Typhoid Fever: Salmonella typhi Antigens

• Typhoid fever is a systemic infection caused by the bacterium Salmonella typhi or paratyphi.
• Typhoid is contracted through the ingestion of food or water contaminated by the excrement of carriers of Salmonella serotype typhi.

Antigenicity

• The O-antigen (somatic) is present in the bacteria's body, providing antigenic variation, resisting alcohol extraction, and is thermostable.
• The H-antigen (flagellar) is in the flagella providing antigenic variation and motility, and undergoes variation by gene rearrangement.
• The Vi-antigen (capsular or envelope), the most superficial, offers virulence.
• The Vi-antigen is a polysaccharide capsule that surrounds the O antigen, protecting the bacteria from antibody attacks.
• The Vi-antigen aids in resistance to antibodies and complement.
• There are three respective antibodies: Anti-O, Anti-H, and Anti-V antibodies.

Mode of Transmission

• Typhoid fever is spread by contaminated food, including meat.
• Typhoid fever is spread by contaminated water supplies.

Pathogenesis

• The organism multiplies in the macrophagic cells of Peyer’s patches, mesenteric lymph nodes, and the spleen after it crosses the intestinal epithelium and invades the regional lymph nodes.
• This causes the Peyer’s patches to become inflamed and possibly ulcerate.
• Bacteremia occurs and spreads to the lungs, gallbladder, kidneys, and CNS.
• Bacteria settle in different organs
• During the invasion, bacteria are phagocytosed by monocytes but can survive intracellularly as facultative intracellular parasites.

Incubation Period

• The incubation period can last 5 to 14 days.
• the incubation period is sometimes longer, 1 to 3 weeks post-exposure period.
• Fever, headache, and abdominal pain are symptoms experienced during the incubation period.

Stages of Enteric Fever

Stage 1

• The onset of bacteremia is marked by fever and influenza-like symptoms with chills, although rigors are rare.
• Symptoms include a dull frontal headache, anorexia, nausea, poorly localized abdominal discomfort, a dry cough, and myalgia, but there are few physical signs.
• Adults normally experience constipation, whereas young children and adults with HIV typically experience diarrhea.
• Epistaxis occurs in ¼ of cases.

Stage 2

• The fever starts low grade and gradually rises, is high and sustained by the second week (39° to 40°C).
• Approximately 5 to 30% of cases develop a few rose spots, blanching erythematous maculopapular lesions that are roughly 2 to 4 mm in diameter.
• Rose spots typically appear on the abdomen and chest and are less usual on the back, arms, and legs.
• Common symptoms include a coated tongue, tender abdomen, hepatomegaly, and splenomegaly.
• Although a relative bradycardia is thought to be common in typhoid fever, it has not been a reliable finding across many regions
• Most patients have intermittent confusion and an apathetic affect.
• Convulsions can occur in kids under the age of five.

Stage 3

• In up to 10% of people, gastrointestinal bleeding is the most common.
• Gastrointestinal bleeding is caused by the destruction of a necrotic Peyer's patch through the wall of an enteric vessel.
• Although the bleeding is usually small and goes away without a blood transfusion, there is a 2% probability that the bleeding is clinically significant and, if a major vessel is implicated, can quickly turn deadly.
• Intestinal perforation is the most significant consequence, occurring in 1 to 3% of hospitalized patients.
• Intestinal perforation is characterized by an acute abdomen or more subtly by worsening abdominal pain, a rising heart rate, and declining blood pressure.
• Reduced degree of consciousness or encephalopathy, frequently accompanied by shock, is connected with high mortality.
• The patient is usually apathetic but conscious.
• Complete stupor or coma is infrequent; people may act agitated, delirious, or obtunded.
• Encephalitis.

Other complications

• Toxic hepatitis occurs within 1-3 weeks, is common, and displays hepatomegaly and elevated ALT. It gets better once the disease improves.
• Toxic myocarditis manifests in 2-3 weeks and is usually severe toxemia.
• Bronchitis, bronchopneumonia: seen in early stage

Convalescence

• Convalescence or chronic consequences

Diagnosis

• CBC results include, low TLC, leucopenia, 4000 to 6000/cmm in the first two weeks, 3000 to 5000/cmm during the next two weeks
• A cmm count of >10,000/cmm may indicate perforation or suppuration.
• ESR is normally decreased.
• In instances of bleeding, normocytic anemia may turn into hypochromic and microcytic anemia.
• Blood cultures are positive when you take more than 15 mL during the first 10 days of infection, positivity may peak at 90% during relapse.
• Less than 30% of cases are positive in the third week.
• In the first week of infection, the test is positive in 80% of cases.
• 90% of cases may be detected via blood culture, which declines to 50% by the third week.
• The count may be low in infants and elderly individuals though roughly 105 to 109 organisms are required for the culture.
• This count may be low in individuals on antacids and H2 receptor blockers.
• Blood culture is positive in 80% of the cases in the first week of infection.
• Blood culture is considered 100% specific.
• Buffy coats may decrease the time for isolation.
• This is subcultured on the MacConkey media.
• Bone marrow culture is believed to be more accurate than blood culture however, is usually unnecessary.
• Salmonella are non-lactose fermenters, motile, and produce H2S.
• A titer of 1:80 O-antibodies suggests the person is not vaccinated.
• A titer of 1:160 is highly indicative of an infection in a non-vaccinated person.
• The titer of 1:40 for antibodies to flagellar antigen (H) is suspicious in unvaccinated individuals.
• Titers are considerably greater in individuals who have been vaccinated.
• H-antigen and antibody titres appear later than antibodies to O-antigen and disappears later than O-antigen antibodies.
• The Vi antigen for S. typhi is used to screen the carrier, antibodies to the Vi-antigen are only positive in 70% of the chronic carriers of S. typhi.