Typhoid

Typhoid infection is caused by the bacterium Salmonella Typhi. While it is prevalent in many parts of the world, most cases identified in the United States are linked to international travel. It is important to distinguish typhoid infection from salmonellosis, a typically milder illness caused by other  Salmonella species, such as S. Typhimurium.

1.0Etiology

• Caused by the bacterium Salmonella Typhi.
• Ingestion of contaminated food or water.
• Contact with an acute case of typhoid fever.
• Inadequate sewerage systems and poor sanitation contaminate water.
• Contact with a chronic asymptomatic carrier.
• Eating food or drinking beverages that are handled by a person carrying the bacteria.

2.0Typhoid Infection

• Any person who ingests typhoid organisms and is not immune can get typhoid. Children acquire typhoid more frequently than adults. 
• Typhoid spreads through fecal-oral transmission, primarily via contaminated food or water, making poor sanitation a key factor in its spread. 
• Individuals infected with typhoid can transmit the disease to others, particularly in areas with inadequate hygiene. 
• Chronic carriers, especially those handling food, play a significant role in the continued transmission of the infection.

3.0Occurrence of Typhoid Fever

• Typhoid is endemic within South Africa, and sporadic cases are reported annually in all provinces. 
• In addition to sporadic endemic disease, clusters and outbreaks may occur. There is an ongoing risk of typhoid fever in any area where water quality and sanitation are not optimal. 
• Contamination of water supplies has resulted in numerous large-scale outbreaks; for example, Delmas (Mpumalanga Province) has experienced repeated outbreaks of typhoid fever, with over 1000 cases in 1993 and over 400 suspected cases and three deaths in 2005. 
• In Harare, Zimbabwe, a typhoid outbreak that began in 2012 is ongoing. It is associated with contaminated water sources, and a number of South African cases are linked to it.

4.0Transmission of Typhoid 

• Typhoid is spread via faecal-oral transmission. The infective dose (the minimum number of organisms required to cause infection) is relatively high at around 100,000 organisms. 
• Typhoid may be spread from person to person by direct contact or through ingestion of contaminated food or water. Infection becomes apparent after an incubation period of 10- 14 days (range 5-21 days).

5.0Sign and Symptoms 

• Typhoid fever is a systemic illness characterised by: 1) fever that is intermittent during the first week but becomes sustained (lasting > 48 hours) thereafter; 2) headache (43-90%), 3) gastrointestinal symptoms such as abdominal pain/cramps, nausea and vomiting, constipation or diarrhoea. 
• Other uncommon clinical signs include relative bradycardia (a lower heart rate than would be expected in the presence of fever and illness), a skin rash ('rose spots'), which are faint-pink spots 2-4cm in diameter that develop on the chest, abdomen, and back, and hepatosplenomegaly (enlarged liver and spleen). 
• Typhoid symptoms overlap with those of several other infectious diseases important in the region, notably malaria. Malaria must be considered first in all persons residing in or with a history of travel to malaria transmission areas who present with fever or a 'flu-like' illness. 
• Since malaria is rapidly progressive but responds well to early treatment, malaria blood tests must be done as a matter of urgency and treatment is provided rapidly.

6.0Pathogenesis of Typhoid Fever

• S. Typhi enters the body through the ingestion of contaminated food or water.
• The bacteria survive the stomach's acidic environment and reach the small intestine.
• In the small intestine, S. Typhi invades the epithelial lining, specifically through M cells in the Peyer's patches.
• Macrophages take up the bacteria in the intestinal mucosa.
• S. Typhi evades destruction by inhibiting the fusion of the phagosome and lysosome, allowing it to survive and replicate inside macrophages.
• The infected macrophages transport the bacteria through the mesenteric lymph nodes into the bloodstream (primary bacteremia).
• The bacteria spread to various organs, including the liver, spleen, bone marrow, and gallbladder.
• After multiplication in reticuloendothelial organs, the bacteria re-enter the bloodstream (secondary bacteremia).
• This leads to systemic infection, causing fever,  abdominal discomfort, and other symptoms.
• The bacteria localize in the gallbladder and can be excreted in bile, leading to re-infection of the intestines.
• Persistent infection can cause:
• Intestinal ulceration and perforation due to the destruction of Peyer's patches.
• Septicemia is the spread of bacteria to other organs.
• Chronic carrier state, where S. Typhi persists in the gallbladder, especially in individuals with gallstones.
• The immune system responds with cell-mediated immunity, but S. Typhi can evade immune detection through its virulence factors, including Vi capsular polysaccharide.
• The infection can persist if the immune response is inadequate, leading to prolonged illness or chronic carriage.

Diagnosis of Typhoid

• Typhoid is diagnosed when Salmonella Typhi is identified in a culture of blood, bone marrow, stool or other tissue. 
• Stool cultures may only become positive after the first week of illness. Blood and stool cultures should be submitted simultaneously. 
• The culture of bone marrow is useful as it may remain positive even after 5 days of antibiotic treatment. 
• Positive cultures are confirmed by agglutination with specific typhoid anti-sera, including the Vi antigen. 
• The Widal test, which looks for antibodies to S. Typhi, may suggest the diagnosis but is not confirmatory. 
• The Widal test also does not supply information on antibiotic resistance, which is important to guide treatment. 

Treatment

• Ciprofloxacin is the drug of choice for the treatment of typhoid. 
• Advantages of treatment with ciprofloxacin include twice-daily dosing, rapid resolution of symptoms, and frequent eradication of carriage post-treatment. 
• Alternative treatment includes 3rd generation cephalosporins (ceftriaxone). 
• About 30% of South African S. Typhi strains resist ampicillin and cotrimoxazole. 
• No high-level resistance to ciprofloxacin in Salmonellae in SA has been detected at present.