Enteric Fever (Typhoid) & Non‑Typhoidal Salmonellosis, 5TH MBBS, by Gidieon Anigbo, M2/M4

Organism & Classification Salmonella spp. = Gram‑negative, motile, non‑spore‑forming bacilli, facultative anaerobe. Typhoidal Salmonella: S. enterica serotype Typhi & Paratyphi A, B, C → cause enteric fever (typhoid/paratyphoid) . Humans are the only natural host/reservoir. Non‑typhoidal Salmonella (NTS) : >2,000 other serotypes (e.g., S. Enteritidis, S. Typhimurium) → cause gastroenteritis ± bacteraemia/focal disease. Animal reservoirs (poultry, livestock, reptiles, pets) + food chain. Enteric Fever (Typhoid) Epidemiology Worldwide but primarily developing countries. Highest attack rate: 5–19 years. More common in males; females more likely to become chronic carriers. Incubation: usually 10–14 days (range 3–21 days, depends on inoculum size). Risk factors: infectious dose ≈10,000 organisms; ↑gastric pH/achlorhydria; gastric/ GI surgery; IBD; prolonged antibiotics; haemoglobinopathies; immunosuppression. Transmission Faecal‑oral route via contaminated food/water. Water‑borne → longer incubation, lower attack rate. Healthcare/laboratory workers can acquire. Pathogenesis Ingested → passes stomach → invades distal ileal mucosa (M cells) → mesenteric lymph nodes → thoracic duct → reticuloendothelial system (liver, spleen, bone marrow, lymph nodes) → primary bacteraemia → multiplication → macrophage apoptosis → secondary sustained bacteraemia → clinical disease. Organisms then seed gallbladder (via bacteraemia or infected bile) → re‑enter gut via bile → reinfect Peyer’s patches. Chronic carriers: shed bacteria in stool for decades (biofilm on gallstones or gallbladder epithelium). Clinical Features – Classic Untreated Course Most important symptom: continuous fever, initially low‑grade, rises progressively in step‑ladder fashion, by week 2 high & sustained (38.8–40.5°C). Week 1: prodrome (chills, headache, anorexia, cough, weakness, sore throat, dizziness, myalgia) → GI symptoms (abdominal pain, nausea, vomiting, diarrhoea more common than constipation). Rose spots (faint, salmon‑coloured, blanching, truncal maculopapular rash) in ~30% at end of week 1. Week 2: abdominal distension, soft splenomegaly, relative bradycardia, dicrotic pulse. Week 3: toxic, anorexic, weight loss, conjunctivitis, tachypnoea, thready pulse, crackles, severe abdominal distension, pea‑soup diarrhoea (foul green‑yellow liquid). May descend into typhoid state (apathy, confusion, psychosis). Necrotic Peyer patches → bowel perforation, peritonitis. Death from toxaemia, myocarditis, intestinal haemorrhage. Week 4: slow improvement if survives. Some become asymptomatic chronic carriers. Complications Common (3rd–4th week without treatment): intestinal perforation, intestinal haemorrhage (erosion of necrotic Peyer’s patch into vessel), typhoid encephalopathy (“muttering delirium” or “coma vigil”). Rare (reduced by prompt antibiotics): pancreatitis, hepatic/splenic abscesses, endocarditis, pericarditis, orchitis, hepatitis, meningitis, nephritis, myocarditis, pneumonia, arthritis, osteomyelitis, parotitis. Diagnosis Gold standard / definitive: culture isolation of S. typhi or S. paratyphi from blood, bone marrow, urine, rose spots, stool, or intestinal secretions. Blood culture yield: ~90% in week 1, ↓ to 50% by week 3 (reduced by prior antibiotics). Stool culture: negative in 60–70% during week 1, becomes positive during week 3. Bone marrow culture: most sensitive (80–95%), remains positive up to 5 days after antibiotics, but very painful. PCR: varying success, not available in resource‑poor countries. Widal test (limitations): measures agglutinating antibodies against O and H antigens. Four‑fold rise in paired sera is more meaningful than single titre. WHO says: not reliable, do not rely too much. False positives: previous infection/vaccination, other Salmonella species, malaria, typhus, chronic liver disease (↑globulins), rheumatoid arthritis, myeloma, nephrotic syndrome. False negatives: early treatment, “hidden organisms”, relapse, poorly immunogenic strains, severe hypoproteinaemia. Non‑specific labs: moderate anaemia, ↑ESR, leucopaenia, neutropaenia, thrombocytopenia, relative lymphopaenia (leucocytosis can occur in children or with perforation), ↑LFTs, ↑bilirubin. Treatment Supportive: rest, tepid sponging, nutrition, paracetamol (250–1000 mg q4–6h). Do not delay antibiotics for confirmatory tests. Empiric: third‑generation cephalosporins & fluoroquinolones (replaced chloramphenicol). Dexamethasone for severely ill (shock, obtundation, stupor, coma). MDR typhoid: resistant to ampicillin, TMP‑SMX, chloramphenicol. XDR typhoid: resistant to chloramphenicol, ampicillin, fluoroquinolones, and third‑generation cephalosporins → only azithromycin, carbapenems, tigecycline remain effective. Chronic carriage (untreated 1–4%): treat with oral amoxicillin, TMP‑SMX, ciprofloxacin, or norfloxacin for 6 weeks. More common in women, infants, biliary abnormalities, Schistosoma haematobium co‑infection. Prevention Improved sanitation + clean water. Avoid untreated water, ice in drinks, ice cream. Vaccination: injectable inactivated or oral live attenuated → partial protection. Recommended for travellers to endemic areas, household contacts of carriers, laboratory workers. Non‑Typhoidal Salmonella (NTS) Reservoirs & Transmission Multiple animal reservoirs (poultry, eggs, undercooked ground meat, dairy, fresh produce contaminated with animal waste). Not human‑restricted. Clinical Syndromes Gastroenteritis (most common): incubation 6–48 hours. Nausea, vomiting, diarrhoea (loose, non‑bloody, moderate volume; can be watery, bloody, or dysenteric), abdominal cramps, fever (38–39°C). Self‑limited: diarrhoea resolves 3–7 days, fever within 72 hours. Invasive disease (high‑risk patients): elderly, malignancy, HIV, diabetes, corticosteroids/immunotherapy, infants, sickle cell disease, malnutrition. Syndromes: bacteraemia, meningitis, septic arthritis, osteomyelitis, cholangitis, pneumonia, endovascular infection, deep abscesses. Diagnosis Isolation of organism from stool (gastroenteritis cannot be distinguished clinically from other enteric pathogens). Treatment Uncomplicated NTS gastroenteritis: do NOT use routine antibiotics (no significant decrease in fever/diarrhoea duration, associated with relapse, prolonged carriage, adverse reactions). Antibiotics indicated for: severely ill (bloody diarrhoea, high fever, extraintestinal infection); infants; elderly; debilitated or immunosuppressed. Empiric antibiotics until susceptibility available. Prevention No vaccine. Handwashing after animal contact, avoid high‑risk foods, food safety (cook, separate, clean, chill). Key Differences (Typhoidal vs NTS) Feature Typhoidal Non‑typhoidal Main illness Enteric fever Acute gastroenteritis ± invasive Reservoir Humans only Animals + food chain + humans Incubation Days to weeks (10–14 d typical) 6–72 hours Bacteraemia Common Uncommon except high‑risk Antibiotics Usually required Not routine in uncomplicated diarrhoea Prevention WASH + typhoid vaccine Food safety + hand hygiene