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 illness 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 the 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, there are many with the illness who have not traveled. 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 or azithromycin. Drug resistance to many antibiotics has rapidly developed worldwide, which makes antibiotic therapy challenging. 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. Prevention of Typhoid fever focuses on food and water safety. Washing hands before eating, eating foods that have been completely cooked and served hot, or fruits that have been personally peeled are important 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.[1][2][3]

There are two United States-licensed 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. 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 are living in non-endemic areas or traveling to an endemic area. Vaccination should be completed two weeks before travel for the injected vaccine and one week before travel for the oral vaccine. The FDA does not recommend the typhoid vaccine for routine immunization of individuals in the United States.[4]

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 cells inactivated bacterial cells 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.

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 and to 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 approved for patients two years of age and older.[5][6]

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 in (7%), but they observed no serious adverse reactions in clinical trials.

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, taking cancer treatment or radiation treatment.

Injectible Vi capsular polysaccharide vaccine is contraindicated in anyone who has had an allergic reaction to any component. There have been no studies conducted in pregnancy, and vaccination is only recommended if absolutely needed. Delay to the second trimester of pregnancy is felt to be prudent.