History

Fact Explanation
Ingestion of contaminated materials [3] 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. [1] 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. [4] Mechanism that support salmonella to invade the host are having lipopolysaccharides and inhibition of antigen presentation via dendritic cells.
Diarrhoea and constipation [2] Commonly fever is followed by diarrhoea. [2] 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 [2] Inflammation causes release of pyrogens and fever, it is of gradual onset and may sustained and associated with chills. [1] Fever is a step ladder pattern fever with increased intensity of peaks with time.
Abdominal pain, nausea, anorexia [2] Fever is followed by diarrhoea, vomiting, abdominal pain as mentioned above. [2] 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. [3]
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846
  2. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 16 August 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x
  3. NEWTON PAULA, KAMAT RIVA. A 10‐Year‐Old Girl with a Rash and Abdominal Pain. CLIN INFECT DIS [online] 2009 March, 48(5):683-684 [viewed 10 September 2014] Available from: doi:10.1086/596761

Examination

Fact Explanation
Febrile [3] Fever is one of the presenting features. [4] At the end of the first week, the fever may be around 103-104°F (39-40°C). Occasionally hypothermia may be present. [5]
Tachycardia/bradycardia [3] Salmonella bacteremia and sepsis may cause tachycardia. Relative bradycardia [3] 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. [3]
Hypotension [5] Salmonella can cause bacteremia and sepsis or may be due to dehydration. [2]
Reduced level of consciousness [1] Salmonella can cause bacteremia and sepsis. Occasionally it can cause typhoid encephalopathy. [4]
Hepatosplenomegaly [1] Splenomegally [3] may be present with a soft enlargement.
Abdominal distension [3] Due to the hepatosplenomegaly. [3]
Rash and typhoid tongue [3] There will be rose spots, which are salmon-colored, blanching, truncal, maculopapules usually resolve within 2-5 days. [4]
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846
  2. KEONG BC, SULAIMAN W. Typhoid and Malaria Co-Infection - An Interesting Finding in the Investigation of a Tropical Fever Malays J Med Sci [online] 2006 Jan, 13(1):74-75 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347907
  3. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 16 August 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x
  4. NEWTON PAULA, KAMAT RIVA. A 10‐Year‐Old Girl with a Rash and Abdominal Pain. CLIN INFECT DIS [online] 2009 March, 48(5):683-684 [viewed 10 September 2014] Available from: doi:10.1086/596761
  5. TI TY, MONTEIRO EH, LAM S, LEE HS. Ceftriaxone therapy in bacteremic typhoid fever. Antimicrob Agents Chemother [online] 1985 Oct, 28(4):540-543 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC180301

Differential Diagnoses

Fact Explanation
Dengue [4] Dengue is a viral infection caused by DEN virus belong to the genus flavivirus within the Flaviviridae family which has 4 serptypes. They might have a history of mosquito bites, exposure to the arthropod vector, Aedes aegypti. Clinical picture includes fever, vomiting, diarrhoea, right hypochondrial pain, retro orbital pain, bodyaches and rash. Hypotension and shock may be in the advanced haemorrhagic disease. [5] Bleeding, thrombocytopenia of <100,000 platelets mm−3, ascites, pleural effusion, haematocrit >20%, severe and continuous abdominal pain, restlessness and/or somnolence, persistent vomiting and a sudden reduction in temperature, associated with profuse perspiration, are might be the signs of plasma extravasation and the imminence of shock. Platelet count may be low with leucopenia. Dengue antigen and antibody testing is helpful to differentiate from the other conditions. [2]
Viral hepatitis [3] Hepatitis is an inflammation of the liver. Hepatittis A and E are faeco orally transmitted. Clinical features would be abdominal pain on the upper right side, dark urine, fatigue, fever, itching, jaundice (yellowish skin color), loss of appetite, and nausea or vomiting. Serologic testing for immunoglobulin M (IgM) antibody to HAV may be helpful. Alanine aminotransferase (ALT) level is elevated. Longtrem complications would be chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). [6]
Appendicitis [7] Abdominal pain may start at the periumbilical regeion, then shifts to the right iliac fossa. It is a colicky pain and be associated with nausea, vomiting, fever and diarrhoea. Person is severely ill with refusing food and water. However the initial symptoms may be nonspecific making diagnosis delayed on certain situations. [7] There will be abdominal tendernes, rigidity, guarding and which may be generalized if they develop peritonitis. Ultrasoud may be helpful to cisualized the inflamed appendix.
Amoebiasis [1] Entamoeba histolytica and Balantidium coli are major source of protozoa causing amoebiasis in human. 90% of infected patients are asymptomatic, Clinical features may vary from dysentery to abscesses of the liver, lungs, or brain. Gastrointestinal symptoms are common. [8] Spread is via a fecal-oral route, and cysts are the infective stage.
References
  1. NESBITT RA, MOSHA FW, KATKI HA, ASHRAF M, ASSENGA C, LEE CM. Amebiasis and comparison of microscopy to ELISA technique in detection of Entamoeba histolytica and Entamoeba dispar. J Natl Med Assoc [online] 2004 May, 96(5):671-677 [viewed 17 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640664
  2. GUZMAN MARIA G., HALSTEAD SCOTT B., ARTSOB HARVEY, BUCHY PHILIPPE, FARRAR JEREMY, GUBLER DUANE J., HUNSPERGER ELIZABETH, KROEGER AXEL, MARGOLIS HAROLD S., MARTíNEZ ERIC, NATHAN MICHAEL B., PELEGRINO JOSE LUIS, SIMMONS CAMERON, YOKSAN SUTEE, PEELING ROSANNA W.. Dengue: a continuing global threat. Nat Rev Micro [online] 2010 December, 8(12):S7-S16 [viewed 17 August 2014] Available from: doi:10.1038/nrmicro2460
  3. PAQUET C, BABES VT, DRUCKER J, SéNéMAUD B, DOBRESCU A. Viral hepatitis in Bucharest. Bull World Health Organ [online] 1993, 71(6):781-786 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2393526
  4. OCHIAI RL, ACOSTA CJ, DANOVARO-HOLLIDAY MC, BAIQING D, BHATTACHARYA SK, AGTINI MD, BHUTTA ZA, CANH DG, ALI M, SHIN S, WAIN J, PAGE AL, ALBERT MJ, FARRAR J, ABU-ELYAZEED R, PANG T, GALINDO CM, VON SEIDLEIN L, CLEMENS JD, THE DOMI TYPHOID STUDY GROUP. A study of typhoid fever in five Asian countries: disease burden and implications for controls Bull World Health Organ [online] 2008 Apr, 86(4):260-268 [viewed 10 September 2014] Available from: doi:10.2471/BLT.06.039818
  5. BHATT S, GETHING PW, BRADY OJ, MESSINA JP, FARLOW AW, MOYES CL, DRAKE JM, BROWNSTEIN JS, HOEN AG, SANKOH O, MYERS MF, GEORGE DB, JAENISCH T, WINT GR, SIMMONS CP, SCOTT TW, FARRAR JJ, HAY SI. The global distribution and burden of dengue Nature [online] 2013 Apr 25, 496(7446):504-507 [viewed 10 September 2014] Available from: doi:10.1038/nature12060
  6. LIANG TJ. Hepatitis B: The Virus and Disease Hepatology [online] 2009 May, 49(5 Suppl):S13-S21 [viewed 10 September 2014] Available from: doi:10.1002/hep.22881
  7. WILSON D, SINCLAIR S, MCCALLION WA, POTTS SR. Acute appendicitis in young children in the Belfast urban area: 1985-1992. Ulster Med J [online] 1994 Apr, 63(1):3-7 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8658993
  8. MCMILLAN A, GILMOUR HM, MCNEILLAGE G, SCOTT GR. Amoebiasis in homosexual men. Gut [online] 1984 Apr, 25(4):356-360 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1432335

Investigations - for Diagnosis

Fact Explanation
Blood [3] , 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.[2] However the sensitivity of the test decreases with increased duration of fever. [1]
Widal test [4] 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. [1]
Polymerase chain reaction(PCR) [4] 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. [5]
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846
  2. BUCKLE GC, WALKER CL, BLACK RE. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010 J Glob Health [online] 2012 Jun, 2(1):010401 [viewed 16 August 2014] Available from: doi:10.7189/jogh.02.010401
  3. CRUMP JA, LUBY SP, MINTZ ED. The global burden of typhoid fever. Bull World Health Organ [online] 2004 May, 82(5):346-353 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622843
  4. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 10 September 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x
  5. PRAKASH P, MISHRA OP, SINGH AK, GULATI AK, NATH G. Evaluation of Nested PCR in Diagnosis of Typhoid Fever J Clin Microbiol [online] 2005 Jan, 43(1):431-432 [viewed 15 September 2014] Available from: doi:10.1128/JCM.43.1.431-432.2005

Investigations - Fitness for Management

Fact Explanation
Full blood count [1] 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.[1]
References
  1. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 16 August 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x

Investigations - Followup

Fact Explanation
Serum electrolytes Electrolyte imbalances are improving as infection settles. [1]
Full blood count [2] Salmonella infection causes leucopenia [2] which may be corrected as improvement occurs.
References
  1. FIELD MICHAEL. Intestinal ion transport and the pathophysiology of diarrhea. J. Clin. Invest. [online] 2003 April, 111(7):931-943 [viewed 07 July 2014] Available from: doi:10.1172/JCI18326
  2. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 16 August 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x

Investigations - Screening/Staging

Fact Explanation
Polymerase chain reaction(PCR) [1] This method can differentiate between S. Typhi CT18, S. Typhi Ty2 and S. Paratyphi A. [1]
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846

Management - General Measures

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. [5]
Management of dehydration and rehydration [5] 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, [5] 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. [3]
Vaccination [4,6] The most important preventive measure is vaccination. [1] There are two types of vaccines currently available: a subunit -Vi polysacharide vaccine and a live attenuated S. Typhi strain (Ty21a). [1] 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. [2]
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846
  2. BUCKLE GC, WALKER CL, BLACK RE. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010 J Glob Health [online] 2012 Jun, 2(1):010401 [viewed 16 August 2014] Available from: doi:10.7189/jogh.02.010401
  3. MUNOS MK, WALKER CL, BLACK RE. The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality. Int J Epidemiol [online] 2010 Apr:i75-87 [viewed 07 July 2014] Available from: doi:10.1093/ije/dyq025
  4. MWEU E, ENGLISH M. Typhoid fever in children in Africa Trop Med Int Health [online] 2008 Apr, 13(4):532-540 [viewed 16 August 2014] Available from: doi:10.1111/j.1365-3156.2008.02031.x
  5. SAMADI AR, ISLAM R, HUQ MI. Replacement of intravenous therapy by oral rehydration solution in a large treatment centre for diarrhoea with dehydration Bull World Health Organ [online] 1998, 76(4):319-324 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2305768
  6. OCHIAI RL, ACOSTA CJ, DANOVARO-HOLLIDAY MC, BAIQING D, BHATTACHARYA SK, AGTINI MD, BHUTTA ZA, CANH DG, ALI M, SHIN S, WAIN J, PAGE AL, ALBERT MJ, FARRAR J, ABU-ELYAZEED R, PANG T, GALINDO CM, VON SEIDLEIN L, CLEMENS JD, THE DOMI TYPHOID STUDY GROUP. A study of typhoid fever in five Asian countries: disease burden and implications for controls Bull World Health Organ [online] 2008 Apr, 86(4):260-268 [viewed 10 September 2014] Available from: doi:10.2471/BLT.06.039818

Management - Specific Treatments

Fact Explanation
Antibiotic treatment [3] Lack of adequate treatment, may be associated with a case-fatality rate of 10–30%. [2] Commonly used antibiotics for the typhoid fever are fluoroquinolone such as ciprofloxacin, ofloxacin and pefloxacin and third-generation cephalosporins such as ceftriaxone or cefotaxime. [1] 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. [4] 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.
References
  1. MARATHE SA, LAHIRI A, NEGI VD, CHAKRAVORTTY D. Typhoid fever & vaccine development: a partially answered question Indian J Med Res [online] 2012 Feb, 135(2):161-169 [viewed 16 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336846
  2. BUCKLE GC, WALKER CL, BLACK RE. Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010 J Glob Health [online] 2012 Jun, 2(1):010401 [viewed 16 August 2014] Available from: doi:10.7189/jogh.02.010401
  3. TI TY, MONTEIRO EH, LAM S, LEE HS. Ceftriaxone therapy in bacteremic typhoid fever. Antimicrob Agents Chemother [online] 1985 Oct, 28(4):540-543 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC180301
  4. NEWTON PAULA, KAMAT RIVA. A 10‐Year‐Old Girl with a Rash and Abdominal Pain. CLIN INFECT DIS [online] 2009 March, 48(5):683-684 [viewed 10 September 2014] Available from: doi:10.1086/596761