Continuing Education Activity

Two United States-licensed vaccines are available for Salmonella typhi, an oral attenuated live virus, and an injectable polysaccharide vaccine. The FDA indicates both vaccines for individuals traveling to an endemic are from a non-endemic area. They are also FDA-recommended for individuals with household exposure to a chronic Salmonella typhi carrier or working in a laboratory setting with potentially contaminated specimens. This activity outlines the indications, mechanism of action, methods and timing of administration, significant adverse effects, contraindications, toxicity, and monitoring for typhoid vaccine, so providers can administer and monitor this vaccine in cases where it is needed.

Objectives:

• Identify the mechanism of action for both types of typhoid vaccine.
• Review the contraindications unique to each type of typhoid vaccine.
• Summarize the target patient population and administration schedule for typhoid vaccines.
• Explain interprofessional team strategies for improving care coordination and communication to properly use typhoid vaccines to optimize patient outcomes against infectious disease.

Indications

Typhoid fever predominantly results from Salmonella enterica serotype Typhi (Salmonella Typhi), gram-negative bacteria that only cause disease in man. The organism is ingested in contaminated food or water and survives the stomach acid. It penetrates the small bowel epithelium and enters the lymphoid tissue. It then spreads by lymphatic and hematogenous routes. Typhoid fever is a progressive "stepwise" fever in the first week of the illness. The fever increases as the bacteremia increases; however, the heart rate may be lower than expected for the corresponding fever. The second week of the disease is characterized by abdominal pain, constipation, and a faint macular rash on the trunk and abdomen. During the third week of illness, when there has been no treatment, enlargement of the liver and spleen may develop, along with ileocecal perforation, peritonitis, and septic shock in up to 30% of people. Death can result in 12% to 30% of untreated illness.

The diagnosis of Salmonella enterica serotype Typhi is confirmed by culture. Cultures are obtainable from blood, stool, urine, bone marrow, duodenal contents, or skin rash. Those who recover have a protracted illness over weeks to months. Typhoid fever results in a carrier state in 5% of people with high levels of excretion of Salmonella Typhi in the stool for over a year. Relapse of fever can occur in about 10% of untreated people. Typhoid fever is most common in low and middle-income countries, with rates greater than 100 per 100,000 person-years in parts of Asia and Africa. Outbreaks in the United States occur every year. While 80% of these 5700 cases are in people who have traveled to regions with endemic Typhoid fever, many with the illness have not traveled at all. Salmonella Typhi usually spreads through the ingestion of contaminated food or water. Fewer organisms are required for infection from water than from food.

Treatment with antibiotics is recommended with empiric treatment until cultures are available. The initial treatment for severe illness is a third-generation cephalosporin, while milder illness may be treated with a fluoroquinolone antibiotic or azithromycin. Drug resistance to many antibiotics has rapidly developed worldwide, making antibiotic therapy challenging.[1] Multidrug-resistant strains are resistant to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol. Resistance to ceftriaxone or azithromycin is rare. Initial antibiotic therapy is best guided by knowledge of the sensitivity pattern for the area where the infection originated.[2][3]

Prevention of Typhoid fever focuses on food and water safety. Washing hands before eating, eating foods that have been thoroughly cooked and served hot, or fruits that have been personally peeled are essential safeguards. Water should come from bottled water personally opened or water that has been boiled or chemically sterilized. Typhoid vaccination is indicated for travelers to endemic areas; however, it is not entirely protective.[4][5]

The first typhoid vaccines were initially developed in the late 19th century. Presently, there are two United States FDA-approved vaccines available for Salmonella Typhi, an oral attenuated live virus and an injectable polysaccharide vaccine. The FDA indicates both vaccines for individuals traveling to an endemic are from a non-endemic area. They are also FDA-recommended for individuals with household exposure to a chronic Salmonella Typhi carrier or are working in a laboratory setting with potentially contaminated specimens.[6] The oral vaccine has some cross activity for Salmonella Perityphi, which also causes illness. The oral attenuated live virus vaccine should not be used in immunocompromised individuals. Immunocompromised individuals include those with HIV/AIDS, those taking steroids for longer than two weeks, or anyone with cancer or taking cancer treatment or radiation treatment. Neither vaccine is indicated for children under the age of two years old. The oral vaccine should not be used in children under six years old. Vaccination is indicated for individuals who have had previous Salmonella Typhi infections if they live in non-endemic areas or travel to an endemic area. Vaccination should be completed two weeks before travel for the injected vaccine and one week before they travel for the oral vaccine. The FDA does not recommend the typhoid vaccine for routine immunization of individuals in the United States.[7]

Mechanism of Action

Oral, live attenuated Ty21a vaccine causes a local immune response in the intestinal tract. The attenuated strain causes lipopolysaccharide biosynthesis inducing a protective immune response. The inactivated bacterial cells in the vaccine lyse before causing a virulent infection due to the intracellular build-up of lipopolysaccharide intermediates. The response requires four doses of vaccine on alternate days.

Vaccination with Typhoid Vi polysaccharide vaccine induced an increase in anti-Vi antibodies. It was 74% effective at preventing infection in children ages two to four in Katmandu, Nepal, during a 20-month follow-up.[8]

Administration

Oral, live attenuated Ty21a vaccine requires four doses of an oral capsule separated by 48 hours. This vaccine requires a booster every two years if continued exposure and re-vaccination every five years. The vaccine schedule should be completed at least one week before potential exposure. The vaccine is approved for patients six years of age and older. It is a live vaccine, so it should not be given in pregnancy or immunocompromised patients.

Vi capsular polysaccharide vaccine administration is by intramuscular injection and only requires a single dose with a booster every two years. It is administered as a 0.5 mL intramuscular injection for a single dose for use in ages two years and older.[9][10] Vaccination should take place at least two weeks prior to potential typhoid exposure.

There are no known dose adjustments necessary in cases of renal or haptic insufficiency for either formulation.

Adverse Effects

Oral TY21a vaccine side effects may include abdominal pain (6.4%), nausea (5.8%), headache (4.8%), fever (3.3%), diarrhea (2.9%), vomiting (1.5%), and skin rash (1.0%). Rates of side effects were similar in the placebo control groups except for nausea.

Injectable Vi vaccine side effects include a malaise (15%), headache (14%), nausea (2%), and diarrhea (2%). Researchers also noted injection site reactions in studies, including tenderness (13%) and pain (7%), but they observed no serious adverse reactions in clinical trials.

Contraindications

Oral TY21a is a live vaccine, so it should not be given in pregnancy or to immunocompromised patients. Immunocompromised individuals include those with HIV/AIDS, those taking steroids for longer than two weeks, or anyone with cancer receiving cancer treatment or radiation treatment. Caution is advised in female patients of reproductive potential.[11] There is a lengthy list of drug interaction contraindications for the oral vaccine (many monoclonal antibodies), and the patient should receive a thorough medication reconciliation before initiating oral vaccine adminstration.

Injectible Vi capsular polysaccharide vaccine is contraindicated in anyone who has had an allergic reaction to any component. There have been no studies conducted on pregnant patients, and vaccination is only recommended if absolutely needed. Delay to the second trimester of pregnancy is felt to be prudent.[12] There is no human data on receiving the injectable vaccine while breastfeeding, but it is likely safe based on the vaccine's properties.[13] Its use in patients receiving interferon-gamma 1b should be avoided.

Monitoring

No monitoring or routine testing is necessary with either formulation.

Toxicity

There is no reported toxicity in the literature.

Enhancing Healthcare Team Outcomes

The typhoid vaccine is not for routine administration in the United States. Healthcare workers who offer this vaccine should be aware that, in most cases, it is recommended for the traveler who is going to part of the globe where typhoid is common. In rare situations, it may be administered to laboratory workers who work with the Salmonella typhi bacteria and those who are in close contact with a typhoid carrier. The nurse practitioner, pharmacist, and primary care provider who frequently prescribe this vaccine should educate the patients on the type of typhoid vaccine available and who should not receive it. The patient should also understand that the effectiveness of the typhoid vaccines is about 80%. Hence, they should also maintain good sanitary practices, including frequent hand washing and not drinking the local water.[14][15]