Typhoid Fever

Definition

Typhoid fever, also called enteric fever, is a severe infection caused by the bacterium, Salmonella typhi. S. typhi is in the same family of bacteria as the type spread by chicken and eggs, commonly known as salmonella poisoning or food poisoning. Unlike the bacteria that cause food poisoning, acquiring the S. typhi bacteria do not result in vomiting and diarrhea as the most prominent symptoms in humans. Instead, persistently high fever is the hallmark of S. typhi infection.

Description

Typhoid fever is passed from person to person through poor hygiene, such as incomplete or no hand washing after using the toilet. This allows S. typhi to enter the food and water supply. The bacteria are ingested and then they pass into the stool and urine of infected patients. They may continue to be present in the stool of asymptomatic carriers—persons who have recovered from the symptoms of the disease but continue to carry the bacteria. This carrier state occurs in about 3% of all individuals who have recovered from typhoid fever. Persons who are carriers of the disease and who handle food can be the source of epidemic spread of typhoid. One such individual gave her name to the expression “Typhoid Mary,” a name given to someone whom others avoid.

Poor sanitary conditions and a lack of clean drinking water are major causes of the outbreaks. Natural disasters are also prime breeding grounds for typhoid fever. The January 2010 earthquake in Haiti displaced hundreds of thousands of people. Human and animal waste accumulated, which caused major diseases such as typhoid fever, cholera, and shigellosis to increase in frequency due to contaminated food and water. Typhoid fever also thrives in overcrowded refugee camps.

Risk factors

The following are the major risk factors for typhoid fever:

Demographics

According to the World Health Organization (WHO), about 21.5 million cases of typhoid fever occur each year resulting in 200,000 deaths. The U.S. Centers for Disease Control and Prevention (CDC) estimates that about 5,700 cases of the disease occur in the United States each year, of which at least three-fourths are acquired while traveling internationally. Around 3–5% of Americans who contract the illness abroad become carriers. Typhoid fever is regularly found in developing countries in Asia, Africa, Latin America, the Caribbean, and Oceania. Eighty percent of cases worldwide are contracted in Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and Vietnam.

Causes and symptoms

S. typhi must be ingested to cause disease. Transmission often occurs when a carrier does not wash hands thoroughly (or not at all) after defecation and serves food to others. This pathway is called the fecaloral route of transmission. In countries where open sewage is accessible to flies, insects land on the sewage, pick up the bacteria, and then land on food to be eaten by humans and contaminate it. In countries with poor sewage treatment facilities and in times of natural disasters such as earthquakes or hurricanes, sewage can contaminate the water supply and typhoid fever can spread by drinking contaminated water.

MARY MALLON (1869–1938)

Mary Mallon was born in Cookstown, Ireland, on September 23, 1869, to Catherine Igo and John Mallon. As a teenager, Mallon left her parents and immigrated to New York to live with an aunt and uncle. Until 1906, when George A. Soper began to study an outbreak of typhoid fever in Long Island, little was known about Mallon.

Soper was called to identify possible causes of an eruption of typhoid fever at a summer house in Oyster Bay, New York. After examining the food and water in a futile attempt to discover contaminants, Soper decided that a human carrier probably transmitted the disease. He soon learned that the cook, Mallon, had disappeared. He tracked Mallon to her new place of employment, expecting her cooperation in dealing with the matter. However, Mallon did not cooperate, and Soper eventually turned the case over to the New York City Department of Health. When Mallon was ultimately caught, she refused treatment and was held for three years as a threat to the public. In 1910, a judge granted her release with the stipulation that she not seek employment as a cook, since the disease was transmitted through food. Mallon agreed but, in 1915, an outbreak of typhoid at a hospital was, once again, linked to her. When Soper investigated this incident, he learned that employees had nicknamed one of the cooks Typhoid Mary.

After Mallon was found, she was taken into custody, and spent the rest of her life at Riverside Hospital. Mallon died on November 11, 1938.

The presence of large numbers of bacteria in the bloodstream (bacteremia) is responsible for a high fever of 103°F–104°F (39–40°C) that can last four to eight weeks in untreated individuals. Other symptoms of typhoid fever include constipation (at first), nausea, extreme fatigue, headache, joint pain, and a rash across the abdomen known as rose spots.

As the disease progresses, bacteria move from the bloodstream into certain tissues of the body, including the gallbladder and lymph tissue of the intestine (called Peyer's patches). The tissue's response to this invasion causes symptoms ranging from inflammation of the gallbladder (cholecystitis) to intestinal bleeding to actual perforation of the intestine. Perforation of the intestine refers to a hole developing in the wall of the intestine with leakage of intestinal contents into the abdominal cavity. This leakage causes severe irritation and inflammation of the lining of the abdominal cavity called peritonitis. Peritonitis is a frequent cause of death from typhoid fever.

Other complications of typhoid fever are liver and spleen enlargement, sometimes so great that the spleen ruptures; anemia (low red blood cell count) due to blood loss from the intestinal bleeding; joint infections, which are especially common in patients with sickle cell disease or immune system disorders; pneumonia caused by a bacterial infection (usually Streptococcus pneumoniae), which is able to take hold due to the patient's weakened state; heart infections; and meningitis and infections of the brain, which cause mental confusion and even coma. It may take a patient several months to recover fully from untreated typhoid fever.

Diagnosis

In some cases, the doctor may suspect a diagnosis of typhoid fever if patients have already developed the characteristic rose spots, or if they have a history of recent travel in areas with poor sanitation. A blood culture confirms the diagnosis. Samples of stool or urine can also be used to grow S. typhi in a laboratory for identification under a microscope. Cultures are the most accurate method of diagnosis. Blood cultures usually become positive in the first week of illness in 80% of patients who have not taken antibiotics.

Treatment

Antibiotics are the treatment of choice for typhoid fever. The choice of a specific antibiotic depends in part on where the infection was acquired, sensitivity of cultures of the bacterium to specific antibiotics, and response to treatment. Drug resistance is an increasing problem, and S. typhi in different parts of the world are resistant to different antibiotics. Forty-three percent of samples of S. typhi collected from patients in the United States were resistant to at least one antibiotic. As of 2018, commonly used drugs were ceftriaxone (Rocephin), chloramphenicol (Chloromycetin), cefoperazone (Cefobid), and Ciprofloxacin (Cipro, Proquin).

Sometimes the bacteria cling to gallstones, and individuals then become a carrier of the disease. Carriers of S. typhi must be treated even when they do not show any symptoms of the infection, because carriers are responsible for most of new cases of typhoid fever. Eliminating the carrier state is a difficult task. It requires treatment with one or even two different medications over a period of four to six weeks. The antibiotics most commonly given are ampicillin (Omnipen, Polycillin, Principen; sometimes given together with probenecid [Benemid]) and amoxicillin (Amoxicot, Amoxil, Dispermox, Moxatag). In the case of a carrier with gallstones, surgery may need to be performed to remove the gallbladder. This measure is necessary because typhoid bacteria are often housed in the gallbladder, where they survive despite antibiotic treatment. In some patients, treatment with rifampin and trimethoprim-sulfamethoxazole is sufficient to eradicate the bacteria from the gallbladder without surgery.

Public health role and response

The U.S. Centers for Disease Control and Prevention (CDC) recommends that if one is traveling to a country where typhoid fever is common (generally outside the United States, Canada, Europe, Japan, Australia, and New Zealand, especially if visiting rural areas) or during epidemic outbreaks, then one may consider being vaccinated against typhoid. The CDC recommends that vaccination should be completed at least one to two weeks before the date of departure so that the vaccine has sufficient time to take effect. Immunization is not 100% effective, so some healthcare providers may recommend taking electrolyte packets along on the trip in case one gets sick. Even if vaccinated, one should always drink only boiled or bottled water and eat well-cooked foods while traveling.

The U.S. National Institutes of Health recommends that a healthcare provider should be summoned if a person has the following:

Prognosis

The prognosis for recovery is good for most patients who receive prompt medical treatment. In the era before effective antibiotics were discovered, about 12% of all typhoid fever patients died of the infection. Subsequently fewer than 1% of patients who received prompt antibiotic treatment died. The mortality rate is highest in the very young and very old and in patients with malnutrition who live in areas where healthcare is limited. The most ominous signs are changes in a patient's state of consciousness, including stupor or coma.

KEY TERMS
Asymptomatic—
A state in which a person experiences no symptoms of a disease.
Bacteremia—
Bacteria in the blood.
Carrier—
A person who has a particular disease agent present within the person's body and can pass this agent on to others but who displays no symptoms of infection.
Epidemic—
A large number of cases of the same disease or infection all occurring within a short time period in a specific location.
Incubation period—
The time between when an individual becomes infected with a disease-causing agent and when symptoms begin to appear.
Mononuclear phagocyte—
A type of cell of the human immune system that ingests bacteria, viruses, and other foreign matter, thus removing potentially harmful substances from the bloodstream. These substances are usually then digested within the phagocyte.
Rose spots—
A pinkish rash across the trunk or abdomen that is a classic sign of typhoid fever.
Sickle cell disease—
An inherited disorder characterized by a genetic flaw in hemoglobin production.

Prevention

Hygienic sewage disposal systems in a community, good water treatment facilities, and proper personal hygiene are the most important factors in preventing typhoid fever. Immunizations are available for travelers who expect to visit countries where S. typhi is a known public health problem. Two vaccines are available, one a shot and the other taken orally. Some of these immunizations provide only short-term protection (for a few months), whereas others may be effective for several years. Efforts are being made to develop vaccines that provide a longer period of protection with fewer side effects from the vaccine itself. The most commonly reported side effects are flu-like muscle cramps and abdominal pain.

See also Endemic ; Traveler's health ; Vaccination .

QUESTIONS TO ASK YOUR DOCTOR

Resources

BOOKS

Adler, Richard, and Elise Mara. Typhoid Fever: A History. Jefferson, NC: McFarland, 2016.

Davis, Charles E. The International Traveler's Guide to Avoiding Infections. Baltimore: Johns Hopkins University Press, 2012.

Wright, Jennifer Ashley. Get Well Soon: History's Worst Plagues and the Heroes who Fought Them. New York: Henry Holt, 2017.

PERIODICALS

Kuperschmidt, Kai. “Drug-resistant Typhoid Fever Becoming an Epidemic in Africa and Asia.” Science, May 11, 2015. http://www.sciencemag.org/news/2015/05/drug-resistant-typhoid-fever-becoming-epidemicafrica-and-asia (accessed April 23, 2018).

McNeil, Donald. “They Swallowed Live Typhoid Bacteria—On Purpose.” New York Times, September 28, 2017. https://www.nytimes.com/2017/09/28/health/typhoid-vaccine-trial.html (accessed April 23, 2018).

WEBSITES

Brusch, John. “Typhoid Fever.” Medscape. https://emedicine.medscape.com/article/231135-overview (accessed April 23, 2018).

U.S. Centers for Disease Control and Prevention. “Typhoid Fever.” https://www.cdc.gov/typhoid-fever/index.html (accessed April 23, 2018).

U. S. National Library of Medicine. “Typhoid Vaccine.” MedlinePlus. https://medlineplus.gov/druginfo/meds/a607028.html (accessed April 23, 2018).

World Health Organization. “Typhoid.” http://www.who.int/immunization/diseases/typhoid/en (accessed April 23, 2018).

ORGANIZATIONS

National Institute of Allergy and Infectious Diseases Office of Communications and Government Relations, 6501 Fisher Lane, MSC 9806, Bethesda, MD, 20892-9806, (301) 496-5717, (866) 284-4107, Fax: (301) 402-3573, ocpostoffice@niaid.nih.gov, https://www.niaid.nih.gov .

U.S. Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30329-4027, (404) 639-3534, (800) 232-4636; TTY: 888-232-6348, http://www.cdc.gov .

World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland, +22 41 791 21 11, Fax: +22 41 791 31 11, info@who.int, http://www.who.int .

Rosalyn Carson-DeWitt, MD
Revised by Tish Davidson, AM

  This information is not a tool for self-diagnosis or a substitute for professional care.