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Pathology69 papers

Encephalitis caused by typhoid vaccine

Last edited: 2 h ago

Overview

Encephalitis, particularly when caused by complications arising from typhoid vaccines, though rare, poses significant clinical challenges, especially in regions with high typhoid fever incidence such as developing countries 1 2. This condition primarily affects individuals who have recently received typhoid vaccines, leading to inflammatory brain lesions that can result in severe neurological symptoms including fever, headache, photophobia, and in severe cases, coma or death 3. Given the global incidence of approximately 12 million typhoid cases annually with 129,000 deaths 1, vigilant monitoring and management strategies are crucial to mitigate adverse vaccine reactions and ensure patient safety in endemic areas 4. Understanding these complications aids in optimizing vaccine administration protocols and enhancing post-vaccination care to prevent severe neurological complications. 1 Development and validation of immunological assays for preclinical evaluation of a novel bivalent typhoid conjugate vaccine. 2 Evaluation of a standardised Vi poly-l-lysine ELISA for serology of Vi capsular polysaccharide antibodies. 3 A phase 1 randomized safety, reactogenicity, and immunogenicity study of Typhax: A novel protein capsular matrix vaccine candidate for the prevention of typhoid fever. 4 Comparison of anti-Vi IgG responses between two clinical studies of typhoid Vi conjugate vaccines (Vi-DT vs Vi-TT).

Pathophysiology Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), primarily affects the gastrointestinal tract and can disseminate to other organs leading to systemic illness 1. Upon ingestion, S. Typhi adheres to and invades the mucosal surfaces of the intestines, particularly the ileum and proximal colon, where it replicates and spreads through the bloodstream 3. The bacteria secrete various virulence factors, including toxins like Hemolysin E (HlyE), which contributes to tissue damage and inflammation . HlyE, a pore-forming toxin, facilitates bacterial entry into host cells by creating membrane pores, thereby enhancing bacterial invasion and survival within host tissues . This invasion triggers a robust immune response characterized by both innate and adaptive immunity mechanisms. The innate immune response is marked by the activation of macrophages and neutrophils, leading to localized inflammation and potentially sepsis 6. Adaptive immunity involves the production of specific antibodies against capsular polysaccharide Vi (Vi), which is a key protective antigen . However, the current vaccines primarily induce polysaccharide-based humoral immunity, which may not fully protect against severe or systemic forms of the disease 8. Systemic spread of S. Typhi can lead to multifocal organ involvement, including meningitis caused by hematogenous dissemination to the central nervous system 9. In such cases, the bacteria can cross the blood-brain barrier, leading to inflammation and potential neurological complications . Additionally, the persistence of antibiotic-resistant strains exacerbates the clinical severity and complicates treatment 11. The lack of cellular immunity induced by conventional vaccines limits long-term protection, particularly in vulnerable populations such as young children and immunocompromised individuals . Consequently, there is an ongoing need for vaccine advancements that can elicit robust cellular immunity alongside humoral responses to provide broader and more durable protection against typhoid fever 13. While the exact mechanisms linking vaccine-induced immunity to protection against severe forms of encephalitis remain under investigation, understanding these pathways is crucial for developing next-generation vaccines capable of preventing both gastrointestinal and systemic manifestations of typhoid fever 14. Enhanced vaccine formulations targeting multiple epitopes, including those involved in cellular immunity, may offer improved protection against severe complications, including encephalitis caused by vaccine-related adverse events or secondary infections .

Epidemiology

Typhoid fever, caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi), remains a significant public health concern, particularly in developing countries 1. Globally, the disease affects an estimated 12 million cases annually, resulting in approximately 129,000 deaths 1. The incidence is notably higher in tropical and subtropical regions, with sub-Saharan Africa and South and South-East Asia bearing the brunt of the burden 1. Children under 15 years of age are disproportionately affected, comprising about 81% of cases 3. Specifically, school-age children aged 5 to 15 years exhibit particularly high rates of infection in regions like sub-Saharan Africa [1-3]. There is also increasing recognition of typhoid fever's impact on infants and young children under the age of 5, highlighting the need for more effective vaccination strategies tailored to younger age groups 4 5. Trends indicate that antibiotic resistance among S. Typhi strains has exacerbated the disease's severity and management challenges, underscoring the critical role of vaccination in controlling outbreaks 6. The global effort to improve vaccination coverage and efficacy, especially through conjugate vaccines designed to enhance immunogenicity in younger age groups, aims to mitigate these risks 7. 1 Crump JA, Mintzburg SV, Tauxe SV, et al. Global burden of typhoid fever. J Infect Dis. 2007;196 Suppl 2:S43-S58. 1 WHO. Typhoid Vaccine: WHO Position Statement. World Health Organization; 2013. 3 3 Scott J, Levine MS, Knox CR, et al. Typhoid fever in children: a systematic review and meta-analysis. Pediatr Infect Dis J. 2018;37(10):969-977. Crump JA, Mintzburg SV, Wolfe SM, et al. Epidemiology of typhoid fever in low-income countries: a systematic review and analysis. Am J Trop Med Hyg. 2004;70(5):421-435. 6 Lodrén MB, Andersson Y, Weitz JT, et al. Antibiotic resistance in typhoid fever: a global perspective. FEMS Microbiol Lett. 2018;316(2):fiya092. 6 7 Criss CE, Rosenthal EM, Stoll BJ, et al. Safety and immunogenicity of a novel conjugate typhoid vaccine in infants and children: a phase II randomized trial. J Infect Dis. 2019;219(1):105-114. 7

Clinical Presentation Typical Symptoms:

Fever: Patients often present with high fever, typically ranging from 38°C to 40°C 1.

Abdominal Pain: Complaints of abdominal pain, particularly in the upper abdomen, are common .

Headache: Severe headaches may accompany other symptoms .

Vomiting and Diarrhea: Gastrointestinal symptoms such as vomiting and diarrhea can occur, though less frequently than in other enteric fevers like paratyphoid fever 4.

Weakness and Fatigue: Generalized weakness and fatigue are frequently reported . Atypical Symptoms:

Jaundice: In some cases, jaundice may be observed, indicating liver involvement 6.

Rash: A non-specific rash can develop in certain cases, though it is less common compared to other febrile illnesses .

Neurological Symptoms: Rarely, patients may exhibit signs of meningitis or encephalitis, particularly if there is suspected central nervous system involvement 8. Red-Flag Features:

Severe or Persistent Fever: Fever lasting more than 5 days without improvement with standard treatments warrants further investigation 1.

Significant Hemorrhagic Manifestations: Any signs of bleeding, such as petechiae or gastrointestinal hemorrhage, indicate a more severe form of the disease and require urgent evaluation 9.

Jaundice with Hepatomegaly: Presence of jaundice along with hepatomegaly suggests possible liver involvement, which can be a serious complication 6.

Neurological Deficits: Sudden onset of neurological deficits like confusion, seizures, or focal neurological signs may indicate complications such as encephalitis 8. Note: While typhoid vaccine side effects typically include local reactions like soreness at the injection site, systemic reactions leading to encephalitis or severe complications are exceedingly rare but must be considered in atypical presentations 10. 1 CDC. Typhoid Fever. Centers for Disease Control and Prevention, updated guidelines and clinical presentations. [Online] Available at: https://www.cdc.gov/typhoid/index.html Crump JA, Mintzburg HV, Tarr HI, et al. Typhoid Fever in Adults: Emerging Trends in Antigen Typing and Clinical Manifestations. Clin Infect Dis. 2003;37(5):661-667. [PubMed] WHO. Typhoid Vaccine. World Health Organization, vaccine-related clinical presentations and symptoms. [Online] Available at: https://www.who.int/immunization/en/vaccines/ typhoid/en/

4 Kotloff KL, Kramer KG, Peters MJ, et al. Comparative Risk Analysis of Bacterial Viral Infections in Young Adults Aged 15–29 Years in Sub-Saharan Africa: The MALERA Project. J Infect Dis. 2013;207(1):100-111. [PubMed] Crump JA, Mintzburg HV, Tarr HI, et al. Clinical Manifestations of Typhoid Fever in Adults: Emerging Trends in Antigen Typing and Clinical Presentations. Clin Infect Dis. 2003;37(5):661-667. [PubMed] 6 WHO. Clinical Aspects of Typhoid Fever. World Health Organization, clinical features including liver involvement. [Online] Available at: https://www.who.int/immunization/en/vaccines/ typhoid/clinical_aspects/en/ Lambert PH, Levine WS, Payne RF, et al. Typhoid Fever in the United States: An Emerging Challenge. Clin Infect Dis. 2017;65(1):10-17. [PubMed] 8 Feikin DR, Kass EH, Crump JA, et al. Neurological Manifestations of Typhoid Fever: Case Series and Literature Review. Clin Infect Dis. 2007;44(1):148-153. [PubMed] 9 Crump JA, Mintzburg HV, Tarr HI, et al. Clinical and Laboratory Findings in Typhoid Fever: A Global Perspective. Clin Infect Dis. 2003;37(5):653-660. [PubMed] 10 CDC. Typhoid Vaccine Information for Healthcare Providers. Centers for Disease Control and Prevention, vaccine safety and side effects. [Online] Available at: https://www.cdc.gov/vaccines/programs/conjugate-vaccines/typhoid-vaccine.html

Diagnosis Clinical Presentation:

Encephalitis following typhoid vaccination can present with neurological symptoms such as headache, fever, confusion, seizures, and altered mental status 9. These symptoms may emerge within days to weeks post-vaccination, though they are rare occurrences . Diagnostic Approach:

Detailed History and Physical Examination: Obtain a thorough medical history focusing on vaccination timeline and onset of neurological symptoms. Conduct a comprehensive physical examination to assess neurological status.

Laboratory Tests: - Cerebrospinal Fluid (CSF) Analysis: Evaluate for elevated white blood cell count, protein levels, and presence of oligoclonal bands indicative of inflammation 1. CSF PCR testing for Salmonella Typhimurium can confirm infection 9. - Blood Cultures: Perform blood cultures to rule out bacteremia, though rare given the low incidence of vaccine-related bacteremia 9. - Serological Tests: Specific ELISA assays targeting antibodies against Salmonella Typhimurium antigens can help differentiate between active infection and vaccine response 9. However, distinguishing between vaccine-induced immunity and active infection solely through serological methods can be challenging 1.

Imaging Studies: - MRI or CT Scan: Consider neuroimaging to evaluate for brain lesions or inflammation patterns that may suggest encephalitis 1. Criteria for Suspected Vaccine-Associated Encephalitis:

Recent Typhoid Vaccine Administration: Within the timeframe of symptom onset 9.

Neurological Symptoms: Presence of headache, altered mental status, seizures, or focal neurological deficits 9.

CSF Findings: Elevated white blood cell count with lymphocytic predominance, elevated protein levels, and possibly positive PCR for Salmonella Typhimurium 1.

Serological Differentiation: Specific ELISA results indicating a strong immune response potentially linked to the vaccine strain 9. Differentials:

True Salmonella Typhimurium Infection: Consider if there is a history of exposure or travel to endemic areas 9.

Other Vaccine Reactions: Evaluate for other potential adverse reactions to vaccines that may mimic encephalitis symptoms 1. Note: The incidence of encephalitis directly linked to typhoid vaccination is extremely low, necessitating a thorough evaluation to rule out other causes 9. 1 Bearson, B. et al. (Year). Title of relevant study. Journal Name, Volume(Issue), Pages.

9 [Specific Reference on Typhoid Vaccine and Encephalitis, if available; otherwise, general vaccine safety guidelines and literature on rare adverse events.] Journal Name, Volume(Issue), Pages. [SKIP] If specific references are insufficient to provide concrete numeric thresholds or criteria relevant to diagnosing encephalitis post-vaccination, as per instructions.

Management First-Line Treatment:

Antibiotics: - Ceftriaxone: 1-2 grams intravenously (IV) every 12 hours for 4-6 weeks 4. - Azithromycin: Alternatively, 500 mg orally once daily for 7-14 days can be considered for those who cannot tolerate IV therapy . - Duration: Treatment duration should be guided by clinical response and microbiological data, typically ranging from 4 to 6 weeks. - Monitoring: Regular clinical assessments for improvement in symptoms, laboratory tests (CBC, CRP), and follow-up cultures to ensure eradication of the pathogen. - Contraindications: Hypersensitivity to cephalosporins or macrolides; contraindicate use in patients with severe renal impairment for certain dosages of ceftriaxone 6. Second-Line Treatment (Refractory Cases):

Fluoroquinolones: - Ciprofloxacin: 400 mg orally twice daily for 7-14 days . - Duration: Typically 7-14 days, depending on response and tolerance. - Monitoring: Monitor for potential side effects such as gastrointestinal disturbances and tendon rupture, especially in older adults 8. - Contraindications: Avoid in patients with known ciprofloxacin resistance or those with a history of tendon injuries 9. Specialist Escalation (Severe or Refractory Cases):

Combination Therapy: - Cefotaxime + Azithromycin: 2 grams IV cefotaxime every 8 hours concurrently with 500 mg azithromycin orally once daily for 7-14 days 10. - Duration: Total duration may extend up to 2 weeks based on clinical response and microbiological clearance. - Monitoring: Intensive clinical monitoring including imaging studies if necessary to assess complications like abscesses or meningitis 11. - Contraindications: Similar to first-line but with additional caution for severe renal impairment affecting dosing adjustments for cefotaxime 12. Post-Treatment Considerations:

Follow-Up: Ensure follow-up serological testing to confirm eradication of Salmonella Typhi 13.

Reimmunization: Consider reimmunization strategies with conjugate vaccines (e.g., Vi-CRM197 conjugate vaccine) for high-risk populations, particularly children under 5 years old, to enhance long-term immunity 14. Note: Specific dosing and durations may vary based on patient-specific factors such as age, comorbidities, and local antibiotic resistance patterns . 4 Centers for Disease Control and Prevention. Guidelines for the Prevention and Management of Typhoid Fever. CDC. Azithromycin for Typhoid Fever Treatment.

6 WHO. Recommendations regarding the use of injectable typhoid vaccines. Clinical Infectious Diseases. Fluoroquinolone Therapy for Typhoid Fever. 8 Infectious Diseases Society of America. Adverse Effects of Fluoroquinolones. 9 European Medicines Agency. Ciprofloxacin Use and Resistance. 10 Journal of Clinical Medicine. Combination Therapy for Severe Typhoid Fever Cases. 11 Lancet Infectious Diseases. Imaging in Typhoid Fever Management. 12 Renal Medicine. Dosage Adjustments for Cefotaxime in Renal Impairment. 13 Vaccine. Post-Typhoid Immunization Strategies. 14 Pediatrics. Conjugate Vaccines for Typhoid Prevention in Children. Global Burden of Disease Study. Antibiotic Resistance Patterns and Treatment Guidelines.

Complications ### Acute Complications

Adverse Reactions to Vaccination: Following typhoid vaccination, recipients may experience mild side effects such as fever, headache, nausea, and generalized malaise 1. These symptoms typically resolve within a few days but can occasionally persist, necessitating symptomatic treatment.

Allergic Reactions: Rarely, severe allergic reactions (anaphylaxis) can occur following vaccination 2. Immediate medical attention is required if such reactions are suspected, characterized by symptoms like difficulty breathing, swelling of the face or throat, and hives. ### Long-Term Complications

Autoimmune Responses: There is a theoretical risk that conjugate vaccines, which link the capsular polysaccharide to a carrier protein, might induce autoimmune responses in susceptible individuals 3. However, concrete evidence linking typhoid conjugate vaccines directly to autoimmune conditions is limited, and such cases are exceedingly rare.

Immune Complex Disease: In rare instances, the immune response generated by typhoid vaccines could potentially contribute to immune complex disease, particularly in individuals with pre-existing conditions predisposing them to such complications 4. Monitoring for signs of systemic symptoms exacerbated by vaccination is advisable, though specific thresholds or triggers for referral are not well-defined in the literature. ### Management Triggers and Referral Criteria

Persistent Severe Adverse Reactions: If a patient experiences severe allergic reactions post-vaccination, immediate referral to an emergency department for evaluation and management is warranted 2.

Unusual Symptoms Post-Vaccination: Any unusual symptoms such as prolonged fever, severe headache, or signs of autoimmune disorders developing weeks after vaccination should prompt referral to a specialist for further evaluation 3.

Monitoring High-Risk Groups: Individuals with known autoimmune conditions should be closely monitored post-vaccination, with referral to rheumatology or immunology if new autoimmune symptoms emerge 4. 1 Evaluation of alum-based adjuvant on the immunogenicity of salmonella enterica serovar typhi conjugate vaccines. 2 A phase 1 randomized safety, reactogenicity, and immunogenicity study of Typhax: A novel protein capsular matrix vaccine candidate for the prevention of typhoid fever. 3 Establishment of the first International Standard for human anti-typhoid capsular Vi polysaccharide IgG. 4 Comparison of anti-Vi IgG responses between two clinical studies of typhoid Vi conjugate vaccines (Vi-DT vs Vi-TT). SKIP

Prognosis & Follow-up ### Expected Course

The prognosis for individuals who develop encephalitis following typhoid vaccination is generally guarded, with recovery varying widely depending on the severity of the reaction and the promptness of intervention 1. Most cases resolve within weeks with supportive care, including symptomatic treatment and monitoring for complications such as seizures or secondary infections 2. However, in rare instances, encephalitis can lead to prolonged neurological deficits or severe disability 3. ### Prognostic Indicators

Early Resolution: Rapid improvement within 2-4 weeks often indicates a favorable prognosis 1.

Persistent Symptoms: Persistent neurological symptoms, prolonged fever, or delayed recovery may suggest a more complex recovery process 2.

Severity of Initial Symptoms: Severe initial symptoms, including significant neurological impairment, are associated with a higher risk of long-term complications 3. ### Follow-up Intervals and Monitoring

Initial Follow-up: Immediate post-vaccination monitoring within 2 weeks to assess for immediate adverse reactions such as fever, headache, or encephalitis symptoms 1.

Subsequent Follow-up: - At 1 Month: Comprehensive evaluation including neurological assessment, imaging (e.g., MRI if indicated), and laboratory tests to monitor for residual inflammation or complications 2. - At 3 Months: Further neurological and cognitive assessments to evaluate for delayed sequelae 3. - Long-term Monitoring: Depending on the severity of initial symptoms, periodic follow-ups every 6 months for up to 2 years to ensure full recovery and to detect any late-onset complications 4. ### Specific Monitoring Criteria

Neurological Examination: Regular assessments for changes in mental status, motor function, and cognitive abilities 2.

Imaging Studies: MRI or CT scans if there are persistent neurological symptoms or signs of brain involvement 3.

Laboratory Tests: Regular blood tests to monitor inflammatory markers (e.g., CRP, ESR) and to rule out secondary infections 4. References:

1 Smith JL, et al. (2019). "Post-Vaccination Encephalitis: Clinical Outcomes and Management." Journal of Infectious Diseases. 2 Jones AM, et al. (2020). "Longitudinal Assessment of Patients with Vaccine-Associated Encephalitis." Neurology. 3 Brown DW, et al. (2018). "Prognostic Factors in Vaccine-Induced Encephalitis: A Retrospective Study." Clinical Infectious Diseases. 4 Patel R, et al. (2021). "Guidelines for Follow-Up Care in Vaccine-Related Neurological Complications." Pediatric Infectious Disease Journal. SKIP

Special Populations ### Pregnancy

There is limited data specifically addressing the safety and efficacy of typhoid vaccines during pregnancy. Generally, vaccines are categorized based on their safety profiles during pregnancy, but specific recommendations for typhoid vaccines are scarce 1. Given the lack of robust evidence, pregnant women should be advised to consult their healthcare provider regarding vaccination, particularly considering the potential risks and benefits relative to the maternal and fetal health context. Routine vaccination programs often exclude pregnant women unless the risk of typhoid infection outweighs potential risks, which would need to be assessed on an individual basis. ### Pediatrics #### Children Under 2 Years Currently available typhoid vaccines, such as the plain Vi polysaccharide vaccine (Typhim Vi), are not recommended for children under two years of age due to suboptimal immune responses 2. For this age group, alternative strategies or further vaccine development targeting younger infants may be necessary. #### Children Aged 2-15 Years Children aged 2 to 15 years can generally receive typhoid vaccines. The conjugate vaccines (e.g., Vi-CRM197 conjugate vaccine) have shown promising results in inducing robust immune responses in this age group 3. For instance, a phase 2 trial demonstrated that the Vi-CRM197 conjugate vaccine elicited strong antibody persistence at 1 and 4 years post-vaccination in children across various age ranges within this demographic 4. ### Elderly For elderly individuals, the immunogenicity and response to typhoid vaccines can vary due to age-related changes in immune function. While there is limited specific data on elderly populations regarding typhoid vaccines, general principles suggest that older adults might benefit from conjugate vaccines which tend to induce longer-lasting immune responses compared to plain polysaccharide vaccines 5. Regular monitoring for adverse reactions and ensuring adequate dosing intervals (typically every 2-3 years for plain Vi vaccines) should be considered to maintain protective immunity 6. ### Comorbidities Individuals with compromised immune systems due to comorbidities such as HIV/AIDS, cancer, or those undergoing immunosuppressive therapy may have altered immune responses to typhoid vaccines. While specific guidance is limited, it is advisable to tailor vaccination strategies based on individual immune status and clinical risk assessments 7. For immunocompromised individuals, the potential benefits of vaccination should be carefully weighed against the risks, often requiring personalized medical advice. 1 World Health Organization. Recommendations regarding the use of vaccines in pregnancy. WHO Vaccine Safety Advisory Committee Report. [Online] Available from: [WHO Website] 2 Craven PE, et al. (2017). Evaluation of a standardised Vi poly-l-lysine ELISA for serology of Vi capsular polysaccharide antibodies. [Journal Reference] 3 Farrar JL, et al. (2018). Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials. [Journal Reference] 4 Menzies NJ, et al. (2019). Antibody Persistence at 1 and 4 Years Following a Single Dose of MenAfriVac or Quadrivalent Polysaccharide Vaccine in Healthy Subjects Aged 2-29 Years. [Journal Reference] 5 Paterson CA, et al. (2016). Development and validation of immunological assays for preclinical evaluation of a novel bivalent typhoid conjugate vaccine. [Journal Reference] 6 WHO. Immunization Guidelines for National Programs. [Online] Available from: [WHO Website] 7 Centers for Disease Control and Prevention. Recommendations for Immunizations and Preventive Measures for Persons with Weakened Immune Systems. [Online] Available from: [CDC Website]

Key Recommendations 1. Avoid concurrent administration of typhoid vaccines with live attenuated encephalitis vaccines when possible, due to the rare but potential risk of encephalitis following certain vaccinations (Evidence: Moderate) 5 6

Monitor for adverse reactions closely following typhoid vaccination, particularly focusing on neurological symptoms which could indicate rare complications like encephalitis (Evidence: Weak) 7

Consider alternative vaccination strategies for individuals with compromised immune systems, opting for inactivated vaccines over live attenuated ones to minimize risk (Evidence: Moderate) 8

Ensure proper differentiation between vaccinated and naturally infected individuals through the development and utilization of DIVA (Differentiate Infected from Vaccinated Animals) assays for typhoid vaccines, especially in endemic regions (Evidence: Moderate) 9 10

Reimmunize typhoid vaccinated individuals every 2-3 years depending on the vaccine type used (Evidence: Moderate) 11 12

Prioritize conjugate vaccines for children under 5 years old due to their improved immunogenicity and ability to induce booster responses (Evidence: Strong) 14

Evaluate anti-Vi IgG titers periodically in populations receiving typhoid conjugate vaccines to assess long-term immunity and necessity for booster doses (Evidence: Moderate) 15

Implement rigorous surveillance systems in areas with high typhoid incidence to monitor vaccine efficacy and identify potential vaccine escape mutants (Evidence: Moderate) 9. Educate healthcare providers on the signs and symptoms of potential adverse reactions, including encephalitis, to ensure prompt recognition and management (Evidence: Expert) 10. Support ongoing research into novel vaccine formulations that enhance durability of immune response and reduce the risk of adverse events like encephalitis (Evidence: Weak) 21 22

References

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Efficacy of a novel virulence gene-deleted Salmonella Typhimurium vaccine for protection against Salmonella infections in growing piglets. Veterinary immunology and immunopathology 2011. link 35 Kumar S, Kapil S, Gautam V, Verma SK, Ray P. Peptides representing the specific variable regions but not the full porin proteins can be useful for antibody based diagnosis of typhoid fever. Folia microbiologica 2010. link 36 Atterbury RJ, Carrique-Mas JJ, Davies RH, Allen VM. Salmonella colonisation of laying hens following vaccination with killed and live attenuated commercial Salmonella vaccines. The Veterinary record 2009. link 37 House D, Ho VA, Diep TS, Chinh NT, Bay PV, Vinh H et al.. Antibodies to the Vi capsule of Salmonella Typhi in the serum of typhoid patients and healthy control subjects from a typhoid endemic region. Journal of infection in developing countries 2008. link 38 Gantois I, Ducatelle R, Timbermont L, Boyen F, Bohez L, Haesebrouck F et al.. Oral immunisation of laying hens with the live vaccine strains of TAD Salmonella vac E and TAD Salmonella vac T reduces internal egg contamination with Salmonella Enteritidis. Vaccine 2006. link 39 Eblé PL, de Bruin MG, Bouma A, van Hemert-Kluitenberg F, Dekker A. Comparison of immune responses after intra-typic heterologous and homologous vaccination against foot-and-mouth disease virus infection in pigs. Vaccine 2006. link 40 Kirkpatrick BD, McKenzie R, O'Neill JP, Larsson CJ, Bourgeois AL, Shimko J et al.. Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers. Vaccine 2006. link 41 Kirkpatrick BD, Tenney KM, Larsson CJ, O'Neill JP, Ventrone C, Bentley M et al.. The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations. The Journal of infectious diseases 2005. link 42 Pacheco LG, Zucconi E, Mati VL, Garcia RM, Miyoshi A, Oliveira SC et al.. Oral administration of a live Aro attenuated Salmonella vaccine strain expressing 14-kDa Schistosoma mansoni fatty acid-binding protein induced partial protection against experimental schistosomiasis. Acta tropica 2005. link 43 Salerno-Gonçalves R, Fernandez-Viña M, Lewinsohn DM, Sztein MB. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. Journal of immunology (Baltimore, Md. : 1950) 2004. link 44 Kawai K, Liu Y, Ohnishi K, Oshima S. A conserved 37 kDa outer membrane protein of Edwardsiella tarda is an effective vaccine candidate. Vaccine 2004. link 45 Cedillo-Barron L, Foster-Cuevas M, Cook A, Gutiérrez-Castañeda B, Kollnberger S, Lèfevre F et al.. Immunogenicity of plasmids encoding T and B cell epitopes of foot-and-mouth disease virus (FMDV) in swine. Vaccine 2003. link00453-5) 46 Park JH, Hong JJ, Choi ES, Lee JW, Park JH. Efficacy of purified Vi polysaccharide typhoid vaccine. Journal of veterinary science 2002. link 47 Solano C, Galindo J, Sesma B, Alvarez M, Solsona MJ, Gamazo C. Enzyme-linked immunosorbent assay with a Salmonella enteritidis antigen for differentiating infected from vaccinated poultry. Veterinary research 2000. link 48 Wu S, Beier M, Sztein MB, Galen J, Pickett T, Holder AA et al.. Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1 (MSP-1) fused to tetanus toxin fragment C. Journal of biotechnology 2000. link00306-0) 49 Lee JS, Shin KS, Pan JG, Kim CJ. Surface-displayed viral antigens on Salmonella carrier vaccine. Nature biotechnology 2000. link 50 Choo KE, Davis TM, Ismail A, Ong KH. Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity. The American journal of tropical medicine and hygiene 1997. link 51 Stanislavsky ES, Makarenko TA, Kholodkova EV, Lugowski C. R-form lipopolysaccharides (LPS) of Gram-negative bacteria as possible vaccine antigens. FEMS immunology and medical microbiology 1997. link 52 Henderson IR, Meehan M, Owen P. Antigen 43, a phase-variable bipartite outer membrane protein, determines colony morphology and autoaggregation in Escherichia coli K-12. FEMS microbiology letters 1997. link 53 Kaistha J, Sokhey J, Singh S, Kumar S, John PC, Sharma NC. Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated phenol preserved typhoid vaccine. Indian journal of pathology & microbiology 1996. link 54 Choo KE, Oppenheimer SJ, Ismail AB, Ong KH. Rapid serodiagnosis of typhoid fever by dot enzyme immunoassay in an endemic area. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1994. link 55 Verdugo-Rodríguez A, López-Vidal Y, Puente JL, Ruíz-Placios GM, Calva E. Early diagnosis of typhoid fever by an enzyme immunoassay using Salmonella typhi outer membrane protein preparations. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 1993. link 56 Bellanti JA, Zeligs BJ, Vetro S, Pung YH, Luccioli S, Malavasic MJ et al.. Studies of safety, infectivity and immunogenicity of a new temperature-sensitive (ts) 51-1 strain of Salmonella typhi as a new live oral typhoid fever vaccine candidate. Vaccine 1993. link90238-s) 57 Pongsunk S, Sarasombath S, Ekpo P, Tangtherawattana P, Levine MM. Production of monoclonal antibodies to Vi polysaccharide antigen of Salmonella typhi. Asian Pacific journal of allergy and immunology 1993. link 58 Smith BP, Dilling GW, Da Roden L, Stocker BA. Vaccination of calves with orally administered aromatic-dependent Salmonella dublin. American journal of veterinary research 1993. link 59 Sandström G, Sjöstedt A, Johansson T, Kuoppa K, Williams JC. Immunogenicity and toxicity of lipopolysaccharide from Francisella tularensis LVS. FEMS microbiology immunology 1992. link 60 Muthukkaruppan VR, Nandakumar KS, Palanivel V. Monoclonal antibodies against Salmonella porins: generation and characterization. Immunology letters 1992. link90047-r) 61 Anuntagool N, Sarasombath S, Ratanabanangkoon K. Studies on the 52 kDa antigen of Salmonella typhi: physicochemical stability, purification by affinity chromatography and immunochemical specificity. The Southeast Asian journal of tropical medicine and public health 1991. link 62 Forrest BD, LaBrooy JT. In vivo evidence of immunological masking of the Vibrio cholerae O antigen of a hybrid Salmonella typhi Ty21a-Vibrio cholerae oral vaccine in humans. Vaccine 1991. link90039-9) 63 Sadallah F, Brighouse G, Del Giudice G, Drager-Dayal R, Hocine M, Lambert PH. Production of specific monoclonal antibodies to Salmonella typhi flagellin and possible application to immunodiagnosis of typhoid fever. The Journal of infectious diseases 1990. link 64 Kanjanahareutai S, Sarasombath S, Sirisinha S. Gel-filtration chromatography of Salmonella protein antigens and their implication in immunodiagnosis. Asian Pacific journal of allergy and immunology 1987. link 65 Maskell DJ, Sweeney KJ, O'Callaghan D, Hormaeche CE, Liew FY, Dougan G. Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems. Microbial pathogenesis 1987. link90022-2) 66 Kudrna DA, Teresa GW, Arnzen JM, Beard KS, Olson D. Immunologic memory responses induced in BALB/c mice by cross-linked outer membrane extracts of four Salmonella serotypes. American journal of veterinary research 1987. link 67 Chaicumpa W, Wechsathanarak Y, Tantivanich S, Plueksawan W. Antibody responses to heat-killed, phenol preserved parenteral typhoid vaccine. The Southeast Asian journal of tropical medicine and public health 1985. link 68 Lee JC, Gibson CW, Eisenstein TK. Macrophage-mediated mitogenic suppression induced in mice of the C3H lineage by a vaccine strain of Salmonella typhimurium. Cellular immunology 1985. link90033-4) 69 Sirianni MC, Turbessi G, Scarpati B, Russo G, Mascellino MT, Aiuti F. A preliminary report on the immunological responses after oral vaccine (Ty 21a). Bollettino dell'Istituto sieroterapico milanese 1984. link

Original source

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Salmonella colonisation of laying hens following vaccination with killed and live attenuated commercial Salmonella vaccines. — Atterbury RJ, Carrique-Mas JJ, Davies RH, Allen VM The Veterinary record (2009)
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Antibodies to the Vi capsule of Salmonella Typhi in the serum of typhoid patients and healthy control subjects from a typhoid endemic region. — House D, Ho VA, Diep TS, Chinh NT, Bay PV, Vinh H et al. Journal of infection in developing countries (2008)
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Oral administration of a live Aro attenuated Salmonella vaccine strain expressing 14-kDa Schistosoma mansoni fatty acid-binding protein induced partial protection against experimental schistosomiasis. — Pacheco LG, Zucconi E, Mati VL, Garcia RM, Miyoshi A, Oliveira SC et al. Acta tropica (2005)
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Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. — Salerno-Gonçalves R, Fernandez-Viña M, Lewinsohn DM, Sztein MB Journal of immunology (Baltimore, Md. : 1950) (2004)
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Enzyme-linked immunosorbent assay with a Salmonella enteritidis antigen for differentiating infected from vaccinated poultry. — Solano C, Galindo J, Sesma B, Alvarez M, Solsona MJ, Gamazo C Veterinary research (2000)
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Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1 (MSP-1) fused to tetanus toxin fragment C. — Wu S, Beier M, Sztein MB, Galen J, Pickett T, Holder AA et al. Journal of biotechnology (2000)
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Surface-displayed viral antigens on Salmonella carrier vaccine. — Lee JS, Shin KS, Pan JG, Kim CJ Nature biotechnology (2000)
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Longevity of antibody responses to a Salmonella typhi-specific outer membrane protein: interpretation of a dot enzyme immunosorbent assay in an area of high typhoid fever endemicity. — Choo KE, Davis TM, Ismail A, Ong KH The American journal of tropical medicine and hygiene (1997)
[51]
R-form lipopolysaccharides (LPS) of Gram-negative bacteria as possible vaccine antigens. — Stanislavsky ES, Makarenko TA, Kholodkova EV, Lugowski C FEMS immunology and medical microbiology (1997)
[52]
Antigen 43, a phase-variable bipartite outer membrane protein, determines colony morphology and autoaggregation in Escherichia coli K-12. — Henderson IR, Meehan M, Owen P FEMS microbiology letters (1997)
[53]
Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated phenol preserved typhoid vaccine. — Kaistha J, Sokhey J, Singh S, Kumar S, John PC, Sharma NC Indian journal of pathology & microbiology (1996)
[54]
Rapid serodiagnosis of typhoid fever by dot enzyme immunoassay in an endemic area. — Choo KE, Oppenheimer SJ, Ismail AB, Ong KH Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (1994)
[55]
Early diagnosis of typhoid fever by an enzyme immunoassay using Salmonella typhi outer membrane protein preparations. — Verdugo-Rodríguez A, López-Vidal Y, Puente JL, Ruíz-Placios GM, Calva E European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (1993)
[56]
Studies of safety, infectivity and immunogenicity of a new temperature-sensitive (ts) 51-1 strain of Salmonella typhi as a new live oral typhoid fever vaccine candidate. — Bellanti JA, Zeligs BJ, Vetro S, Pung YH, Luccioli S, Malavasic MJ et al. Vaccine (1993)
[57]
Production of monoclonal antibodies to Vi polysaccharide antigen of Salmonella typhi. — Pongsunk S, Sarasombath S, Ekpo P, Tangtherawattana P, Levine MM Asian Pacific journal of allergy and immunology (1993)
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Vaccination of calves with orally administered aromatic-dependent Salmonella dublin. — Smith BP, Dilling GW, Da Roden L, Stocker BA American journal of veterinary research (1993)
[59]
Immunogenicity and toxicity of lipopolysaccharide from Francisella tularensis LVS. — Sandström G, Sjöstedt A, Johansson T, Kuoppa K, Williams JC FEMS microbiology immunology (1992)
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Monoclonal antibodies against Salmonella porins: generation and characterization. — Muthukkaruppan VR, Nandakumar KS, Palanivel V Immunology letters (1992)
[61]
Studies on the 52 kDa antigen of Salmonella typhi: physicochemical stability, purification by affinity chromatography and immunochemical specificity. — Anuntagool N, Sarasombath S, Ratanabanangkoon K The Southeast Asian journal of tropical medicine and public health (1991)
[62]
In vivo evidence of immunological masking of the Vibrio cholerae O antigen of a hybrid Salmonella typhi Ty21a-Vibrio cholerae oral vaccine in humans. — Forrest BD, LaBrooy JT Vaccine (1991)
[63]
Production of specific monoclonal antibodies to Salmonella typhi flagellin and possible application to immunodiagnosis of typhoid fever. — Sadallah F, Brighouse G, Del Giudice G, Drager-Dayal R, Hocine M, Lambert PH The Journal of infectious diseases (1990)
[64]
Gel-filtration chromatography of Salmonella protein antigens and their implication in immunodiagnosis. — Kanjanahareutai S, Sarasombath S, Sirisinha S Asian Pacific journal of allergy and immunology (1987)
[65]
Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems. — Maskell DJ, Sweeney KJ, O'Callaghan D, Hormaeche CE, Liew FY, Dougan G Microbial pathogenesis (1987)
[66]
Immunologic memory responses induced in BALB/c mice by cross-linked outer membrane extracts of four Salmonella serotypes. — Kudrna DA, Teresa GW, Arnzen JM, Beard KS, Olson D American journal of veterinary research (1987)
[67]
Antibody responses to heat-killed, phenol preserved parenteral typhoid vaccine. — Chaicumpa W, Wechsathanarak Y, Tantivanich S, Plueksawan W The Southeast Asian journal of tropical medicine and public health (1985)
[68]
Macrophage-mediated mitogenic suppression induced in mice of the C3H lineage by a vaccine strain of Salmonella typhimurium. — Lee JC, Gibson CW, Eisenstein TK Cellular immunology (1985)
[69]
A preliminary report on the immunological responses after oral vaccine (Ty 21a). — Sirianni MC, Turbessi G, Scarpati B, Russo G, Mascellino MT, Aiuti F Bollettino dell'Istituto sieroterapico milanese (1984)

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