Enteric Fever

Enteric fever is produced by Salmonella organisms.

It includes
typhoid fever, caused by S. typhi,
paratyphoid fever, caused by
S. paratyphi A
S. schottmuelleri (S. paratyphi B)
S. hirschfeldii (S. paratyphi C)

Epidemiology.

The World Health Organization has estimated that 12.5 million cases occur annually
worldwide (excluding China).

Water & Food

Because humans are the only natural reservoir of S. typhi, direct or indirect
contact with an infected person (sick or chronic carrier) causes infection. Ingestion of
foods or water contaminated with human feces is the most common mode of
transmission. Water-borne outbreaks occur due to poor sanitation and direct fecal-oral
spread and poor personal hygiene. Fish cultivated in water contaminated by sewage are
also a source of infection.
Congenital transmission
by transplacental infection from a bacteremic mother to her fetus.
During delivery transmission is possible, by fecal-oral route from a carrier
mother.

Pathogenesis.

Hyperplasia of Peyer's patches Æ necrosis Æ ulceration Æ bleed. Ulceration

heals without scarring. Strictures and intestinal obstruction never occur after typhoid
fever. The inflammatory lesion of mucosa may penetrate produce perforation. The
mesenteric lymph nodes, liver, and spleen are congested and show focal necrosis.
Inflammation of the gallbladder may be seen. Bronchitis is common. Pneumonia, septic
arthritis, osteomyelitis, pyelonephritis, endophthalmitis, and meningitis are also seen

Bacteremia is necessary to produce the enteric fever. The number of bacteria

required to cause disease in volunteers is 105 –109 Salmonella. typhi organisms. Stomach
acid can kill salmonella. After attachment to brush borders, the bacteria enters intestinal
epithelium, through the Peyer's patches. Then to intestinal lymph nodes, where
multiplication takes place within the mononuclear cells. Monocytes carry these
organisms into the mesenteric lymph nodes. Organisms reach the bloodstream through
the thoracic duct, causing bacteremia. Organisms reach the reticuloendothelial cells in the
liver, spleen, and bone marrow After proliferation in the reticuloendothelial system,
bacteremia recurs. The gallbladder is susceptible to get infected. Multiplication in the
walls of the gallbladder produces large numbers of salmonellae, which reach the intestine
through the bile.

The surface Vi capsular antigen found in S. typhi interferes with phagocytosis by

preventing the binding of C3 to the the bacterium. Circulating Endotoxin causes the
prolonged fever and toxic symptoms. Endotoxin-induced cytokine production causes the
systemic symptoms. Diarrhea is due to toxin related to cholera toxin
Cell-mediated immunity is important in protecting against typhoid fever. Carriers show
impaired cellular immunity - Carriers excrete large number of virulent bacilli in the stool

Clinical manifestations.

The incubation period is - 7–14 days

The clinical manifestations of enteric fever depend on age.

1. School-Age Children and Adolescents.

2. Infants and Young Children (<5 yr).
3. Neonates
During the 1st wk of illness
Onset of is insidious. - develop over 2–3 days
Fever
Malaise
Anorexia
Myalgia
Headache
Abdominal pain.
diarrhea - during the early stage- constipation later
Nausea and vomiting -suggest a complication.
Cough and epistaxis
Severe lethargy
Temperature, - high fever within 1 wk, - reaching 40°C (104°F).

During the 2nd wk of illness,

Symptoms increase in severity

1. Fever
2. Fatigue
3. Anorexia
4. Cough
5. Abdominal. pain
6. CNS - disoriented, and lethargic. Delirium and stupor

Physical findings –

1. Relative bradycardia, - disproportionate to fever.

 2. Hepatomegaly
3. splenomegaly
4. distended abdomen with diffuse tenderness
5. A macular or maculopapular rash (i.e., rose spots) appears on about the 7th–10th
day. Lesions are usually discrete, erythematous, and 1–5 mm in diameter; the
lesions are slightly raised, and blanch on pressure. They appear in crops of 10–15
lesions on the lower chest and abdomen and last 2–3 days. They leave a slight
brownish discoloration of the skin on healing. Cultures of the lesions have a 60%
yield for Salmonella organisms.

6. Rhonchi and creps may be heard

7. symptoms and physical findings gradually resolve within 2–4 wk,
8. Patients may be emaciated by the end of the illness.
9. Enteric fever caused by non-typhoidal Salmonella is usually milder, with a shorter
duration of fever and a lower rate of complications.

Infants and Young Children (<5 yr)

1. Rare in this age group in

2. Mild at presentation, making the diagnosis difficult.
3. Culture-proves typhoid fever.
4. Diarrhea is more common - leading to a diagnosis of ADD.
5. May present with signs and symptoms of lower respiratory tract infection.

Neonates

1. Enteric fever during pregnancy- abortion and premature delivery,

2. May be transmitted vertically.
3. Begins within 3 days of delivery.
4. Vomiting, diarrhea, and abdominal distention are common.
5. Temperature is variable
6. Seizures may occur.
7. Hepatomegaly, jaundice, anorexia, and weight loss

Diagnosis

1. blood cultures are positive in 40–60% , clot culture likely to be more succesful
2. Stool and urine cultures become positive after the first week.
3. The stool culture may be positive during the incubation period.
4. Repeated blood cultures - in suspected cases.
5. Cultures of bone marrow - during later stages of the disease, when blood cultures
may be sterile; Culture of bone marrow is the single most sensitive method of
diagnosis (positive in 85–90%) NOT influenced by prior antimicrobial therapy.
6. cultures of mesenteric lymph nodes, liver, and spleen
7. Stool and urine cultures are positive in chronic carriers.
 8. Polymerase chain reaction - S. typhi in the blood - diagnosis within a few hours.
This is specific and sensitive than blood cultures, even at low level of bacterimia
9. Widal's test -- Serology is of less use- may be useful in epidemiologic studies.
Widal's test measures antibodies against O and H antigens of S. typhi. Because
many false-positive and false-negative results occur, diagnosis of typhoid fever by
Widal's test alone is prone to error.

Laboratory Findings.

1. A normochromic, normocytic anemia - related to intestinal blood loss or bone

marrow suppression.
2. Blood leukocyte counts are low - leucopenia, usually not below 2500 cells/cu mm
3. When pyogenic abscesses develop, leukocytosis may reach 20,000–25,000/cu mm
4. Thrombocytopenia
5. Liver function test results are altered
6. Proteinuria
7. Stool - leukocytes and blood are seen.

Differential Diagnosis

1. ADD
2. viral fever
3. Bronchitis or bronchopneumonia
4. sepsis with other bacterial pathogens
5. infections caused by intracellular microorganisms--tuberculosis, brucellosis,
tularemia, leptospirosis, and rickettsial diseases
6. viral infections - infectious mononucleosis and anicteric hepatitis
7. Malignancies - leukemia and lymphoma

Treatment
1. Antimicrobial therapy
2. Shock
3. Supportive treatment
4. Carrier

Antimicrobial therapy --one of the drugs -

1. Chloramphenicol (50 mg/kg/24 hr PO or 75 mg/kg/24 hr IV in four equal doses),
rate of relapse is higher, it can cause serious adverse effects
2. ampicillin (200 mg/kg/24 hr IV in four to six doses)
3. amoxicillin (100 mg/kg/24 hr PO in three doses)
4. trimethoprim-sulfamethoxazole (10 mg of TMP and 50 mg of SMX/kg/24 hr PO
in two doses.
Most children become afebrile within 7 days;
Treatment of uncomplicated cases continued for at least 14 days, or 5–7 days after
defervescence
Very short courses of therapy suggested are
oral cefixime (20 mg/kg/24 hr in two divided doses for 8 days)
ceftriaxone (50 mg/kg/24 hr IM for 5 days) or
oral ofloxacin (15 mg/kg/24 hr for 2 days).
In adults, ciprofloxacin at a dose of 500 mg bid for 7–10 days is effective
In children therapy with ceftriaxone (or cefotaxime) continued until culture result is
available.

Shock -
A short course of dexamethasone, using 3 mg/kg for the initial dose, followed by 1 mg/kg
every 6 hr for 48 hr, improves the survival rate of patients with shock, obtundation,
stupor, or coma. This does not increase the incidence of complications if antibiotic
therapy is adequate.

Supportive treatment
1. Fluid and electrolyte balance
2. Intestinal hemorrhage if severe, blood transfusion is needed.
3. Surgical intervention in intestinal perforation.
4. Platelet transfusions for thrombocytopenia that causes intestinal hemorrhage
5. Use paracetamol for fever never aspirin

Carrier -
Eradication is difficult
4–6 wk of high-dose ampicillin (or amoxicillin) plus probenecid or TMP-SMX results in
an approximately 80% cure rate of carriers
Ciprofloxacin - adults.
In cholelithiasis or cholecystitis, antibiotic alone is not successful; cholecystectomy -is
recommended.

Complications
GIT
1. Severe intestinal hemorrhage - drop in temperature and blood pressure and an
increase in the pulse rate.
2. Intestinal perforation occurs after the 1st wk of the disease. size, - pinpoint or
large occur in the distal ileum -a marked increase in abdominal pain, tenderness,
vomiting, signs of peritonitis. Sepsis with gram-negative bacilli and anaerobes
3. Hepatitis and cholecystitis
4. Pancreatitis = increase in serum amylase
5. parotitis
Respiratory System
6. Pneumonia - super infection with other organisms
CVS
7. Toxic myocarditis =arrhythmias, sinoatrial block, ST-T change , cardiogenic
shock.
8. endocarditis
 9. Thrombosis and phlebitis
CNS
10. Neurological complications =
I. increased intracranial pressure
II. cerebral thrombosis
III. acute cerebellar ataxia
IV. chorea
V. aphasia
VI. deafness
VII. psychosis
VIII. transverse myelitis
IX. Peripheral and optic neuritis
X. Meningitis
Others-
11. bone marrow necrosis,
12. pyelonephritis,
13. Nephrotic syndrome,
14. orchitis,
15. suppurative lymphadenitis.
16. osteomyelitis and septic arthritis = common in children with hemoglobinopathies.

Prognosis.

Depends on prompt therapy,

age of the patient,
previous state of health,
causative Salmonella serotype,
appearance of complications.
mortality rate is less than 1%. - higher if delay in diagnosis, hospitalization, and
treatment.
Infants and those with underlying debilitating disorders are at higher risk.
Complications, such as gastrointestinal perforation or severe hemorrhage, meningitis,
endocarditis, and pneumonia, is associated with high morbidity and mortality rates.

Relapse --if not treated with antibiotics.

resemble the acute illness. - milder and of shorter duration. –
who excrete S. typhi 3 mo or longer after infection are excretors,
at 1 yr are chronic carriers.
1–5% become chronic carriers. - biliary tract or urinary carriage occur

Prevention.

1) improved sanitation
2) clean running water
3) personal hygiene measures
4) hand washing
 5) attention to food preparation practices
6) carriers should be prevented from working in food- or water-processing
activities
7) Vaccine

Three vaccines against S. typhi are available.

1. TAB - -
Parenteral heat-phenol inactivated vaccine efficacy = 50–75%
Adverse effects, including fever, local reactions, and headache
Two doses - administered subcutaneously 4 wk apart.
Booster doses are necessary every 3 yr.
2. Typhoral –
Oral, live-attenuated preparation of the Ty21a strain of S. typhi.
Efficacy = 65–80%.
Three enteric-coated capsules are given on alternate days, and the entire series is
repeated every 5 yr. adverse effects are rare. Keep capsules in cold chain. No antibiotics
are given for a week before and after ingestion of oral vaccine.
Not recommended for children < 6 yr of age and immunodeficiency syndromes.

3. Typhim Vi
Capsular polysaccharide
2 yr of age or older.
A single intramuscular dose, with a booster every 2 yr.

Travelers & Hospital staff

Typhoid vaccination is recommended

Vaccine is not a substitute for personal hygiene and selection of foods and drinks
None of the vaccines has efficacy of 100 %.