Enteric (Typhoid) fever

Dr Venkatesh Jallu
Introduction
• Salmonella Typhi and Salmonella Paratyphi are restricted to human
hosts, in whom these organisms cause enteric (typhoid) fever.
• The remaining serotypes are called - Nontyphoidal Salmonella(NTS)
can colonize the gastrointestinal tracts of a broad range of animals,
including mammals, reptiles, birds, and insects.
• More than 200 serotypes of Salmonella are pathogenic to humans, in
whom they often cause gastroenteritis and can be associated with
localized infections and bacteremia.
PATHOGENESIS
-Contaminated food or water.
-Infectious dose – as less as 200 colony-forming units (CFU) but the
ingested dose is an important determinant of incubation period and
disease severity.
Acid suppression therapy (achlorhydric disease)
Loss of Intestinal integrity - inflammatory bowel disease, cytotoxic
chemotherapy, prior gastrointestinal surgery.
Alteration of the intestinal microbiome by antibiotic administration
increase susceptibility to Salmonella infection.
• Once S. Typhi and S. Paratyphi reach the small intestine, they
penetrate the mucus layer of the gut and traverse the intestinal
layer through phagocytic microfold (M) cells that reside within
Peyer’s patches.
• Disseminate throughout the body in macrophages via the lymphatics
and colonize reticuloendothelial tissues (liver, spleen, lymph nodes,
and bone marrow). Patients have relatively few or no signs and
symptoms during this initial incubation stage
• Hepatosplenomegaly due development of a specific acquired cell-
mediated immune response to S. Typhi colonization.
• The recruitment of mononuclear cells and lymphocytes to Peyer’s
patches can result in marked enlargement and necrosis of the
Peyer’s patches.(which may be mediated by bacterial products).
• Many strains produce a toxins, which contributes to systemic
symptoms and unusual neuropsychiatric states (severe typhoidal
illness).
• NTS( non typhoidal salmonella) gastroenteritis leukocyte infiltration
into both the large- and small-bowel mucosa.
• ENTERIC FEVER is a systemic disease characterized by fever and
abdominal pain and caused by dissemination of S. Typhi or S.
Paratyphi.
• The disease was initially called typhoid fever because of its clinical
similarity to typhus.
• Later typhoid fever was clearly defined pathologically as a unique
illness on the basis of its association with enlarged Peyer’s patches
and mesenteric lymph nodes.
• Based anatomic site of infection - the term enteric fever was
proposed
EPIDEMIOLOGY
• Enteric fever
• Urban > Rural areas
• Children and adolescents > other age groups.
Risk factors include
-contaminated water or ice.
-Flooding.
-Food and drinks purchased from street vendors,
-Raw fruits and vegetables grown in fields fertilized with sewage,
-Lack of hand washing and toilet access.
-Prior Helicobacter pylori infection (an association probably related to chronically
reduced gastric acidity).
• Multidrug-resistant (MDR) strains of S. Typhi emerged which are
Resistance to chloramphenicol, ampicillin, and trimethoprim.
• With the increased use of fluoroquinolones –Resistant to
ciprofloxacin have emerged on the Indian subcontinent and have
spread world wide
Clinical features
• Hallmark features of this disease—fever and abdominal pain
• The incubation period for S. Typhi ranges from 5 to 21 days,
depending on the inoculum size and the host’s health and immune
status.The most prominent symptom is prolonged fever which can
continue for up to 4 weeks if untreated.
• S. Paratyphi A causes milder disease than S. Typhi, with
predominantly gastrointestinal symptoms.
Headache
Chills
Cough
Sweating
Myalgias
Malaise(a general feeling of discomfort, illness, or unease)
Arthralgia
• Gastrointestinal manifestations included
• Anorexia
• Abdominal pain
• Nausea
• Vomiting
• Diarrhea
• Constipation
Physical findings
-Coated tongue
-Abdominal tenderness.
-Rash -rose spots
Hepatosplenomegaly
Epistaxis
Relative bradycardia
• Rose spots - a faint, salmon-colored, blanching, maculopapular rash
located primarily on the trunk and chest. The rash is evident in ~30%
of patients at the end of the first week and resolves without a trace
after 2–5 days,Salmonella can be cultured from punch biopsies of
these lesions,difficult to detect in highly pigmented patients.

• Neurologic manifestations include - meningitis, Guillain-Barré

syndrome.
• Gastrointestinal bleeding
• Intestinal perforation in the third and fourth weeks of illness due to
hyperplasia, ulceration, and necrosis of the ileocecal Peyer’s patches.
• Chronic carriage is more common among women, infants, and
persons who have biliary abnormalities.

• Chronic carriage is associated with an increased risk of gallbladder

cancer, which is much more common in locales where S. Typhi is
common, such as the Indian subcontinent.
 Mary Mallon also known as Typhoid Mary, was an Irish-born cook believed to have infected 53 people with
 typhoid fever, three of them died,
First person in the United States identified as an asymptomatic carrier of the disease.
She was twice forcibly quarantined by authorities,Mallon died after a total of nearly 30 years in isolation
DIAGNOSIS
-CBC – Leukopenia and Neutropenia are detectable.
Leukocytosis is more common among children and in cases
complicated by intestinal perforation.

-Elevated values in liver and muscle enzyme levels

Isolation of S. Typhi or S. Paratyphi from blood, bone marrow, rose

spots, stool. The sensitivity of -Blood culture is only 40–80%.
-Bone marrow culture is >80% sensitive
• The classic Widal serologic test is simple and rapid but has limited
sensitivity and specificity.

• Rapid point-of-care tests that detect antibodies to outer-membrane

proteins or to Vi or O:9 antigen are available for detection of S. Typhi;
they are moderately sensitive and specific.
TREATMENT
-The Choice of antibiotics depends on the susceptibility of the strains in
the area of residence or travel.
- High prevalence of Ciprofloxacin-resistance on the Indian
subcontinent, fluoroquinolones should no longer be used for
empirical treatment of enteric fever.
- Oral- Cefixime 200 mg BD for 10- 14 days
or
Azithromycin 1000mg OD for 5 days
-Iv- Ceftriaxone 2gm in 100 ml NS iv OD for 10- 14 days
PREVENTION AND CONTROL
• Typhoid vaccines are commercially available:
• (1) Ty21a, an oral live attenuated S. Typhi vaccine (given on days 1, 3,
5, and 7, with revaccination with a full 4-dose series every 5 years);
• 2) Vi CPS, a parenteral vaccine consisting of purified Vi polysaccharide
from the bacterial capsule (given in a single dose, with a booster
every 2 years)
Thank you :-)