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CHOLERA, DIARRHOEA MANAGEMENT, AND TYPHOID FEVER

(Park's Preventive and Social Medicine)

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PART 1: CHOLERA

Definition

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Epidemiological Determinants (Epidemiological Triad)

A. Agent Factors

B. Reservoir of Infection

• Man is the only known reservoir - either a case or a carrier
• 75% of infected people are asymptomatic but shed vibrios in faeces for 7-14 days
• 20% develop acute watery diarrhoea with severe dehydration
• Mild/asymptomatic cases maintain the endemic reservoir

C. Types of Carriers in Cholera

1. Preclinical/Incubatory carriers - short duration (incubation 1-5 days); potential patients
2. Convalescent carriers - excrete vibrios for 2-3 weeks post-recovery; more likely without effective antibiotic treatment; can become chronic
3. Contact/Healthy carriers - subclinical infection from association with a case or contaminated environment; duration usually <10 days; gall bladder not infected
4. Chronic carriers - rare; longest known carrier was excreting vibrios for 10+ years

D. Infective Material and Dose

• Stools and vomit of cases/carriers
• Cholera stools: ~10^7-10^9 vibrios/mL; average patient excretes 10-20 litres
• Carriers: 10^2-10^5 vibrios/gram of stool
• Infective dose in normal person: ~10^11 organisms needed (dose-related disease)

E. Period of Communicability

• Cases: 7-10 days
• Convalescent carriers: 2-3 weeks
• Chronic carriers: 1 month to 10+ years

F. Environmental/Host Factors

• Peri-urban slums, disasters, displacement camps (disrupted water/sanitation)
• Hypochlorhydria, blood group O (higher susceptibility)
• Malnourished children and HIV-positive individuals are at greater risk

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Clinical Features

• Sudden onset of profuse rice-water diarrhoea (no fecal smell initially)
• Followed by vomiting
• Rapid severe dehydration - sunken eyes, loss of skin turgor, cold clammy skin
• Muscular cramps (due to electrolyte loss)
• Suppression of urine (oliguria/anuria)
• Rapid pulse, hypotension, shock

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Laboratory Diagnosis of Cholera

Specimen Collection

• Rubber catheter method (best; 26-28 gauge soft rubber catheter, 4-5 cm into rectum) - preferred method
• Rectal swab - cotton-tipped wooden swab dipped in holding medium (VR medium or alkaline peptone water)
• Transport media: Venkatraman-Ramakrishnan (VR) medium, alkaline peptone water, or Cary-Blair medium

Methods

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Management of Cholera

Cornerstone: Rapid Replacement of Fluid and Electrolytes

• WHO/UNICEF standard ORS composition (mmol/L):
  • Sodium: 75, Chloride: 65, Glucose: 75, Potassium: 20, Citrate: 10, Osmolarity: 245
• ORS can replace up to 1 litre/hour of fluid loss
• For mild-moderate dehydration in cholera: ORT is sufficient

• For severe dehydration or those unable to drink
• Preferred IV fluids: Ringer's Lactate (Hartmann's solution) - the IV fluid of choice for cholera
• Adults with severe dehydration: 100 mL/kg in 3 hours
• Children: 100 mL/kg in 3-6 hours

• Drug of choice: Doxycycline (single dose 300 mg for adults)
• Alternatives: Tetracycline, Ciprofloxacin, Erythromycin (for children and pregnant women)
• Azithromycin is preferred for children and pregnant women
• Note: Antibiotics are an adjunct - not a substitute for fluid replacement

• 20 mg/day for children under 5 years for 10-14 days
• Reduces duration and severity

• Continue feeding throughout illness; breastfeeding especially important for infants

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Control of Cholera

Three Pillars of Control:

1. Control of reservoir (cases and carriers)
2. Control of transmission (sanitation)
3. Immunization

1. Control of Reservoir

• Early case detection and notification
• Isolation of cases
• Treatment: Fluid replacement + antibiotics
• Disinfection of stools, vomit, bedding (chlorinated lime 5%, bleaching powder)
• Carrier detection: Bacteriological stool examination, especially of food handlers, water works employees, and contacts of cases
• Treatment of carriers: Tetracycline; chronic carriers working as food handlers should be removed from their occupation

2. Environmental Control (Sanitation - the "Weakest Link")

• Safe water supply (chlorination: residual chlorine 0.5 mg/L at point of use)
• Proper sewage disposal
• Food hygiene and inspection
• Fly control
• Personal hygiene - hand washing

3. Immunization

• Oral cholera vaccines (OCVs) are the vaccines of choice:
  • Dukoral (WC-rBS): Whole-cell killed + recombinant B subunit; 2 doses, 1-6 weeks apart; 85-90% protection for 6 months, 50% for 3 years in endemic areas
  • Shanchol/mORCVAX: Bivalent (O1 + O139); 2 doses; no buffer needed
• OCVs are recommended by WHO for epidemic preparedness and outbreak response
• Old parenteral killed whole-cell vaccine: effective but strong side effects; no longer recommended routinely
• Cholera vaccine does NOT provide complete protection and should not replace water/sanitation measures

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PART 2: ACUTE DIARRHOEAL DISEASES - MANAGEMENT

Definition

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Clinical Types of Diarrhoeal Disease (WHO Classification)

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Assessment of Dehydration (WHO/IMCI)

Degrees of Dehydration

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ORS (Oral Rehydration Solution)

WHO Revised Low-Osmolarity ORS (2002)

Home-Made ORS (SSSF)

• Sugar-Salt Solution (SSS): 1 litre boiled water + 1 level teaspoon salt (5 g) + 8 level teaspoons sugar (40 g)
• Rice water with salt also recommended as a home fluid

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Treatment Plans for Diarrhoea (WHO 3-Plan Approach)

PLAN A: Treat Diarrhoea at Home (No Dehydration)

1. Give more fluids than usual - ORS, rice water, dal water, plain clean water
2. Continue feeding - breastfeed more frequently; do not restrict diet
3. Give zinc - 20 mg/day for 10-14 days (children <6 months: 10 mg/day)
4. Return if: child does not get better in 3 days, or develops any danger sign (blood in stool, very frequent stools, repeated vomiting, high fever, not eating/drinking normally)
5. Amount of ORS to give: <2 years: 50-100 mL after each stool; 2-10 years: 100-200 mL; older: as much as wanted

PLAN B: Treat Some Dehydration with ORS (Oral Rehydration Therapy)

1. Amount: 75 mL/kg body weight ORS over 4 hours
2. Method: Give by cup/spoon or nasogastric tube if unable to drink
3. Reassess after 4 hours and reclassify dehydration
4. If no improvement or severe dehydration develops - move to Plan C
5. Continue breastfeeding throughout

PLAN C: Treat Severe Dehydration Rapidly (IV Fluids)

• Preferred: Ringer's Lactate (or normal saline if Ringer's not available)
• Adults: 100 mL/kg in 3 hours (1st 30 mL/kg in 30 min, then 70 mL/kg in 2.5 hrs)
• Children <1 year: 100 mL/kg in 3 hours (1st 30 mL/kg in 1 hr, then 70 mL/kg in 2 hrs)
• Children >1 year: 100 mL/kg in 3 hours (1st 30 mL/kg in 30 min, then 70 mL/kg in 2.5 hrs)
• Begin ORS (5 mL/kg/hr) as soon as able to drink
• Reassess every 1-2 hours

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Specific Treatments

Zinc

• Reduces duration of diarrhoea by 25% and incidence in subsequent 2-3 months by 25%
• Children <6 months: 10 mg/day for 14 days
• Children ≥6 months: 20 mg/day for 14 days
• Available as dispersible tablets or syrup

Antibiotics in Diarrhoea

Feeding

• Do not withhold food or dilute feeds
• Breastfeeding: continue uninterrupted
• Complementary foods: resume normal diet as early as possible
• Extra meal per day for 2 weeks after diarrhoea resolves (catch-up nutrition)

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Prevention and Control of Diarrhoeal Diseases

Components of Diarrhoeal Diseases Control Programme (WHO)

1. Case management - ORT + feeding + zinc + selective antibiotics
2. Preventive measures - safe water, sanitation, hygiene (WASH)
3. Specific protective measures:
   • Promotion and support of breastfeeding (reduces diarrhoea incidence by 25 times)
   • Improved weaning practices
   • Use of safe water
   • Handwashing with soap
   • Safe disposal of child's stools
4. Health education
5. Monitoring and evaluation

India's Diarrhoeal Diseases Control Programme

• Launched in 1978, strengthened as National Oral Rehydration Therapy Programme
• ORS packets distributed through health facilities, ASHA workers, and anganwadis
• Diarrhoea Prevention Indicators: % of children with diarrhoea given ORS, % given increased fluids
• Diarrhoea Treatment Indicators: % of cases correctly managed, ORS coverage

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PART 3: TYPHOID FEVER

Definition

• Continuous fever for 3-4 weeks
• Relative bradycardia (Faget's sign)
• Involvement of lymphoid tissues (Peyer's patches)
• Considerable constitutional symptoms

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Epidemiological Determinants

A. Agent Factors

• Agent: Salmonella typhi (primary); S. paratyphi A and B (less common)
• Antigens: Three main antigens - O (somatic), H (flagellar), Vi (virulence)
• Phage typing: ≥80 phage types; useful epidemiological tool for tracing outbreak source
• Intracellular survival: S. typhi survives intracellularly in tissues
• Resistance: Readily killed by drying, pasteurization, and common disinfectants

B. Reservoir of Infection

• Man is the only known reservoir (cases and carriers)
• Cases: Mild to severe; infectious as long as bacilli appear in stool/urine
• Carriers:
  • Temporary (incubatory, convalescent): Convalescent carriers excrete for 6-8 weeks
  • By 3 months, <4% still excreting; by 1 year, ~3% carrier rate
  • Chronic carriers: Those excreting for >1 year after clinical attack; 2-5% of cases become chronic
  • Organisms persist mainly in the gall bladder and biliary tract in chronic carriers
  • Faecal carriers more frequent than urinary carriers
  • "Typhoid Mary": Famous chronic carrier responsible for >1300 cases in her lifetime

C. Sources of Infection

• Primary: Faeces and urine of cases or carriers
• Secondary (vehicles): Contaminated water, food, fingers, and flies (5 Fs: Food, Fingers, Flies, Fluids, Fomites)

D. Modes of Transmission

• Water-borne (most common in epidemics)
• Food-borne (shellfish, milk, ice cream, salads)
• Contact (person-to-person, rare)
• Flies (mechanical transmission)

E. Host Factors

• Age: Highest incidence 5-19 years; after 20 years, incidence falls (acquired immunity)
• Sex: More cases in males (increased exposure); but carrier rate higher in females
• Immunity: Serum antibodies not the primary defence; cell-mediated immunity is more important
• O antibodies appear day 6-8; H antibodies appear day 10-12 after onset

F. Environmental Factors

• Sub-standard water and sanitation
• Overcrowding, poverty
• Seasonal peaks during summer and monsoon (India)

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Clinical Features

• Incubation period: 10-14 days (range: 3-60 days)
• Week 1: Step-ladder fever, headache, malaise, relative bradycardia, coated tongue
• Week 2: Fever plateaus (39-40°C), splenomegaly, hepatomegaly, rose spots (2-4 mm maculopapular, on trunk, evanescent, 20-30% cases)
• Week 3: Complications risk - intestinal perforation, haemorrhage
• Week 4: Defervescence (gradual recovery)
• Complications: Intestinal perforation (most serious surgical emergency), haemorrhage, typhoid hepatitis, myocarditis, encephalopathy

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Laboratory Diagnosis of Typhoid

(a) Microbiological (Definitive)

(b) Serological - Widal Test (Felix-Widal)

• Measures agglutinating antibodies against O and H antigens
• O antibodies: appear day 6-8 after onset
• H antibodies: appear day 10-12 after onset
• Sensitivity: Only moderate (can be negative in up to 30% of culture-proven cases)
• Limitations:
  • False negatives: prior antibiotic treatment blunts antibody response
  • False positives: cross-reaction with other Salmonella serotypes, Enterobacteriaceae; also malaria, typhus, cirrhosis, bacteraemia
• A 4-fold rise in paired sera (acute + convalescent) is more meaningful than a single titre

(c) Newer Diagnostic Tests

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Control of Typhoid Fever

1. Control of reservoir
2. Control of sanitation (the weakest link in transmission)
3. Immunization

1. Control of Reservoir

a. Cases

• Early diagnosis (blood + stool culture)
• Notification (notifiable disease)
• Isolation: In hospital; isolate until 3 bacteriologically negative stools and urine on 3 separate days
• Treatment (see below)
• Disinfection: Terminal disinfection of excreta, linen, utensils (phenol, bleaching powder)

b. Treatment

• Drug of choice: Fluoroquinolones (Ciprofloxacin) - first choice for susceptible strains
  • Ciprofloxacin 500 mg BD for 7-10 days (or 10-14 days for complicated cases)
  • Defervescence occurs within 3-5 days
• Multidrug-resistant (MDR) typhoid (resistant to Chloramphenicol + Ampicillin + Co-trimoxazole):
  • Fluoroquinolones remain effective for most MDR strains
  • For fluoroquinolone-resistant strains: Azithromycin (mild-moderate) or Ceftriaxone (severe)
• Other drugs (historical/alternatives):
  • Chloramphenicol (original drug of choice, now limited use due to MDR)
  • Ampicillin, Co-trimoxazole
• For complications:
  • Intestinal perforation: Surgery + broad-spectrum antibiotics
  • Dexamethasone for severe toxicity/encephalopathy

c. Carriers

• Identification: Stool and urine cultures on 3 separate occasions
• Treatment of chronic carriers: Ampicillin or Amoxicillin + Probenecid for 4-6 weeks; or Ciprofloxacin for 28 days
• Cholecystectomy may be required for carriers with cholelithiasis (gallstones)
• Food handlers who are carriers must be excluded from handling food until confirmed free

2. Control of Sanitation

• Safe water supply is the single most important measure
• Proper sewage disposal and sanitation
• Food hygiene: pasteurization of milk, proper cooking of shellfish
• Fly control
• Personal hygiene - hand washing before food preparation/eating and after defecation

3. Immunization - Anti-Typhoid Vaccines

(a) Vi Polysaccharide Vaccine (Injectable)

(b) Ty21a Vaccine (Oral, Live-Attenuated)

(c) Vi-Conjugate Vaccine (TCV - Typhoid Conjugate Vaccine)

• Vi polysaccharide conjugated to carrier protein
• Effective in children <2 years (overcomes limitation of plain Vi vaccine)
• India included TCV (Typbar-TCV) in national immunization schedule for children 9 months to 15 years
• Single dose, provides longer protection, boostable
• WHO pre-qualified; recommended for routine immunization in typhoid-endemic countries

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Summary Comparison Table

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Quick Exam Recall Points

Cholera

• Rice-water diarrhoea - no fever initially; massive fluid loss (10-20 L/day)
• Exotoxin acts via adenylate cyclase-cyclic AMP system
• Dark field microscopy - "shooting stars" appearance
• IV fluid of choice = Ringer's Lactate; oral = low-osmolarity ORS (245 mOsm/L)
• Antibiotic = Doxycycline (single 300 mg dose for adults)
• Bleaching powder 6 mg/L kills vibrios instantly
• Carriers detected by purged stool (Magnesium sulphate)

Diarrhoea Management

• Plan A (no dehydration): Extra fluids at home + zinc + continue feeding
• Plan B (some dehydration): 75 mL/kg ORS over 4 hours
• Plan C (severe dehydration): IV Ringer's Lactate 100 mL/kg
• Zinc: 20 mg/day x 14 days (reduces duration by 25%, recurrence in next 3 months by 25%)
• Anti-diarrhoeals (loperamide etc.) are CONTRAINDICATED

Typhoid

• Only reservoir = Man; chronic carriers excrete for >1 year (gall bladder)
• "Typhoid Mary" - >1300 cases in her lifetime
• Widal: O antibodies day 6-8, H antibodies day 10-12; moderate sensitivity only
• Gold standard lab = Bone marrow culture (>90% yield)
• Treatment = Fluoroquinolones (Ciprofloxacin); MDR - use Ceftriaxone or Azithromycin
• Isolate until 3 negative stool + urine cultures
• Vi-polysaccharide vaccine: single dose, ≥2 years, revaccinate every 3 years
• Ty21a oral: 3 doses (Day 1, 3, 5), ≥5 years, revaccinate every 3 years
• TCV (Typbar-TCV): works in children <2 years, included in India's immunization schedule