GARCIA, JOVELYN K.

TYPHOID FEVER
I. PATHOGENESIS
Bacteria, once ingested reaches the blood circulation through the Peyer’s patches and leads to
septicemia and subsequent seeding of organs, including spleen , liver, kidneys, and gallbladder.
 Transmission : fecal-oral route
 Reservoir : humans only
 Causative agent : Salmonella enterica subspecies enterica serovarTyphi
 Gram negative bacilli that can survive acidic pH of stomach
1. Ingestion of bacteria
2. Bacteria reach small intestine then phagocytosed by the intraluminal dendritic cells. These
infiltrated dendritic cells stick to the lining of intestine causing inflammation of mucosa
leading to diarrhea.
3. Concentration in the Peyer’s patches where they continuously multiply
4. They later go with the flow of the lymph through lymphatic vessel to seed reticulo-
endothelial tissues such as liver, spleen, bone marrow, as well as the lymph nodes
5. They multiply and enter the bloodstream to seed other parts of the body
6. Bacteria reaches the gallbladder and further multiply and are released with bile
7. Small intestine is further reinfected. Some are excreted via stool and others re-infiltrate the
mucosa to concentrate and re-infect the Peyer’s patches.
II. LABORATORY DIAGNOSIS: SEROLOGICAL AND/OR MOLECULAR TECHNIQUES
 FELIX- WIDAL TEST
 High rate of false positivity and false negativity
 This test measures agglutinating antibody levels against O and H antigens.
 RESULT: fourfold rise in the antibody titer between convalescent and acute sera
is diagnostic
 TYPHIDOT TEST
 This test is based on dot ELISA technique and makes use of 50 kD antigen to
detect specific IgM and IgG antibodies to S. Typhi
 RESULT:
 IgM detected - Acute typhoid fever (early phase of infection)
 Both IgM and IgG is positive - Acute typhoid fever (middle phase)
 IgM negative, IgG positive - Past infection
 TUBEX TEST
 Involves O9 antigen
 A drop of test serum is mixed with a drop of reagent A. Two drops of reagent B
are then added and the contents are mixed. The set of tubes is then placed on a
magnet-embedded stand, across which they are slid several times.
 Colour chart is provided for the purpose of scoring
 RESULT: Red indicates negativity while increasing blueness denotes increasing
positivity
 IMMUNOGLOBULIN M DIPSTICK TEST
 Detection of S. typhi-specific IgM antibodies in serum or whole blood samples
 Based on the binding of S. typhi-specific IgM antibodies to S. typhi LPS antigen
 Wetted test strip is incubated in a mixture of sample and detection reagent.
After incubation, test strip is rinsed with water and allowed to dry
 RESULT:
 negative if no staining of the antigen line occurs
 graded 1+, 2+, 3+ or 4+ if there is weak, moderate strong or very strong
staining as indicated by comparison with a coloured reference strip.
 Currently, DNA probes and polymerase chain reaction are being increasingly evaluated for
the diagnosis of typhoid fever. DNA probes although not commercially available, have been
developed for identifying S. typhi from bacterial culture isolates and from blood. PCR is still
in experimental stage
III. MANAGEMENT
Appropriate antibiotic therapy in time considerably reduces mortality and morbidity. Along with
general supportive measures
 ANTIMICROBIAL THERAPY
 Fluoroquinolones
 ofloxacin, ciprofloxacin, fleroxacin, perfloxacin
 optimal choice of treatment
  Chloramphenicol
 risk of agranulocytosis
 beta-lactams are considered safe treatment for pregnancy
 Azithromycin (Zithromax) are preferred drug for uncomplicated typhoid fever
 Ceftriaxone (Rocephin) are preferred for treating hospitalized and seriously ill
patients
 Traditional alternatives
 Ampicillin and amoxicillin
 Trimethoprim-sulfamethoxazole
 MANAGEMENT OF COMPLICATIONS
 Patients with intestinal haemorrhage need intensive care, monitoring and blood
transfusion.
 If perforation is confirmed, surgical repair should not be delayed longer than six
hours.
 In the event of a relapse, the absence of schistosomiasis should be confirmed
 MANAGEMENT OF CARRIERS
 If cholelithiasis or schistosomiasis is present the patient probably requires
cholecystectomy
 Clearance of up to 80% of chronic carriers can be achieved with the administration
of 750 mg of ciprofloxacin twice daily for 28 days or 400 mg of norfloxacin.
IV. PREVENTION
The major routes of transmission of typhoid fever are through drinking water or eating food
contaminated with Salmonella typhi. Prevention is based on ensuring access to safe water and by
promoting safe food handling practices. Health education is paramount to raise public awareness
and induce behaviour change.
 SAFE WATER
 Safe drinking water should be made available to the population trough a piped
system or from tanker trucks.
 Drinking-water can be made safe by boiling it for one minute or by adding a
chlorine-releasing chemical
 FOOD SAFETY AND SANITATION
 Appropriate food handling and processing is paramount and the following basic
hygiene measures must be implemented or reinforced during epidemics:
 Proper sanitation contributes to reducing the risk of transmission of all diarrhoeal
pathogens including Salmonella typhi.
 VACCINATION
 The live-attenuated oral vaccine containing the Ty21a strain of S. Typhi is given as a
four-dose series, with 1 day between each dose.
 Inactivated typhoid vaccine (shot) is given as one dose providing protection. It
should be given at least 2 weeks before travel to allow the vaccine time to work. A
booster dose is needed every 2 years for people who remain at risk.
REFERENCES:
 Bope, E. T., Kellerman, R. D., & Conn, H. F. (2016). Conns current therapy 2016. Philadelphia, PA:
Elsevier.
 Reynolds, J. C. (2016). Netter collection of medical illustrations: digestive system. Place of
publication not identified: Elsevier - Health Science.
 Vaishnavi, C. (2013). Infections of the gastrointestinal system. New Delhi: Jaypee Brothers Medical
Pub.
 Arieti, D., Nieva, J., & Swiller, R. (2011). Prognosis disaster: the environment, climate change,
human influences, vectors, disease and the possible end of humanity? Bloomington, IN:
Authorhouse.
 Khosla, S. N. (2008). Typhoid fever, its cause, transmission and prevention. New Delhi: Atlantic &
Distributors.
 Auerbach, P. S., Cushing, T. A., & Harris, N. S. (2017). Auerbachs wilderness medicine. Philadelphia,
PA: Elsevier.
 Typhoid VIS. (2013, June 18). Retrieved November 13, 2017, from
https://www.cdc.gov/vaccines/hcp/vis/vis-statements/typhoid.html
 Background document: The diagnosis, treatment and prevention of typhoid fever.
(2003). Communicable Disease Surveillance and Response Vaccines and Biologicals, 03(7).
Retrieved November 14, 2017, from www.who.int/vaccines-documents/.