Lecture 5. typhoid fever 3

General description of infectious diseases with fecal-oral mechanism of trans mission . Typhoid fever . Paratyphoid A and B . Sorokhan MD, PhD Bukovinian State Medical University Department of the infection diseases and epidemiology

TYPHOID FEVER
Typhoid fever - a severe multisystemic infection caused by Salmonella typhi , characterized by :
the classic prolonged fever ;
sustained bacteremia without endothelial or endocardial involvement ;
intoxication;
skin rash;
and bacterial invasion of and multiplication within the mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer patches.

Etiology
Salmonellae are gram-negative, flagellate, motile , nonsporulating, facultative anaerobic bacilli.
Salmonella typhi organism

Etiology
These bacilli ferment glucose, reduce nitrate to nitrite, and synthesize peritrichous flagella when motile. S . typhi produce gas upon sugar fermentation.

Etiology
All s almonellae are grouped based on the somatic O antigen and further divided into serotypes based on flagellar H and surface virulence (Vi) antigens.

Epidemiology
S . typhi and S . paratyphi are pathogenic exclusively in humans. The source of infection is sick human or bacteriocarrier. People are typically infected with S . typhi through food and beverages contaminated by a chronic stool carrier (fecal-oral route of transmission) . Less commonly, carriers may shed the bacteria in urine , saliva and breast milk . Typhoid fever is potentially fatal if untreated.

Epidemiology
Typhoid fever occur worldwide but primarily in developing nations where sanitary conditions are poor.

Epidemiology
World map showing incidence of typhoid fever.
♦ Strongly endemic
♦ Endemic
♦ Sporadic cases
It is endemic in Asia, Africa, Latin America, the Caribbean, and Oceania. Typhoid fever affects 13-17 million people yearly and kills an estimated 600,000.

Pathophysiology
After successfully passing through the stomach, any Salmonella subspecies may be phagocytized by the gut ’ s intraluminal dendritic cells, causing inflammation that leads to diarrhea. Peyer patches are grossly visible aggregates of 5-100 lymphoid follicles in the small bowel submucosa; these patches are larger and more numerous distally.

Pathophysiology
From blood or from the liver via bile ducts, it infects the gallbladder and reenters the gastrointestinal tract in the bile, spreading to other hosts via stool. In addition, it occasionally invades the urinary tract and spreads via urine.
After primary intestinal infection, further seeding of the Peyer patches occurs through infected bile. They may become hyperplastic and necrotic with infiltration of mononuclear cells and neutrophils, forming ulcers that may hemorrhage through eroded blood vessels or perforate the bowel wall, causing peritonitis.

Pathology
The hallmark histologic finding in typhoid fever is infiltration of tissues by macrophages (typhoid cells) that contain bacteria, erythrocytes, and degenerated lymphocytes. Aggregates of these macrophages are called typhoid nodules, which are found most commonly in the intestine, mesenteric lymph nodes, spleen, liver, and bone marrow but may be found in the kidneys, testes, and parotid glands.
After initially being ingested in contaminated food such as shellfish, or water, the Salmonella typhi bacteria migrate through the intestinal mucosa of the terminal ileum into the submucosal lymph nodes. Provider CDC/Armed Forces Institute of Pathology.

Pathology
In the intestines, 4 classic pathologic stages occur in the course of infection:
hyperplastic changes;
necrosis of the intestinal mucosa;
sloughing of the mucosa;
the development of ulcers. The ulcers may perforate into the peritoneal cavity.

Pathology
In the mesenteric lymph nodes, the sinusoids are enlarged and distended by large collections of macrophages and reticuloendothelial cells. The spleen is enlarged, red, soft, and congested; its serosal surface may have a fibrinous exudate. Microscopically, the red pulp is congested and contains typhoid nodules. The gallbladder is hyperemic and may show evidence of cholecystitis. A liver biopsy specimen from a person with typhoid often shows cloudy swelling, balloon degeneration with vacuolation of hepatocytes, moderate fatty change, and focal typhoid nodules. Intact typhoid bacilli can be observed at these sites.

Mortality/Morbidity
Early antibiotic therapy has transformed a previously life-threatening illness of several weeks ’ duration with an overall mortality rate approaching 20% into a short-term febrile illness with low mortality.

Complaints
Untreated typhoid fever lasts at least 4 weeks. The incubation period of typhoid fever is 7-14 (range, 3-60) days. In paratyphoid infection, the incubation period ranges from 1-10 days. Patients often experience chills, sweating , poor apetite , dry cough, a dull headache, and muscle pain before the onset of a high fever. Some patients, especially in India and Africa, may present with confusion and delirium.

Complaints As bacteremia develops, the incubation period ends. Patients often experience chills, diaphoresis, anorexia, dry cough, a dull frontal headache, and myalgias before the onset of a high fever. About 20-40% of patients present with abdominal pain. The incidence of constipation versus diarrhea varies geographically, perhaps because of local differences in diet or S . typhi strains or genetic variation. Unusual modes of onset include isolated severe headaches that may mimic meningitis. S . typhi infection may cause an acute lobar pneumonia. In the early stages of the disease, rigors are rare unless the person also has malaria. This is not an unusual pairing of diseases. Patients may present with arthritis only, urinary symptoms, severe jaundice, or fever.

Physical exam
The classic signs of enteric fever include fever, toxemia, delirium, abdominal pain, constipation, and hepatosplenomegaly.
Fever occurs in 75-85% of patients in the first week and is often initially remittent but becomes steady. The individual ’ s temperature often rises to as high as 39-40°C ( 103-104 °F) by the beginning of second week.

Physical exam
At approximately the end of the first week of illness, about a third of patients develop bacterial emboli to the skin known as rose spots. These are considered a classic symptom in typhoid fever, but they occasionally appear in shigellosis and nontyphoidal salmonellosis.
Rose spots

Physical exam Rose spots on the chest of a patient with typhoid fever due to the bacterium Salmonella typhi . Rose spots constitute a subtle, extremely sparse (often <5 spots), salmon-colored, blanching, truncal, maculopapular rash with 1- to 4-cm lesions that generally resolve within 2-5 days.

Physical exam
Relative bradycardia and a dicrotic pulse are also common during the first week. During the second week of illness, the patient is toxic-appearing and apathetic with sustained fever. The abdomen is slightly distended, and soft splenomegaly is common.

Physical exam
In the third week, the patient grows more toxic and anorexic with significant weight loss. The patient may have a thready pulse, tachypnea, conjunctivitis, and crackles over the lung bases. Pyrexia persists. The patient may enter into a typhoid state of apathy, confusion, and even psychosis. Patients may develop polyneuropathy. Abnormal cerebrospinal fluid should prompt a search for a different cause.

Physical exam
Meanwhile, the patient commonly has pronounced abdominal distension. Some individuals may produce liquid, foul, green-yellow diarrhea (pea soup diarrhea). At this stage, the patient may die from overwhelming toxemia, myocarditis, intestinal hemorrhage, or perforation due to necrotic Peyer patches. Rare complications of enteric fever include pancreatitis, meningitis, orchitis, and osteomyelitis.

Physical exam
During the fourth week, the fever, mental state, and abdominal distension slowly improve over a few days, but intestinal complications may still occur in surviving untreated individuals. Weight loss and debilitating weakness last months. Relapses occur in 10% of patients, mostly during the first 2-3 weeks of convalescence.

Physical exam
One to four percent of untreated patients become chronic carriers, defined as individuals who excrete Salmonella for more than 1 year. Some individuals may continue to excrete the bacterium for decades. Chronic carriers have a greater risk for carcinoma of the gallbladder and other gastrointestinal malignancies; chronic carriers had a 6-fold increase in the risk of death due to hepatobiliary cancer. This may be due to chronic inflammation caused by the bacterium.

Differential diagnoses
The differential diagnosis of typhoid fever requires consideration of many disease processes characterized by fever and abdominal complaints. Early in the disease the predominance of fever and upper respiratory tract symptoms may suggest influenza or other viral infections. Cough and fever suggest acute bronchitis and, when coupled with rales, raise the question of bacterial pneumonia. Headache, confusion, and fever may prompt consideration of bacterial or aseptic meningitis or meningoencephalitis.

Differential diagnoses
Delirium, catatonia, or coma may suggest a diagnosis of psychosis or other neuropsychiatries illness. The abdominal findings may lead to a consideration of acute appendicitis, acute cholecystitis, or intestinal infarction. Bacillary, amebic or ischemic colitis may enter the differential diagnosis if blood diarrhea occurs. As fever continues over a period of weeks, other possibilities might include brucellosis, yersinosis, lymphoma, inflammatory bowel disease, bacterial endocarditis, miliary tuberculosis, malaria, sepsis, epidemic typhus and many other diseases.

Workup
Culture :
Blood culture , intestinal secretions culture (vomitus or duodenal aspirate), and stool culture can be used for patients with typhoid fever who present within the first week of onset ;

Specific serologic tests :
The Widal test was the mainstay of typhoid fever diagnosis for decades. It is used to measure agglutinating antibodies against H and O antigens of S . typhi. Neither sensitive nor specific, the Widal test is no longer an acceptable clinical method ;
Indirect hemagglutination, indirect fluorescent Vi antibody, and indirect enzyme-linked immunosorbent assay (ELISA) for immunoglobulin M (IgM) and IgG antibodies to S . typhi polysaccharide, as well as monoclonal antibodies against S . typhi flagellin, are promising, but the success rates of these assays vary greatly in the literature.

Other nonspecific laboratory studies :
Most patients with typhoid fever are moderately anemic, have an elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and relative lymphopenia ;
Most also have a slightly elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) and decreased fibrinogen levels ;
Circulating fibrin degradation products commonly rise to levels seen in subclinical disseminated intravascular coagulation (DIC) ;
Liver transaminase and serum bilirubin values usually rise to twice the reference range ;
Mild hyponatremia and hypokalemia are common ;
Leukopenia occurs in a minority of patients.

Medical Care
Diet
Fluids and electrolytes should be monitored and replaced diligently. Oral nutrition with a soft digestible diet is preferable in the absence of abdominal distension or ileus.
Activity
Bed rest .

Antibiotics
Levomycetin - 500 mg PO/IV q4h until defervescence, then q6h for a total course of 14 d.
Amoxicillin - 1 g PO q8h.
Ciprofloxacin - 20-30 mg/kg/d PO bid for 14 d.
Cefotaxime - 2 g IV q6h.
Ceftriaxone - 1-2 g IV q12h.
Cefoperazone - 2-4 g/d IV/IM divided bid; not to exceed 12 g/d.
Ofloxacin 200-400 mg PO q12h.
Levofloxacin - 500 mg PO qd for 7-14 d.

Corticosteroids
Dexamethasone - 3 mg/kg PO/IM/IV initially, followed by 8 doses of 1 mg/kg q6h.

Outpatient Care
After discharge, patients should be monitored for relapse or complications for 3 months after treatment has commenced.
A fter disease resolution, 3 stool cultures in one-month intervals should be performed to rule out a carrier state.

Prevention
Travelers to endemic countries should avoid raw unpeeled fruits or vegetables since they may have been prepared with contaminated water; in addition, they should drink only boiled water.
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.

Vaccine
In endemic areas, mass immunization with typhoid vaccines at regular intervals considerably reduces the incidence of infections. Routine typhoid vaccination is indicated for :
travelers to endemic areas ;
persons with intimate exposure to a documented S . typhi carrier (eg, household contact) ;
and microbiology laboratory personnel who frequently work with S . typhi.

Vaccine
There are 2 typhoid fever vaccines :
injected Vi capsular polysaccharide (Typhim Vi) antigen ;
enteric Ty21a (Vivotif Berna) live-attenuated vaccine .

Complications
The 2 most common complications of typhoid fever include intestinal hemorrhage and perforation ;

Prognosis
The prognosis among persons with typhoid fever depends primarily on the speed of diagnosis and initiation of correct treatment. Generally, untreated typhoid fever carries a mortality rate of 10-20%. In properly treated disease, the mortality rate is less than 1%.

Thank you for your attention!

Lecture 5. typhoid fever 3

by sorokhan on Mar 30, 2011

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