Typhoid fever overview

# Overview
Typhoid fever, also known as enteric  fever and Salmonella typhi infection, is an illness caused by the bacterium Salmonella enterica serovar typhi. Common worldwide, it is transmitted through the  fecal-oral routethe ingestion of food or water contaminated with feces from an infected person. The bacteria then multiply in the bloodstream of the infected person and are absorbed into the digestive tract and eliminated as waste.

# Historical perspective
Around 430426 B.C., a devastating plague, which some believe to have been typhoid fever, killed one-third of the population of Athens, including Pericles, the state's leader. A 2006 study detected DNA sequences similar to those of the bacterium responsible for typhoid fever in a DNA sample dating back to the time of the epidemic.  Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.
The most notorious carrier of typhoid feverthough by no means the most destructivewas Mary Mallon, also known as Typhoid Mary. In 1907, Mallon became the first American carrier to be identified and traced. She was a cook in New York who was believed to be the source of infection for several hundred people. She is closely associated with forty-seven cases of the illness and three deaths.
In 1897, Almroth Edward Wright developed an effective vaccine for typhoid fever. Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality.

# Classification
There is no established classification system for typhoid fever. However, typhoid fever may be informally classified based on duration of illness, serologic type, severity of illness, and virulence factors.

# Pathophysiology
The sequence of events in the pathogenesis of typhoid fever include innoculation, gastrointestinal infection, systemic involvement, and chronic carrier state. The presence of the C282Y mutation and CFTR polymorphisms may confer protection against typhoid fever. 

# Causes
Typhoid fever is caused by Salmonella enterica serotype Typhi (Salmonella Typhi). Salmonella Typhi is a flagellated, facultatively anaerobic, gram negative bacillus that belongs to the Enterobacteriaceae family and contains three important antigens: O, H, and Vi.

# Differentiating typhoid fever from other diseases
Typhoid fever must be differentiated from other diseases that cause fever, diarrhea, and dehydration, such as Ebola, Shigellosis, Malaria, Lassa fever, Brucellosis, Viral hepatitis, leptospirosis, rheumatic fever, typhus, appendicitis, dengue fever, toxoplasmosis, rickettsial diseases, leishmaniasis, tuberculosis, and mononucleosis.

# Epidemiology and Demographics
- An estimated 16-33 million cases of typhoid result in 500,000 to 600,000 deaths annually. In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths.
- Worldwide, typhoid fever is most prevalent in overcrowded areas with poor hygiene and sanitation. Typhoid fever remains common in the developing world, where it affects about 21.5 million people each year. 1-6% of infected individuals will develop a chronic infection in the gall bladder.
- The incidence of typhoid fever varies in different parts of world. Age, race, gender, and certain environmental factors affect the distribution of disease among different groups.

# Risk factors
Common risk factors in the development of typhoid fever are:
- travel to endemic areas
- poor hygiene habits
- poor sanitation conditions
- contact with recently infected person
- recent use of antibiotics
- achlorhydria

# Screening
There are no screening guidelines for typhoid fever. However, chronic carriers can be screened using ELISA to detect antibodies against the Vi antigen.

# Natural history, complications and prognosis
- The symptoms of typhoid fever usually develop between 5 and 21 days after ingestion of the causative organism. If left untreated, patients will develop complications in the second or third week of illness such as intestinal hemorrhage, bleeding, and other life-threatening illnesses. Without therapy, the illness may last for 3 to 4 weeks and mortality rates range between 12% and 30%.
- Common complications of typhoid fever include:
intestinal perforation
intestinal hemorrhage
typhoid encephalopathy
meningitis
disseminated intravascular coagulation
miscarriage
relapse
- intestinal perforation
- intestinal hemorrhage
- typhoid encephalopathy
- meningitis
- disseminated intravascular coagulation
- miscarriage
- relapse
- Prognosis of typhoid fever varies depending on the incidence rate. The mortality rate of typhoid fever in endemic areas is 1-4% with treatment. However, the mortality rate in the areas with low incidence of typhoid fever is less than 1% with treatment.

# Diagnosis
The diagnosis of typhoid fever is based on history, physical examination, labortary findings, and other diagnostic tests and imaging studies.

## History and Symptoms
- Obtaining a complete and accurate history is the most important aspect of diagnosing typhoid fever. It provides insight into cause, risk factors, and associated comorbid conditions.
- Common symptoms of typhoid fever are:
incremental increase in temperature initially and than sustained fever as high as 40C (104F)
profuse sweating
influenza-like symptoms (e.g., chills, malaise, headache)
diarrhea
constipation
loss of appetite
nausea
vomiting
- incremental increase in temperature initially and than sustained fever as high as 40C (104F)
- profuse sweating
- influenza-like symptoms (e.g., chills, malaise, headache)
- diarrhea
- constipation
- loss of appetite
- nausea
- vomiting

## Physical Examination
Physical examination findings are dependent upon the timing of presentation. Common physical examination findings for a patient presenting early in the course of the disease include stepwise increase in temperature, bradycardia, abdominal tenderness, and hepatosplenomegaly. In the third week of illness or later, a patient may present with signs of complications.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of typhoid fever include:
- decreased hemoglobin
- decreased or increased leukocyte count
- elevated CRP
- abnormal liver function tests

## X ray
X ray findings may be helpful in diagnosing complications of typhoid fever such as lobar pneumonia, intestinal perforation and osteomyelitis.

## Other diagnostic tests
Other diagnostic studies associated with typhoid fever include microbial culture, serology and PCR. However, microbial culture is the gold standard tests for diagnosing typhoid fever.

## CT
CT scans are commonly reserved for patients with complications of typhoid fever such as intestinal perforation, bleeding, and abscess formation. CT scans may be helpful in differentiating typhoid fever from other diseases.

## MRI
MRI may be helpful in diagnosing complications of typhoid fever such as neurological complications, liver and splenic  abscesses, osteomyelitis, and typhoid spine.

## Ultrasound
Ultrasonography may be helpful in diagnosing complications of typhoid fever and differentiating it from other diseases presenting with similar symptomatology.

## Other Imaging Findings
Other imaging findings which may be helpful in diagnosing complications of typhoid fever and differentiaing it from other conditions presenting with similar symptoms include barium enema, upper endoscopy, echocardiography, and ECG.

# Treatment

## Medical Therapy
The mainstay of therapy for typhoid fever is antimicrobial therapy. Patients with uncomplicated typhoid fever are treated with either Azithromycin or a fluoroquinolone, whereas patients with severe or complicated forms of the disease are treated with either Ceftriaxone, Cefotaxime, or a fluoroquinolone.

## Primary Prevention
Effective measures for the primary prevention of typhoid fever include vaccination, improving personal hygiene and sanitation, ensuring proper sewage disposal, avoiding overcrowding, and avoiding close contact or sharing utensils with people already suffering from typhoid.

## Secondary Prevention
There are no established guidelines for secondary prevention of typhoid fever. However, early diagnosis and prompt and adequate treatmentincluding the administration of antibiotics, good nursing care, maintenance of fluid electrolyte balance, adequate nutrition, steroids in severe cases, and cholecystectomymay help prevent development of the chronic carrier state.