OVERVIEW

In tropical areas, one of the most common causes of infectious diarrhea is from contaminated foods such as fruits and vegetables. These contaminated foods are infected with a variety of pathogens. However, one of the most common culprits is Salmonella species, the causative agent of typhoid fever.

WHAT IS TYPHOID FEVER?

What then is typhoid fever? Typhoid fever (enteric fever), simply is an acute illness primarily caused by Salmonella enterica, as well as the subspecies enterica serovar typhi and to a lesser extent Salmonella paratyphi A, B and C.

When left untreated, it progresses to potentially fatal complications such as intestinal bleeding, bowel perforation and death within a month of its onset. More often, most survivors are left with long-term neuropsychiatric deficits.

MODE OF TRANSMISSION

Humans are the only natural host and reservoir for the pathogen. The pathogen is shed in the stool of asymptomatic persons (carriers) or in the stool or urine of persons with active infection.

This infection is mainly transmitted through ingestion of food or water contaminated with fecal matter. In most developing areas, where hygiene is an issue, it is normally spread into community food or water supplies after defecation.

Endemic areas, have a more frequent spread of the pathogen via water than food. This is due to inadequate sanitary measures. In most developed countries, the transmission is mainly through food that has been contaminated during its preparation. This normally from asymptomatic persons (carriers).

Flies are vectors of this organism, by spreading it from feces to food.
Transmission by direct contact (fecal-oral route) which occasionally occurs in children during play and in adults during sexual activity is also common. Hospital personnel are also at risk when adequate precautions are not taken, in changing soiled bedclothes of infected patients.

The organism enters via the gastrointestinal tract and gains access to the bloodstream. This is normally via the lymphatic vessels. It causes intestinal ulceration, bleeding and perforation in severe cases.

EPIDEMIOLOGY

Worldwide, typhoid fever primarily occurs in developing nations whose sanitary conditions are inadequate. It is endemic in Asia, Africa, Latin America, the Caribbean, and Oceania but the majority of cases come from Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and Vietnam.

Typhoid fever is prevalent in the underdeveloped areas of these countries. It infects about 21.6 million people and kills about 200,000 people every year.
Most documented cases involve school-aged children and young adults. Nevertheless, there has been a higher incidence of very young children and infants. Presentation in these age groups normally is atypical, ranging from a mild febrile illness to severe convulsions, making a diagnosis of a Salmonella typhi infection unlikely.

PATHOPHYSIOLOGY

Once the organism reaches the stomach, it has a high acid tolerance, hence it is able to survive pH levels as low as 1.5. In addition, it begins to target Peyer patches (sites of lymphatic tissue in the small intestines). These sites act as the primary pathway for the gut to present antigens to the immune system.

However, the Salmonella typhi has specialized fimbriae (finger-like extensions) that attach to the epithelial cells over these patches. This makes the organism to be phagocytized and transported through the lymphatic vessels.

Now in the lymphatic fluid, it undergoes bacterial mediated endocytosis (BME) where virulent proteins are injected into epithelial cells disrupting the normal brush border cells of the intestines. This attracts macrophages to the site to prevent further damage.

When the macrophages arrive, it engulfs the organism. However, it fails to destroy it because it has capsular polysaccharides which prevent recognition of the pathogen by immune surveillance mechanisms. This makes the Salmonella typhi travel undetected in the immune system.

The organism also uses the organelles of the macrophage such as the vacuole and Golgi apparatus to ensure its replication leading to further infection. It also produces certain virulent factors like Salmonella pathogenicity island-2 which prevents the digestion of the organism by NADPH and nitric oxide synthase when within the macrophage.

SIGNS AND SYMPTOMS

The incubation period of Salmonella typhi is usually 1-2 weeks, and the duration of illness is about 3-4 weeks. Onset is gradual with fever, headache, joint pain (arthralgia), pharyngitis, constipation, anorexia and abdominal pain and tenderness.

Less common symptoms include: non-productive cough and nose bleeding.
Without treatment, there is a stepwise rise in temperature over 2 to 3 days (normally 39 to 40℃) which remains elevated for another 10 to 14 days. After it gradually falls in the 3rd week and reaches normal temperature in the 4th week.

Common central nervous system symptoms include delirium or coma in severe cases. About 10 to 20% of patients present with discrete pink, blanching skin lesions (rose spots) appearing on the chest and abdomen during the 2nd week. This resolves in 2 to 5 days.

Splenomegaly, leukopenia, anemia, proteinuria, and liver function abnormalities are also present. Acute cholecystitis and hepatitis may occur.

DIAGNOSIS

Your health practitioner can diagnose you of typhoid fever through the following:

● Detailed history taking with an emphasis on your travel history.
● Recent history of frequent travels to tropical endemic areas.
● Taking samples of stool, urine and blood for laboratory analysis.
● Antibody titers of the specimen.
Liver function tests.

Treatment

Typhoid fever is treated mainly with antibiotics which target Salmonella typhi. Some antibiotics your health practitioner may recommend or prescribe are:

● 2nd Generation cephalosporins
● Fluoroquinolones

Antibiotic resistance is becoming an increasing concern in endemic areas, so susceptibility testing is needed in guiding the drug selection.

Nutrition is maintained with frequent feeding. Laxatives and enemas should be avoided in febrile patients. Corticosteroids are added to antibiotics to treat severe toxicity. A surgical approach is mandatory when intestinal perforation sets in. A carrier state is excluded when 3 stool culture tests within regular monthly intervals are negative.

Carriers are normally treated with antibiotics such as amoxicillin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP/SMX).

PREVENTION

Here are some ways to prevent Salmonella infections. They are as follows:

● Thorough cooking of poultry, eggs and ground beef.

● Not eating or drinking foods that contain raw eggs or raw (unpasteurized) milk.

● Thorough washing of farm products.

● Washing hands after using the toilet or changing diapers.

● Washing hands, kitchen work surfaces and utensils with soap and water immediately after they have come in contact with raw meat or poultry.

● Washing hands with soap after touching reptiles, birds or chicks, and after contact with feces of a pet.

● Do not allow infected persons to handle food preparation or water distribution.
Note that, Ty21a strain, a live-attenuated oral typhoid vaccine is given to travelers in endemic regions. It may also be considered for household or other close contacts or carriers.

KEY POINTS.

● Typhoid fever is contracted by ingestion of contaminated food or water.
● Typhoid fever presents with poor appetite, headaches, generalized aches and pains, fever and lethargy.
● Approximately 3-5% of patients become carriers of the bacteria after the acute illness.
● About 200,000 people die of typhoid fever each year.
● Typhoid fever spreads more frequent in water than in food in developing areas.
● Flies are common vectors of typhoid fever.