Typhoid Fever (Enteric Fever)

Typhoid fever is a potentially deadly disease. Typhoid fever is caused by a bacterium, Salmonella typhi. Paratyphoid fever is a serious illness that is similar to typhoid fever, but it is caused by a different bacterium, Salmonella paratyphi. Most patients have high fevers, generalized fatigue, headache, and loss of appetite. Typhoid fever can be prevented through vaccination. Most travelers who get infected with typhoid fever did not receive the vaccination prior to travel. If you contract typhoid fever and survive, you can become a carrier who infects others. Without treatment, 10%-30% of patients with typhoid fever die, and even with appropriate antibiotics, approximately 1% of patients still die.

Typhoid fever is a potentially life-threatening infectious disease caused by a bacterium, Salmonella typhi. It mainly occurs in developing countries (especially Southern Asia), but it is seen in travelers from industrialized countries who visit where typhoid infections are common (endemic). The World Health Organization estimated that there are about 22 million cases of typhoid fever and 200,000 deaths annually. The disease is characterized by sustained high fever (103 F-104 F) and generalized fatigue. Headache and loss of appetite are very common. If left untreated, symptoms can last for months.

A physician in Paris first described typhoid fever in 1829. The first vaccine to prevent typhoid fever was introduced in 1896. However, availability and widespread use of vaccines against typhoid fever have failed to materialize. As a consequence, especially in developing countries, the disease continues be a significant problem. Before adequate antibiotic therapy was developed, untreated mortality from typhoid fever was 10%-30%. With the advent of modern medicine and antibiotic therapy, mortality has dropped to approximately 1%-4%.

Typhoid Mary is probably the most famous example of carrier of Salmonella typhi, the cause of typhoid fever. After some people are infected with the bacteria, they recover from the illness, but the bacteria are still present in their body. These carriers continue to shed the bacteria and infect others even though they have no symptoms. Typhoid Mary was a woman who lived in New York City in the early 20th century. She worked as a cook and infected at least 49 people, of which three died. She refused to stop working as a cook and was ultimately jailed to protect the public.

Typhoid fever is caused by a bacterium, Salmonella typhi. These bacteria adhere to ileal tissue in the GI tract, survive in macrophage cells, are carried to mesenteric lymph nodes, and reach the lymphatic system. They are further carried to the liver, spleen, and bone marrow. The bacteria then break out of the macrophages and enter the blood; some reach the gallbladder and then go into the GI tract where some are shed with the feces and others infect the patient through the GI tract.

Most people who get typhoid fever live in developing countries of South and East Asia, Africa, Latin America, and the Caribbean. Travelers from developed countries are also at risk, especially if they fail to become immunized prior to traveling. The disease does appear to be increased if people are living close together and if there is poor sanitation and food hygiene.

The bacterium that causes typhoid fever, Salmonella typhi, is only found in humans. People who are sick with the disease or people who are chronic carriers of the disease have the bacterium in their intestines and shed it into their feces. During the acute illness, the bacterium is also found in the patient's bloodstream. The disease is contracted by either eating food or drinking water that has been handled by a person infected with the bacteria or by consuming food or beverages that have been contaminated by sewage containing S. typhi in the water used to prepare the food.

Typhoid fever is contagious because the patient sheds the bacteria in their stool, which can then contaminate food and water sources and thus be transmitted to uninfected people. Some people become carriers. A carrier does not show any signs or symptoms of the illness, but they still have bacteria in their stool. These carriers can easily transfer the infecting bacteria, as Typhoid Mary did back in the early 20th century.

The classic symptom of typhoid fever is sustained fevers as high as 103 F-104 F (37.5 C-38 C). The fever is minimal in the first few days of the illness and increases over time to high fevers. Other common symptoms include

• weakness,
• generalized malaise (exhaustion and fatigue),
• headache,
• relatively slow heart rate (brachycardia) compared to the high fever (pulse-temperature disassociation),
• stomach pains (abdominal pain),
• diarrhea,
• constipation,
• loss of appetite.

Some patients will also have a distinctive rash on their chest and abdomen, which is rose-colored and flat (rose spots). Some patients will have an enlarged liver and spleen (hepatosplenomegaly). If left untreated, the illness last approximately one month and carries a 10%-30% mortality rate, which is usually due to intestinal hemorrhage or perforation.

The time from exposure to the bacterium to onset of symptoms (the incubation period) is variable and ranges from six to thirty days. The onset of symptoms (see above) is very gradual over a few days. These symptoms get progressively worse.

In patients with a history of travel and gradual onset of fever that is increasing in severity, typhoid fever must be considered. Often antibiotic therapy is started based on history alone. In order to try and confirm the diagnosis, cultures are taken of the patient's stool and blood. Sometimes a bone marrow biopsy and culture will be performed. However, these cultures, especially the stool cultures, may be negative in the early stages of the disease. Ancillary tests (radiographs, CT, and MRI) may be used to find complications of typhoid fever such as bowel perforation and abscesses in organs like the liver or bones.

A number of different antibiotics are used to treat typhoid fever. In most parts of the world, fluoroquinolones (usually Ciprofloxacin or Ofloxacin) are the drug of choice for empiric treatment of typhoid fever. However, in recent years, there has been increasing fluorquinolone-resistant and multidrug-resistant strains (resistant to ampicillin, amoxacilline, chloramphenicol, and trimethoprim-sulfamethoxazole) of Salmonella typhi. Recently, some physicians have started using azithromycin, but azithromycin-resistant strains have already been identified. There are other alternative antibiotics when resistance is suspected. Most commonly used antibiotics in multidrug-resistant strains are the injectable third-generation cephalosporins (for example, ceftriaxone (Rocephin) or cefotaxime (Claforan).

Most patients will still have fevers for the first three to five days of antibiotic treatment and may actually feel worse. If no clinical improvement is noted in the patient after five days, resistance should be suspected, along with possible alternative diagnoses.

With appropriate antibiotic therapy, most patients recover from the disease. However, as many as 30% of people who do not receive therapy will die. It has been estimated that there are as many as 22 million infections annually and 200,000 deaths. Annually, in the United States, there are about 300-400 cases and only one or two deaths each year. Most of those who got sick had failed to receive a vaccination prior to travel.

Typhoid fever kills hundreds of thousands of people annually each year. Most deaths occur in developing countries where the disease is common. With adequate treatment, less than 1% of victims should die. There is a concern that multi-antibiotic-resistant strains of bacteria are becoming more common worldwide.

A person with typhoid fever is contagious anywhere from days to years (if they become a chronic carrier); some researchers suggest a few individuals may be contagious indefinitely.

Although being vaccinated is an important first step toward preventing typhoid fever, travelers to countries where typhoid fever is common must remember that the vaccine is only about 60%-70% effective. Travelers must be careful not to consume raw foods or water from local sources when traveling to areas where typhoid fever is common. It is recommended that you only drink bottled water or boil local water for at least one minute, only eat food that is well cooked and still hot and steaming just before consumption, eat only fruit that you can peel immediately prior to consumption, and avoid food from street vendors. Do not put ice in any drinks when visiting countries with endemic typhoid fever.

In order to meaningfully decrease the global burden of typhoid fever, there are continued international efforts to increase vaccine availability to developing countries. Travelers to countries with known increased incidence of typhoid fever should be vaccinated prior to travel. Travelers wishing to know if they should be vaccinated should consult the Centers for Disease Control and Prevention web site for the latest recommendation (http://wwwnc.cdc.gov/travel/).

There are two vaccines available to prevent typhoid fever (Table 1). The first one is a capsule (Ty21a), which is taken as four doses (one pill first day, one pill on day three, one pill on day five, one pill on day seven). This vaccine is preferred by many because it is not an injection and lasts longer (five years). The problem is that the pill (oral vaccine), because it is a live vaccine, cannot be used in children under 6 years of age or in patients with compromised immune systems and those taking certain medications. The other vaccine is a shot (Vi). This vaccine is a killed vaccine and can be utilized in children as young as 2 years of age. The vaccine is also safe in patients with compromised immune systems; however, the shot vaccine must be repeated every two years. The pills must be started two weeks prior to the trip, and the shot must be given two weeks prior to travel.

As with any medication, the vaccine could cause a serious problem (for example, an allergic reaction). However, side effects from typhoid vaccine are generally mild and self-limited. Side effects of the shot include redness and soreness at the injection site, fevers, and headache. Side effects of the oral vaccine (the pill form) include fever, headaches, nausea, vomiting, and rash.

Paratyphoid fever is an illness very similar to typhoid fever, but it is caused by a different bacterium, Salmonella enterica serotypes or serovars paratyphi A, B (tartrate negative), or C. Paratyphoid fever is often not as severe an illness as typhoid fever, but early symptoms are essentially the same as typhoid fever.

Both typhoid fever and cholera are contracted from consuming contaminated water or food. However, the classic symptom of cholera is prolific diarrhea, which is much less common with typhoid fever.