The causal organism of typhoid enteric fever is Salmonella typhi. The two prevalent disease-causing strains are Salmonella bongori and Salmonella enterica. Out of the two strains, Salmonella enterica is the major causative agent of disease in humans. The bacteria are found in the small intestine of humans. This disease is generally prevalent in areas where water supply and sanitation are sub-standard. The disease can spread sporadically, epidemically, or endemically.
The spread of disease is primarily through infected faecal matter; other secondary sources can be contaminated water, food, fingers, or flies. According to WHO, 3 million deaths and 1.3 billion cases of infection per year are observed. India accounted for 2.22 million cases of typhoid fever in 2017 and 493 deaths. Despite new drugs and vaccines coming to market, typhoid causes high morbidity.
Causes of Typhoid Fever
Typhoid is caused by Salmonella enterica serotype typhi. The bacteria exhibit the following characteristics.
Gram-negative bacteria have a thin outer membrane made of lipopolysaccharide. The LPS layer acts as endotoxin and is a key factor in determining virulence in the organism.
Major antigens present on the outer surface are H, O, and Vi antigens.
Belong to the bacillus community as they show rod-shaped morphology.
The bacteria is flagellated, hence motile.
They are facultatively anaerobic and can grow at 5-45 degrees Celsius.
Humans are the only carrier to spread disease via the faecal-oral route.
Incubation Cycle of Salmonella Typhi
Depending upon bacterial load or to say inoculum size, the typhoid fever incubation period varies from 3 days to 60 days. The period of communicability exists as long as rod-shaped bacteria are observed in excreta.
Salmonella typhi is an intracellular pathogen that has the ability to spread and proliferate in the intestinal lumen.
It is administered to the human body via contaminated food or water.
Once Salmonella reaches the intestine, the onset of the infectious cycle occurs.
These bacteria can break through the intestinal epithelium and invade the M cell of Peyer’s patch. Peyer’s patch is a lymphoid node present in the stomach.
Inside these tissues, they increase their number and spread to mesenteric cells, and enter the systemic circulation.
As they spread through the blood, they affect the reticuloendothelial system, which includes the liver, spleen, and gallbladder.
In less severe cases, salmonella typhi infecting humans remains restricted to the intestinal lumen, where they bring about the acute inflammatory response which leads to ulceration.
The inflammatory response damages the intestine, resulting in symptoms like fever, abdominal pain, and diarrhoea.
The diagram below shows the incubation cycle of Salmonella typhi as it invades the human host.
Symptoms of Typhoid
The most widely used test to investigate typhoid is the Widal test. This test relies on antigen-antibody interaction. The patient serum is collected and mixed with bacterial suspension of Salmonella typhi having a specific antigen. If the patient's serum is rich in antibodies, they will adhere to antigens present in dead Salmonella suspension. This reaction results in agglutination or clumping, indicating a positive result. The Widal test is used for the quantitative assessment of the sample. Some rapid diagnostic tests like Tubex, Test-IT, and Typhidot are also used for prognosis.
Treatment of Typhoid Fever
Oral rehydration therapy: It is the most common and widely used therapy to combat diarrhoea. It replenishes the body with important vitals or electrolytes lost due to frequent stool discharge.
Antibiotics: Generally, fluoroquinolone like ciprofloxacin is used as a first-line treatment. Otherwise, Cefotaxime, a third-generation drug, is the preferred choice. Antibiotic treatment reduces fatality and results in speedy recovery. Drugs like ampicillin and chloramphenicol are not used as Salmonella species have become resistant to these drugs. This is referred to as multi-drug resistance.
Resistance toward ciprofloxacin is a significant issue seen in especially Asian countries. Many countries are shifting to the use of ceftriaxone as a first-line treatment, which is injected to cure patients. Also, azithromycin is used to treat multidrug-resistant species. This drug is administered orally and is relatively cheap.
Vaccination: There are two vaccines that have been approved to prevent typhoid. Firstly the live oral Ty21a (Vivotif) and injectable typhoid polysaccharide vaccine (Typhim Vi). Both vaccines are effective and are administered to migrants travelling to epidemic zones. The vaccines are effective in controlling the upsurge of a typhoid outbreak. These vaccines are available at a nominal price so that each community has the advantage of preventing disease. Other preventive measures include:
Washing hands frequently before eating and using sanitiser in the absence of water is necessary.
Avoid drinking contaminated water, especially in the rainy season.
Avoid using ice cubes in drinks as they can be loaded with infection.
Eating well-cooked food and avoiding refrigerated or canned food products ensures greater safety.
Avoid consuming food from street vendors as they have a greater chance of contamination.
Proper consultation by a doctor and timely medication speeds the recovery.
Avoiding contact with an infected person can save it from the disease being spread.
Globally estimated cases of typhoid fever are around 11-21 million, with a death rate of 200,000 per year.
Two new vaccines Oral Ty21a vaccine and the polysaccharide vaccine, are being used to protect against disease.
Oral Ty21a is an enteric-coated capsule vaccine, while the polysaccharide vaccine is injected intramuscularly.
What are the characteristics of Salmonella typhi which make it virulent?
Ans: Salmonella typhii produces endotoxin and has an outer LPS layer, which makes it resistant to antibiotic action. Also, it has the property of adhesion and invasion into the cell.
How is typhoid different from typhus fever?
Ans: Typhoid and typhus are both bacterial origin diseases, but the transmission mode is different. Typhus is spread by fleas, whereas typhoid spreads through the faecal-oral route.
The typhoid fever incubation period is the time gap between the encounter of infection and the appearance of the first sign of illness. The incubation period is directly dependent on the bacterial load.
This disease is transmitted through the faecal-oral route and affects the intestinal lumen of humans. The only carrier of the disease is human.