Typhoid Fever

I.      Definition

Typhoid fever is so named because it bears a superficial resemblance to typhus, a rickettsial disease. It is an acute illness caused by the typhi variant of Salmonella enteric that may lead to septicemia by its invasiveness. It is transmitted through the ingestion of food and drink contaminated by the feces or urine of infected people. It may also be transmitted directly by handling patients, using a contaminated toilet and neglecting hygiene. The infection is also known as “Enteric Fever”

II.    Morphologic Description

Salmonella are motile; they ferment glucose, but never lactose or sucrose, with acid and sometimes gas; and most of them produce hydrogen sulfide but not urease. Here are some of its characteristics:

·         Gram-negative

·         Non-spore forming

·         Facultative

·         Rod-shaped

·         Peritrichous flagella

·         Capsulated

·         Anaerobic

These gram-negative enteric bacteria are named and designated according to the following antigens:

·         H (flagellar) antigen – a protein that helps the organism to evade the immune system. It is used to agglutinate the organism

·         O (somatic, cell wall) antigen – a lipopolysaccaride that elicits inflammatory responses. It is also used to agglutinate the organism

III.  Pathogenesis

1. When ingested, the salmonella transverses the acid barrier of the stomach that may cause the decrease of stomach acidity or intestinal integrity which increases the susceptibility of the infection.

2. The bacteria then penetrates the mucous layer of the gut and transverse the intestinal layer through phagocytic microfold (M) cells that reside within the Peyer’s patches (ulcers). Here, it will form ruffles in normally nonphagocytic epithelial cells. These ruffles reach out and enclose adherent bacteria within large vesicles by a process reffered as BME (bacterial-mediated endocytosis). The salmonella will encode a type III secretion system that inject virulence proteins in the epithelial cells. These proteins disrupt the normal brush border and force the cell membrane ruffles, which engulf the bacilli and create vesicles. These vesicles carry the bacteria across the cytoplasm and are presented to macrophages.

3. The bacterium infiltrates the mesenteric lymph nodes and the phagocytes of the liver and spleen.

4. When the bacteria are shed into the bloodstream, fever and symptomatic stage is manifested.

5. If left untreated, serious medical complications may develop. The bacteria may infect the organs of the reticuloendothelial system, thoracic duct where macrophages are killed.

6. Reinfection of the small intestine may occur due to the flow of the bile.

IV.    Signs and Symptoms

First week	Second week	Third week
Fever (39.4-40˚C)	Continuing high fever	Delirious
Headache	Diarrhea (pea-soup stool) or severe constipation	Motionless and exhausted (typhoid state)
Weakness & Fatigue	Weight loss	Life-threatening complication may develop
Abdominal pain	Rose spots (2-4mm)	Leucopenia & anemia
Diarrhea	Extremely distended abdomen
Rash

In some people, the small intestine develops areas of ulceration that are vulnerable to hemorrhage, perforation, and peritonitis. Its presence in the circulatory system may lead to nodules or abscesses in the liver or urinary tract. Here are some complications that may develop by this infection if left untreated:

·         Intestinal perforation – most fatal complication; common during 3^rd week

·         Intestinal hemorrhage – indicated by rare abdominal pain, rise in pulse rate, sudden fall in temperature, sweating and hypotenstion

·         Encephalopathy – agitation to delirium and coma; may cause liver failure

V.      Diagnosis

The typhoid fever requires the isolation of S. typhi or S. paratyphi in a blood, stool and bone marrow samples. Positive results for the microorganism are tabulated below:

Culture Media	Positive Result
HEA (Hektoen Enteric Aagar)	Blue green w/ black center
SS (Salmonella Shigella Agar)	Colorless w/ a black center
MacConkey Agar	Yellow to colorless
EMB	Colorless

For typhoid bacilli in the bile duct or gall bladder, best specimen for the patient is bone marrow culture.

VI.    Period of Communicability

Infected persons are communicable as long as organisms are excreted in the feces or urine, typically beginning during the first week after onset and continuing through convalescence and for a variable period.

VII.  Incubation Period

Ø  Usual range: 8-14 days

Ø  Parathyroid fever: 1-10 days

Ø  Convalescent carrier: 6 months

Ø  Persistent carrier: positive stool culture for a year

Ø  Chronic carrier: positive stool culture for a year

VIII.     Prognosis

The prognosis depends on several factors:

Ø  The dose and the virulence of the salmonella

Ø  The general resistance and health of the population involved

Ø  The time and stage of the disease at which treatment is started

Ø  The effectiveness of treatment

Typhoid fever mortality rates vary between 10% and 32%. Relapses involving acute illness occur in 5-20% of the illness’ cases. Some 1-5% of patients carrying the disease apparently become chronic carriers. And complications occur in 10-15% of patients, particularly those who have been ill for more than two weeks.

IX.    Prevention and Treatment

   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 behavior change particularly in hygiene. 

   Specific treatment for the infection includes chloramphenicol, ampicillin or trimethoprim w/ sulfamethoxazole, an alternative for chloramphenicol. While for non-specific treatment, acetaminophen or paracetamol and hydrotherapeutic measures will be prescribed for febrile patients. 

   In cases of epidemic, introduction of vaccine is recommended. (e.g. Typhim Vi) However, vaccination doesn’t provide absolute immunity. It may develop the disease if the patient receives a large dose of the virulent bacilli. Immunization is indicated in foreign travel where typhoid fever is endemic, epidemic, and in areas exposed to a known typhoid occurrences.