20.7 Enteric Fever, Arboviral Infection & Tissue Parasites

3. Enteric Fever (Typhoid & Paratyphoid Fevers)

Enteric fever is a systemic invasive bacteriological infection caused by Salmonella enterica subspecies enterica serovars Typhi and Paratyphi (A, B, and C). Transmission occurs via the faecal-oral route through ingestion of food or water contaminated with human excreta, predominantly in South Asia (India, Pakistan, Bangladesh), Southeast Asia, and sub-Saharan Africa. The incubation period spans 7 to 21 days (1–3 weeks).

Clinical Manifestations by Week of Illness

• Week 1 (Bacteraemic Phase): Insidious onset of a 'stepwise' or 'ladder-like' climbing remittent fever, throbbing frontal headache, dry cough, malaise, and constipation (more common than diarrhoea in adults initially). Physical examination demonstrates relative bradycardia (Faget's sign / sphygmocaloric dissociation), where the pulse rate is inappropriately low for the degree of pyrexia.
• Week 2 (Lymphoid Hyperplasia & Organ Seeding): Sustained high plateau pyrexia ($39\text{–}40^\circ\text{C}$), abdominal distension, right lower quadrant tenderness, and hepatosplenomegaly. In approximately $30%$ of light-skinned patients, transient 'rose spots' appear: subtle, 2–4 mm, blanching salmon-pink macules concentrated on the anterior chest and abdomen that resolve within 3 to 5 days. Constipation gives way to foul-smelling, green 'pea-soup' diarrhoea.
• Week 3 (Complication Phase — The "Typhoid State"): Severe toxaemia, profound delirium ('coma vigil' / muttering delirium), and high risk of life-threatening gastrointestinal complications arising from necrosis and ulceration of hyperplastic Peyer's patches in the terminal ileum:
  1. Intestinal Haemorrhage: Rapid drop in haemoglobin, melena, or haematochezia.
  2. Ileal Perforation: Acute peritonitis with sudden severe abdominal pain, guarding, tachycardia, and free subdiaphragmatic gas on erect abdominal radiography.

Diagnostic Culture Yields & Antimicrobial Resistance

• Diagnostic Sensitivity Across Stages:
  • Blood Culture: Diagnostic in Week 1 ($60\text{–}80%$ sensitivity), dropping to $< 30%$ by Week 3.
  • Stool Culture: Positive in Week 2 and Week 3 ($50\text{–}60%$), reflecting biliary excretion and sloughing of Peyer's patches.
  • Urine Culture: Positive in Week 3 ($25%$).
  • Bone Marrow Aspirate Culture: The single most sensitive diagnostic test ($> 90%$) throughout all stages of illness; remains positive even after 5 days of prior antibiotic therapy.
  • Note: The historical Widal agglutination serological test is obsolete due to abysmal sensitivity and cross-reactivity.
• Antimicrobial Therapy (BIA Guidance):
  • High rates of fluoroquinolone resistance (ciprofloxacin / ofloxacin) secondary to gyrA mutations exist throughout Asia.
  • First-Line Regimen: Intravenous ceftriaxone ($2\text{ g}$ once daily for 10–14 days) for severe/hospitalized disease, or oral azithromycin ($1\text{ g}$ daily on Day 1, then $500\text{ mg}$ daily for 6 days) for uncomplicated illness.

4. Arboviral Infections & Zoonoses: Dengue & Leptospirosis

Dengue Fever

• Virology & Transmission: Flavivirus (4 antigenically distinct serotypes: DENV 1–4) transmitted by the diurnal (daytime-biting) urban mosquitoes Aedes aegypti and Aedes albopictus.
• Classic Dengue ("Breakbone Fever"): Sudden high fever, retro-orbital pain exacerbated by eye movement, intense myalgias and arthralgias ("breakbone"), facial flushing, leukopenia, and thrombocytopenia. An evanescent macular erythema evolves into a characteristic maculopapular rash sparing small circular areas, famously described as "islands of white in a sea of red".
• Severe Dengue (Dengue Shock Syndrome):
  • Paradoxically develops during the critical defervescence phase (Days 3 to 7) as the fever drops.
  • Pathophysiology: Antibody-Dependent Enhancement (ADE). Prior infection with one DENV serotype produces non-neutralizing cross-reactive IgG antibodies. Upon secondary infection with a different serotype, these antibodies bind virions and facilitate massive uptake into monocytes via Fc receptors, triggering catastrophic macrophage activation, cytokine storm, and diffuse microvascular permeability.
  • Hallmarks: Marked plasma leakage causing ascites, pleural effusions, severe haemoconcentration (haematocrit rise $\ge 20%$), profound thrombocytopenia ($< 100 \times 10^9\text{/L}$), and hypovolaemic shock.
  • Management: Meticulous fluid resuscitation with isotonic crystalloids guided by haematocrit monitoring. Avoid NSAIDs/aspirin (increases haemorrhage risk).

Leptospirosis (Weil's Disease)

• Transmission: Caused by the spirochaete Leptospira interrogans. Acquired through mucosal or abraded skin contact with freshwater, damp soil, or canal water contaminated with the urine of infected rodents (rats) or cattle. High risk in kayakers, canoeists, triathletes, sewer workers, and flood survivors.
• Clinical Presentation:
  • Anicteric Leptospirosis ($90%$): Biphasic illness: acute septicaemic phase with high fever, severe headache, and intense calf and lumbar muscle tenderness, accompanied by pathognomonic conjunctival suffusion (diffuse scleral hyperaemia without purulent exudate).
  • Icteric Leptospirosis (Weil's Disease, $10%$): Severe, potentially fatal form characterized by the triad of:
    1. Deep Jaundice: Disproportionately high conjugated bilirubin with only mild-to-moderate transaminase elevation (direct bilirubin-transaminase dissociation).
    2. Acute Kidney Injury: Severe oliguric or non-oliguric tubulointerstitial nephritis, classically with hypokalaemia early in disease due to impaired proximal tubular sodium reabsorption.
    3. Pulmonary Haemorrhage / ARDS: Severe alveolar haemorrhage presenting with hemoptysis and bilateral infiltrates.
• Diagnosis: Microscopic Agglutination Test (MAT), blood/urine PCR.
• Treatment: Intravenous ceftriaxone ($1\text{–}2\text{ g}$ daily) or intravenous benzylpenicillin for severe disease; oral doxycycline for mild illness.

5. Tissue Parasitic Infections: Amoebic Abscess & Schistosomiasis

Amoebic Liver Abscess vs. Pyogenic Liver Abscess

Schistosomiasis (Bilharzia)

Acquired by wading, swimming, or bathing in freshwater lakes (e.g., Lake Malawi, Lake Victoria) containing intermediate host aquatic snails (Bulinus or Biomphalaria). Free-swimming cercariae penetrate intact human skin, transform into schistosomulae, and migrate through the lungs to the portal venous system.

• Acute Schistosomiasis (Katayama Fever): An immune-complex hypersensitivity syndrome developing 2 to 8 weeks post-exposure as adult flukes begin laying eggs. Characterized by sudden fever, urticaria, dry cough, wheeze, hepatosplenomegaly, and striking peripheral blood eosinophilia.
• Chronic Schistosomiasis by Species:
  • Schistosoma haematobium (Urinary Schistosomiasis): Adult flukes inhabit the vesical and pelvic venous plexuses. Ova traverse the bladder wall, eliciting granulomatous inflammation. Presents with painless terminal haematuria, dysuria, ureteric strictures, hydronephrosis, and calcification of the bladder wall on pelvic radiography. A major global risk factor for squamous cell carcinoma (SCC) of the urinary bladder (not transitional cell carcinoma).
  • Schistosoma mansoni & Schistosoma japonicum (Hepatosplenic Schistosomiasis): Flukes reside in the inferior and superior mesenteric venules. Ova wash back into the intrahepatic portal venules, inciting granulomatous fibrotic reactions that produce pathognomonic Symmers' pipe-stem periportal fibrosis. This leads to severe non-cirrhotic, presinusoidal portal hypertension, massive splenomegaly, and bleeding oesophageal varices, with normal baseline hepatocellular synthetic function (normal albumin and INR until late terminal bleeding).
• Diagnostic Confirmation: Detection of characteristic ova in terminal urine collected between 10:00 and 14:00 (S. haematobium: prominent terminal spine) or stool (S. mansoni: prominent sharp lateral spine; S. japonicum: small, inconspicuous lateral knob).
• Treatment: Oral praziquantel ($40\text{ mg/kg}$ in single or divided doses, repeated at 4–6 weeks to eliminate late-maturing worms).