Typhoid Fever

Typhoid Fever

Prof. Nooruddin JafferProfessor of Medicine

Hamdard Medical College

Karachi Pakistan

Introduction Typhoid fever is a severe multisystemic illness

characterized by the classic prolonged fever, sustained bacteremia, and bacterial invasion and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer patches.

Introduction

Occurs only in humans

Potentially fatal if untreated.

Typhoid fever is most prevalent in underdeveloped countries

Epidemiology

Typhoid and paratyphoid fever infections are encountered worldwide but are primarily found in those countries of the developing world where sanitary conditions are poor.

Indian subcontinent, Southeast and Far East Asia, the Middle East, Africa, Central America, and South America.

Epidemiology

In endemic areas, children aged 1-5 years are at the highest risk because of waning passively acquired maternal antibody and a lack of acquired immunity.

Etiologic Agent

Causative agent is Salmonella typhi, a gram-negative bacteria, member of genus Salmonella and familyEnterobacteriaceae

Salmonellae are grouped based on the somatic O and further divided into serotypes based on flagellar H a gram-negative and surface Vi (virulence) antigens.

Transmission

Contaminated food and beverages handled by persons shedding S typhi from stool (or less commonly urine)

Water from sewage contaminated with S typhi.

Transmission

Increased susceptibility is related to• Increased bacterial load: Ingestion of 105

organisms led to clinical disease in 25%, ingestion of 107 in 50%, and 109 organisms in 95%.

• A gastric pH of > than 1.5 • Patients on antacids• Gastrectomy• Achlorhydria due to aging

Pathogenesis

The hallmark of typhoid fever is the invasion of and multiplication within the mononuclear phagocytic cells in the liver, spleen, lymph nodes, and Peyer patches of the ileum.

Pathogenesis

From the Peyer patches S typhi is internalized and transported to the underlying lymphoid tissues.

Then the organisms travel to the mesenteric lymph nodes, multiply, and then enter the blood stream via the thoracic duct (transient primary bacteremia) to seed other tissues.

Pathogenesis

Then the organisms may invade any organ but most commonly are found in reticuloendothelial tissues of the liver, spleen, bone marrow, gallbladder, and Peyer patches in the terminal ileum.

Pathogenesis

The Peyer patches become hyperplastic with infiltration of chronically inflamed cells, which may lead to necrosis of the superficial layer and ulcer formation, with potential hemorrhage from blood vessel erosion or peritonitis from transmural perforation

Symptoms

The incubation period averages 10-20 (range 3-56) days.

Patients remain asymptomatic during the incubation period

As bacteremia develops, patient notices the onset of fever, which typically increases in a step-wise fashion over 2-3 days.

Symptoms

Constipation and mild nonproductive cough are common.

Abdominal pain and diarrhea Delirium Anorexia, weakness, malaise.

Signs

Relative bradycardia

Pink papules (rose spots)(2-4mm) that fade with pressure develop on the upper abdomen and lower chest between the 7th and 12th days caused by bacterial embolization

Signs

During the second week of illness, the patient has a toxic appearance and seems apathetic with sustained pyrexia.

The abdomen is distended slightly, and splenomegaly is common

Signs

In the third week, patient’s toxicity increases and weight loss is common. A delirious state (typhoid state) emerges.

Abdominal distension develops, and liquid, foul, green-yellow diarrhea occurs

thready pulse and tachypnea, Death occur at this stage from toxemia,

myocarditis, intestinal hemorrhage, or perforation.

Signs

In the fourth week, the fever, mental state, and abdominal distension slowly improve but intestinal complications may still occur.

Convalescence is prolonged, and most relapses occur at this stage

Complications

Intestinal

• Intestinal hemorrhage• perforation

Complications

Hepatobiliary

• Mild elevation of transaminases • Jaundice• Hepatitis with hepatomegaly • Pancreatitis

Acute renal failure

Complication

Cardiac

• Nonspecific electrocardiographic changes • Toxic myocarditis• Pericarditis

Complication

Neuropsychiatric

• A toxic confusional state, characterized by disorientation, delirium, and restlessness

• Facial twitching or convulsions

• Encephalomyelitis • Multiple brain abscesses

Complications

Hematologic

• DIC• Hemolytic-uremic syndrome• Hemolysis

Investigations

Anemia, Elevated ESR, Thrombocytopenia, and relative Lymphopenia.

Elevated PT and APTT, Liver transaminase values are usually

elevated to twice the reference range, as is serum bilirubin.

Mild hyponatremia and hypokalemia are common.

Investigation

Definitive diagnosis of typhoid fever requires isolation of the organism from blood or bone marrow.

The most sensitive method of isolating S typhi is obtaining a bone marrow aspirate (BMA) culture (90% sensitive).

Investigation

If BMA cannot be performed, blood, intestinal secretions, and stool culture findings are usually positive in approximately 85-90% of patients with typhoid fever during the first week, declining to 20-30% later in the course of the disease.

Investigation

• The Widal test is the traditional serologic test. The test measures agglutinating antibodies against flagellar (H) and somatic (O) antigens of S typhi.

Investigation

Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay for immunoglobulin M (IgM) and immunoglobulin G antibodies to S typhi polysaccharide are available.

Investigation

Although not commercially available, DNA probes have been developed for identifying S typhi from bacterial culture isolates and directly from blood.

Treatment

Antibiotic therapy is essential and should begin empirically if the clinical evidence is strong.

Antimicrobials shorten the course, reduce the rate of complications if begun early, and reduce the case-fatality rate.

Treatment Because of the efficacy and low relapse and carrier

rates associated the fluoroquinolones and the third-generation cephalosporins are the antibiotics of choice to treat MDR typhoid fever.

Because of its low cost, chloramphenicol is still used

in other areas where local strains are sensitive.

Treatment

The cost and need for IV administration are significant disadvantages of third-generation cephalosporins

Furazolidone and azithromycin are also used to treat typhoid in children

Treatment of carriers

• Prolonged courses of amoxicillin or co-trimoxazole

• Ciprofloxacin (750 mg bid) and norfloxacin (400 mg bid) have been much more effective,

• In nonendemic countries, patients should be kept under bacteriological surveillance after clinical recovery until 6 consecutive negative results are obtained on fecal and urine cultures.

Treatment

Surgical intervention is favored for management of intestinal perforation.

Early diagnosis is key to lower mortality.

Cholecystectomy can be performed for eradicating the carrier state.

Prevention

In endemic countries, the most cost-effective strategy for reducing the incidence of typhoid fever is the institution of public health measures to ensure safe drinking water and sanitary disposal of excreta.

Prevention

Health care workers should pay strict attention to adequate hand washing and safe disposal of feces and urine.

Prevention

Immunization with typhoid vaccines at regular intervals also considerably reduces the incidence of infections.

Vaccination is indicated for travelers to areas associated with a risk of exposure , persons with intimate exposure (eg, household) to a documented S typhi carrier, and microbiology laboratory personnel.

Vaccines

Vi capsular polysaccharide vaccine

Ty21is an oral vaccine containing live attenuated S typhi Ty21a strains in an enteric-coated capsule

Parenteral heat-phenol–inactivated vaccine

Patient Education

Typhoid vaccination is recommended at least 1 week prior to travel to highly disease-endemic areas

Because the protection offered by vaccination is at best partial, close attention to personal, food, and water hygiene should be maintained.

Thank You