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Typhoid Pathogenesis Clinical Picture and Treatment


Typhoid Pathogenesis Clinical Picture and Treatment

What is typhoid fever?

Typhoid (Typhoid fever, брюшной тиф, حمى التيفوئيد) is a life threatening systemic bacterial infection caused by bacteria of the genus Salmonella, it is characterized by signs and symptoms affecting the whole body, such as malaise, fever, chills, aches and pains, loss of appetite, persistent headache and severe intestinal irritation with an eruption of roseolous rash on the trunk; However, symptoms may vary from mild to severe and without prompt treatment, it can cause serious complications and may lead to death.

Mortality rate of typhoid in endemic regions with high incidence of typhoid fever (more than 100/100,000 cases per year):

Typhoid fever affects nearly 20 million people annually, it caused 22 million illnesses and resulted in 216 510 deaths during 2000 and 2001. [2]

Is Typhoid Fever a contagious disease?

Typhoid is a highly contagious bacterial infection. Salmonella typhi is present in the feces and urine of the infected person, where it can spread to humans.

Where is Typhoid most common?

Typhoid fever is most common in Africa, east and central Asia, and Latin America, where it is considered to be endemic. Travelers to these regions are especially at risk.


What is typhoid fever caused by?

Salmonella typhi is the causative agent of typhoid fever.

Source of infection – A sick person or carrier, Salmonella typhi can spread to others through feces, urine, and potentially saliva.

Mechanism of infection

How is typhoid fever spread from person to person?

Typhoid fever is transmitted by ingestion of Salmonella typhi through contaminated food or water or when contaminated fecal particles from an infected host are somehow ingested by another host (fecal oral route).

Clinical manifestations

Incubation period for typhoid fever ranges from 7 to 21 days

What are the symptoms of typhoid fever?

Typhoid is characterized by a very gradual onset, symptoms usually develop gradually and progresses slowly.

Intoxication syndrome – In typhoid, symptoms develop gradually and, fever may also rise, reaching 39-40 °c in a period of 4 to 6 days.

Character of temperature

1- Continuous Curves on Wunderlich
2- Full-wave on botkins
3- Ramp to Spike on kildishev

Other symptoms alongside temperature include weakness, fatigue, anorexia, persistent headache, and insomnia.

Changes in the cardiovascular system: These changes can result in relative bradycardia (heart rate lags behind temperature) and Pulse Dicrotism.

Changes in the digestive tract: Gastrointestinal problems and symptoms also may begin as mild changes that worsen gradually, usually, people with typhoid suffer of gastrointestinal symptoms such as macroglossia (abnormally large tongue, glossitis) that can cause functional and anatomical difficulties, it presents most commonly as a mass or swelling of the tongue, which may also cause the tongue to appear smooth with teeth marks on side of tongue (crenated tongue or crenulated tongue). In most cases, the tongue is dry and covered with gray, shaggy, thick coat, which appears as gray to brown coated tongue with dark patches on it (brown coated tongue). In addition to macroglossia, people with typhoid suffer of other gastrointestinal symptoms such as throat ulcers that usually appear as white spots on the tonsil area (ulceration of the tonsils), meteorism due to intestinal paresis, dullness in the right iliac fossa (symptom Padalka), hepatosplenomegaly. Less commonly, tonsillitis can be caused by typhoid.

Pale skin, hyperhidrosis (excessive palms and feet sweating), and swollen hands and feet (symptom Filipovic).

Rash: Eruption of red spots on the chest and abdomen that shows after around 10 days of illness, roseolous rash, scanty, characterized by intense itching – appearance of additional rash elements is common in the period following the primary onset; rash during convalescence suggests the possibility of recurrence.

What are the complications of typhoid fever?


  • Toxic shock (crisis period)
  • Intestinal bleeding
  • Intestinal perforation (from the beginning of the third week)
  • Myocarditis
  • Pneumonia

Differential diagnosis is performed with:

Lab tests

How is typhoid fever diagnosed?

Blood tests: In the blood, manifestations of early-onset typhoid fever include leukocytosis and leukopenia, but after early-onset typhoid, patients often progress through typhoid’s stages. In the advanced stages of typhoid fever manifestations may include elevated stab neutrophils accompanied by a left shift in the ratio of immature to mature neutrophils, relative lymphocytosis, eosinophilia and accelerated erythrocyte sedimentation rate (ESR).

Which test is used for confirmation of typhoid fever?

Serological methods: PHA and Vi-PHA (Vi-passive hemagglutination assay) to detect Vi antibody and O antibody to S. typhi – titer greater than or equal to 1:200 confirms the diagnosis. ELISA urine test to look for the bacteria that cause Typhoid fever.

Bacteriological diagnosis: seeding hemo, copro- and urinal cultures into media containing bile (media Rapoport, Bile Broth).


How to treat typhoid fever?

Causative treatment

What antibiotics treat typhoid fever?

The drug of choice is chloramphenicol 2.0 g per day, in severe cases, the dose is increased to 3.0 g per day especially in the period of total febrile and the subsequent 10 days period of normal temperature (to prevent recurrence);  However, ampicillin and fluoroquinolone derivatives are often used to treat cases with increased resistance to chloramphenicol.

Pathogenetic therapy – drugs for the purpose of detoxification.

Symptomatic agents

When complications: anti shock therapy, hemostatic therapy.

Surgical treatment is indicated in case of bowel perforation.

Immediate discharge of patients is recommended only after receiving 3 consecutive negative results of stool culture, urine and bile. When analysis results show traces of S.typhi the patient must remain in the hospital for at least 21 days of normal temperature, this is the minimum accepted period before discharging the patient.

About 3-5% of patients will develop chronic typhoid infection (lifelong carriers), because of L-forms (wall-free bacteria) intracellular persistence in the macrophages (MFS cells or Mfs) and dendritic cells (DCs). The process is lifelong, it occurs in the form of two series of successive stages – latency and isolation.


How can we prevent typhoid fever?

Vaccines for preventing typhoid fever

How long does it take for the typhoid vaccine to be effective?

Ty21a and Vi polysaccharide, were effective in preventing typhoid fever, the typhoid vaccine should be given at least thirty days before you travel to high risk areas.

How often do you need to get a typhoid vaccine?

Live Typhoid Vaccine (Oral)

Four doses of typhoid vaccine, given two days apart, are needed for protection. The last dose should be given at least one week before traveling to high risk regions.

Booster vaccinations are recommended every five years for population groups and individuals who are at continuous risk of infection with typhoid bacteria.

Inactivated typhoid vaccine (shot)

One dose of typhoid vaccine, given at least 2 weeks before traveling to high risk areas provides best protection.

A booster dose is needed every two years for population groups and individuals who remain at risk. However, because the vaccine won’t provide complete protection, these steps are recommended when traveling to high-risk zones:

Maintain proper hygiene to minimize your risk of infection, wash your hands often with warm, running water, and antibacterial soap. Frequent hand washing with antibacterial soap and water is the best way to control typhoid infection.

Avoid drinking water from untreated natural sources.

Wash vegetables and fruits under cold running water before eating them, wash and prepare fruit and vegetables to prevent food infection. Always wash vegetables and fruits before cutting and not after cutting them to protect food from contamination.

Cook or reheat food correctly, the core temperature of high risk food should reach at least 75℃ for more than two minutes. Cooking and reheating are the most effective ways to eliminate any harmful bacteria. Eating food that isn’t properly reheated or cooked could give you food poisoning.

Store high-risk food in a freezer at temperatures of -18°C or below, freezing of food at such temperatures will prevent bacteria multiplying. Keep high-risk food in a refrigerator at temperatures of 5 °C or below.





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