typhoid/ paratyphoid

Question 1

What is the pathogens behind enteric fever?

Answer 1

Pathogens belong to Enterobacteriaceae

• [Typhoidal serovars] Typhoid fever = systemic infection caused by Salmonella enterica serotype typhi (S typhi); paratyphoid fever (similar but often less severe disease) = S paratyphi A, B, C
• [Non-typhoidal serovars] S typhimurium and S enteritidis causes a gastroenteritis and extraintestinal disease, and can infect humans and animals

Question 2

what is the presentation of patients with typhoid fever?

Answer 2

Incubation period 10-14 day

Classical 3-4 week subacute presentation:

1st week

• Rising stepwise fever and chills, bacteraemia
• Diarrhoea (more in children), constipation (more in adults)
• Relative bradycardia (pulse temperature dissociation)

2nd week

• Abdominal pain
• Rose spots: small (1-5 mm) faint salmon-coloured blanching non-tender erythematous maculopapular lesions on trunk and abdomen (rose spots are a hallmark of enteric fever, but uncommon)

3rd week

• Sustained high grade fever (sustained high grade fever with long incubation time suggests typhoid fever)
• Hepatosplenomegaly. In endemic areas, typhoid fever should be a differential diagnosis for a patient with fever + jaundice/abnormal LFTs

Metastatic infx

• Focal abscesses
• Osteomyelitis

Long-term carrier status (even if cleared of invasive typhoid) 🡪 if doing food handling, can be a source of infx

Question 3

What are the investigations of typhoid and paratyphoid fever?

Answer 3

• FBC: Anaemia, Leukopenia/leukocytosis
• LFT: Transaminitis (in the hundreds, vs viral hepatitis in the thousands)
• Blood culture is the mainstay of diagnosis, with Salmonella being isolated in 30-90%, positive in the 1st 2 weeks only
• Bone marrow aspirate culture is positive in 80-95% of typhoid patients ) but is invasive so it is usually not warranted
• Stool and urine culture positive from 2nd to 4th weeks.
• Serology: Widal test (limited use): High false positive and false negative
• Salmonella (especially enteritidis [non-typhoidal]) is the most common cause of G- bacteraemia in HIV 🡪 perform HIV testing. Also consider non-HIV predisposing conditions (e.g. SLE, liver cirrhosis, solid organ cancer, HIV, TNF antagonists)

Question 4

which antibiotics are typhoid increasingly resistant to?

Answer 4

• Chloramphenicol
• Ampicillin
• Trimethoprim, sulfonamides
• Fluoroquinolones: Ciprofloxacin (esp in South Asia)
• 3rd gen cephalosporins (in pakistan)

Question 5

what is the management of typhoid fever?

Answer 5

• Resistance to ciprofloxacin has meant that mainstay of mx has now changed to:
• Oral azithromycin OR IV ceftriaxone

Question 6

How is enteric fever transmitted?

Answer 6

• Transmitted by ingestion of food or water contaminated with faeces (faecal-oral)
• Risk factors: contaminated water supply, eating ice cream, flavoured ice drinks or food from street vendors, raw fruit and vegetables grown in fields fertilised with sewage
• About 10% of individuals recovering from untreated typhoid fever may excrete S typhi in the stools for ≥ 3 months

Question 7

How does S. typhi invade the body?

Answer 7

• avoids triggering off an early inflammatory response in the gut of the human host
• invades the gut mucosa in the terminal ileum through specialised antigen-sampling cells (M cells): Salmonella pathogenicity islands (SPIs) 🡪 type III secretion system 🡪 invasion of non-phagocytic epithelial cells
• invading bacteria are taken up by macrophages, reach the intestinal lymphoid tissue, are drained into mesenteric nodes, the thoracic duct, and into the general circulation (primary bacteraemia) 🡪 organism reaching the liver, spleen, bone marrow, and other parts of the reticuloendothelial system within 24 h of their ingestion, where they survive and replicate in cells of monocytic lineage.

Question 8

What is the complication of typhoid fever?

Answer 8

• Intestinal haemorrhage or perforation
• Toxic myocarditis
• Confusion, convulsions, encephalitis
• Haemolytic anaemia (especially in G6PD deficiency)
• Renal failure
• Abscesses in liver, spleen, bone etc

Question 9

What is the management of typhoid

Answer 9

Patients should be hospitalised during antibiotic treatment.

Rehydration and other supportive care.

Current drugs of choice:

• PO Ciprofloxacin 500 mg bd x 7-10 days (if sensitive to ciprofloxacin and nalidixic acid)
• IV Ceftriaxone 2-3g once daily x 10-14 days
• Alternative: PO Azithromycin 1g once then 500mg once daily x 5-7 days
• N.B. 70-90 % of isolates in some parts of Nepal, India and Vietnam are nalidixic acid resistant strains.

Dexamethasone 3mg/kg then 1mg/kg 6 hourly x 8 doses for severe typhoid fever (as suggested by delirium, shock and altered mental status) decreases mortality.

Relapse rate 1-6% with newer antibiotics (10-25% with chloramphenicol)

Question 10

how does paratyphoid fever?

Answer 10

• Maybe clinically mild or asymptomatic
• Nausea, vomiting, fever, diarrhoea, and cramping—usually occur within 8 to 72 hours of ingesting contaminated food or water
• Less than 5% of non-typhoidal salmonella gastroenteritis develop bacteraemia and may result in extra-intestinal manifestations including endocarditis, mycotic aneurysm and osteomyelitis.

Question 11

What is the management of chronic carrier state of typhoid fever?

Answer 11

One to four percent of adults become chronic carriers despite antibiotics.

Follow-up stool evaluation to document stool clearance after treatment:

• Three consecutive stool samples taken at weekly intervals no sooner than two weeks after completion of antibiotic treatment.
• Chronic carriers (positive stool samples after 6 months): give prolonged course of ciprofloxacin (750 bd orally for 1 month) and perform abdominal ultrasound; cholecystectomy may be necessary if gallstones are present and prolonged antibiotic treatment fails.