Typhoid conjugate vaccines (TCVs)

Typhoid conjugate vaccines (TCVs) are a prescription medication in the vaccine class.

Typhoid conjugate vaccines (TCVs) are approved to prevent typhoid fever that is caused by certain bacteria called Salmonella Typhi( S. Typhi). It is recommended to administer at least 2 weeks before the expected exposure to S. Typhi.

It is used in routine national immunisation programmes, especially in areas with a high risk of developing typhoid infection.

Typhoid conjugate vaccines (TCVs) are administered parenterally, immediately entering circulation. They travel throughout the body, causing the immune system to manufacture defence-related antibodies without significant metabolic activity. Elimination gradually occurs as the immune response develops.

The common side effects of Typhoid conjugate vaccines (TCVs) include pain, swelling, redness at the injection site, malaise, headache, nausea, and diarrhoea.

Typhoid conjugate vaccines (TCVs) are available as a suspension for injection.

Typhoid conjugate vaccines (TCVs) are available in India, Germany, Canada, the United States, the United Kingdom, Canada and Australia.

Typhoid conjugate vaccines (TCVs), belonging to the vaccine class, stimulate immunity by producing antibodies against Salmonella Typhi.

The Typhoid Conjugate Vaccine (TCV) activates by integrating a harmless carrier protein with a fragment of the Salmonella Typhi bacterium's outer coating (Vi-polysaccharide). After injection, the immune system detects the compound as a foreign matter and produces particular antibodies against the Vi-polysaccharide. These antibodies inhibit Salmonella Typhi's ability to bind to human cells and spread infection by neutralising the Vi antigen on its surface. TCV also stimulates T-cell responses, enhancing long-term immunity. This dual process sets up the body to identify and combat the bacteria, providing a strong immunity against typhoid fever and lowering its prevalence in populations that were given vaccinations.

Typhoid conjugate vaccines (TCVs) are available as a suspension for injection.

Suspension for injection: To be administered parenterally, as applicable.

Typhoid conjugate vaccines (TCVs) can be used as follows:

• Prevention of typhoid fever that S. Typhi causes.
• Recommended for travellers to high-risk areas
• Used in routine immunization programs
• reduce disease incidence and transmission.

Typhoid conjugate vaccines (TCVs) can help support the following health benefits:

• Prevention: Salmonella Typhi causes severe typhoid fever, effectively prevented with the typhoid conjugate vaccine (TCV). TCV minimises the probability of infection by boosting immunity, especially in high-risk areas where typhoid poses a severe threat to health.
• Community Immunity: Widespread Typhoid conjugate vaccine (TCV) immunization protects individuals and establishes herd immunity. S.Typhi transmission is significantly reduced when a substantial percentage of the population is immunized. As a result, the community's typhoid infection rates are decreased, and unvaccinated people are indirectly protected, including those not medically eligible for vaccination. Herd immunity is facilitated by high vaccination rates, protecting the unvaccinated and lowering typhoid infection rates in the community.
• Long-Term Immunity: Compared with some other typhoid vaccines, TCV provides longer-lasting protection. This reduces the need for booster doses over time, which benefits regions with poor access to healthcare and resources. It lowers the burden on healthcare systems and accelerates immunization programmes.
• High-Risk Populations: TCV is especially helpful for high-risk groups, such as those who inhabit typhoid-prone areas, travellers who visit endemic regions, and healthcare workers who could be exposed to the bacterium. These populations at risk are better protected from infection by vaccination.

Typhoid conjugate vaccines (TCVs) are approved for its use in the following clinical indications:

• Typhoid fever prevention in infants who are less than 6 months old and in adults up to the age of 45.
• Campaigns for mass vaccination to stop the spread of the illness in the case of a typhoid breakout or epidemic.
• Certain high-risk groups include healthcare professionals or people with specific health conditions.
• Individuals who are travelling or visiting areas with a risk of typhoid infection.

Parenterally: Typhoid conjugate vaccines (TCVs) are available in powder for injection. Children younger than two should get typhoid conjugate vaccinations (TCVs) intramuscularly in the vastus lateralis (a muscle in the thigh) or the deltoid. It should not be injected into the GLUTEAL MUSCLE-like buttock areas or where a nerve trunk might be present. It should be administered intramuscularly only and not intravenously, intradermally or subcutaneously.

It can be only given by a healthcare professional in a hospital setting or during routine immunization programs.

After administration, the healthcare provider will document the vaccination, including the date, time, dose, and injection site.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Typhoid conjugate vaccines (TCVs) are available as a suspension for injection.

Suspension for injection: 0.5 ml single dose

Dosage Adjustment for Adult Patients

Typhoid prophylaxis

A single dose of 0.5 mL TCV is administered to adults (primary dose)

Booster: Recommended especially for individuals travelling to regions with a continued risk of typhoid exposure. The dose can vary but is often given every two to three years, depending on the vaccine brand.

Typhoid conjugate vaccines (TCVs) are available as a suspension for injection.

Typhoid conjugate vaccines (TCVs) should be used to prevent typhoid fever, along with no appropriate dietary restrictions. Consuming regular foods and drinks before and after receiving the vaccine is safe.

However, it is always recommended to maintain a balanced and healthy diet to support overall immune system function, which can boost the effectiveness of vaccines.

The dietary restriction should be individualized as per patient requirements.

Typhoid conjugate vaccines (TCVs) may be contraindicated in the following conditions: -

• Anaphylaxis reactions
• Allergic to natural rubber latex
• Severe immunosuppressive condition
• Blood or Plasma Transfusion

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Children with weak immune systems, such as those with HIV infection or cancer or who are taking certain drugs, may not respond as well to the TCVs and may consult a healthcare professional who might suggest modifying the vaccine schedule or giving additional doses to these people to improve protection.
• It may be advisable to postpone the vaccination if the child is currently experiencing a fever or a moderate to severe sickness.
• Healthcare professionals should assess the risks and benefits of the vaccination in case of any severe allergic reactions or a severe reaction to a previous dose of the TCVs.
• TCVs are not typically recommended during pregnancy unless there is a specific risk of exposure to S. typhi.

There is insufficient scientific evidence regarding the use and safety of the Typhoid conjugate vaccines (TCVs) in the breastfeeding population.

Safe to use during pregnancy.

There is no sufficient scientific evidence traceable regarding the use and safety of Typhoid conjugate vaccines (TCVs) in concurrent use with any particular food.

The adverse reactions related to Typhoid conjugate vaccines (TCVs) can be categorized as

• Common: Pain, redness, swelling, redness at the injection site, mild fever, tiredness and headache.
• Less Common: Muscle and joint pain, chills and GI symptoms like nausea or diarrhoea.
• Rare: Severe allergic reactions.

The clinically relevant drug interactions of the Typhoid conjugate vaccines (TCVs) are briefly summarized here:

• Immunosuppressants- Drugs like prednisone or cyclosporine suppress the immune system and may reduce the effectiveness of Typhoid conjugate vaccines (TCVs).
• Antibiotics: Antibiotics are often used to treat certain bacterial infections, which can interfere with the effectiveness of the Typhoid conjugate vaccines (TCVs). It is recommended not to take it concurrently and advised to adjust the vaccination schedule or consider additional doses of the Typhoid conjugate vaccines (TCVs).
• Other Vaccines: Typhoid conjugate vaccines (TCVs) are often administered alongside other childhood vaccines. To reduce any risk, medical professionals frequently adhere to vaccination regimens considering the time and space of vaccines.

The common side of Typhoid conjugate vaccines (TCVs) includes the following-

• Pain, redness, and swelling at the site where the shot was given.
• Malaise
• Headache
• Joint pain
• Nausea
• Diarrhoea
• Fever
• Fatigue
• Tiredness
• Headache
• Vomiting

The Typhoid conjugate vaccines (TCVs) should be prudent in the following group of special populations.

• Pregnancy:

Pregnancy Category: C. Safe during pregnancy, but when taken in high doses, use with caution if the benefits outweigh the risks.

TCVs are usually considered safe during pregnancy; they are mainly advised when there is a significant risk of exposure to typhoid fever. Unless the risk of exposure is very high, routine vaccinations are normally not recommended during pregnancy.

• Paediatrics:

In paediatrics, the typhoid conjugate vaccine (TCV) protects against typhoid fever, lowering the risk of life-threatening disease and health complications. TCV is a safe and effective remedy that improves public health by preventing the transmission of this bacterial infection in children.

Dosage Adjustment for Paediatric Patients

Typhoid prophylaxis

Minimum ages: 6 months;

Vaccination schedule:

Typhoid conjugate vaccines (Vi-PS): Single 0.5 mL dose at 9-12 months and a booster during the second year of life.

The need for revaccination following a booster of Typbar-TCV® not yet determined

Catch-up vaccination: 

Recommended throughout the adolescent period, i.e. 18 years

• Geriatrics:

There is no sufficient scientific evidence regarding the use and safety of Typhoid conjugate vaccines (TCVs) for geriatric populations.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of Typhoid conjugate vaccines (TCVs) for lactating mother populations.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdosage of Typhoid conjugate vaccines (TCVs) rarely occurs as healthcare professionals administer them according to specific or precise dosing guidelines.

There is no specific antidote or treatment for excessive intake of TCVs. Medical attention should be sought immediately when an overdose is suspected, followed by monitoring any adverse effects or allergic reactions. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Pharmacodynamics of Typhoid conjugate vaccines (TCVs):

Typhoid conjugate vaccines (TCVs) have a physiological mechanism that plays a role in their pharmacodynamics. In Typbar-TCV, non-toxic Tetanus Toxoid is conjugated with Vi polysaccharide, which increases the vaccine's immunogenicity, stimulating an effective immunological response. Typbar-TCV causes an immunological response that is T-cell reliant, in contrast to the prior strain. The active involvement of T cells triggers the development of Vi antibodies, which effectively neutralise the Vi antigen and prevent infection.

Typbar-TCV provides a complete defence against typhoid fever by leveraging the usage of the immune system's capabilities. This development strengthens individual protection while advancing more significant public health measures, which will lower the prevalence of this fatal illness in areas where it still poses a serious health risk. Thus, Typbar-TCV is a significant advance in the continuing global efforts to combat and eventually eliminate the threat of typhoid fever.

Pharmacokinetics of Typhoid conjugate vaccines (TCVs):

• Absorption: TCVs are injected, typically intramuscularly, and the vaccine's components enter the bloodstream, bypassing the absorption from the gastrointestinal tract.
• Distribution: The vaccine's components, including the polysaccharide capsule and carrier protein, are distributed throughout the body after entering the bloodstream. They might travel to immune system areas like lymph nodes and other places where the immunological response is initiated.
• Metabolism: TCVs do not undergo significant metabolism in the body and function as antigens by stimulating the immunological response.
• Elimination: The immune system produces antibodies in response to the vaccine's components that it detects as foreign invaders. As the body's immune system responds, TCV components are gradually eliminated from the blood.

• Neuzil, Kathleen M et al. “Early Insights From Clinical Trials of Typhoid Conjugate Vaccine.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 71,Suppl 2 (2020): S155-S159.
• Saha, Samir K et al. “Typhoid Conjugate Vaccine: An Urgent Tool to Combat Typhoid and Tackle Antimicrobial Resistance.” The Journal of infectious diseases vol. 224,12 Suppl 2 (2021): S788-S791. doi:10.1093/infdis/jiab443
• Birkhold, Megan et al. “Typhoid Conjugate Vaccines: Advancing the Research and Public Health Agendas.” The Journal of infectious diseases vol. 224,12 Suppl 2 (2021): S781-S787.
• Sahai, N., Arunachalam, D.K., Morris, T. et al. An observer-blinded, cluster randomised trial of a typhoid conjugate vaccine in an urban South Indian cohort. Trials 24, 492 (2023).

• Inform the caregivers of the schedule for administering the TVCs doses, whether it's a single dose or includes booster shots and also mention the importance of completing the vaccination.
• Assure caregivers that TCV immunizations are generally safe, with only minor, short side effects. Encouraging them to immediately report any unexpected or severe responses to the healthcare physician and, whenever applicable, to use reporting systems like the Vaccine Adverse Event Reporting System (VAERS)
• Inform caregivers of the recommended immunization schedule, which usually consists of two or three doses, depending on the vaccine brand. Also, mention the ages at which the doses should be administered and give the Vaccine Information Statements, which must be disclosed before immunization by the National Childhood Vaccine Injury Act of 1986 about the Centres for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines), these resources are freely accessible.

https://cdsco.gov.in/opencms/resources/UploadCDSCOWeb/2018/

https://www.indianpediatrics.net/oct2014/785 figure1.pdf

https://www.ncbi.nlm.nih.gov/books/NBK470571/

https://invc.co.in/typhoid/typbar-tcv-vaccination#