1-2). Compared with enriched qPCR as reference, direct blood qPCR had sensitivity 91.1% (ttr) and 94.1% (invA), with 100% specificity reported in both comparisons (elaskary2025validationofstool pages 4-5).
Typhidot performed poorly in the Ghana study: sensitivity/specificity vs culture 35%/45%, and vs PCR 61%/53%, implying risk of misdiagnosis and inappropriate antibiotic use in endemic settings if used alone (sam2024diagnosticperformanceof pages 1-2).
Direct abstract-supported quote (Typhidot performance): The Ghana study concludes a “sub-optimal performance of the Typhidot RDT… with a higher chance for misdiagnosis and misapplication of antibiotics” (sam2024diagnosticperformanceof pages 1-2).
In a large Canadian cohort (2018–2024), outcomes were favorable with effective care: 0% 30-day mortality, 97% clinical cure within 30 days, 3% relapse within 30 days, and median hospitalization 1 day (IQR 1–4) (lo2025currentantimicrobialsusceptibility pages 5-7). Complications included sepsis/septic shock and rare intestinal perforation, indicating potential severity even in high-resource settings (lo2025currentantimicrobialsusceptibility pages 4-5).
Modern management is dominated by AMR constraints, especially reduced fluoroquinolone susceptibility. In British Columbia, ciprofloxacin resistance was 96% in 2024 and the authors recommend avoiding empiric ciprofloxacin; ceftriaxone remained ~96–100% susceptible for Typhi and 100% for Paratyphi across years, and azithromycin susceptibility was high with rare nonsusceptible isolates (lo2025currentantimicrobialsusceptibility pages 1-2, lo2025currentantimicrobialsusceptibility pages 5-7). Median effective antibiotic duration was 12 days (IQR 10–14) (lo2025currentantimicrobialsusceptibility pages 4-5).
In Bangladesh surveillance, MDR was far less common in Paratyphi A (0.8%) than Typhi (20.2%), but fluoroquinolone non-susceptibility and rising azithromycin resistance were noted as threats in some settings (rahman2025comparativeepidemiologyof pages 1-2).
Key action ontology suggestions include blood culture, PCR/qPCR, antibiotic therapy, vaccination, and WASH interventions (artifact-01) (lo2025currentantimicrobialsusceptibility pages 1-2, elaskary2025validationofstool pages 1-2, rahman2025comparativeepidemiologyof pages 1-2).
Primary prevention is based on WASH and safe food/water handling (chakraborty2024typhoid¶typhoid pages 1-2, rahman2025comparativeepidemiologyof pages 1-2). Travel-focused prevention stresses pre-travel counselling, food/water precautions, and typhoid vaccination (lo2025currentantimicrobialsusceptibility pages 7-8). However, typhoid vaccines “do not protect against paratyphoid” (lo2025currentantimicrobialsusceptibility pages 7-8). This gap is a principal driver of current paratyphoid vaccine development (alfini2024designofa pages 1-2, chakraborty2024typhoid¶typhoid pages 4-5).
Typhoidal Salmonella (including Paratyphi) are described as human-restricted (host range confined to humans), implying no animal reservoir for paratyphoid fever transmission in the same way as non-typhoidal Salmonella (nazir2025combattingsalmonellaa pages 2-3, ranjan2026salmonellainfectionsglobal pages 19-20). This contrasts with NTS reservoirs in domestic and wild animals (zizza2024foodborneinfectionsand pages 6-8).
A key constraint in paratyphoid research is the human restriction of typhoidal Salmonella. Nevertheless, multiple experimental systems are used:
Rodent models (adapted): A 2024 review describes a physiological mouse model enabling oral S. Typhi infection in wild-type BALB/c mice by co-administering iron (0.32 mg/g body weight) with desferrioxamine (25 mg/kg), achieving liver/spleen/bone marrow involvement similar to humans (chakraborty2024typhoid¶typhoid pages 6-7). This approach is used for studying pathogenesis and vaccine immunogenicity, and informs paratyphoid modeling strategies.
In vitro models: Human intestinal epithelial cell cultures and macrophage/immune-cell assays are widely used to dissect SPI-1 invasion, SCV survival, and immune modulation by effectors such as SteE/SteD/SpvD (ranjan2026salmonellainfectionsglobal pages 7-8).
Human studies: Live-attenuated Paratyphi A candidate CVD 1902 (ΔguaBA ΔclpX) has been evaluated in Phase 1 humans (single dose ~10^9–10^10 CFU) and elicited CD4+ and CD8+ T-cell responses (bansal2024geneticengineeringof pages 3-4).
1) Emergence of XDR Paratyphi B with mechanistic resolution (2024): East China genomic analysis identifies plasmid-borne ramAp as a driver of broad resistance via AcrAB-TolC efflux upregulation, underscoring One Health surveillance needs (peng2024emergenceofrarely pages 11-12).
2) Paratyphi A vaccine R&D maturation (2024): A rational-design glycoconjugate study shows immunogenicity depends on O:2 size, saccharide:protein ratio, cross-linking, and O-acetylation, guiding product development (alfini2024designofa pages 1-2). Table/Figure evidence from this paper is shown in the retrieved cropped table/figure regions (alfini2024designofa media c76829e9, alfini2024designofa media 5fca7cec, alfini2024designofa media 6729a2bb).
3) Diagnostics reality-check in endemic settings (2024): Typhidot RDT performed poorly versus culture and PCR in Ghana, supporting policy emphasis on validated diagnostics to reduce misapplication of antibiotics (sam2024diagnosticperformanceof pages 1-2).
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(alfini2024designofa media 5fca7cec): Renzo Alfini, Martina Carducci, Luisa Massai, Daniele De Simone, Marco Mariti, Omar Rossi, Simona Rondini, Francesca Micoli, and Carlo Giannelli. Design of a glycoconjugate vaccine against salmonella paratyphi a. Vaccines, 12:1272, Nov 2024. URL: https://doi.org/10.3390/vaccines12111272, doi:10.3390/vaccines12111272. This article has 10 citations.
(alfini2024designofa media 6729a2bb): Renzo Alfini, Martina Carducci, Luisa Massai, Daniele De Simone, Marco Mariti, Omar Rossi, Simona Rondini, Francesca Micoli, and Carlo Giannelli. Design of a glycoconjugate vaccine against salmonella paratyphi a. Vaccines, 12:1272, Nov 2024. URL: https://doi.org/10.3390/vaccines12111272, doi:10.3390/vaccines12111272. This article has 10 citations.