Typhoid fever is predominantly caused by 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 can be obtained 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 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 is usually spread 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. Severe illness is initially treated with 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 pealed 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.
There are two United States-licensed vaccines available for Salmonella Typhi, an oral attenuated live virus, and an injectable polysaccharide vaccine. Both vaccines are indicated by the FDA 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 1 week before travel for the oral vaccine. The FDA does not recommend typhoid vaccine for routine immunization of individuals in the United States.
Oral, live attenuated Ty21a Vaccine (Vivotif) 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 and 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 (Vivotif) 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 5 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 should not be given in pregnancy and to immunocompromised patients.
Vi Capsular Polysaccharide Vaccine (Typhim Vi) is given 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.
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%). Injection site reactions are also observed in studies, including tenderness (13%), and pain in (7%). No serious adverse reactions were observed in clinical trials.
Oral TY21a is a live vaccine, so should not be given in pregnancy or to immunocompromised patients. Immunocompromised individuals include those with HIV/AIDS, those taking steroids for longer than 2 weeks, or anyone with cancer, taking cancer treatment or radiation treatment.
Injectible Vi Capsular Polysaccharide Vaccine (Typhim Vi) is contraindicated in anyone who has had an allergic reaction to any component. Studies in pregnancy have not been completed, and vaccination is only recommended if needed. Delay to the second trimester of pregnancy is felt to be prudent.
No monitoring is required.
No toxicity is reported.
The typhoid vaccine is not for routine administration in the US. 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 vaccines available and who should not receive it. The patient should also be told that the effectiveness of the typhoid vaccines is about 80% and hence, they should also maintain good sanitary practices including frequent hand washing and not drinking the local water.
|||Simiyu K,Jamka L, Typhoid in a Kenyan Village: Its Impact, Its Prevention. The American journal of tropical medicine and hygiene. 2018 Nov [PubMed PMID: 30404685]|
|||Booth JS,Goldberg E,Patil SA,Barnes RS,Greenwald BD,Sztein MB, Effect of live oral attenuated Typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4 T memory responses in humans. International immunology. 2018 Oct 20 [PubMed PMID: 30346608]|
|||Jin C,Torresi J, Typhoid vaccine responses in travellers treated with immunosuppressive therapy. Journal of travel medicine. 2018 Jan 1 [PubMed PMID: 30325433]|
|||Britto CD,Wong VK,Dougan G,Pollard AJ, A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid. PLoS neglected tropical diseases. 2018 Oct [PubMed PMID: 30307935]|
|||Angelo KM,Haulman NJ,Terry AC,Leung DT,Chen LH,Barnett ED,Hagmann SHF,Hynes NA,Connor BA,Anderson S,McCarthy A,Shaw M,Van Genderen PJJ,Hamer DH, Illness among US resident student travellers after return to the USA: a GeoSentinel analysis, 2007-17. Journal of travel medicine. 2018 Jan 1 [PubMed PMID: 30202952]|
|||Bentsi-Enchill AD,Pollard AJ, A Turning Point in Typhoid Control. The Journal of infectious diseases. 2018 Nov 10 [PubMed PMID: 30189009]|
|||Mogasale VV,Ramani E,Mogasale V,Park JY,Wierzba TF, Estimating Typhoid Fever Risk Associated with Lack of Access to Safe Water: A Systematic Literature Review. Journal of environmental and public health. 2018 [PubMed PMID: 30174699]|
|||Balasubramanian R,Im J,Lee JS,Jeon HJ,Mogeni OD,Kim JH,Rakotozandrindrainy R,Baker S,Marks F, The global burden and epidemiology of invasive non-typhoidal Salmonella infections. Human vaccines [PubMed PMID: 30081708]|