The Assignment: Typhoid Fever

Typhoid fever, or enteric fever, is not very common in the US as only 400 cases per year are diagnosed; three-quarters of these are in international travelers. In fact, over 70% of cases are seen within 30 days of returning from international travel, often the Indian subcontinent or Latin America where it is endemic. Worldwide, it is much larger concern, with over 21 million cases occurring and 200,000 of them resulting in death. Caused by bacteria, it is often seen in areas and countries where sanitation is not well-enforced. As it is potentially fatal, rapid diagnosis and treatment is mandatory.

Background

Typhoid fever is a systemic infection of the bacterium Salmonella enterica, most commonly serotypes typhi and paratyphi, found exclusively in humans. After ingesting the bug, the Salmonella subspecies invades through the gastrointestinal tract and multiplies in immune cells (specifically the mononuclear phagocytic cells) in the liver, spleen, lymph nodes and Peyer patches. As it travels through the intestinal layers, the bacterium forms protective layers, helping it survive the body's defense mechanisms; it often uses one of the killing cells (macrophage) as a safehaven, traveling and multiplying within the vesicle. Salmonella also enters the bloodstream and surrounding organs, quickly becoming a systemic illness.


Interestingly, Salmonella can withstand acidic environments up to a certain pH. When the pH reaches 1.5 or less, the bacteria die; this is the typical pH of gastric acid. Any patient taking antacids, reflux medication (proton pump inhibitors or histamine-2 receptor blockers), or who have had a gastrectomy or have another illness affecting gastric pH levels are at an increased risk of typhoid fever.

Transmission

People infected with Salmonella carry the bacteria in their bloodstream and GI tract. This is often transmitted to drinking water and food, making fecal contamination of water supplies a significant problem. Also, food from street vendors are often more frequently infected with the organism. About 5% of people infected may maintain a chronic carrier state (excretion of the bacterium for over one year) and therefore unknowingly continue to spread disease.

Clinical Features

Typhoid fever often has an insidious onset of nonspecific symptoms, including fever, dull frontal headache, constipation, malaise, anorexia, chills, and myalgia. Symptoms usually begin after an incubation period that varies based on dose of organism, often ranging between 7-14 days; paratyhoid fever often shows a shorter incubation time.
The incubation ends and symptoms begin as bacteremia develops. Often nonspecific symptoms will appear before the onset of a high fever (103-104 F). Abdominal pain will be the presenting symptom in 20-40% of patients. Diarrhea and vomiting is relatively uncommon in the presentation of typhoid fever although may vary based on geography, perhaps due to changes in diets, strain of organism or other factors; constipation is a more common symptoms, believed to be secondary to swollen Peyer patches causing obstruction of the ileocecal valve.

One unique symptom of typhoid fever includes rose spots on the skinat the end of the first week, seen in approximately one third of patients. This is a bacterial embolic phenomenon and are occasionally seen with shigellosis or nontyphoidal salmonellosis. The rose spots are very subtle and sparse (potentially no more than five spots total) and are described as a truncal salmon-colored maculopapular rash with lesions less than 5cm that blanch. These lesions often resolve within two to five days.

If typhoid fever continues untreated through the second week, the patient appears more toxic. Through the end of the second week and beyond, more severe symptoms may appear, including confusion, delirium, increasing abdominal distention that may lead to perforation of the intestines, and death. On the other hand, symptomatic improvement occurs two days after initiating treatment with the patient markedly improved after four to five days.

Diagnosis

Serologic tests and cultures are the means for diagnosis. DNA assays that identify Salmonella antibodies or antigens should be confirmed with cultures. Definitive diagnosis requires isolation of the organism; this can come from blood, bone marrow, emesis, stool, or urine with bone marrow being the most sensitive for S. typhi although also the most traumatic.

In general, most patients will be moderately anemic with an elevated erythrocyte sedimentation rate, decreased platelets and white cells. Liver transaminases and bilirubin levels are elevated to roughly twice that of normal. Mild hyponatremia and hypokalmia are also commonly seen.

Treatment

When typhoid fever is suspected, a doctor needs to be seen immediately. Antibiotic therapy is the means for treatment and should be started empirically if clinical suspicion is high. Commonly prescribed antibiotics include ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin. In addition to antibiotics, adequate fluid must be repleted with electrolytes and nutrition as needed.

Unfortunately increasing resistance to antimicrobial agents, including fluoroquinolones, and this may lead to a dramatic increase in typhoid fever-related fatalities.
If taking treatment for typhoid fever, take the full course as directed by the doctor. It is also important to avoid serving food to others as the risk of spreading the organism is high.

Prevention

Two basics steps can be taken to prevent typhoid fever: avoid risky food and drink and appropriate vaccination before departure to endemic international areas. All water should be bought in a sealed bottle or boiled before drinking. Anything that may have been made with potentially contaminated water, such as ice or popsicles, that have not been cooked should be avoided. Eat only foods that have been properly cooked and are served hot and steaming. Avoid any raw vegetables or fruits that are not peeled before eating, and peel these directly after washing hands properly. Finally avoid food that is sold from street vendors as it is difficult to keep food on the street clean.

A notable decrease in cases has been observed since the mid-1990s with possible correlation attributed to the vaccination. Two vaccination options are possible, either intramuscularly or orally, and are highly encouraged for international travel.

Typhoid Fever. http://www.emedicine.com/med/topic2331.htm July 24,2006
CDC