Typhoid fever - Clinicals, Diagnosis, and Management

Infectious diseases

Clinicals - History

Fact Explanation
Ingestion of contaminated materials Typhoid fever is a systemic disease due to the human specific Gram-negative pathogen Salmonella enterica serotype, Salmonella Typhi (S. Typhi) that causes intestinal and extra-intestinal manifestations. Transmission of the disease occurs through faecal-oral route. Ingestion of contaminated water,food and consuming raw milk products, fruits and vegetables, and inadequate sanitation, poor hygiene are major causative factors for the initiation of the pathogenesis. Incubation period is 10-14 days. Mechanism that support salmonella to invade the host are having lipopolysaccharides and inhibition of antigen presentation via dendritic cells. Ingestion of contaminated materials
Typhoid fever is a systemic disease due to the human specific Gram-negative pathogen Salmonella enterica serotype, Salmonella Typhi (S. Typhi) that causes intestinal and extra-intestinal manifestations. Transmission of the disease occurs through faecal-oral route. Ingestion of contaminated water,food and consuming raw milk products, fruits and vegetables, and inadequate sanitation, poor hygiene are major causative factors for the initiation of the pathogenesis. Incubation period is 10-14 days. Mechanism that support salmonella to invade the host are having lipopolysaccharides and inhibition of antigen presentation via dendritic cells.
Diarrhoea and constipation Commonly fever is followed by diarrhoea. Inflamed peyer patches causes obstruction of the intestinal lumen causing constipation. Foul, green-yellow, liquid diarrhea might be seen in third week of the disease and is called pea soup diarrhea. Diarrhoea and constipation
Commonly fever is followed by diarrhoea. Inflamed peyer patches causes obstruction of the intestinal lumen causing constipation. Foul, green-yellow, liquid diarrhea might be seen in third week of the disease and is called pea soup diarrhea.
Fever Inflammation causes release of pyrogens and fever, it is of gradual onset and may sustained and associated with chills. Fever is a step ladder pattern fever with increased intensity of peaks with time. Fever
Inflammation causes release of pyrogens and fever, it is of gradual onset and may sustained and associated with chills. Fever is a step ladder pattern fever with increased intensity of peaks with time.
Abdominal pain, nausea, anorexia Fever is followed by diarrhoea, vomiting, abdominal pain as mentioned above. Gastrointestinal symptoms develops in the first week of illness. Abdominal pain, nausea, anorexia
Fever is followed by diarrhoea, vomiting, abdominal pain as mentioned above. Gastrointestinal symptoms develops in the first week of illness.
Rash Bacterial invasions in the skin will be evident by rose spots, which are salmon-colored, blanching, truncal, maculopapules usually resolve within 2-5 days. Round, maculopapular lesions may be seen over the abdomen and other areas of the body. Rash
Bacterial invasions in the skin will be evident by rose spots, which are salmon-colored, blanching, truncal, maculopapules usually resolve within 2-5 days. Round, maculopapular lesions may be seen over the abdomen and other areas of the body.

Clinicals - Examination

Fact Explanation
Febrile Fever is one of the presenting features. At the end of the first week, the fever may be around 103-104°F (39-40°C). Occasionally hypothermia may be present. Febrile
Fever is one of the presenting features. At the end of the first week, the fever may be around 103-104°F (39-40°C). Occasionally hypothermia may be present.
Tachycardia/bradycardia Salmonella bacteremia and sepsis may cause tachycardia. Relative bradycardia develops in the second week of the illness. Dicrotic pulse is double beat, with the second beat weaker than the first. Tachycardia/bradycardia
Salmonella bacteremia and sepsis may cause tachycardia. Relative bradycardia develops in the second week of the illness. Dicrotic pulse is double beat, with the second beat weaker than the first.
Features of dehydration: sunken eyes, reduced skin turgor, dry skin, reduced urine output Diarrhoea and reduced fluid intake causing dehydration. Features of dehydration: sunken eyes, reduced skin turgor, dry skin, reduced urine output
Diarrhoea and reduced fluid intake causing dehydration.
Hypotension Salmonella can cause bacteremia and sepsis or may be due to dehydration. Hypotension
Salmonella can cause bacteremia and sepsis or may be due to dehydration.
Reduced level of consciousness Salmonella can cause bacteremia and sepsis. Occasionally it can cause typhoid encephalopathy. Reduced level of consciousness
Salmonella can cause bacteremia and sepsis. Occasionally it can cause typhoid encephalopathy.
Hepatosplenomegaly Splenomegally may be present with a soft enlargement. Hepatosplenomegaly
Splenomegally may be present with a soft enlargement.
Abdominal distension Due to the hepatosplenomegaly. Abdominal distension
Due to the hepatosplenomegaly.
Rash and typhoid tongue There will be rose spots, which are salmon-colored, blanching, truncal, maculopapules usually resolve within 2-5 days. Rash and typhoid tongue
There will be rose spots, which are salmon-colored, blanching, truncal, maculopapules usually resolve within 2-5 days.

Investigations - Diagnosis

Fact Explanation
Blood , stool and bone marrow culture Bacteria can be isolated from the blood, stool or bone marrow. Most commonly using method is blood culture with a , 50% sensitivity. However the sensitivity of the test decreases with increased duration of fever. Blood , stool and bone marrow culture
Bacteria can be isolated from the blood, stool or bone marrow. Most commonly using method is blood culture with a , 50% sensitivity. However the sensitivity of the test decreases with increased duration of fever.
Widal test Used to detect the antibodies against Salmonella specific O (somatic) and H (flagellar) antigens in the serum and usually these antibodies appear in the 2nd week of the disease. Widal test
Used to detect the antibodies against Salmonella specific O (somatic) and H (flagellar) antigens in the serum and usually these antibodies appear in the 2nd week of the disease.
Polymerase chain reaction(PCR) This is able to detect very small number of bacteria within 4-5 days of onset of infection. The specific gene sequence of the bacterium, can be detected specifically and rapidly by PCR. Polymerase chain reaction(PCR)
This is able to detect very small number of bacteria within 4-5 days of onset of infection. The specific gene sequence of the bacterium, can be detected specifically and rapidly by PCR.

Investigations - Management

Fact Explanation
Serum electrolytes Electrolyte imbalances are improving as infection settles. Serum electrolytes
Electrolyte imbalances are improving as infection settles.
Full blood count Salmonella infection causes leucopenia which may be corrected as improvement occurs. Full blood count
Salmonella infection causes leucopenia which may be corrected as improvement occurs.
Full blood count This is important to rule out the other conditions that may present with fever, such as bacterial infections ( increased white cell count-leucocytosis), viral infections causing elevated lymphocyted and dengue causing reduced platelets. Typhoid fever may also have leucopenia as a finding. Full blood count
This is important to rule out the other conditions that may present with fever, such as bacterial infections ( increased white cell count-leucocytosis), viral infections causing elevated lymphocyted and dengue causing reduced platelets. Typhoid fever may also have leucopenia as a finding.
Polymerase chain reaction(PCR) This method can differentiate between S. Typhi CT18, S. Typhi Ty2 and S. Paratyphi A. Polymerase chain reaction(PCR)
This method can differentiate between S. Typhi CT18, S. Typhi Ty2 and S. Paratyphi A.

Management - Supportive

Fact Explanation
Controlling pain, fever and vomiting Analgesics and antipyretics can be used to control the any associated pain and fever. Antiemetics can be used for vomiting. Dehydration needs to be corrected. Controlling pain, fever and vomiting
Analgesics and antipyretics can be used to control the any associated pain and fever. Antiemetics can be used for vomiting. Dehydration needs to be corrected.
Management of dehydration and rehydration There is loss of fluid and electrolytes during the diarrhoea leads to dehydration, hyponatraemia, hypokalaemia, and metabolic acidosis. Currently recommended oral rehydration solution has a total osmolarity of 311 mmol/l with sodium (75 mmol/L), potassium, chloride, citrate and glucose anhydrous in adequate amounts. As The glucose-sodium co-transporter is preserved in diarrhoeal diseases, the ORS can provide the deficient fluids and electrolytes in diarrhoea.
Management of mild to moderate dehydration, requires rehydration with 50-100ml/kg over 3-4 hours. Usually around 60 ml of ORS per each stool is required for the replacement. Severe cases need intravenous fluid replacement with 0.9% normal saline/ringer's lactate.
Management of dehydration and rehydration
There is loss of fluid and electrolytes during the diarrhoea leads to dehydration, hyponatraemia, hypokalaemia, and metabolic acidosis. Currently recommended oral rehydration solution has a total osmolarity of 311 mmol/l with sodium (75 mmol/L), potassium, chloride, citrate and glucose anhydrous in adequate amounts. As The glucose-sodium co-transporter is preserved in diarrhoeal diseases, the ORS can provide the deficient fluids and electrolytes in diarrhoea.
Management of mild to moderate dehydration, requires rehydration with 50-100ml/kg over 3-4 hours. Usually around 60 ml of ORS per each stool is required for the replacement. Severe cases need intravenous fluid replacement with 0.9% normal saline/ringer's lactate.
Vaccination The most important preventive measure is vaccination. There are two types of vaccines currently available: a subunit -Vi polysacharide vaccine and a live attenuated S. Typhi strain (Ty21a). Development of DNA vaccine for typhoid fever
which targets the epitope selection is currently under research. Vaccines are recomended for individuals at or above 6 years of age who are travelers to high risk areas or have intimate exposure.
Vaccination
The most important preventive measure is vaccination. There are two types of vaccines currently available: a subunit -Vi polysacharide vaccine and a live attenuated S. Typhi strain (Ty21a). Development of DNA vaccine for typhoid fever
which targets the epitope selection is currently under research. Vaccines are recomended for individuals at or above 6 years of age who are travelers to high risk areas or have intimate exposure.
Prevention Provision of clean water and sanitation systems are of great importance in preventing typhoid fever. Prevention
Provision of clean water and sanitation systems are of great importance in preventing typhoid fever.

Management - Specific

Fact Explanation
Antibiotic treatment Lack of adequate treatment, may be associated with a case-fatality rate of 10–30%. Commonly used antibiotics for the typhoid fever are fluoroquinolone such as ciprofloxacin, ofloxacin and pefloxacin and third-generation cephalosporins such as ceftriaxone or cefotaxime. There is antimicrobial resistance to bacteria in the carriers with gallstones as they form a biofilm on the gallbladder. Emergence of multidrug resistance (MDR) is a recognizing complication in the treatment of salmonella. Antibiotic treatment
Lack of adequate treatment, may be associated with a case-fatality rate of 10–30%. Commonly used antibiotics for the typhoid fever are fluoroquinolone such as ciprofloxacin, ofloxacin and pefloxacin and third-generation cephalosporins such as ceftriaxone or cefotaxime. There is antimicrobial resistance to bacteria in the carriers with gallstones as they form a biofilm on the gallbladder. Emergence of multidrug resistance (MDR) is a recognizing complication in the treatment of salmonella.
Surgical treatment If there are complications like intestinal perforation, surgery is required.

Patient may fail to respond to the antibiotics and become a typhoid carrier where there can be a chronic hepatobiliary carriage. Cholecystectomy is needed in these cases even though it is not always successful. Cholecystectomy can be combined with antibiotics like amoxycillin for more success in the treatment of carriers.
Surgical treatment
If there are complications like intestinal perforation, surgery is required.

Patient may fail to respond to the antibiotics and become a typhoid carrier where there can be a chronic hepatobiliary carriage. Cholecystectomy is needed in these cases even though it is not always successful. Cholecystectomy can be combined with antibiotics like amoxycillin for more success in the treatment of carriers.

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