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Typhoid Vaccine, Inactivated (Subcutaneous Route, Injection Route) Description and Brand Names

Description and Brand Names

Drug information provided by: IBM Micromedex

Descriptions

Typhoid fever is a serious disease that can cause death. It is caused by a germ called Salmonella typhi and is spread most often through infected food or water. Typhoid may also be spread by close person-to-person contact with infected persons (such as occurs with persons living in the same household). Some infected persons do not appear to be sick, but they can still spread the germ to others.

Typhoid fever is rare in the U.S. and in other areas of the world that have good water and sewage (waste) systems. However, it is a problem in parts of the world that do not have such systems. If you are traveling to certain countries, or to remote, out-of-the-way areas, typhoid vaccine will help protect you from typhoid fever. The U.S. Centers for Disease Control (CDC) currently recommend caution in the following areas of the world:


  • Africa

  • Asia

  • Latin America

Typhoid vaccine given by injection helps prevent typhoid fever but does not provide 100% protection. Therefore, it is very important to avoid infected persons and food and water that may be infected, even if you have received the vaccine.

To get the best possible protection against typhoid, you should complete the vaccine dosing schedule at least 1 week before you travel to areas where you may be exposed to typhoid.

Also, if you will be traveling regularly to parts of the world where typhoid is a problem, you should get a booster (repeat) dose of the vaccine every 3 years.

Typhoid vaccine is to be used only by or under the supervision of a doctor.

Portions of this document last updated: April 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.


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Typhoid Vaccination for International Travel

What Is Typhoid Fever?

Typhoid fever, or typhoid, spreads through contaminated food or water. Caused by Salmonella typhi, typhoid fever is an acute illness infecting about 21.5 million people worldwide.

Typhoid fever can be fatal in up to 10% of reported cases. There has been an increase in the number of drug-resistant strains of Salmonella typhi since 1989. Unfortunately, drug resistance is spreading worldwide due to overcrowding, poor sanitation, inadequate control of infections and extensive international travel, trade and population movements.

Humans are the sole hosts of the bacteria which is shed in feces from 6 weeks to 3 months after infection. Most common symptoms include fever, anorexia, abdominal discomfort and headaches.

What Is the Typhoid Fever Vaccine?

There are two vaccines available to prevent typhoid fever:

  • Vivotif (Typhoid Vaccine Live Oral Ty21a) – Also known as ‘typhoid pills’, Vivotif is made from attenuated live bacteria. The vaccine provides up to five years’ protection and is approved for use in individuals over six-years-old. Vivotif is taken orally over the course of four doses.
  • Typhoid Vaccine (Injectable) – Made from inactive bacteria, the injectable typhoid vaccine provides protection for up to two years. This vaccine is approved for use in individuals over two-years-old.

The risk of either typhoid vaccination causing serious harm is rare and reactions to either vaccine are generally mild.

 

Do I Need a Typhoid Vaccine?

The typhoid vaccine is recommended for almost all international travelers. You may need the vaccine if they will be visiting smaller cities or rural areas.

The vaccine is highly recommended for regions with drug-resistant typhoid. This includes large portions Asia and Africa.

Where Does Typhoid Fever Occur?

The CDC recommends travelers headed to developing countries, where exposure to contaminated food or water is likely, receiving the typhoid vaccine. Over the past 10 years, travelers from the United States to Asia, Africa, and Latin America have been especially at risk.

How Long Does the Typhoid Vaccine Last?

The duration of typhoid vaccine protection varies based on the type of immunization you receive. Oral typhoid vaccines provide five years of protection while injectable offers two years protection. Be sure to speak with a travel health specialist on which vaccine is right for you.

Where Can I Get the Typhoid Vaccine?

Both typhoid vaccines are in-stock and available at all Passport Health travel clinics throughout North America. Meet with a travel medicine specialist today to discuss your travel plans and receive your vaccine.

 

Customer Reviews

Passport Health – Typhoid Vaccination

Overall rating: 5 stars – 20 reviews

❮❯

★★★★★

“The Best Customer Service Ever!!“
“The nurse was amazing. She went above and beyond to help my son when he lost his last pill of Typhoid. He had 1 pill left to finish his dose when he forgot it in a hotel. When I found out I reached out to Passport Health on what to do when medicine is lost. I was put in touch with the nurse to try and figure out a solution on how to get my son his last pill before he left to Thailand. Carol was kind and patient, she helped us find a solution and followed up to make sure the medicine was received. The bottom line is, in this day and age you don’t find customer service like this anymore, when I was in a panic she made me feel everything was going to be ok and it was. Thank you from the bottom of my heart.”

★★★★★

“Speedy Service“
“I called PH because I needed a typhoid shot for a mission trip that needed a last-minute replacement. No one else in Syracuse had the shot, and I had started to think I wouldn’t be able to get it, but PH found a spot for me the same morning I called.”

★★★★★

“Necessary“
“Took both my kids to get vaccinated for Typhoid.”

★★★★★

“Great Service“
“The process was super easy, they go in details about the pro and cons of each vaccines that arerequired, or recomended and what options there are for the vaccines (like typhoid which comes in 2 types, pills and shot) finally they provide you with additional services like a document on your destination country which includes details about healthcare system of the country (is it save to have transfusion there?) and all kind of other general travel info.

★★★★★

“Thorough & professional“
“Administered Typhoid shot in little time with no problems.”

★★★★★

“Excellent very educational“
“the nurse went over every scenario and disease that could possibly happen while my daughter visits Peru. She also explained to her how to take her malaria and typhoid pill. We also purchased the travelers medicine pouch in case she gets a stomach bug traveling.”

★★★★★

“Great Service“
“My visit to PassportHealth in New York made me even more excited to travel. I received lots of information from the Director and she administered my Typhoid vaccine herself. It was quick and painless. I will absolutely return for future vaccinations.”

★★★★★

“Excellent Friendly Service“
“I, my wife, and a friend needed yellow fever and Typhoid vaccinations for a trip to South America. We arrived for our appointments early and were taken on time. Everyone was very courteous, polite and friendly. The required inoculations were expertly administered. The shots were barely noticed when given.”

★★★★★

“Very pleasant, thorough visit!“
“Great experience at the office – super informative, walked me through all of the health precautions, what to bring, what to look out for, and a lot of material to read and have on hand for my travels. Went for Typhoid shot, and came away with great advice, and reading materials.”

★★★★★

“My Dad & I“
“My 86 year old father and I are going to Cuba. The RN was great giving us suggestions, explaining their products yet not pushing them at you. She told us what to be concerned about and take precautions, and what not to worry about. She had also been to Cuba so she was an excellent resource beyond the awesome job she did. Then she gave us our Typhoid shots I’m scared of needles even though I’m an RN too, she did such a good job–no pain. I hold other nurses at a standard being one myself. Great technique and she is very personal so she distracts you duriythe injection. All in all a great experience and you come out confident about where your going.”

★★★★★

“Excellent and quick“
“The RN provided an excellent and speedy intake interview and vaccination – making the processes quite pleasant. She provided additional information for Typhoid, which I also got but wasn’t planning on getting the vaccination. I planned on getting Yellow Fever. I will come to Passport Health for my future travel needs; the operators over the phone were also quite excellent and helpful in providing me with last minute appointments.”

★★★★★

“Very Thorough“
“I received very thorough information on the vaccines needed from the clinic. She offered coffee, tea and water as well as some ice to keep my Typhoid vaccine cold in transit.”

★★★★★

“Easy Vaccination“
“I needed only a typhoid vaccine for an upcoming trip, but the Passport Health nurse printed out and reviewed with me all the recommended vaccines and area where, for example, malaria is prevalent to insure that I had all the immunizations I needed. I was not rushed; she was very pleasant and helpful.”

★★★★★

“First Visit“
“The nurse covered what immunizations were needed in all four countries that we plan to visit in Africa. She also provided travel tips on what not to eat/drink, and what to take if we were to become sick. Besides selling us the Typhoid pills (note: best to bring a small cooler so that you can keep the pills below 45 degrees until you return home), she also has for sale other helpful meds available.”

★★★★★

“An excellent Experience“
“I have visited Passport Health on two occasions in prep for my travels to Bali and Indonesia. Both visits were thorough and informative. I actually got Typhoid meds on my first visit and came home to check my medical records before taking Hep A. I was very pleased with the care items reviewed during my visit and have purchased additional items to ensure that I would get the most out of my travel. i.e. water bottles, mosquito spray, and sunscreen. Looking forward to enjoying my travels thanks to the counseling I received through Ms. Hennessy.”

★★★★★

“Very quick“
“I was able to secure, via on-line, an appointment within 2 days. Arrived at the appointment and since I filled out forms on line Doreen was ready to review with me. She answered all o my questions and in addition to the Typhoid shot, I was able to secure my Malaria medicine. In and out in less than 20 minutes. I have already recommended to my friends that travel”

★★★★★

“Helped us out in a bind“
“Passport Health helped us get the vaccines we needed on short notice. They also had the 5 year oral Typhoid vaccine that is unavailable elsewhere.”

★★★★★

“Very helpful“
“The woman was very helpful, showing me the region I would be visiting and giving clear instructions on taking the oral Typhoid pills. The injections were all over before i realized it. Very skillful.”

★★★★★

“Getting ready for Africa“
“My husband and I are planning a trip to Africa in the next few months. We went to the Frisco, TX location of Passport Health to receive our inoculations and oral medications for typhoid and malaria prevention. The RN was very knowledgeable, helpful and everything required was in stock. The inoculations were done professionally and we were both pleased with the service. Would definitely recommend Passport Health.”

★★★★★

“Fast & Efficient“
“Had a wonderful quick visit. I was on my way to work that morning so it was great to have everything explained to me really carefully and clearly. I was offered 2 options for the typhoid vaccine, which was great! And the man who helped me was lovely!”

 

 

On This Page:
What Is Typhoid Fever?
What Is the Typhoid Fever Vaccine?
Do I Need a Typhoid Vaccine?
Who Should Get a Typhoid Vaccine?
Where Does Typhoid Fever Occur?
Where Can I Get the Typhoid Vaccine?

Typhoid fever – Vaccination – NHS

Vaccination against typhoid fever is recommended if you’re travelling to parts of the world where the condition is common.

High-risk areas

Typhoid is found throughout the world, but it’s more likely to occur in areas where there’s poor sanitation and hygiene. 

High-risk areas include:

  • the Indian subcontinent
  • Africa
  • south and southeast Asia
  • South America

Vaccination is strongly recommended if you’re going to be staying or working with local people, or if you’re going to be staying for prolonged periods in areas where sanitation and food hygiene are likely to be poor.

In the UK, most people who get typhoid fever develop it while visiting India, Pakistan or Bangladesh. It’s therefore particularly important that you’re vaccinated if you’re visiting these countries.

Vaccination against typhoid fever is usually free on the NHS from GP surgeries. Private travel clinics also offer the vaccine for about £30.

Choosing a typhoid vaccine

In the UK, the 2 main vaccines available to prevent typhoid fever are:

  • Vi vaccine – given as a single injection
  • Ty21a vaccine – given as 3 capsules to take on alternate days

Combined typhoid and hepatitis A injections are also available for people aged 15 or over. Protection against hepatitis A lasts 1 year and protection against typhoid lasts 3 years.

The vaccines work by stimulating your body to create antibodies (infection-fighting proteins) that prevent you getting ill if you become infected with the typhoid bacteria.

But neither typhoid vaccine is 100% effective, so you should always take precautions when eating food and drinking water abroad.

As the Ty21a vaccine contains a live sample of Salmonella typhi bacteria, it isn’t suitable for people with a weakened immune system – for example, people receiving certain types of treatment, such as chemotherapy. 

It also isn’t usually recommended for children under 6, whereas children can have the Vi vaccine from 2 years of age.

It’s unclear whether the Vi and Ty21a vaccines present a risk to pregnant or breastfeeding women. But vaccination should be considered if there’s a significant risk of getting typhoid.

The typhoid vaccine should ideally be given at least 1 month before you travel, although if necessary it can be given closer to your travel date.

Booster vaccinations are recommended every 3 years if you continue to be at risk of infection with typhoid bacteria.

Side effects of typhoid fever vaccine

After having the typhoid fever vaccine, some people have temporary soreness, redness, swelling or hardness at the injection site.

About 1 in every 100 people have a high temperature (fever) of 38C (100.4F) or above.

Less common side effects include:

Severe reactions are rare for both typhoid vaccines.

Read more about routine NHS vaccinations.

Advice for travellers

Whether you have been vaccinated against typhoid or not, it’s important to take basic precautions when travelling in countries where typhoid fever is present.

For example:

  • only drink bottled water from a bottle that was properly sealed, or water that’s been recently boiled 
  • avoid ice cream and don’t have ice in your drinks
  • avoid uncooked fruit and vegetables, unless you have washed them in safe water or peeled them yourself
  • avoid shellfish, seafood and salads

Read more about food and water abroad.

Page last reviewed: 18 June 2018
Next review due: 18 June 2021

Uses, Side Effects, Dosage, Precautions

Typhoid vaccines are used to prevent typhoid fever in children and adults. Typhoid fever (simply referred to as typhoid) is an infectious disease caused by a bacteria called Salmonella typhi that can lead to high fever, diarrhea, vomiting, pneumonia, encephalitis (inflammation of the brain), and, in some cases, death.

The disease, commonly associated with poor hygiene and public sanitation, can be prevented with one of two vaccines:

Universal Images Group / Getty Images

The vaccines work by stimulating the production of immune cells called antibodies that “recognize” S. typhi and prevent it from establishing an infection.

Typhoid is a major global health concern with around 21 million new cases and over 150,000 deaths each year. While relatively rare in the United States, around 5,700 cases are diagnosed annually, usually involving travelers who have been to parts of the world where typhoid is endemic. 

Uses

Typhoid vaccines are not uses for the routine immunization of people in the United States. Rather, they are indicated for use in specific populations, namely:

  • Travelers to areas where a recognized risk of exposure to typhoid exists
  • People who live with or have intimate contact with someone who has typhoid fever
  • Workers in microbiology labs who handle S. typhi samples

Typhoid vaccination is not required for international travel but is recommended for those traveling to parts of Africa, Asia, Central America, and South America where there is a recognized risk of S. typhi exposure.

Neither of the two vaccines are inherently “better” than the other, and both offer only partial protection against typhoid fever.

When planning a trip overseas, check the vaccination requirements and travel advisories for your destination on the CDC traveler’s health website.

Before Use

There are certain people in whom typhoid vaccines may cause harm and need to be avoided. Typhim Vi and Vivotif are both contraindicated for use in people who have a history of allergy to any components of the vaccine.

As a live vaccine, Vivotif poses possible health risks to people who are immunocompromised. These include people with HIV, organ transplant recipients, people undergoing chemotherapy, and children with primary immunodeficiency (PID).

Live vaccines have the potential to revert to their virulent state in immunocompromised people, causing the very diseases they are meant to prevent. Although this has not been established with Vivotif, it is still contraindicated for use in people with immunodeficiency as a precaution.

Dosage

The recommended dosage of typhoid vaccines varies by the vaccine type and age. The vaccines are supplied as follows:

  • Typhim Vi: Either as a single-use prefilled syringe or a multi-dose vial.
  • Vivotif: A blister pack of pink-and-white capsules. 
Vaccine Ages Schedule
Typhim Vi 2 years and over A single 0.5-milliliter (mL) intramuscular injection
Vivotif6 6 years and over One capsule per day taken on alternate days (days 1, 3, 5, and 7)

Revaccination is recommended for international travelers who frequent endemic regions. For Typhim Vi, revaccination is recommended every 2 years. for Vivotif, revaccination may only be needed every 5 years.

How to Take and Store

Typhim Vi is administered by a healthcare professional. The injection is given either to the deltoid muscle of the shoulder or the upper part of the outer thigh (anterolateral thigh). To ensure ample protection, the injection should be given at least 2 weeks prior to departure to an endemic region.

Vivotif is self-administered and should be taken 1 hour before food with a cold or lukewarm drink. Failing to follow these dietary instructions can undermine if the effectiveness of the vaccine. The vaccination series should be completed at least 1 week before travel to an endemic region.

Vivotif capsules should not be stored at room temperature but rather refrigerated at temperatures between 35.6°F to 46.4° F (2° C to 8° C). Do not freeze.

Even after vaccination, you will still need to take standard precautions to avoid S. typhi at your destination. This includes avoiding untreated drinking water, avoiding raw fruits and vegetables, and washing your hands frequently.

Side Effects

Side effects can occur with both Typhim Vi and Vivotif, although most tend to be mild and resolve on their without treatment. Side effects are a bit more common with Typhim Vi, affecting as many as one in six users.

Typhim Vi

  • Malaise (14.8%)

  • Injection site tenderness (13%)

  • Headache (13%)

  • Injection site pain (7. 4%)

  • Nausea (3.7%)

  • Diarrhea (3.7%)

Vivotif

  • Abdominal pain (6.4%)

  • Nausea (5.8%)

  • Headache (4.8%)

  • Fever (3.3%)

  • Diarrhea (2.9%)

  • Vomiting (1.5%)

  • Rash (1.0%)

Severe reactions—including the potentially life-threatening whole-body allergy known as anaphylaxis—are rare with typhoid vaccines. In fact, a 2019 review of studies in the Journal of Allergy and Clinical Immunology reported no cases of anaphylaxis out of 164,483 doses of typhoid vaccine administered.

Warnings and Interactions

Vivotif should not be used in anyone who is sick with fever or has an acute gastrointestinal illness as doing so may only make symptoms worse. In such cases, it is best to wait until the illness resolves before pursuing the live vaccine.

Neither animal nor human studies have not been conducted to assess the safety of Typhim Vi or Vivotif during pregnancy. With that said, the vaccines are classified as Pregnancy Category C drugs, meaning that the benefits of the vaccines may outweigh the potential risks. Speak with your doctor if you are pregnant, breastfeeding, or planning to get pregnant to make a fully informed choice.

Certain drugs and treatments can interact with Typhim and Vivotif. These include immunosuppressants that blunt the overall immune response and may temper the production of defensive antibodies. These include:

Vivotif can also interact with anti-malaria drugs like Aralen (chloroquine) and Larium (mefloquine), both of which can impair the effectiveness of the vaccine. The interaction appears to be mild, but inform your doctor if you are taking or planning to take anti-malaria drugs before starting Vivotif.

Always advise your doctor about any drugs you take before getting the typhoid vaccine. In some cases, the medication may need to be temporarily stopped to ensure an ample immune response to the vaccine.

How to Choose

There are both pros and cons to Typhim Vi and Vivotif, and one may be better for some people than for others. If in doubt about which vaccine is right for you, speak with your doctor.

Typhim Vi

  • Not self-administered

  • Requires one dose

  • Cannot be used in children under six years

  • Can be used in immunocompromised people

  • Must be given at least 2 weeks before travel

  • Revaccination needed every 2 years

Vivotif

  • Self-administered

  • Requires four doses over 7 days

  • Cannot be used in children under two years

  • Cannot be used in immunocompromised people

  • Series must be completed at least 1 week before travel

  • Revaccination needed every 5 years

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

  1. Van Camp RO, Shorman M. Typhoid vaccine. In: StatPearls [Internet]. Updated February 16, 2021.

  2. Sanofi Pasteur. Package insert – Typhim Vi. Updated March 2020.

  3. Crucell Switzerland Ltd. Package insert – Vivotif. Updated September 2013.

  4. Centers for Disease Control and Prevention. National typhoid and paratyphoid fever surveillance. Updated November 27, 2018.

  5. Jackson B, Iqbal S, Mahon B, et al. Updated recommendations for the use of typhoid vaccine — Advisory Committee on Immunization Practices, United States, 2015. MMWR Morb Mortal Week Rep. 2015;64(11)305-8.

  6. Centers for Disease Control and Prevention. Typhoid fever and paratyphoid fever: vaccination. Updated November 18, 2020.

  7. McNeil MM, DeStefano F. Vaccine-associated hypersensitivity. J Allergy Clin Immunol. 2018 Feb;141(2):463-72. doi:10.1016/j.jaci.2017.12.971

Verywell Health is part of the Dotdash publishing family.

Typhoid Vaccines – Take on Typhoid

Typhoid is spread by infected human waste, so safe food, clean water, improved sanitation, and good hygiene (WASH) practices are key to preventing the disease. Because of the significant burden of typhoid and the growing threat of drug resistance, the role of vaccines alongside WASH interventions is critical in high-risk, typhoid-endemic areas. This is especially important among rural and hard-to-reach communities where progress in medical services, infrastructure, and development may be slow. Additionally, typhoid vaccines are valuable for travelers, food workers (including street vendors), household contacts of typhoid carriers, and laboratory workers.

Currently available typhoid vaccines

Three classes of typhoid vaccines are currently recommended by the World Health Organization (WHO).

Name Typhoid conjugate vaccine (TCV) Ty21a Vi capsular polysaccharide vaccine (ViCPS)
Tradename(s) (Manufacturer) Typbar TCV® (Bharat Biotech)
TYPHIBEV (Biological E)
Vivotif® (PaxVax) Typhim Vi® (Sanofi Pasteur) Typherix (GlaxoSmithKline)
Administration Intramuscular injection Oral capsules Intramuscular injection
Age >6 months of age >6 years of age >2 years of age
Number of doses 1 dose 3 to 4 doses 1 dose with boosters every 2 to 3 years
Duration of protection >3 years*
*Studies currently underway with Typbar TCV
7 years 2 years
Effectiveness >80%*
*Interim analysis data from the TyVAC efficacy study in Nepal with Typbar TCV
50% to 80% 50% to 80%

Uptake of the Ty21a and ViCPS vaccines in typhoid-endemic countries have been low. The Ty21a vaccine requires numerous doses, and the ViCPS vaccine has short-lived protection. Additionally, neither vaccine is amenable to use in children younger than two years of age, which limits the potential health benefits and prevents use in routine childhood vaccination programs. Gavi, the Vaccine Alliance does not provide funding for Ty21a or ViCPS vaccines.

New typhoid conjugate vaccines (TCVs) address the limitations of prior vaccines. These vaccines are of particular interest to the global health community because TCVs have the potential to overcome many of the challenges that impeded uptake of earlier vaccines, including longer-lasting protection*, fewer doses, and suitability for children younger than two years of age, allowing for inclusion in routine childhood immunization programs. Many TCVs are under development, and four have been licensed in India.

Typbar TCV, manufactured by Bharat Biotech Ltd., was prequalified by WHO in late 2017 and recommended by WHO in 2018. It is administered in a single dose and approved for children six months of age and older.

TYPHIBEV, manufactured by Biological E, was prequalified by WHO in late 2020. It is administered in a single dose and approved for children over six months of age. Clinical studies show that it is safe when given at 9 months of age concurrently with measles vaccine, and its immune response profile is similar to that of Typbar TCV.

Another advanced TCV candidate is called PedaTyph™, which is manufactured by Bio-Med and is licensed in India for children three months of age and older. Efficacy trials of PedaTyph have found more than 90 percent efficacy against typhoid. However, it has not been submitted for WHO prequalification. Seven other TCV candidates are in various stages of development.

World Health Organization recommendations

The WHO position paper on typhoid vaccines, published in 2018, states:

WHO recommends programmatic use of typhoid vaccines for the control of typhoid fever. […] Among the available typhoid vaccines, TCV is preferred at all ages in view of its improved immunological properties, suitability for use in younger children and expected longer duration of protection. Countries may also consider the routine use of ViPS vaccine in individuals aged 2 years and older, and Ty21a vaccine for individuals aged more than 6 years. In choosing a typhoid vaccine, the costs, programmatic issues and duration of protection should be considered.

WHO recommends the introduction of TCV to be prioritized in countries with the highest burden of typhoid

disease or a high burden of antimicrobial resistant S. Typhi. Decisions on the age of TCV administration,
target population and delivery strategy for routine and catch-up vaccination should be based on the local
epidemiology of typhoid fever, including antimicrobial resistance patterns, and programmatic considerations
of the routine childhood immunization programme.

In November 2017, Gavi announced a US$85 million funding window to support the introduction of TCV in developing countries. Gavi applications for TCV introduction support are open for eligible countries.

Outbreak response and planned introductions

In Sindh Province, Pakistan, Karachi and Hyderabad have faced an ongoing outbreak of extensively drug resistant typhoid since 2016. In response, an emergency vaccination campaign was launched in January 2018. Following this effort, in November 2019, Pakistan became the first country to introduce TCVs into their routine childhood immunization program with the launch of a phased introduction beginning in Sindh Province.

In February 2019, Zimbabwe launched an emergency response vaccination campaign in Harare and surrounding communities in response to recurring outbreaks of typhoid in 2017 and 2018. The campaign was the first in sub-Saharan Africa to use the new TCV and the first funded by Gavi. The government of Zimbabwe is planning to introduce TCV into its national routine immunization schedule in 2021. Similarly, Liberia is preparing to introduce TCV in 2021.

*Interim data from ongoing TyVAC studies indicate protection greater than two years.

Photo: PATH/Gabe Bienczycki

Schedule, Cost, Types & Side Effects

Last Updated on

Typhoid is a major health concern in India, with children being more prone to it than adults. This contagious disease spreads through contaminated food and water and is caused by a bacteria known as salmonella typhi. It can impair physical and cognitive development in children. The best way to prevent typhoid is to immunise your baby against it at the right time.

Also Read: Influenza Vaccine for Babies and Kids

Typhoid Vaccine – What Is It?

Typhoid vaccines help prevent typhoid. Vaccination against this disease is vital, otherwise, it can lead to serious complications. Typhoid is also known to adversely affect young children. There are different types of vaccines available that prevent typhoid – you must always consult your paediatrician to know which would suit your toddler.

Also Read: How to Make Vaccination Fun for Kids

Types of Typhoid Vaccinations

Typhoid is a serious problem and should not be taken lightly. There are two types of typhoid vaccinations:

  • Typhoid Polysaccharide Vaccine
  • Typhoid Conjugate Vaccine

Who Should Get Immunised Against Typhoid?

Generally, typhoid vaccination is recommended for:

  • People travelling to and around typhoid-ridden countries like India
  • People who are in close contact with an infected person
  • People who work with salmonella typhi bacteria in India

In India, however, routine typhoid vaccination is advised as we are more prone to infections. Typhoid vaccine for babies can be given as early as the age of 9-12 months.

The Typhoid Conjugate Vaccine or TCV is administered when the baby is between 9 and 12 months old. As per IAP guidelines, there is no need to give a booster dose of TCV.

Also Read: Child Vaccination and Growth Tracker

Typhoid Vaccine Cost in India

The cost of typhoid vaccine in India may vary depending on the type of vaccine (polysaccharide or conjugate), and the brand of vaccine used.

Typhoid Vaccine Schedule

The typhoid vaccine schedule in India is included in the list of mandatory vaccinations suggested by the paediatrician, right after the birth of a baby. But before giving it to a baby, remember these important things:

  • Number of Doses
    Only a single dose of TCV in enough between 9 to 12 months of age.
  • Recommended Ages
    Ideally, the typhoid shot is recommended for children older than 2 years of age. it has to be repeated every 3 years. Alternatively, TCV can be given at the age of 9-12 months.

 Things to Avoid Before or After Getting the Typhoid Vaccine

Before giving your child the typhoid vaccine, keep these things in mind:

  • This vaccine cannot be given if your child is allergic to any component of the vaccine. The doctor must be made aware of allergies if any, much before the vaccination is given.
  • Your child must not be even moderately ill at the time of getting the vaccination.
  • Anyone who has had a severe reaction to the previous dose of the same vaccine should not be given another dose.

Although the typhoid vaccine is absolutely safe, your child may develop a fever for a day or two after the vaccine is taken. You need not panic. Visit the doctor immediately if the fever persists for too long.

What Happens If Your Child Misses the Dose

If you are worried that your toddler may have missed the vaccine at 9 months, don’t worry – you can still give it to her before she turns one. Moreover, TCV can be given to your child at any time.

Possible Risks and Side-Effects of the Vaccine

Typhoid vaccine side-effects are generally mild – they tend to go away in a few days. In rare cases, there may be an allergic reaction. The side-effects have been discussed below:

1. Serious Side-Effects

Generally, the typhoid vaccine does not have any serious side-effects. Contact your paediatrician in case of:

  • Signs of a severe allergic reaction like dizziness, hives, and swelling of the face and throat
  • Difficulty breathing
  • Weakness
  • Very high fever
  • Changes in behaviour

Although rare, these may manifest within a few hours of taking the vaccination.

2. Less Serious Side-Effects

Some less severe side-effects of the typhoid shot are:

  • Fever
  • Headache
  • Redness and swelling
  • Itching and soreness at the place where the injection is given
  • General discomfort

Typhoid is a serious disease that is best prevented in young children. If you are alert and careful, you can ensure a healthy childhood for your little one. Regular vaccinations and timely care will help you in doing just that.

Disclaimer: This information is for the purpose of reference alone. Please consult your paediatrician regarding the actual vaccination schedule.

Resources and References: Mayo Clinic

Also Read: Typhoid in Babies

Typhoid Fever | History of Vaccines

Symptoms and Causative Agent

Typhoid fever is a bacterial disease caused by Salmonella typhi. While rare in industrialized countries, typhoid fever is a significant threat in some low-income countries.

Symptoms of typhoid fever range from mild to serious and usually develop one to three weeks after exposure to the bacteria. Symptoms include fever, headache, nausea, constipation or diarrhea, loss of appetite, and a rose-colored rash on the body.  

Typhoid fever symptoms are similar to those of other common gastrointestinal illnesses. The only way to know that a person is ill with typhoid is to have their blood or feces tested for Salmonella typhi.

Transmission

Typhoid fever spreads from person to person via contaminated food and water. Transmission is via the fecal-oral route, meaning that contaminated feces (and sometimes urine) may enter water supplies or food supplies, which may then be consumed by and infect others.  Salmonella typhi lives only in humans; there is no animal reservoir for the bacteria.

About 21 million cases of typhoid fever and 220,000 deaths occur annually worldwide.

Treatment and Care

Typhoid fever is found more commonly in densely populated areas where water supplies are vulnerable to contamination. Good water sanitation methods and proper storage and handling of food and water can help prevent spread of S. typhi.

Antibiotics are the only effective treatment for typhoid fever. Most patients improve after beginning antibiotic treatment, especially if the disease is detected early.

Complications

Typhoid fever may lead to intestinal bleeding and perforation. This in turn can cause severe abdominal pain, nausea, vomiting, and sepsis. Surgery may be needed to repair the intestinal damage.

Less common complications that can occur are inflammation of the heart muscle, inflammation of the lining of the heart and valves, pneumonia, inflammation of the pancreas, meningitis, kidney or bladder infections, and delirium.

Available Vaccines and Vaccination Campaigns

Two typhoid vaccines are licensed for use in the United States; these are typically reserved for people traveling to areas where typhoid fever is common or for people who may come into direct contact with the disease.

Ty21a is a live, attenuated vaccine given in oral capsule form. Within the first two years of vaccination, the vaccine is moderately effective at preventing disease. Three years after initial vaccination, the vaccine offers no protection. The minimum age for this vaccine is six years.

Vi capsular polysaccharide (ViCPS) is an injected subunit vaccine. In clinical trials, it reduced disease rates by nearly 66%, though effectiveness wanes after several years. The minimum age for this vaccine is two years.

Typhoid conjugate vaccine (TCV), not available in the United States, was approved for use in India in 2013 and in late 2017 was pre-qualified by the World Health Organization (WHO). This new vaccine may be given to infants six months of age and older. It offers protection for up to five years after immunization.

U.S. Vaccination Recommendations

Typhoid fever vaccination is neither required nor recommended for routine use in people who live in the United States. Vaccination with Ty21a or ViCPS may be recommended for travel to areas where there is a risk for typhoid infection. Travelers are usually advised to take the typhoid vaccine one to two weeks before departure.

TCV has recently been recommended by the WHO for control of typhoid fever because of its long-lasting immunological effects and its suitability even for very young children. Both Ty21a and ViCPS are also approved by the World Health Organization for typhoid fever control.


Sources

Anwar, E., Goldberg, E., Fraser, A., Acosta, C.J., Paul, M., Leibovici, L. Vaccines for preventing typhoid fever. The Cochrane Database of Systematic Reviews 1: CD001261. 2014. Accessed 01/25/2018.

Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Diseases. Typhoid Fever. Accessed 01/25/2018.

CDC. Typhoid Fever Vaccination. Accessed 01/25/2018.

The Mayo Clinic. Typhoid Fever. Accessed 01/25/2018.

Szu, S.C. Development of Vi conjugate – a new generation of typhoid vaccine. Expert Review of Vaccines 12 (11): 1273–86. November 2013. Accessed 01/25/2018.

World Health Organization. Typhoid Fever. Accessed 01/25/2018.

World Health Organization. Typhoid Fever Vaccines. Accessed 01/25/2018.

World Health Organization. Typhoid Fever Vaccines: Position Statement. March 2018. Accessed 4/2/2018.

 

Last update 03 April 2018

Vaccination against typhoid fever

We provide vaccination against typhoid fever. Safe, fast, in 8 districts of St. Petersburg.

Typhoid fever is a severe intestinal infection caused by the bacterium Salmonella and affects the intestines. The disease proceeds in an acute form, often with relapses, and is manifested by prolonged fever, diarrhea and general intoxication of the body. Complications of typhoid fever are life-threatening, as they can provoke intestinal ulcers, intra-abdominal bleeding and toxic shock.

The most common way of transmission of the disease is through household contact with a sick person or through water. Thorough hygiene is necessary to reduce the risk of infection, however, even in this case, the risk of getting sick remains. Vaccination against typhoid fever remains the best way to protect against infection, which allows you to acquire persistent immunity in 80% of cases.

Other names: typhoid vaccination, typhoid immunization

Who needs typhoid vaccination and when?

People who are in direct contact with patients are at risk.The situation is complicated by the fact that the symptoms of infection appear only 2-3 weeks after infection, and the fact of the disease may be subtle.

Persons most at risk of contracting typhoid fever:

  • residing in regions endemic for typhoid fever (including with one-time outbreaks)
  • traveling to dangerous regions (states of Africa, Asia, South America, etc.)
  • 90,025 employed in the field of public utilities (water supply, work with household waste, etc.))

  • health workers involved in the decontamination of infectious areas during typhoid fever outbreaks
  • Vaccine laboratory workers
  • 90,025 other cases suggesting contact with the sick.

How is typhoid vaccination carried out?

The vaccine is injected intramuscularly or under the skin in the upper part of the shoulder once. The vaccine provides immunity from typhoid fever for 3 years. If the risk of infection after this period persists, vaccination is repeated.

Are there any contraindications to vaccination?

There are no specific contraindications to typhoid vaccination. It is worth discussing with the doctor the advisability of vaccination in cases of exacerbation of diseases, allergic reactions and general weakening of the body.

Direct contraindications to any vaccinations are serious diseases (such as HIV, tuberculosis, etc.), pregnancy and intolerance to vaccine components.

What documents are required for measles vaccination?

In the centers of “Medical Commission No. 1” only a passport is required.Take with you, if present, a vaccination certificate with information about previous vaccinations.

Where and when can I contact?

You can get vaccinated against typhoid fever in any convenient center “Medical Commission No. 1”. We operate in 8 districts of St. Petersburg and have all the necessary licenses for this type of activity. In our clinics, only proven safe vaccines are used, a doctor’s consultation is provided.

Why is it worth contacting the “Medical Commission No. 1”?

Reliable – our centers have all the necessary licenses for this type of service.Vaccination is carried out by certified specialists with extensive experience. Only high quality drugs are used.

Fast – registration for the service is available by phone and on our website, where you can choose a convenient time and the nearest branch. The vaccination procedure and consultation with a therapist will take a few minutes.

Convenient – our clinics are located in 8 districts of St. Petersburg and work seven days a week.

You can get a consultation or make an appointment by phone +7 (812) 380-82-54

Make an appointment >>>

90,000 Typhoid vaccine helped immune cells attack other pathogens

Scanning electron microscopy Salmonella enterica

Muhsin Özel, Gudrun Holland, Rolf Reissbrodt / RKI

Some vaccines lead to nonspecific activation of the immune response.A Liverpool-based research team studied the immune system response to the administration of a live, attenuated typhoid fever vaccine, Ty21a. It turned out that Ty21a alters the expression of genes of immune cells and affects their activity in response to other antigens, that is, it helps to fight other pathogens. Article published in Science Advances.

According to the body’s readiness to fight foreign objects, they distinguish
congenital and acquired immunity. The first has the ability to effectively attack dangerous
biomaterial that enters the body for the first time.It is realized by phagocytes,
granulocytes and some lymphocytes. The acquired immunity works quickly only when the object re-enters the body. T- and B-lymphocytes are responsible for it.

Vaccines are used to train the body’s immune cells before meeting a real infection. For example, for the prevention of measles,
rubella, poliomyelitis, tuberculosis, people are injected with weakened live strains of these
microorganisms. Immune cells remember them and when they hit them again
the active strain is more quickly recognized and killed.Vaccines have recently been shown to
against tuberculosis (BCG, Bacillus Calmette-Guerin), measles and oral polio vaccine
increase the efficiency of the immune system as a whole, reducing the overall mortality in
the case of infectious diseases.

A group of scientists from the University of Liverpool and the Liverpool School of Tropical Medicine led by Melita Gordon
Gordon) has demonstrated the non-specific effect of the oral Ty21a vaccine against
strain Salmonella typhi , causing
typhoid fever.They analyzed monocyte receptors in volunteers after two
weeks, three and six months after vaccination. It turned out that after three months the genes
some receptors are more actively expressed, for example TLR-4 and TLR-5. Since monocytes circulate in
blood for about a day, the researchers concluded that what was happening
epigenetic change in the regulation of genes of the precursor of these cells.

Scientists also cultured in vitro T-
and B-lymphocytes, monocytes of the control and vaccinated Ty21a groups and assessed
their activity after stimulation with different antigens.For example, monocytes
vaccinated volunteers secreted more interferon-γ, and B-lymphocytes – more interleukin
4 in response to antigen of the fungus Candida
albicans
. The authors noted that compared to other vaccines that produce similar effects,
Ty21a is safer and cheaper. And thanks to the stimulating nonspecific
its effect on immunity can be included in vaccination programs.

Two variants of the action of the vaccine on the immune system.Above: traditional formation of specific memory of cells of adaptive immunity. Bottom: the vaccine enhances the nonspecific activity of innate immunity cells aimed at destroying various pathogens.

S. H. Pennington et al., 2019

At the beginning of this year, WHO added vaccination refusal to the list of global threats to humanity.As part of the fight against this problem, scientists have considered options for spreading information about the importance of vaccines on Twitter. It turned out that the more popular were the posts without direct links to the source.

Ekaterina Kharybina

Clinical Study Typbar patients and healthy volunteers will receive Typbar-TCV vaccine: Typbar-TCV vaccine – Clinical Trials Register

Detailed Description

Description of the research project: Previously, it was shown that IFN-gamma and IL-17 are increased in patients with typhoid fever.Infection with S. Typhi has been shown to elicit antibody responses against a number of key typhoid antigens (LPS) (HlyE, Flagellar protein FliC and chaperone protein EcpD). In intestinal diarrheal cholera, MAIT cells are activated and LPS-associated specific antibody responses. In a model study, it was shown that memory cells of CD8 + T-lymphocytes are key correlates of defense against typhoid fever. The live attenuated typhoid (TY21a) vaccine also induces MAIT cells after immunization.IL-12, IL-15, IL-18 have been shown to induce memory-like NK cells in a mouse model, and IL-21 induces memory-like NK cells that protect against Mycobacterium tuberculosis. Role of activated MAIT cells and cytokines inducing memory-like NK cells of typhoid fever are currently unknown. One of the multiple kill mechanisms used by neutrophils is the release of neutrophils. extracellular traps (NET), which contain myeloperoxidase (MPO), elastase, lysozyme, and Infection causes the release of NET to trap microbial pathogens.isolated from patients with typhoid fever, secrete NET, and this release of neutrophils NET is primed by vaccination with a subunit conjugate vaccine. Study Intervention: Typbar-TCV is a capsular polysaccharide of Vi tetanus toxoid. conjugate vaccine. Typbar-TCV is the world’s first clinically validated typhoid conjugate vaccine. This vaccine is WHO prequalified and approved for use in children and infants under 2 years of age. In a Phase III clinical trial, a single dose of Typbar-TCV produced 4-fold seroconversion rates of 98.05%, 99.17%, and 92.13% in subjects over 6 months to 2 years of age, 2 to 15 years, and 15 up to 45 years, respectively.The vaccination team will receive 25 mcg of Typbar-TCV vaccine as a 0.5 ml single intracellular dose. Storage conditions: the vaccine will be stored at + 2-8C and the cold chain will be maintained at all times. Study Participants and Sample Collection: Researchers will collect 8-10 ml of blood. from adults and 3-5 ml of blood from children with suspected typhoid fever (age 1-59 years) at registration (day 1) and if the patient has a confirmed culture of S. Typhi / Paratyphi then two more blood samples will be taken (2-5 days and 27-33 days later).the researchers will collect 8-10 ml of blood from adults and 3-5 ml from children. before vaccination (day 0) and two more blood samples after one dose of vaccination on day 7 (6-8 days later) [13] and on day 30 (27-33 days later). Peripheral blood mononuclear cells (PBMC) and neutrophils will be isolated from blood samples and used for various (Polymorphprep kit). Plasma samples will be separated to measure the antibody response to infection and vaccination. Patient Management Antibiotics and other necessary medications will be provided at the discretion of the clinician.Once typhoid culture is confirmed, antibiotic treatment for fever will be adjusted based on the antibiotic susceptibility pattern. the patient does not respond to the oral antibiotic, then we will give him an injectable antibiotic. the patient does not respond to the injected antibiotic and / or other complications occur, then the patient will be hospitalized. Researchers are conducting another study of typhoid fever. where the patients are in the various health facilities of Mirpur as well as icddr, b Dhaka Hospital.Patient treatment will be supported by other ongoing typhoid fever. project. Laboratory Test Procedure: MAIT and NK Cell Assay: Isolated PBMCs are stained with fluorochrome-labeled antibodies. and performed flow cytometric phenotyping (obtaining ≥ 50,000 live cells on FACS-Aria). MAIT cells will be defined as living (DAPI-) CD3 + CD4-CD161hiVα7.2 + cells, expressed as a percentage of the total CD3 + and CD38 lymphocytes, used as a marker of cell activation.The researchers will also assess the circulating frequency of live CD3 + CD8 + CD4-CD161loVα7.2 + cells, which are believed to be MAIT derivatives associated with absent or decreased cytokine secretion in vitro. CD4 + (live CD3 + CD8-CD4 +) T cell responses in study subjects will be assessed in different subsets of T memory (TM) defined by their expression of CD45RA and CD62L, i.e. central T memory (TCM; CD45RA-CD62L +), T effector memory (TEM; CD45RA-CD62L-) and T effector memory CD45RA + (TEMRA; CD45RA + CD62L-), follicular T (CD3 + CXCR5 +) and Naïve T cells (TN: CD45RA + CD62L +).Activated NK cells as live CD3-, CD45 +, CD56 +, CD69 +, CD40L +, CD16 + cells and memory such as NK cells, such as live CD3-CD56 + CD16 + NKp46 + CD27 +. Cytokine analysis: isolated lymphocytes will be stimulated with S. Typhi antigens (whole cells, MP and LPS) for 48 hours and for 5 days and the culture supernatant will be harvested and stored until analysis at -70 ° C. Cytokines in the culture supernatant will be analyzed using a multiplex bead (Luminex). Quantification of NET: Neutrophils will be isolated from peripheral blood based on the previously described method.NET release will be measured using the NET Neutrophil Assay Kit (NET Assay Kit, Creative Biomart, NY, USA). .NETosis will be quantified by measuring the levels of elastase that are released from neutrophils and the mediated destruction of NETs will be quantified by measuring bacterial viability. Analysis of NETs Mediated Killing: An analysis will be performed to determine the effectiveness of NETs in killing S. Typhi, CFU. An overnight culture of S. Typhi will be co-incubated with freshly isolated human neutrophils in a 96-well culture plate and incubated at 37ºC.After 3 hours After incubation, the wells are aspirated and washed with PBS. Dilutions 1:10 and 1: 100 will be 100 μl of each dilution plated onto Brain Heart Infusion Agar (BHI). the plates will be incubated at 37 ° C with 5% CO2. The CFU will be calculated after 24 hours. hours of incubation and after 3 days of culture, until the increase in the number of colonies is observed. Analysis of intracellular neutrophil metabolites: Neutrophils will be isolated from the blood and incubated at 37ºC for 1 hour for recovery.The incubation medium will be aspirated and 1 ml dry Ice (-80ºC) cold 80% methanol will be added. The wells are shaken for 1 min and then centrifuged at 15 K rpm for 1 min. The supernatant is collected in tubes and stored at -80 ° C until use. Before analysis, samples are removed from -80ºC and allowed to equilibrate to room temperature. The supernatant (75 μl) is transferred in tandem for liquid chromatography. the mass spectrometry (LC-MS) tube is closed. Ten microliters of sample will be automatically loaded into the LC-MS System for metabolite separation and mass spectrometric analysis.Antibody responses to plasma lipopolysaccharides (LPS). Plasma antibody responses to S. LPS typhoid in patients and vaccinated patients will be measured using ELISA methods. microtiter plates will be coated with LPS and incubated with plasma (1:10 dilution) followed by successive 3-fold dilutions. Plates will be rinsed and horseradish anti-human IgA, IgG and IgM peroxidase conjugated antibodies will be added. designed using 0.1% ortho-phenylenediamine (OPD) and 0.1% hydrogen peroxide (h3O2) and OD will be measured at 492nm.A 2-fold or higher antibody response will be considered a significant response. Transcriptomic analysis: 3 ml of blood will be drawn from a subgroup of adult patients and vaccinated. collected in Tempus RNA tubes (applied biosystem), and the RNA will be extracted from the blood, transcriptome sequencing will be performed in Shanghai, China (BGI), which provides laboratory services, and the data will be analyzed using next generation RNA sequencing to see gene expression Profile …Differential gene expression will be analyzed using the DESeq package. (Bioconductor). The resulting sequence reads will be normalized between patients / vaccinated. compared to a healthy control group. a ratio greater than 2 and less than 0.5 will be considered. essential. …

Types of vaccines | GOBUZ “Kola Central District Hospital”

The discovery of the vaccination method launched a new era of disease control.

The grafting material contains killed or strongly weakened microorganisms or their components (parts).They serve as a kind of dummy that trains the immune system to respond correctly to infectious attacks. The substances that make up the vaccine (vaccinations) are not capable of causing a full-fledged disease, but they can enable the immune system to remember the characteristic signs of microbes and, when meeting with a real pathogen, quickly identify and destroy it.

Vaccine production became widespread at the beginning of the twentieth century, after pharmacists learned how to neutralize bacterial toxins. The process of weakening potential infectious agents is called attenuation.

Today, medicine has more than 100 types of vaccines for dozens of infections.

According to their main characteristics, drugs for immunization are divided into three main classes:

  1. Live vaccines. Protect against poliomyelitis, measles, rubella, influenza, mumps, chickenpox, tuberculosis, rotavirus infection. The basis of the drug is weakened microorganisms – pathogens. They are not strong enough to develop significant malaise in the patient, but they are enough to develop an adequate immune response.
  2. Inactivated vaccines. Vaccinations against influenza, typhoid fever, tick-borne encephalitis, rabies, hepatitis A, meningococcal infection, etc. Includes dead (killed) bacteria or their fragments.
  3. Toxoids (toxoids). Specially processed bacterial toxins. On their basis, inoculation material is made against whooping cough, tetanus, diphtheria.

In recent years, another type of vaccine has appeared – molecular .The material for them is recombinant proteins or their fragments synthesized in laboratories using genetic engineering methods (recombinant vaccine against viral hepatitis B).

Source: Vaccine Specialists

90,000 VACCINES: FROM JENNER AND PASTER TO OUR DAY

Infectious diseases at all times have been the main enemies of man. History knows many examples of the devastating consequences of smallpox, plague, cholera, typhoid, dysentery, measles, flu. Suffice it to recall that the decline of Ancient Greece and Rome is associated not so much with the wars they waged as with the monstrous plague epidemics that destroyed most of the population.In the XIV century, the plague killed a third of the population of Europe. Due to the smallpox epidemic, 15 years after the invasion of Cortez, less than 3 million people remained of the 30 millionth Inca empire. The influenza pandemic (the so-called “Spanish flu”) in 1918-1920 claimed the lives of about 40 million people, and the number of cases amounted to about 500 million people. This is more than the losses on the battlefields of the First World War, where 8 million 400 thousand people died and 17 million people were injured.

The majestic cathedral that adorns the square of the Italian city of Siena could have looked even more grandiose if it were not for the plague epidemic.

One of the traditional methods of attenuating viruses is growing in animal cells.

Recombinant technologies make it possible to obtain a weakened virus in a shorter time.

Timeline of vaccine development

Return of childhood infections after cessation of mass vaccination.

DNA vaccination consists in introducing a DNA fragment encoding protective antigens and cytokines directly into muscle tissue.

In search of remedies for infectious diseases, people have tried many things – from spells and conspiracies to disinfectants and quarantine measures. However, it was only with the advent of vaccines that a new era of infection control began. Vaccines contain whole microorganisms (weakened or killed) or their individual components. They are not capable of causing disease and serve as a kind of training “dummy”. Thanks to the vaccine, the immune system remembers the characteristic features of the enemy and, when it encounters a live pathogen, immediately recognizes it and destroys it.

The term “vaccine” comes from the French word vacca – cow. It was introduced by Louis Pasteur in honor of the English physician Edward Jenner, who undoubtedly can be considered a pioneer in the field of vaccine prevention. In 1796, while practicing in the village, Jenner noticed that farmers who work with cows infected with vaccinia do not get smallpox. He vaccinated the boy with vaccinia and proved that he had become immune to smallpox. This method, invented at a time when neither bacteria nor viruses were yet discovered, became widespread in Europe, and later formed the basis for the elimination of smallpox throughout the world.However, it was only a century later that a scientific approach to vaccination was proposed. Its author was Louis Pasteur, who applied his concept of infectious pathogens to create a vaccine against rabies.

The development of new vaccines was in full swing at the beginning of the 20th century, when methods of stable attenuation (weakening) of microorganisms appeared, eliminating the risk of developing a disease, and the possibility of using neutralized bacterial toxins for vaccination was discovered.

Since then, more than 100 different vaccines have appeared that protect against more than forty infections caused by bacteria, viruses, and protozoa.

Classic vaccine preparations can be divided into three groups:

1. Live vaccines. The active principle in them are weakened microorganisms that have lost the ability to cause disease, but stimulate the immune response. This group includes vaccines against measles, rubella, polio, mumps and influenza.

2. Inactivated vaccines. They contain killed pathogenic microorganisms or their fragments. An example is vaccines against influenza, tick-borne encephalitis, rabies, typhoid fever.

3. Toxoids (toxoids) – bacterial toxins in a modified harmless form. These include well-known and widely used vaccines against diphtheria, tetanus, pertussis.

With the beginning of the rapid development of molecular biology, genetics and genetic engineering methods, a new class of vaccines appeared – molecular vaccines. They use recombinant proteins or protein fragments of pathogenic microbes synthesized in the cells of laboratory strains of bacteria, viruses, yeast.So far, only three such drugs have entered into practice: the recombinant vaccine against hepatitis B, the vaccine against Lyme disease and the detoxified pertussis toxin, which is included in the DTP vaccine used in Italy.

Vaccines have allowed humanity to achieve incredible results in the fight against infections. Smallpox, a disease that annually claimed the lives of millions of people, has been completely eradicated in the world. This is one of the most outstanding events of the twentieth century, which in importance is on a par with the flight of man into space.Poliomyelitis has practically disappeared, and the global elimination of measles continues. The incidence of diphtheria, rubella, whooping cough, mumps, viral hepatitis B and many other dangerous infectious diseases has been reduced by hundreds and even thousands of times.

UNTIL THE FULL VICTORY IS STILL LONGER

Despite impressive successes, infectious diseases are still one of the leading causes of death: according to the World Health Organization (WHO), they account for up to 30% of the annual deaths on the planet.The most dangerous are acute respiratory tract infections, primarily influenza and pneumonia, human immunodeficiency virus infection, intestinal infections, tuberculosis, viral hepatitis B, and malaria.

According to the forecast of experts from WHO, Russia and the United States, an outbreak of new or recurring infections can occur at any time and anywhere in the world. Unknown microorganisms are brought into the human population from natural foci almost every year. Over the past 30 years, we have encountered 40 new dangerous microorganisms, which in many cases have created a real threat to the life and health of hundreds of thousands of people.Among them are the Ebola virus, the causative agent of Legionnaires’ disease, HIV, coronaviruses and other pathogens.

Often, against the background of epidemiological well-being, people stop vaccinating,
stipulated by national health systems, and then infections that were considered
long vanquished, are returning. In the last decades of the whooping cough epidemic,
diphtheria, poliomyelitis and measles are registered in Japan, Russia, Azerbaijan,
Georgia, Tajikistan, Ukraine, Haiti, Venezuela and Colombia.Indicative
an example with the return in the mid-90s to the territory of Russia of diphtheria, which
until that time met only occasionally. As a result of the anti-vaccination campaign,
deployed by pseudo-specialists, more than 100 thousand people fell ill with diphtheria,
several thousand of them died. And only mass vaccination of children allowed
stop the epidemic.

The migration of people and animals leads to the spread of microorganisms to new territories. Massive outbreaks of infectious diseases occur even in countries with well-developed health systems, such as the United States.In 1999, cases of West Nile fever, a virus transmitted by birds, were reported in New York. By 2002, this disease was observed in 44 states. More than four thousand people fell ill, of which about three hundred died.

In May 2003, there were reports of illness caused by the monkeypox virus. In the United States, it was carried by rodents, which were brought from Africa as exotic pets. The disease did not become widespread only because anti-epidemic measures were taken in time.

Of the new infections that have penetrated the human population, it is enough to mention the outbreak of the so-called atypical pneumonia (severe acute respiratory syndrome) in China and the facts of human infection with the avian influenza virus (H5N1). In the first case, the cause was a modified coronavirus carried by bats. It took about a year to eliminate the disease. In the second case, mass diseases of poultry have led to the fact that over a hundred people have become infected with the avian influenza virus over the past three years, half of them have died.Fortunately, this virus is not yet transmitted from person to person and therefore does not cause epidemics among people. But a number of scientists believe that the exchange of genes between the avian and human variants of the virus is quite probable, as a result, new variants, highly pathogenic for humans, may appear (see Science and Life No. 9, 2003 – Ed. ).

VACCINES AGAINST “NON-INFECTIOUS” DISEASES

At the beginning of the twentieth century, the great Russian scientist II Mechnikov suggested that somatic (that is, “bodily”) diseases and malignant tumors are infectious in nature.”Over time,” he wrote, “it will probably be possible to discover parasites not only in diseases of a typically infectious nature, but also in diseases of a completely different kind.” The scientist predicted that there are parasites of malignant tumors, as well as microbes – the causative agents of sugar disease. I.I.Mechnikov’s hypothesis received brilliant confirmation.

Epidemiologists from different countries note that during the seasonal rise in the incidence of influenza, the number of hospitalized people with cardiovascular problems and cerebrovascular accidents increases.At the same time, mortality from myocardial infarctions and strokes also increases, sometimes tens of times. Often, a viral infection leads to myocarditis and endocarditis – diseases in which heart tissue is affected. When the USA began to vaccinate children against mumps, an unintended “side” effect appeared: the incidence of endocarditis sharply decreased. The survey confirmed that the majority of patients suffering from this serious disease, leading to heart disease, had mumps in early childhood.It is possible that atherosclerosis has an infectious nature, since the presence of chlamydia and some other microorganisms was found in atherosclerotic plaques of the coronary vessels and aorta of a person.

It has already been proven that stomach and duodenal ulcers, as well as gastritis, are associated with infection. The bacterium Helicobacter pylori , the discovery of which was marked by the Nobel Prize in 2005 (see “Science and Life” No. 12, 2005 – Ed. ), is found in 50% of patients with gastritis, in 70-90% of patients with a stomach ulcer and in 95% of persons suffering from a duodenal ulcer.

When a person is infected with retroviruses, reoviruses, cytomegalovirus and Epstein-Barr virus, antibodies are formed that attack the cells of the pancreas, which can lead to the development of insulin-dependent diabetes. In 10-20% of patients with congenital rubella syndrome, that is, in children whose mothers had rubella in the last trimester of pregnancy, carbohydrate metabolism disorders also develop. Tumors of the stomach, genitalia, and liver are also associated with bacteria or viruses in many cases.

How do microorganisms affect the development of diseases that are not considered infectious? First of all, the organ begins to perform its function worse due to the fact that microbes destroy infected cells. Experiments with cell cultures suggest that mumps, rubella, and Coxsackie B viruses act by this mechanism.

It is possible that in some cases the virus only initiates the pathological process, and further tumor growth occurs without the participation of microorganisms.This hypothesis was proposed by the Russian immunologist L.A. Zilber when constructing a viral theory of the origin of tumors. Sometimes microorganisms simply enhance the action of other adverse factors, and in some cases, the infectious pathogen triggers an autoimmune process directed against the cells of the target organ.

Since many noncommunicable diseases are associated with microbes, there is hope of using existing vaccines for prevention. The first evidence has been obtained that vaccines against hepatitis B virus have the ability to prevent the development of a liver tumor – hepatocarcinoma.Since Taiwan began to vaccinate children against hepatitis B, the incidence of hepatocarcinoma has decreased by 50%, and the death rate from it by 70%.

Several potential papillomavirus vaccines have already been tested to prevent the development of genital cancers. A preclinical study of the H. pylori whole cell vaccine for the prevention of gastric and duodenal ulcers has been completed.

DNA IS IN BATTLE

It is not always possible to create vaccines against new infections using old proven technologies.Some microorganisms, such as the hepatitis B virus, are nearly impossible to grow in cell culture to produce an inactivated vaccine. In many cases, vaccines based on killed germs are ineffective, and live vaccines are too dangerous. Great hopes were pinned on vaccines based on recombinant antigen proteins (this was the way they created a vaccine that protects against hepatitis B in the 1980s). But it has now become apparent that many recombinant vaccines elicit a weak immune response.This is likely due to the fact that such preparations contain a “naked” protein and lack other molecular structures, often required to trigger an immune response. For recombinant vaccines to come into practice, enhancers (adjuvants) are needed to stimulate antigenic activity.

Over the past 10 years, a new direction has emerged – genetic immunization. It is also called DNA vaccination, since it is not an antigen protein that is injected into the body, but nucleic acid (DNA or RNA), which encodes information about the protein.A real opportunity to use this technology in medicine and veterinary medicine appeared in the mid-90s of the last century. The new approach is quite simple, cheap and, most importantly, versatile. Relatively safe systems have now been developed that ensure efficient delivery of nucleic acids into tissues. The desired gene is inserted into a plasmid (DNA ring) or into a safe virus. Such a carrier vector enters the cell and synthesizes the required proteins. The transformed cell turns into a “factory” for the production of vaccines right inside the body.The vaccine “factory” is capable of operating for a long period – up to a year. DNA vaccination leads to a complete immune response and provides a high level of protection against viral infection.

Using the same plasmid or viral vector, it is possible to create vaccines against various infectious diseases by changing only the sequence coding for the required antigen proteins. This eliminates the need to work with dangerous viruses and bacteria, and the complex and expensive procedure for purifying proteins becomes unnecessary.DNA vaccine preparations do not require special storage and delivery conditions; they are stable for a long time at room temperature.

DNA vaccines have already been developed and tested against infections caused by hepatitis B and C viruses, influenza, lymphocytic choriomeningitis, rabies, human immunodeficiency (HIV), Japanese encephalitis, as well as causative agents of salmonellosis, tuberculosis and some parasitic diseases (leishmaniasis, malaria). These infections are extremely dangerous for humanity, and attempts to create reliable vaccines against them by classical methods have been unsuccessful.

DNA vaccination is one of the most promising areas in the fight against cancer. Different genes can be introduced into the tumor: those that encode cancer antigens, genes for cytokines and immunomodulators, genes for “killing” the cell. All these genes can be used simultaneously, organizing a massive attack with weapons of different types.

However, before DNA vaccination enters medical practice, it is necessary to ensure the safety of such drugs, to study the duration of the immunity they induce and the consequences for the immune system.

VACCINES “BY CALCULATION”

The rapid development in the last decade of genomics, bioinformatics and proteomics has led to a completely new approach to the creation of vaccines, called “reverse vaccinology” (reverse vaccinology). This term clearly expresses the essence of a new technological technique. If earlier, when creating vaccines, scientists followed a descending line, from the whole microorganism to its components, now the opposite path is proposed: from the genome to its products.This approach is based on the fact that most of the protective antigens are protein molecules. With a complete knowledge of all the protein components of any causative agent, it is possible to determine which of them are suitable as potential candidates for inclusion in a vaccine formulation, and which are not.

To determine the nucleotide sequence of the complete genome of an infectious microorganism, if not several days, then several weeks are enough. Moreover, preliminary work on obtaining “libraries” of DNA clones of the pathogen has long been performed using standard sets of enzymes.Modern devices for automatic determination of the nucleotide sequence in DNA molecules allow up to 14 million reactions per year. Complete decoding of the genome and its description with a list of encoded proteins take several months.

By performing computer (in silico) analysis of the genome, the researcher receives not only a list of encoded proteins, but also some of their characteristics, for example, belonging to certain groups, possible localization within a bacterial cell, connection with a membrane, and antigenic properties.

Another approach to the selection of vaccine candidates is to determine the activity of individual genes of microorganisms. For this, the level of synthesis of messenger RNA of all gene products produced in the cell is measured simultaneously. This technology makes it possible to “calculate” the genes involved in the spread of infection.

The third approach is based on proteomic technology. Its methods make it possible to detail the quantitative and qualitative characteristics of proteins in cell components.There are computer programs that, based on the amino acid sequence, can predict not only the three-dimensional structure of the protein under study, but also its properties and functions.

Using these three methods, it is possible to select a set of proteins and their corresponding genes that are of interest for creating a vaccine. As a rule, this group includes about 20-30% of all genes of the bacterial genome. For further verification, it is necessary to synthesize and purify the selected antigen in quantities required for immunization of animals.Protein purification is carried out using fully automated devices. Using modern technology, a laboratory of three researchers can isolate and purify more than 100 proteins within a month.

For the first time, the principle of “reverse vaccinology” was used to obtain a vaccine against meningococci of group B. In recent years, vaccine preparations against streptococci Streptococcus agalactiae and S. pneumoniae , Staphylococcus aureus, bacteria Porphyromonas gingivalis have been developed in this way, causing inflammation gums, asthma-provoking microorganism Chlamydia pneumoniae and the causative agent of severe malaria Plasmodium falciparum .

It is important not only to create a vaccine, but also to find the best way to deliver it to
organism. Now there are so-called mucosal vaccines that are administered
through the mucous membranes of the mouth or nose, or through the skin. The advantage of such drugs
the fact that the vaccine enters through the entrance gate of the infection and thereby stimulates
local immunity in those organs that are the first to be attacked by microorganisms.

THERAPEUTIC VACCINES

Conventional vaccines are designed to prevent disease: a healthy person is vaccinated in order to “arm” the body in advance with means of fighting infection (an exception is Pasteur’s rabies vaccine, which is used after being bitten by a rabid animal; its effectiveness is explained by the long incubation period of this viral disease).But recently, the attitude towards vaccines solely as a prophylactic agent has changed. Therapeutic vaccines have appeared – drugs that induce an immune response in patients and thereby contribute to the recovery or improvement of the condition. Such vaccines target chronic diseases caused by bacteria or viruses (in particular, hepatitis B and C viruses, papillomavirus, HIV), tumors (primarily melanoma, breast or rectal cancer), allergic or autoimmune diseases (multiple sclerosis, diabetes Type I, rheumatoid arthritis).

Existing therapeutic vaccines for the treatment of chronic inflammatory diseases caused by bacteria or viruses are obtained by classical methods. Such vaccines contribute to the development of immunity to the microorganisms included in their composition and activate innate immunity.

One of the most important goals of therapeutic vaccine developers is HIV infection. A series of preclinical and clinical trials of several drugs have already been carried out. Their ability to induce the development of cellular immunity in healthy people is beyond doubt.However, there is still no convincing evidence that vaccines suppress the multiplication of the virus in patients.

Dendritic vaccines are promising for the treatment of immunosuppression in cancer. They are made on the basis of dendritic cells – a special type of leukocytes that search for potentially dangerous microorganisms. Dendritic cells “patrol”, first of all, mucous membranes and skin, that is, organs in contact with the external environment. Upon encountering a pathogenic bacterium or virus, dendritic cells absorb the alien and use its antigen proteins in order to activate the immune system to fight the enemy.

The scheme for making a dendritic vaccine is as follows: cells are isolated from the patient’s blood, which give rise to dendritic cells, and they are multiplied in laboratory conditions. At the same time, antigen proteins are isolated from the patient’s tumor. Dendritic cells are kept together with tumor antigens for some time so that they remember the image of the enemy, and then they are injected into the patient. This stimulation of the immune system forces the body to actively fight the tumor.

Dendritic vaccines can be used to treat both spontaneous tumors and neoplasms associated with viruses.The first results of trials of dendritic anticancer vaccines in humans (in small groups of patients with stage IV disease) showed the harmlessness of such vaccines, and in some cases a positive clinical effect was recorded.

In mice, dendritic vaccines help prevent carcinoma from reoccurring after tumor removal. This allows us to hope that they will be effective in prolonging the relapse-free period of cancer patients after surgery.

In the XX century, the successes of vaccinology were determined, first of all, by victories over the next
dangerous infection.With the development of our understanding of the work of the immune system
the scope of vaccines is constantly expanding. There is hope that in the 21st century
vaccines will help reduce the incidence of diabetes, myocarditis, atherosclerosis
and other “non-communicable” diseases. Drug development is in full swing
for immunoprophylaxis and immunotherapy of oncological diseases. In perspective
– creation of means of immunological protection against drug addiction and smoking, design
vaccines for the treatment and prevention of allergies, autoimmune diseases.

See in the issue on the same topic

O. SUGOY – Strategic vaccine.

Typhoid fever – the ominous satellite of humanity

: 20 Aug 2019, Chromosome Singing History, Volume 83,
Number 3

“The following vaccinations are recommended …” – you can find such a mention in small print in a travel guide when going on vacation to an exotic country.Glancing through the list of recommendations, the gaze rests on the words – “typhoid fever.” Why do you need vaccinations against a forgotten disease that no one of your acquaintances was ill with? The error will be in the question itself. What makes you think that typhoid fever is not among us? And today people are dying from this disease. Typhoid fever was, is and will be a threat that awaits its moment and opportunity. The roots of its history go back to the distant past of our species, and it did not end with the advent of such benefits of civilization as hygiene and antibiotics, but found a new future

Typhoid fever is caused by bacteria from the genus Salmonella .Both Salmonella and their relatives Escherichia, to which the well-known E. coli belongs, inhabit most of the intestines on the planet. Here are just E. coli and its brethren are mostly useful symbionts that help digest food. And the genus Salmonella is doing the opposite, mowing down entire populations of species. And man is no exception.

The classification of modern Salmonella is based on the study of their antigenic structure and is very complex, but from the point of view of infectiousness, doctors are interested in two independent forms (species): S.enterica and S. bongorica . These are twins with different specializations: the first harms warm-blooded, the second – cold-blooded reptiles and fish (Fookes et ​​al ., 2011). Given the age of separation from common ancestors (about 100 million years ago), it is possible that somewhere in the Cretaceous period, the most frightening lizards could suffer from the most frightening diarrhea caused by prehistoric salmonellosis.

Among S. enterica we will find 2,500 serotypes or species specializing in the species diversity of our planet.Most of them, once in our body, cause similar consequences and symptoms, united under the general name of a terrible disease – typhoid fever.

In the depths of antiquity

Antiquity is relatively poor in describing diseases, but this is not because of the reluctance or unscientific approach of the ancients, but because of the similarity of symptoms and the inability to separate pathologies. And who will describe in detail the isolated cases of the disease when it comes to the poor citizen of Sparta, and not about the personality of the scale and scope of Caesar.

Fortunately for scientists, typhus does not choose victims based on their importance. Thus, the seemingly uninterrupted series of conquests of Alexander the Great was apparently interrupted by either Salmonella or Plasmodium malaria (Cunha, 2004). The disease lasted from May 29 to June 10, 323 BC. e., and the case took place in Babylon, where the most likely infectious diseases at that time were malaria and typhoid. But further in the diagnosis of Alexander, everything is not easy.

The first systemic descriptions of typhoid fever symptoms were given by the famous Hippocrates: the main ones are fever, impaired consciousness, bloating, a pale pink rash and, of course, diarrhea (Khosla, 2008).In Alexander’s case, we have only a few symptoms: cold sweats, fever, weakness and delirium in the last days of life.

But before the appearance of medical thermometers in the first half of the 18th century. the concept of fever was an evaluative characteristic recorded from the words of witnesses. Both Hippocrates, Arrian and Plutarch used the word “fever” in very different contexts. It is enough to accept that a slight inaccuracy was made in the description (for example, the frequency of the rise in temperature was not indicated), and we will be forced to leave only malaria.But on the basis of the symptoms described, scientists are still leaning towards typhoid (Emmeluth, 2004).

When the founder of the Roman Empire, Guy Octavian Augustus, fell ill, we were left with a description of a severe fever without chills or pauses, weakness and abdominal pain. In 23 BC. e. Anthony Musa, a doctor for the rich, who prescribed aromatic oils and walks in the fresh air, was summoned to the court of the sick Augustus. Anthony recommended cold baths, compresses, and plenty of fluids. And after a couple of weeks, the emperor really felt better (Prioreschi, 1998).

Plague of Athens

The most striking example of mass cases of typhoid fever in antiquity is the “plague of Athens” (430-426 BC), which changed the appearance of Hellas and, according to some historians, was one of the reasons for the decline of Hellenic civilization. In Athens, she claimed every fourth life. Until now, the cause of this epidemic is the subject of thousands of scientific disputes and dozens of equally controversial dissertations. But let’s try to objectively look at what we know today.

For the necessary material, we first have to descend into the mass grave pit at the ancient Kerameikos cemetery in Athens.It dates back to about 430 BC. e., the height of the epidemic. Second, to get acquainted with the description of the epidemic given by Thucydides, an ancient Greek historian, scientist and philosopher who himself had been ill and recovered (Burns, 2010). Defining his goal as “finding the truth”, Thucydides called himself “the enemy of anecdotes, fictions, poetic embellishments”, declaring that he “does not strive for amusement,” and opposed his work to the works of poets and “logographers” mindlessly recording facts.

According to Thucydides, the disease “originated in Ethiopia, being introduced to the Greeks through Egypt and Libya.”He associates it with the influx of refugees and the military and poor hygiene. The plague itself is described as “so strong and deadly that no one could remember a similar one anywhere else.” It all started with “severe pain in the head, redness and inflammation of the eyes, then the inner throat and tongue became blood-red, and breathing was noisy and unpleasant. This was followed by sneezing and hoarseness, shortly thereafter the pain, along with a violent cough, penetrated into the chest. And when it settled in the stomach, vomiting began, bile cleansing took place with great anguish … Outwardly, the bodies of the infected were neither too hot nor too pale … But the internal heat was unbearable, they could not tolerate even the lightest linen clothes, nothing but nakedness … Many had an indefatigable thirst … slept from impotence … Most died of internal heat within 7-9 days … but if the disease receded, then it never returned to this person … “( The History of the Peloponnesian War …, 1989, p.115-118).

1994-1995 at the site of mass graves, it was possible to find the remains of about one and a half hundred Athenians buried in a mass grave – a simple pit of irregular shape. The bodies of the victims formed more than five successive layers. In the lower layers, most lay in an orderly fashion, with their heads pointing in one direction. The upper ones represented a real pile of bodies. The hasty and non-religious method of burial, coupled with the dating, suggests that this is an epidemic burial ground, not a war burial.In the latter case, individual graves or cremation are more likely. In addition, mass graves are generally quite rare in the ancient Greek world.

For the study, a dental pulp was taken from three randomly selected remains, which was not subject to decay and, moreover, sterile, where fragments of microbial DNA were found (Papagrigorakis et ​​al ., 2006). They managed to decipher and compare with the genomes of modern microorganisms. The results showed the greatest (up to 93%) coincidence with the bacterium Salmonella enterica , serotype tiphy (typhoid).Combining these data with the stories of Thucydides and other authors, we can make a retrospective diagnosis: typhoid fever.

However, there is a lot of criticism regarding this study. In conditions of unsanitary conditions in a closed city, a dozen epidemics of various diseases can break out, merging into a common pestilence. Will three dental pulps be enough to determine the cause of the plague of Athens, the largest epidemic of antiquity? Perhaps yes, and perhaps not, but one thing we know for sure: typhus participated in this “dance of death.”

“War is the father of everything” (Heraclitus)

But what escaped the attention of a military historian was the connection between the disease and the war. Before typhus hit the city, he did not travel alone, but with the armies. And the army, imprisoned in the city among the thousandth civilian population, revealed the epidemic potential of the disease in full.

The Roman Empire replaced the Greek civilization. Was the famous Roman legion a breeding ground for disease and plague? Yes and no.Each legion commander commanded a detachment of 5,000 soldiers, including cavalry and auxiliary troops. The well-being of many people and animals, kept in concentration, was supported by their own medical personnel, who were released from general military duties. But five centuries of the apogee of the Roman military machine up to AD 476. e., during which armies with golden eagles conquered Western Europe, the Middle East and North Africa with their little-studied endemic diseases, became a challenge to the doctors – contemporaries of these campaigns.

Roman medicine marched victoriously after the legions. The greatest doctors of the day, like Claudius Galen, were able to describe the symptoms of diseases such as typhoid, malaria, schistosomiasis, smallpox, and dysentery.

V 4 V. n. e. Flavius ​​Vegetius Renatus was the first to raise issues of sanitation and hygiene in the armed forces, in particular while the troops were camped. Another well-known physician, Cornelius Celsus, has compiled an extensive catalog of medicines and advice on how to use them.Pliny linked the onset of dysentery symptoms to poor water quality and encouraged soldiers to chew blackberry leaves and even the bark of deciduous trees (Belfiglio, 2017). For fever, fenugreek was recommended, which was usually used for diseases of horses. Dill was prescribed for fever and chamomile for headaches (Bell, 2005). And Quintus Gargilius Marcial, who systematized the rules and methods of growing medicinal plants, in fact, took pharmacology one step further (Spurr, 2016).

The ideas of Roman doctors, fantastic in innovation and detail, were far ahead of their time, and the foundations of hygiene and a scientific approach that they laid gradually separated effective drugs and measures from ineffective ones.The first remedies in their composition were close to those that began to be used later. The same fenugreek, for example, does indeed have an anti-inflammatory effect, and the salicylate-rich willow bark, centuries later, turned into aspirin.

Roman doctors did not hear anything about microbiology, but they knew that diseases can be transmitted from one person to another. And analyzed the ways of their transmission and distribution.

This was largely facilitated by the scientific exchange. Many doctors of that time were educated in medical schools in Cnidus, Athens and other cities in Greece, as well as in Egypt.On the basis of deduction methods, ideas about the existence of pathogenic microorganisms were born in these schools. In the 1st century. BC e. Mark Terenty Varro wrote: “There is a pathogen, it is too small alive to be noticed; it enters the body through the mouth and nose, multiplies and produces many diseases that are resistant to treatment. ”

Thucydides’ observation that the Athenians, who had recovered from the plague, no longer fell ill and could help the sick without risking their lives, was very important. And the Roman scientific community did not pass him by.Lacking the means to distinguish between viruses and bacteria, and only in vague theories guessing about the existence of the microworld, the Roman pioneers of science nevertheless began to build the first theories of immunity.

King Mithridates of Pontus became the first person in the world to take advantage of the idea of ​​immunization. He looked for recovered or non-sick soldiers among the recovered soldiers and checked their immunity when in contact with the sick. As a result, 15 volunteers with congenital / acquired immunity were sent to the hospital during the typhus epidemic.

But everything that the Roman doctors knew and developed, all the foundations that were laid by the Greek medical schools, will go into oblivion for a long time along with the collapse of the Roman Empire. And everyone who follows them will have to start over.

Shakespeare Fever

The era of migration of peoples and medieval medicine brought practically nothing to the fight against typhus. For a long time, the disease received the abstract name “fever”, mixed with a dozen similar diseases, including typhus.There is no detailed description of large-scale epidemics, no dated burials … But typhus has not gone anywhere, and the stories of any long gatherings of people in one place stubbornly remind of it. This is especially evident in the examples of the famous siege battles.

The culmination of all medieval wars was the Hundred Years War between England and France, and its most striking event was the Battle of Agincourt. We will find traces of our pathogen if we turn to one of the sieges that preceded this battle. We are talking about the siege of Harfleur in Normandy, just a stone’s throw from Agincourt.Headed the campaign and the siege of Henry V, the same prince, burner and friend of Falstaff from the works of Shakespeare.

In August 1415, an 8,000-strong army laid siege to Harfleur with a garrison of one hundred men. The city surrendered in September of the same year, but at the same time several thousand people and horses stood in one place for more than a month. During this time, Henry lost a quarter of his army: the reason is bloody diarrhea and fever. All military units that carried out sieges both in Antiquity and in the Middle Ages faced this constant trinity of problems: cholera, dysentery and typhoid, or, in medieval terms, fever, diarrhea and rash.It does not matter whose army it was: Edward III during the siege of Calais in 1346 or the crusaders in 1097 near Antioch (Riley-Smith, 2003).

But the siege of Harfler is not an accidental example. Henry’s army was largely reduced by the rational actions of the besieged, and not at all an epidemiological accident. As the troops approached the city, the townspeople opened the floodgates of a nearby dam, flooding the surrounding fields. The siege in the flooded area cost Henry almost the entire company: the disease took even such high-ranking people as Richard Courtney, Bishop of Norwich, and at least 1,500 sick soldiers had to be sent home (Curry, 2015; Prestwich, 1996; Sumption, 1990).

What was the lesson of this siege that was never learned? The main method of spreading typhoid is oral-fecal. Dirty water or vegetables fertilized with sewage is a surefire way to provoke an epidemic.

But in order to fight the disease, you must first make a diagnosis. To do this, it is necessary to separate all similar diseases and pathogens and create a single concept of the disease, within which it will be possible to study its pathogenesis and search for drugs.

But it will take another 250 years before, in 1659, the English doctor Thomas Willis, one of the founders of the Royal Society of London, accurately describes typhoid fever, based solely on clinical observations of his patients. And thus will lay the next, after Thucydides, stone in the scientific foundation for understanding disease (Emmeluth, 2004).

New diseases – new doctors

The gradual increase in the rate of industrialization of society in modern times was accompanied by its pluses and minuses.Overpopulation, hunger, new diseases from the colonies on the one hand, and the flowering of scientific thought on the other. All this was mixed, and from this mixture the foundation of a new medicine emerged.

New diseases – new scientists. Pierre Charles Alexandre Louis, the French physician who laid the foundations for epidemiological research, was the first to standardize case management, create tables and instructions for filling them out. This scrupulous and meticulous doctor was one of the first to describe the characteristics and symptoms of typhoid fever according to his own standards.

The systematized materials on typhoid have created an excellent base for studying it, but there was still a lack of puzzle pieces, namely the basic knowledge of where typhus comes from. Many recognized the link between typhoid and contaminated food or drink, but did not understand exactly how the disease was transmitted. For example, the American sanitary engineer George Soper believed that one of the types of freshwater molluscs was the culprit, and actively fought these mollusks.

Until the 1860s.in Russia, the division of typhus into typhus and typhoid was not recognized. This is not surprising: lice and other parasites common for that time, lubricated the symptoms.

Russian doctors received their first experience abroad. For example, S.P. Botkin, who actually laid the foundations of the epidemiological community in Russia, trained with the most eminent doctors in Konigsberg, Würzburg and Berlin. He began large-scale research in Russia not only of typhus, but also scarlet fever, diphtheria, smallpox and cholera.
Botkin’s students continued his research, not outstripping the Germans, but not inferior to them. N. A. Vinogradov, professor and then dean of Kazan University, published the results of his own research on typhus: “On the treatment of intermittent fever with cold water” (1860), “On nested skin pigmentation in prolonged intermittent fever” (1884). A huge contribution to the isolation of typhus during the Serbian-Turkish war was made by V.T. Pokrovsky, who himself died of this disease.

In 1896.in Tomsk, the first station in Siberia for the production of medicinal sera was created. In the pre-war years, up to 30 types of vaccines, serums and toxoids were produced there. Already during the First World War, a large-scale production of a triple vaccine for typhoid-paratyphoid-dysentery was established

The English rural physician William Budd (Moorhead, 2002) made the first steps in determining the pathways and mechanisms of transmission of typhus. In 1838, during an outbreak of typhoid fever in a local village, he came to the conclusion that “poisons” multiply in the intestines of patients, are present in their secretions and can be transmitted to healthy people through contaminated water.To prevent further spread of the disease, he proposed strict isolation of patients.

In 1841, Budd moved to Bristol, where he began his career as a surgeon. At this time, cholera was raging in London and other large cities of England, despite the fact that many doctors could not distinguish it from typhus. At one time, the English doctor John Snow studied in great detail the cholera outbreak on Broad Street in London, when more than 500 people died. It was with his submission that the scientific world received the definition of “hotbed of infection”, “double blind experiment”, learned about the fecal method of spreading cholera and typhus through the sewer.Budd, based on his theory and reading Snow’s essay on the cholera epidemic, took steps to protect Bristol’s water supply from fecal waters. Agree, this sounds smarter than fighting snails. Budd declared the importance of the work of other scientists, his Bristol fellow physicians Frederick Brittan and Joseph Griffiths Swain, who tried to refute the theory prevailing at the time that bad miasms in the air were the cause of disease.

The fact that, on the basis of Budd and Snow’s research, conclusions were finally drawn and that water treatment plants began to be built is not a common conclusion from scientific work, but rather a consequence of the accumulated heap of problems.By the second half of the 19th century. industrialization and urban growth have led to a significant deterioration in sanitation in urbanized areas. When Prince Albert of England died in 1858, it was suspected that the cause of his death was typhoid fever. His death moved this stumbling block, on the one hand, forcing to investigate the causes of this disease, on the other, launching a large-scale reconstruction of the sewage system.

But differentiating typhus without understanding what the pathogen looks like and where to look for it was not easy.However, the scientists did not give up. Changes in the intestinal mucosa in 1816-1819. discovered by the outstanding French physician Pierre Fidel Bretonneau. A number of accurate descriptions of typhoid fever were added in 1837 by the American William Gerhard, who divided the type into typhus and abdominal, carefully classifying the symptoms (Smith, 1980). Unfortunately, the scientific community at the time did not recognize such a division and still considered typhoid as a single disease. Although typhus is caused by completely different microorganisms – rickettsia, which had yet to be studied.

By the end of the XIX century. almost everyone knew about typhoid: how to get sick, how much to get sick, what the symptoms would be – practically everything, except for the most important thing: what is it?

It was not possible to move the matter until Joseph Lister in 1830 made a microscope with a point of precise focusing of the original image, where the curious eye of a scientist could fit. The second problem was detailing: the image resolution remained at the level of the inventor of the microscope, Leeuwenhoek, until in the 1870s. Ernest Abbe did not use immersion lenses with water and oil.Thus, focus appeared, and the clarity of the image increased tenfold (Gaffky, 1884).

German national team

With the improvement of technologies, the problem of identifying the causative agent of typhoid fever was finally shifted: in 1880, the German bacteriologist Karl Ebert found and described the potential culprit – the bacillus bacillus. Four years later, this conclusion was confirmed by his compatriot Georg Gaffki, who gave the bacillus the name Eberthella typhi (Struck, 1881).Bingo! Now we know exactly the enemy by sight.

Once the bacterium was identified, typhoid fever diagnosis became much easier. It was enough to take a patient with the symptoms described by Gerhard, look in his biomaterials with the help of Lister’s lens for the bacillus described by Ebert, and then check with Gaffka’s clarifications. And the diagnosis is ready: typhus!

To move even one step further, the bacillus itself was needed, in the literal sense of the word. Gaffki learned to isolate it from materials taken from patients.But he could not have done it alone – here we are dealing with the German school of epidemiology. Gaffki worked under the guidance of the famous Robert Koch, who received the Nobel Prize for his discovery of the tubercle bacillus, and one of Koch’s assistants was Julius Petri, the inventor of the “Petri dish” for the cultivation of microorganisms. Gaffki has devoted years to perfecting bacilli cultivation methods. It was he who mastered the mass cultivation of bacteria in Petri dishes, filling them with gelatin to increase their number, or phenol to kill them.

The legacy of Koch and his team lives on. Richard Pfeiffer and Wilhelm Kolle, Koch’s students and assistants, proved in 1896 that vaccination with killed bacteria leads to the patient becoming immune to typhoid fever. Scientists introduced the phenol-killed typhoid bacillus into a volunteer, following his immunological response, in fact, creating one of the first inactivated vaccines (Groeschel and Hornick, 1981). Almost 2 thousand years after Mithridates of Pontus and only a few months earlier than the British, Sir Almroth Wright, managed to do it.At a conference in New York in 1913, the American military doctor Frederick Russell stated that the publication of the research by Pfeiffer and Collet preceded Wright’s article, giving the palm to the Germans.

In the USA, the vaccine appeared thanks to Russell’s work only in 1909. In this race, the Americans were seriously behind the Europeans, and it was just a race. Military conflicts in the world did not stop, and the epidemiological situation in the affected cities could not change instantly. At the end of the XIX century.the death rate from typhoid fever in Chicago alone was about 65 per 100 thousand people per year.

Typhoid Mary

But even with microbiological knowledge and a working vaccine, scientists were far from fully understanding the mechanism of the disease. And surprises like the story of Mary Mallon have puzzled and horrified generations of learned minds (Marineli et ​​al ., 2013).

Mary came to the United States from Ireland and made a living working as a cook.On August 4, 1906, she settled into the family of the banker Warren, who rented a house in a fashionable area on Long Island. And an amazing thing happened: in the absence of typhus epidemic in the city at that time from August 27 to September 3, 11 people fell ill in the family at once.

The owners of the house were extremely concerned about this, and they hired doctors to look for possible causes. The investigation was led by sanitary engineer George Soper. After visiting her previous jobs, he learned that in the past couple of years she had already changed employers eight times, and each time she quit when she got sick with typhus around her (Bull, 1939).At the request of Soper, Mary was arrested. The analysis showed such a high level of carriage of the infection that the newspapers gave her the nickname “typhoid Mary”. She was isolated in a separate house on the grounds of Riverside Hospital, as far away from crowds as possible.

But the story didn’t end there. After Mary’s complaints to the press about her unfair imprisonment, the restrictions were lifted on her subject to voluntary renunciation of the professions related to cooking. Mary agreed and disappeared.In order to “debut” in 1915 as the cause of a new typhus epidemic in one of the maternity hospitals, where it infected 25 people among the staff alone. As a result, she was returned back, practically to captivity, where she spent the rest of her life.

But her example revealed a big problem in the need to investigate such epidemics from start to finish, including the search for a “zero” patient. All this has led to a tougher monitoring of typhoid diseases and a systematic observation. Mary died in 1938 – by that year 237 latent typhus carriers had been found and placed under compulsory custody in the United States (Marineli et ​​al ., 2013).

But if by the end of the XIX century. there was already a vaccine and there were methods to prevent and spread the disease, why was Mary not cured and returned to society?

In 1896, the French bacteriologist George Vidal informed the world that he had developed a rapid test for typhoid fever using the serum of recovered patients. Simply put, it was now easy to find out if you have immunity or need to be vaccinated.

Antibiotics or vaccines?

The search for an effective cure for typhus dragged on until 1947.when the antibiotic chloramphenicol was discovered. Already in 1951, its chemical structure and synthesis methods were published, which made it the first synthetic antibiotic in the world of mass production. Chloramphenicol, a broad-spectrum drug, worked well against typhoid fever, reducing the death rate among cases by almost six times. Unfortunately, it turned out to have side effects that are much more severe than those found in modern annotations (Emmeluth, 2004).

As the level of vaccination and education increased, the incidence rate in Russia fell steadily. In 1913, there were 24.2 cases of typhus per 100 thousand people, and in 1936 – already only 9.2 (Demographic modernization of Russia …, 2006). In the pre-war 1940, this index increased, but since the 1960s. began to decline again, reaching a record low 5 people per 100 thousand people by 1986 (National Economy of the USSR …, 1987)

Worst of all, Wright’s prediction began to come true: the typhoid agent quickly began to develop antibiotic resistance (Hogwood, 2007).In 1948, chloramphenicol was first used to treat typhoid fever, and after a quarter of a century, resistance to it was revealed during outbreaks in Mexico, India, Vietnam, Thailand, Korea and Peru (Multidrug-resistant typhoid …, 1996).

Today, 27 million people fall ill with typhoid fever every year, and about 200,000 die (almost exclusively in developing countries) (Crump et ​​al ., 2004). Because of the easy availability of over-the-counter antibiotics, these millions of patients are actively using them.The number of patients multiplied by uncontrolled self-medication is the reason for the emergence of drug resistance in bacteria. Today, 70 years after the beginning of the era of antibiotic therapy, we are forced to use new drugs: second-generation fluoroquinolones and third-generation cephalosporins .

But treating typhoid with even the most “fresh” antibiotics is often ineffective. For example, in patients with gallstone disease, Salmonella is involved in the formation of biofilm on the gallbladder , a well-protected species of microbial community whose members become immune to various types of treatment.And in this case, it is almost impossible to defeat the disease. As part of biofilms, the pathogen can “sleep” for several years before a person becomes ill again, as, for example, in the case of tuberculosis. The development of such properties in Salmonella is not good for humanity.

At the same time, the effectiveness of new drugs is constantly decreasing. Thus, cefixime , a third-generation cephalosporin recommended by WHO, is not only more expensive, but also relatively less effective than older antibiotics (Basnyat, 2007).

Today, the only real way to protect yourself from typhoid is vaccination. Since the time when vaccination was carried out with a bacterium killed by heated phenol, science has not stood still. For example, phenol was replaced by acetone.

A whole-cell vaccine based on the bacillus killed by acetone was created almost simultaneously in England and Germany. It turned out to be better, because it did not destroy the Vi polysaccharide, with the help of which typhoid bacteria are encapsulated in unfavorable conditions, ensuring their survival in the patient’s body.Arthur Felix and his colleagues at the Lister Institute in London have shown a serological response against this polysaccharide in typhoid fever (Felix et ​​al ., 1935).

In 1960, this vaccine successfully passed large-scale clinical trials in Yugoslavia, the USSR, Poland and Guyana. It is still used in some places, but in most countries it was abandoned due to side effects, since in almost every third vaccinated person it caused the symptoms inherent in this disease.

Because of the side effects and low efficacy of killed vaccines, as well as increasing antibiotic resistance, more reliable remedies are needed. Scientists have focused their efforts on creating a vaccine based on live bacteria that would induce a greater immune response. Since the wild strain poses a significant threat to a healthy person, by 1983 a weakened strain was developed, in which the genes responsible for the production of the Vi polysaccharide were changed.The Ty21a vaccine was the first live oral typhoid vaccine. It has proven to be effective and has been licensed in 56 countries in Asia, Africa, the United States and Europe (Levine et ​​al ., 1999).

The result of a thousand-year conflict of human civilization with Salmonella enterica , serotype typhi , in fact, became three vaccines. And, according to WHO, this confrontation is still far from over.

Mikhail Glukharev, author of the Russian-speaking

popular science blog ScientaeVulgaris,

dedicated to medicine, science

and humanities

Literature

Emmeluth D.Typhoid fever. Broomall, United States, 2004.112 p.

Khosla S. N. Typhoid fever its cause, transmission and prevention. New Delhi Atlantic Publ., 2008.248 p.

Papagrigorakis M. J. et al. DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens // Int J Infect Dis. 2006. V. 10 (3). P. 206-214.

Crump J. A., Luby S. P., Mintz E. D. The global burden of typhoid fever // Bull World Health Organ.2004. V. 82. P. 346-353.

WHO, 2003. Background document: The diagnosis, treatment and prevention of typhoid fever. World Health Organization, Geneva.

WHO, 2007. Typhoidfever. World Health Organization.

: 20 Aug 2019, Chromosome Singing History, Volume 83,
Number 3

Medical center vaccination services Guarantee

Vaccination Center Medical Center “Guarantee”.Vaccination of children and adults. Vaccination prices.

All over the world, the main method of immunoprophylaxis of the population of children and adults is preventive vaccination ( vaccinations ), which protects the body from serious infectious diseases. The essence of vaccination is to obtain a persistent immune response in a person to an injected antigen that causes a certain infectious disease. The method is intended to prevent or significantly weaken the course of the disease when a person interacts with an infection in everyday life.

According to the World Health Organization (WHO), routine immunization of children with vaccinations is the most effective in the fight against diseases such as polio, tetanus, diphtheria, whooping cough, measles and mumps. In modern immunoprophylaxis, vaccines have been developed against Tuberculosis, hepatitis, meningococcal, hemophilic infections, which have proven their effectiveness by millions of healthy vaccinated people.

In the medical center “Guarantee ” vaccination of children and adults is carried out within the timeframes established by the national calendar of preventive vaccinations approved for Russia.

Schedule of vaccination of children in Russia.

age

vaccination name

Newborns (in the first 12 hours of life)

First vaccination against viral hepatitis B

Newborns (3-7 days)

Vaccination against tuberculosis

1 month

Second vaccination against viral hepatitis B

3 months

First vaccination

4.5 months

Second vaccination against whooping cough, diphtheria, tetanus and polio

6 months

The third vaccination against pertussis, diphtheria, tetanus and poliomyelitis and the third vaccination against viral hepatitis B

12 months

Vaccination against measles, rubella, mumps

18 months

First revaccination against whooping cough, diphtheria, tetanus and poliomyelitis

20 months

Second revaccination against poliomyelitis

6 years

Second vaccination against measles, rubella, mumps

6-7 years old (1st grade)

First revaccination against tuberculosis *

7-8 years old (2nd grade)

Second booster vaccination against diphtheria and tetanus (without pertussis component)

13 years

Rubella vaccination (girls).Vaccination against viral hepatitis B (previously not vaccinated)

14-15 years old (9th grade)

The third revaccination against diphtheria and tetanus (without pertussis component). Third revaccination against poliomyelitis
Second revaccination against tuberculosis **

Adults

Revaccination against diphtheria and tetanus every 10 years

* Revaccinate children who are not infected with tuberculosis and who have a negative Mantoux test.

** Revaccinate children who are not infected with tuberculosis, with a negative Mantoux test, who have not received the vaccine at the age of 7.
Each of the vaccines has its own timing, scheme and route of administration (by mouth, intramuscularly, subcutaneously, intradermally). In some cases, one vaccination is sufficient to develop long-term immunity (single vaccination). In others, multiple injections (revaccinations) are required, because the level of antibodies gradually decreases and repeated doses are necessary to maintain the required amount of antibodies.

Indications for vaccination.

In Russia, indications for mass vaccination of population are approved by the Ministry of Health of the Russian Federation. Below is a list of diseases and age categories of citizens undergoing preventive immunization.

  • Vaccination against viral hepatitis B is indicated for all children and adults aged 1 to 55 years who have not been previously vaccinated.
  • Rubella vaccination and revaccination against rubella is indicated for men from 1 to 18 years old and women from 1 to 25 years old if they were not sick, not vaccinated, vaccinated against rubella once or have no information about rubella vaccinations …
  • Vaccination against measles and revaccination against measles is indicated for all children and adults aged 1 to 35 years if they were not sick, not vaccinated, vaccinated against measles once or have no information about measles vaccinations. In the age group 36-55 years, under the same conditions, measles vaccination is indicated for representatives of some professions.
  • Vaccination against influenza is indicated for children from 6 months, schoolchildren and students; adults working in certain professions and positions; pregnant women; adults over 60; conscripts; persons with chronic diseases of the lungs, cardiovascular system, metabolic disorders and obesity.

In case of epidemic indications, in addition to routine vaccination, vaccination is carried out against hemophilic infection, chickenpox, pneumococcal infection, poliomyelitis, mumps, diphtheria, viral hepatitis B, measles, meningococcal infection, shigellosis, viral hepatitis A, typhoid fever, cholera, gum , Q fever, tick-borne viral encephalitis, leptospirosis, rabies, anthrax, plague, tularemia.

In European countries, the absence of childhood vaccinations – vaccinations in a child is considered poor parental care for his health.