Start of typhoid vaccine as nationwide vaccination campaign against typhoid and as an additional vaccine in national immunization schedule starting on April 8, 2022(Chaitra 25,2078) in Nepal

The national immunization schedule of Nepal was updated on March 25, 2022

Introduction

The British pathologist Almroth Wright generally is credited with the initiation of typhoid vaccination in 1896. His claims of priority were challenged as early as 1907 in favor of Richard Pfeiffer, a German bacteriologist and a student of Robert Koch. A review of the original literature of the 1890s and the early 1900s revealed that several groups were working on the typhoid vaccine at the same time and that the credit for the initiation of typhoid vaccine studies should be shared by these two great researchers.                                      

The Ministry of Health and Population (MoHP) decided to launch a typhoid vaccination campaign in Nepal from April 08, 2022, to May 01, 2022 (Chitra 25, 2078 to Baishakh 18, 2079) to vaccinate 15 months to 15 years-aged children in Nepal. A single dose of Typhoid Conjugate Vaccine (TCV) produced by TYPHIBEV (Biological E Ltd.) is 96.95% effective to protect against Typhoid Fever. Typhoid Conjugate Vaccine (TCV) which is going to be used in Nepal is more effective than other vaccines. 

Even though without improving water and sanitation conditions, waterborne diseases including typhoid cannot be defeated, the Ministry of Health and Population of Nepal is planning to launch a nationwide vaccination campaign against typhoid from April 8 to cover as large a mass of typhoid cases as possible. Around seven million children between the ages of 15 months and 15 years will be immunized with a vaccine during the month-long campaign. 

 

The vaccine will also be included in the regular immunization list once the campaign is over. Once the typhoid vaccine is included in the regular immunization list, the number of vaccines provided through the regular immunization program will reach 13(that is 13 antigens).

 

Typhoid fever, usually called typhoid, is a highly contagious disease caused by Salmonella typhi A and Salmonella paratyphi A and B which spread through contaminated food or water. Symptoms of infection include persistent high fever, weakness, stomach pain, headache, diarrhea or constipation, cough, and loss of appetite. The disease can be fatal in up to 10 percent of the reported cases. Typhoid fever can be a life-threatening disease.

 

Typhoid fever has been documented throughout the world but the problem is acute in the areas where safe drinking water and sanitation is a problem. Nepal has also recorded major typhoid outbreaks in the past, but very few cases have been reported in the last few years. 

 

Reasons for vaccination

• The typhoid vaccine can prevent typhoid fever.

Transmission and problem of typhoid fever

People who are actively ill with typhoid fever and people who are carriers of the bacteria that cause typhoid fever can both spread the bacteria to other people.  When someone eats or drinks contaminated food or drink, the bacteria can multiply and spread into the bloodstream, causing typhoid fever.

People who do not get treatment can continue to have fevers for weeks or months. As many as 30% of people who do not get treatment die from complications of typhoid fever. There are fewer antibiotic treatment options as drug-resistant typhoid bacteria have become more common in many parts of the world.

Typhoid fever is common in many regions of the world, including parts of East and Southeast Asia, Africa, the Caribbean, and Central and South America.  Typhoid fever is not common in the United States.

 

Types of typhoid vaccine

There are three vaccines to prevent typhoid fever.

Inactivated typhoid vaccine(whole-cell killed typhoid vaccine) is an inexpensive vaccine against whole-cell Salmonella typhi A and Salmonella paratyphi A and B. It is administered as an injection (shot) subcutaneously. Two doses of the vaccine are administered subcutaneously 4 weeks apart in children > 6 months old and required revaccination every 2-3 years. As catch up it may be given to children at or beyond 2 years of age((first dose) and is repeated every 2-3 years. One dose is recommended at least 2 weeks before travel. Repeated doses are recommended every 2-3 years for people who remain at risk.

Live typhoid vaccine Ty21a(a strain of Salmonella typhi A) is administered orally (by mouth). It may be given to people 6 years and older. One capsule is taken every other day, for a total of 4 capsules. The last dose should be taken at least 1 week before travel. Each capsule should be swallowed whole (not chewed) about an hour before meals with cold or lukewarm water. A booster vaccine is needed every 5 years for people who remain at risk. Important: live typhoid vaccine capsules must be stored in a refrigerator (not frozen).

Vi capsular polysaccharide vaccine(against Salmonella typhi A) is administered as an injection (shot)  intramuscularly or subcutaneously. Vi polysaccharide unconjugated vaccine is used at and above 2 years every 3 years and Vi polysaccharide conjugated vaccine is used below 2 years of age but  ≥9 months of age in children and also in adults as a single dose.

 

 

Detail on Typhoid Conjugate Vaccine (TCV)  

Indications

• Prevention of typhoid fever in children as of 6 months and adults up to 45 years of age:

        -in endemic areas
        -in mass immunization campaigns in the event of an

         outbreak  or humanitarian emergency context, based on risk

          assessment 

Composition, forms, route of administration

• Typhoid (polysaccharide) conjugate vaccine

•  Suspension for injection in the multidose vial, for IM injection into the anterolateral part of the thigh in children < 2 years, and into the deltoid muscle in children ≥ 2 years. DO NOT ADMINISTER INTO THE GLUTEAL MUSCLE.

Dosage and vaccination schedule

• Child and adult: 0.5 ml single dose
• Routine vaccination-Child at 9 months or during the 2^nd year of life: one single dose at the same time as other recommended vaccines. Follow national recommendations.

• Catch-up vaccination-Child up to 15 years: one single dose. Follow national recommendations.

Contra-indications, adverse effects, precautions

•  Do not administer in case of allergic reactions to any component of the vaccine.
• Vaccination should be postponed in the event of severe acute febrile illness; minor infections are no contra-indications.
•  May cause mild reactions at the injection site (pain, redness at the injection site), fever, headache, and myalgia; rarely: anaphylactic reactions.
•  If administered simultaneously with other vaccines, use different syringes and injection sites. 
•   Pregnancy: no contra-indication
• Breast-feeding: no contra-indication
•  Typhoid conjugate vaccine does not protect against Salmonella Paratyphi or other types of non-typhi salmonella.
• Shake before use to homogenize the vaccine.
• Storage: between 2 °C and 8 °C. Do not freeze  
• Once opened, store the vial between 2 °C and 8 °C for 6 hours maximum.  

 

Recommendation of typhoid vaccine

(Although routine typhoid vaccination is not recommended in many countries including the United States now)

• Travelers to parts of the world where typhoid is common. (Note: typhoid vaccine is not 100% effective and is not a substitute for being careful about what you eat or drink.)
• People in close contact with a typhoid carrier.
• Laboratory workers who work with Salmonella typhi bacteria.

Typhoid vaccine may be given at the same time as other vaccines.

Risks of a vaccine reaction

• Pain from the shot, redness, or swelling at the site of the injection, fever, headache, and general discomfort can happen after inactivated typhoid vaccine.
• Fever, headache, abdominal pain, diarrhea, nausea, and vomiting can happen after a live typhoid vaccine.

·       People sometimes faint after medical procedures, including vaccination. Tell your provider if you feel dizzy or have vision changes or ringing in the ears.

·       As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, another serious injury, or death.

 

What should be done if there is a serious problem after vaccination?

An allergic reaction could occur after the vaccinated person leaves the clinic. If you see signs of a severe allergic reaction (hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, or weakness), get the person to the nearest hospital.

 

Discussion on a plan to use of typhoid vaccine in the regular immunization schedule in Nepal

Although authorities concerned are in the final phase of launching the vaccine campaign, there are divided opinions among experts about it. Some say mass vaccination against typhoid and the jabs’ inclusion in the regular immunization list is needed, as it lessens the morbidity and mortality rates, but others believe authorities are launching the program without having convincing scientific evidence on the prevalence of the disease.

Those not very keen on typhoid mass vaccination say the program should be made more specific by launching it in the hotspots and the areas where the condition of drinking water and sanitation is very poor. We don’t have convincing and scientific evidence about the typhoid disease burden in the country. It would be better if we could make the program more evidence-based.

In 2015, the Epidemiology and Disease Control Division carried out a study in Chitwan and Kathmandu to know the prevalence of typhoid. Doctors involved in the study found typhoid cases but not in significant numbers. It was found that hospitals were not performing stool cultures in significant numbers; typhoid cases were fewer.

The Ministry of Health and Population said that data from the last five years show that around 450,000 people get sick with typhoid every year. And typhoid is among the top three diseases that are caused by contaminated food and water, and the fourth cause of hospitalization in Nepal, according to the data of the last three years maintained by the Health Management Information System.

A study carried out at Patan Hospital in the past found 1,062 people per 100,000 have been infected with typhoid. The number of infected people over 100 in every 100,000 is considered a high prevalence.

Experts, however, question the authenticity of the Health Management Information System’s data. “Our Health Management Information System cannot keep the record of all the people inoculated with particular vaccines and vaccine doses, so how can we rely on the information it provides?'' questioned a former official at the Department of Health Services, requesting anonymity. “How many stool samples were tested to claim 450,000 people were infected with typhoid every year. And do we have the capacity to test those samples?”

Vaccines for other diseases, which are being provided in the regular immunization program work lifelong, but that is not the case with the typhoid vaccine, which has to be taken every five years except the new generation of typhoid conjugate vaccines which are safe and provide long-lasting immunity in children.  As the government has been including the said vaccine in the regular immunization list, why not include the cholera vaccine, some wonder.

Experts also raised questions about the sustainability of the program after the inclusion of the typhoid vaccine in the regular immunization list, as aid agencies do not always provide the jabs. On top of that, typhoid is not like any other disease which can be eradicated, as it can occur in areas where sanitation and water conditions are poor. We have not had a major outbreak of typhoid for the last several years but that does not mean the problems will not arise again.

Without improving water and sanitation conditions, problems of other waterborne diseases cannot be addressed. To improve water and sanitation problems, long-term investments and multisectoral approaches are needed.

Instead of including the typhoid vaccine in the regular immunization list, authorities could launch the program in areas where drinking water and sanitation is problematic. No vaccine is 100 percent effective and infection of typhoid largely depends on how healthy food and water we eat and drink. Problems of typhoid and other waterborne diseases will not stop unless the condition of water and sanitation improves. 

Health Ministry officials claimed that the inclusion of the typhoid vaccine doesn't increase the economic burden, as the vaccine doses and all logistical expenditures have been provided by the Global Alliance for Vaccine and Immunization. They claimed that the cost of typhoid vaccination will not be high compared to the morbidity rate even after the aid agencies stopped the support in the vaccination.

“Typhoid patients have been found throughout the country and hundreds of thousands of people get infected every year with the disease,” Dr Bibek Kumar Lal, director of the Family Welfare Division, said. “And what is concerning is antimicrobial resistance is very high in the antibiotic used in the typhoid treatment. So we opted for typhoid vaccination.”

The Health Ministry said the World Health Organization has provided a pre-qualified certificate for the typhoid conjugate vaccine, which Nepal has planned to include in the regular immunization programs and nationwide campaigns. The National Immunization Advisory Committee also recommended for inclusion of the typhoid vaccine in the regular immunization list.

 “If the vaccine is effective and scientific evidence supports that vaccination is necessary there is nothing wrong in including the vaccine in the regular immunization list,” said Dr Bhagwan Koirala, chairman of Nepal Medical Council, the national regulatory body of medical doctors. “But vaccination cannot be a replacement for the water and sanitation program and data must support that vaccination is necessary.” 

Summary

Parenteral Vi polysaccharide conjugate and oral Ty21a are both acceptable forms of typhoid vaccine. The Vi polysaccharide conjugate vaccine is administered as a single injection and is approved for adults and children aged ≥9 months or during the 2^nd year of life: one single dose at the same time as other recommended vaccines.

 

References

1.https://pubmed.ncbi.nlm.nih.gov/7043706/

2. Kathmandu post of 2022/03/15

3. Vaccine Information Statement Typhoid Vaccine (10/30/19), Department of Health and Human Services Centers for Disease Control and Prevention

4. The Ministry of Health and Population of Nepal

5.https://publichealthupdate.com/guideline-for-typhoid-vaccination-campaign-2022/

6. Indian Academy of Pediatrics

7. https://medicalguidelines.msf.org/viewport/EssDr/english/typhoid-conjugate-vaccine-tcv-45449310.html