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Malaria: From Basics to Clinical with Differential Diagnosis

"Humanity has but three great enemies: Fever, famine, and war; of these by far the greatest, by far the most terrible, is fever." - William Osler, 1896

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1. Overview and Epidemiology

• P. falciparum - predominates in sub-Saharan Africa, New Guinea, Hispaniola
• P. vivax - Central/South America, most of Asia, Horn of Africa
• P. malariae - most endemic areas, especially sub-Saharan Africa
• P. ovale - mainly Africa
• P. knowlesi - Southeast Asia (from macaque monkeys)

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2. Causative Species

• Harrison's Principles of Internal Medicine 22E (2025), Ch. 231

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3. Life Cycle and Pathogenesis

Hepatic (Pre-erythrocytic) Stage

1. Infected female Anopheles mosquito injects sporozoites during a blood meal
2. Sporozoites travel to the liver within minutes, binding hepatocytes via thrombospondin-related adhesive protein and circumsporozoite protein (binding heparan sulfate proteoglycans)
3. Intrahepatic schizogony: one sporozoite produces 10,000-30,000 daughter merozoites
4. Infected hepatocytes burst, releasing merozoites into the bloodstream
5. In P. vivax and P. ovale, some forms remain dormant as hypnozoites (cause of relapses weeks to years later)

Erythrocytic Stage

1. Merozoites invade red blood cells (RBCs) - via binding to glycophorin (sialic acid residues) using a lectin-like molecule
2. Intraerythrocytic stages: ring trophozoite → trophozoite → schizont → merozoites (rupture and re-invade every 48 h for most species, 24 h for P. knowlesi)
3. Some trophozoites differentiate into gametocytes (the mosquito-infective stage)
4. When parasitemia reaches ~50/μL blood (~100 million parasites total), symptomatic illness begins

Key Pathogenic Mechanism of P. falciparum: Cytoadherence

• Schizonts express PfEMP1 (P. falciparum erythrocyte membrane protein 1) on knob-like extensions of the RBC surface
• PfEMP1 binds endothelial adhesion molecules: ICAM-1, VCAM-1, CD36
• This causes sequestration of infected RBCs in deep capillary beds (brain, kidney, placenta), which is the key mechanism of severe disease
• Normally, RBCs bear negatively charged surfaces that repel endothelium; PfEMP1 overcomes this barrier

Mosquito Stage (Sexual Cycle)

• Male gametocyte exflagellates in the mosquito midgut
• Fusion with female gametocyte → zygote → ookinete (penetrates gut wall) → oocyst → releases sporozoites that migrate to salivary glands

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4. Transmission Routes

• Mosquito bite (principal route) - infected female Anopheles, most active dusk to dawn
• Blood transfusion
• Needle sharing (injection drug use)
• Organ transplantation
• Congenital (maternal-fetal)
• "Airport malaria" - infected mosquito transported on aircraft, bites passengers/staff at destination without the disease establishing locally

• Rosen's Emergency Medicine, Ch. 122

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5. Clinical Features

Incubation Period

• P. falciparum: 7-14 days (range 7-30 days; rarely up to 1 year if partial prophylaxis)
• P. vivax/P. ovale: 8-30 days (hypnozoite relapses months to years later)
• P. malariae: 15-30+ days (recrudescence decades later possible)
• P. knowlesi: 9-12 days

Prodrome

The Classic Malarial Paroxysm (Febrile Cycle)

Note: Classic periodicity is often absent early in the illness, especially in non-immune travelers. Fever may be continuous or irregular initially.

Uncomplicated Malaria

• Fever (universal), headache, myalgia, arthralgia, nausea, vomiting, diarrhea
• Splenomegaly (common with repeated infections)
• Mild anemia
• Jaundice (mild)

Severe/Complicated Falciparum Malaria (WHO Criteria)

• Unarousable coma (Blantyre Coma Score < 3 in children; GCS < 11 in adults), seizures
• Pathology: sequestration of parasitized RBCs in cerebral microcirculation, ring hemorrhages, Dürck's granulomas
• Mortality 15-20% even with treatment

Malaria in Pregnancy

• Falciparum malaria: fetal loss, premature labor, low birth weight (~170 g reduction), maternal anemia
• Placental sequestration of infected RBCs (even in asymptomatic women)
• Maternal HIV co-infection worsens outcomes
• Unstable transmission areas: pregnant women prone to severe malaria with hypoglycemia, pulmonary edema

Malaria in Children

• Severe malarial anemia and cerebral malaria predominate
• Febrile convulsions common
• Hypoglycemia more frequent
• Splenomegaly, malnutrition from recurrent infections

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6. Diagnosis

A. Peripheral Blood Smear (Gold Standard)

• Thick smear: detects parasites (concentration method, more sensitive, lower parasite density detectable)
• Thin smear: species identification, parasitemia quantification
• Repeat smears every 12-24 hours if initial smear is negative but suspicion remains high

B. Rapid Diagnostic Tests (RDTs)

• Detect malaria antigens (HRP-2 for P. falciparum, pLDH or aldolase for other species)
• Sensitivity 95%+ for P. falciparum at >100 parasites/μL
• Results in 15-20 minutes
• Limited by: false negatives at low parasitemia, HRP-2 gene deletions (P. falciparum), inability to quantify
• Positive HRP-2 may persist for weeks after treatment (not useful for treatment response)

C. PCR

• Most sensitive (can detect submicroscopic parasitemia)
• Best for species confirmation, drug resistance genotyping
• Not for emergency diagnosis due to turnaround time

D. Laboratory Findings (Non-specific but Supportive)

• Thrombocytopenia (very common, often < 150,000; <50,000 in severe disease)
• Elevated LDH, bilirubin (hemolysis)
• Low haptoglobin
• Normocytic anemia
• Elevated creatinine (renal involvement)
• Hypoglycemia
• Elevated inflammatory markers (CRP, PCT) - but non-specific

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7. Treatment

Uncomplicated Malaria

• Artemether-lumefantrine (most widely used; 6-dose regimen over 3 days with fatty food)
• Artesunate-amodiaquine
• Artesunate-mefloquine
• Dihydroartemisinin-piperaquine
• Atovaquone-proguanil (20/8 mg/kg/day x 3 days with food) - preferred for travelers

• Chloroquine (if sensitive) OR ACT PLUS
• Primaquine (0.25-0.5 mg base/kg/day x 14 days) to eliminate hypnozoites and prevent relapse
• MUST screen for G6PD deficiency before primaquine (causes severe hemolysis in G6PD-deficient patients)
• Tafenoquine (single dose alternative to primaquine, also requires G6PD screening)

Severe/Complicated Falciparum Malaria (Medical Emergency)

• 12.4 mg/kg IV stat, then 2.4 mg/kg at 12 h and 24 h, then daily if needed
• Children < 20 kg: 3 mg/kg per dose
• 35% lower mortality vs. quinine in Southeast Asia; 22.5% lower in Africa

• Artemether 3.2 mg/kg IM stat, then 1.6 mg/kg/day IM (erratic absorption)
• Quinine dihydrochloride 20 mg salt/kg over 4 h, then 10 mg salt/kg over 2-8 h every 8 h (monitor for QTc prolongation, hypoglycemia)

• Continuous blood glucose monitoring (especially with quinine)
• IV dextrose for hypoglycemia
• Anti-convulsants (IV diazepam for seizures; prophylactic phenobarbital not recommended)
• Careful fluid management (avoid fluid overload causing pulmonary edema)
• Renal replacement therapy for AKI
• Exchange transfusion (controversial; may be considered for > 10% parasitemia)
• NOT recommended: High-dose glucocorticoids, heparin, dextran, desferrioxamine (shown to be harmful or ineffective)
• ICU care and frequent reassessment

Transmission Blocking

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8. Chemoprophylaxis

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9. Differential Diagnosis

Primary Differential Diagnoses

Key Differentiating Points

• Malaria: no eosinophilia (eosinophilia points to helminth infection)
• Malaria: thrombocytopenia is very common but non-specific
• Malaria: smear or RDT is diagnostic - always perform in febrile traveler
• In endemic areas: incidental parasitemia can coexist with another infection (especially in children) - treat for both if in doubt
• P. falciparum malaria in non-immune traveler: do not wait for classic periodicity - it may never appear before the patient deteriorates

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10. Complications at a Glance

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11. Special Populations

• Pregnancy: Falciparum associated with placental sequestration, low birth weight, maternal mortality. ACT (except artesunate monotherapy in 1st trimester) + IPTp (intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine) recommended by WHO.
• Asplenic patients: Higher risk of severe disease; extra vigilance for prophylaxis.
• Sickle cell trait: Partial protection against severe falciparum malaria (selective pressure underlying HbS prevalence in endemic areas).
• G6PD deficiency: Primaquine and tafenoquine are absolutely contraindicated in severe G6PD deficiency; screening mandatory.

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12. Prevention

• Insecticide-treated bed nets (ITNs) - single most effective intervention
• Indoor residual spraying (IRS)
• Chemoprophylaxis for travelers (see table above)
• RTS,S/AS01 (Mosquirix) and R21/Matrix-M - approved malaria vaccines; primarily for children in Africa; 30-75% efficacy against clinical malaria
• Larval source management, environmental control

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• Harrison's Principles of Internal Medicine 22E (2025), Ch. 231 - Malaria
• Robbins & Kumar Basic Pathology, Ch. 10 - pp. 392-394
• Rosen's Emergency Medicine: Concepts and Clinical Practice, Ch. 122
• Goldman-Cecil Medicine, Ch. 316
• Brenner & Rector's The Kidney (renal complications)

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🌡️ Typhoid Fever - From Basics to Clinical (Simple Version)

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1. What Is Typhoid? (The Simple Story)

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2. The Culprit: What Causes It?

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3. How Does It Spread? (Simple Chain of Infection)

Infected person's poop/urine
        ↓
Contaminates water or food
        ↓
You eat or drink it
        ↓
Bacteria enter your body
        ↓
You get sick (and can then spread it too)

• Drinking unclean water or water mixed with sewage
• Eating street food or unwashed fruits/vegetables
• Ice made from contaminated water
• Food handled by someone who is infected (even if they look healthy)
• Chronic carriers - people who recovered from typhoid but still carry the bacteria silently in their gallbladder and pass it in their stool for years

• People living in or traveling to South Asia (India, Pakistan, Bangladesh, Nepal), Southeast Asia, Africa, and Latin America
• Young children and teenagers in endemic areas
• Anyone drinking unclean water

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4. How Does It Enter and Spread in the Body? (The Journey of the Bacteria)

Step 1 - Swallowed

Step 2 - Gut Wall Entry

Step 3 - Lymph Nodes (The "First Base")

Step 4 - Into the Blood (Bacteremia)

Step 5 - Organs Get Infected

Step 6 - Second Bacteremia = Full Illness

Step 7 - Back to the Gut (The Dangerous Bit)

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5. What Happens in the Body (Pathology)

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6. Timeline of the Illness (Week by Week)

Incubation Period (Days 1-14, no symptoms)

• Average 10-14 days from swallowing the bacteria to feeling sick
• Can range from 5 to 21 days depending on how much bacteria you swallowed and your immunity

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🗓️ Week 1 - "Something is Wrong"

• Fever starts low and rises step by step each day (step-ladder pattern)
• Headache (very common, ~80% of patients)
• Dry cough (~30%)
• Body aches, tiredness, feeling generally unwell
• Constipation more common than diarrhea early on
• The patient doesn't look very sick yet - easily mistaken for flu

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🗓️ Week 2 - "Full Blown Illness"

• High fever (39-40.5°C / 103-105°F) - continuous, not going up and down like malaria
• Relative bradycardia - the heart rate is lower than expected for such a high fever (normally fever raises heart rate, but in typhoid the bacteria slow it)
• Rose spots appear on the trunk and chest

• Coated tongue (white fur on the tongue)
• Distended, tender abdomen
• Spleen and sometimes liver become enlarged (hepatosplenomegaly)
• Patient looks toxic and very unwell
• Diarrhea may develop ("pea soup" diarrhea - loose, greenish)

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🗓️ Week 3 - "The Danger Zone" ⚠️

• High fever continues
• Complications start appearing:
  • Intestinal perforation (ulcers burst through the gut wall) - sudden severe abdominal pain, board-like abdomen, peritonitis
  • Intestinal bleeding - blood in stool
• Patient may become confused, drowsy ("muttering delirium")
• Most deaths occur in this week if untreated

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🗓️ Week 4 - Recovery (if treated) or Deterioration (if not)

• With treatment: fever comes down, patient improves
• Without treatment: fever gradually settles but patient is very weak
• Relapses can occur in 5-10% of patients even after antibiotics
• Untreated typhoid has 10-20% mortality (mostly in young children)

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7. Symptoms Summary Table

Key teaching point: Typhoid is a great "masquerader." It doesn't always present classically. Many patients have no abdominal pain, no rose spots, and no bradycardia. The only constant feature is prolonged fever with a history from an endemic area.

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8. Complications (When Things Go Wrong)

Dangerous (Life-threatening) Complications

Other Complications

• Meningitis, Guillain-Barre syndrome (nerve damage)
• Pneumonia
• Hepatitis (liver inflammation)
• Cholecystitis (gallbladder infection)
• Pancreatitis
• Hemolytic anemia
• Hemophagocytic syndrome (HLH) - rare but life-threatening (macrophages start destroying blood cells)

The Carrier State

• After recovery, 1-5% of patients become chronic carriers
• Bacteria live silently in the gallbladder (especially if gallstones present)
• They shed bacteria in stool for years with no symptoms
• This is a major source of ongoing transmission in the community

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9. Diagnosis (How Do Doctors Confirm It?)

A. Blood Culture - The Best Test 🥇

• Most reliable: Positive in 80-90% of patients during the first week of fever
• You take blood and grow the bacteria in a lab
• Takes 3-5 days for results
• Sensitivity drops after antibiotics are started

B. Bone Marrow Culture - The Most Sensitive 🥇🥇

• Can still be positive even after antibiotics have been started
• But it's invasive (needle into the bone) - reserved for cases where blood culture is negative but suspicion is high

C. Stool and Urine Culture

• Stool culture becomes positive in week 2-3 (when bacteria re-enter the gut via bile)
• Less sensitive than blood culture

D. Widal Test (The Old Test - Controversial)

• Blood test that looks for antibodies against S. typhi (H and O antigens)
• Problems:
  • Takes 7-10 days to turn positive (antibodies take time to develop)
  • Many false positives (can be positive from past infection, other Salmonella, or even vaccination)
  • Many false negatives early in disease
  • Not reliable alone - needs to be combined with clinical picture
• Still widely used in low-resource settings because it's cheap
• A rising titre (4-fold rise in paired samples) is more meaningful than a single reading

E. Typhidot / Rapid Antigen Tests

• Detect IgM and IgG against S. typhi
• Faster and more specific than Widal
• Increasingly available in endemic countries

F. PCR

• Very sensitive and specific
• Not widely available in most endemic areas

Typical Lab Findings (Non-specific but helpful)

Memory trick: Most bacterial infections raise the WBC. Typhoid lowers it. If you see a patient with prolonged fever, travel history, and low WBC - think typhoid!

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10. Treatment (How Do You Treat It?)

First-line Antibiotics

Drugs That No Longer Work Well (Due to Resistance)

• Chloramphenicol - was first-line for decades, now MDR strains resist it
• Ampicillin
• Co-trimoxazole (trimethoprim-sulfamethoxazole)

Drug-resistant Typhoid - A Growing Crisis

• MDR (Multi-Drug Resistant) = Resistant to chloramphenicol + ampicillin + co-trimoxazole
• XDR (Extensively Drug Resistant) = Also resistant to fluoroquinolones AND 3rd gen cephalosporins
  • XDR typhoid emerged in Pakistan (Sindh province) in 2016 and is spreading
  • XDR is treated with azithromycin or carbapenems (last resort)

For Severe Typhoid (Shock, Encephalopathy, High Fever)

• Add dexamethasone (steroid) - reduces inflammation and mortality in very severe cases
• IV fluids for rehydration
• Blood transfusion if anemia is severe
• Surgery if intestinal perforation occurs (emergency bowel repair + peritonitis washout)

Follow-up

• Relapses occur in 5-10% - treat again with same antibiotic (bacteria usually remain sensitive)
• Check stool cultures after treatment to confirm clearance
• Chronic carriers: prolonged antibiotics (ciprofloxacin x 4 weeks) can eliminate carriage in many; cholecystectomy (gallbladder removal) if antibiotics fail

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11. Differential Diagnosis (What Else Can Look Like Typhoid?)

Quick Clinical Clue Table

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12. Prevention (How to Stop It?)

Personal Hygiene (Most Important!)

• "Boil it, cook it, peel it, or forget it" - the traveler's rule
• Drink only boiled or bottled water
• Avoid ice made from tap water
• Avoid street food and raw vegetables in endemic areas
• Wash hands thoroughly after toileting and before eating

Vaccination

• TCV is now recommended by WHO for children in endemic areas (given from 6 months of age)
• Neither vaccine is 100% protective - good hygiene is still essential

Public Health Measures

• Clean water supply and sewage treatment - the single biggest prevention
• Identifying and treating chronic carriers (especially food handlers)
• Proper food hygiene and inspection

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13. Quick Summary Card

TYPHOID IN A NUTSHELL
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Caused by:     Salmonella Typhi (bacteria)
How spread:    Contaminated food/water (feco-oral route)
Incubation:    10-14 days (range 5-21)
Key symptoms:  Prolonged fever + headache + coated tongue
Classic signs: Relative bradycardia + rose spots + splenomegaly
Labs:          Leukopenia (LOW white cells!) + mild liver enzymes↑
Diagnosis:     Blood culture (gold standard)
Danger:        Gut perforation in week 3-4
Treatment:     Ceftriaxone (IV) or Azithromycin (oral)
Prevention:    Clean water + hand hygiene + vaccination
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

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• Harrison's Principles of Internal Medicine 22E (2025), Ch. 171 - Enteric (Typhoid) Fever
• Robbins & Kumar Basic Pathology - Ch. 13
• Tintinalli's Emergency Medicine, Ch. 162
• Park's Textbook of Preventive and Social Medicine

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🦟 Dengue Fever - From Basics to Clinical (Simple Version)

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1. What Is Dengue? (The Big Picture)

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2. The Culprit: What Causes Dengue?

🔑 Getting infected with one type gives you lifelong protection only against that type. You can get dengue up to 4 times in your lifetime - once with each serotype. And the second infection is often MORE severe than the first.

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3. How Does It Spread? (The Transmission Story)

The Main Route: Mosquito Bite

Infected person's blood
        ↓
Mosquito (Aedes aegypti) bites and sucks infected blood
        ↓
Virus multiplies inside the mosquito (takes ~8-12 days)
        ↓
Infected mosquito bites another person
        ↓
You get dengue

• Smaller than a regular mosquito
• Has distinctive white stripes on black body and legs
• Bites during the day (especially morning and late afternoon) - unlike malaria mosquitoes that bite at night
• Breeds in small collections of clean, stagnant water - flower pots, tyres, water tanks, bottle caps, even the base of a toilet
• Lives close to humans - a domestic mosquito
• Aedes albopictus (tiger mosquito) can also transmit dengue but is less efficient

Other (Rare) Routes

• Vertical transmission (mother to baby during pregnancy/delivery) - ~20% risk
• Blood transfusion or organ donation
• Breastfeeding (rare)
• Needlestick injury in healthcare settings

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4. How the Virus Makes You Sick (Pathogenesis)

Step 1 - The Mosquito Injects the Virus

Step 2 - Virus Spreads to Lymph Nodes

Step 3 - Virus Gets Into the Blood (Viremia)

Step 4 - Your Immune System Launches a War

• High fever
• Severe muscle and bone pain
• Headache

Step 5 (In Severe Dengue) - The Vessels Start Leaking

• Rising hematocrit (blood gets thicker as fluid leaks out)
• Swelling in the belly (ascites) and chest (pleural effusion)
• Shock if enough fluid leaks out

Why Does the 2nd Infection Cause Worse Disease? - Antibody-Dependent Enhancement (ADE)

When you had your first dengue infection, your body made antibodies against that serotype. When you get infected with a different serotype, those old antibodies try to fight but can't neutralize the new virus. Instead, they grab onto the virus and carry it directly into macrophages via Fc receptors - like a Trojan Horse. This makes the infection worse, causing more viral replication and more severe inflammation. This is called Antibody-Dependent Enhancement (ADE).

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5. Classification of Dengue (The WHO System)

The 2009 WHO Classification (Most Used Today):

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6. The Three Phases of Dengue - The Story of the Illness

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🔴 Phase 1 - FEBRILE PHASE (Days 1-3)

• Sudden high fever (39-40°C / 102-104°F) - starts abruptly, like someone switched a switch
• Severe headache - especially behind the eyes (retro-orbital pain - pain when you move your eyes or press on them)
• Severe muscle, joint, and bone pain - so bad the old name was "Breakbone Fever" - patients feel like their bones are breaking
• Facial flushing - face looks red and flushed
• Nausea, vomiting, loss of appetite
• Mild rash (flushing of face, neck, chest - not the classic rash yet)
• Sore throat, injected (red) throat

• Leukopenia (WHITE BLOOD CELLS FALL) - very characteristic, starts early
• Platelets begin to drop

🧠 Easy way to remember: Dengue = "FETCH" - Fever sudden, Eyes hurt (retro-orbital), Throbbing bones (breakbone), Check blood (low WBC), High temperature fast

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⚠️ Phase 2 - CRITICAL PHASE (Days 3-7, around defervescence)

• Blood vessel walls become leaky
• Fluid (plasma) leaks from vessels into tissues
• This phase lasts only 24-48 hours but can be lethal

• ⚡ Severe abdominal pain or tenderness
• ⚡ Persistent vomiting (≥3 times in 24 hours)
• ⚡ Sudden bleeding from nose, gums, or skin (mucosal bleeding)
• ⚡ Blood in vomit or stool
• ⚡ Swelling of belly or fluid around lungs
• ⚡ Lethargy, restlessness, or sudden irritability
• ⚡ Liver enlargement >2 cm
• ⚡ Rapid decrease in platelet count alongside rising hematocrit

• Platelets crash (can go below 20,000 - normal is 150,000-400,000!)
• Hematocrit rises by ≥20% (blood is concentrating as fluid leaks out)
• Liver enzymes (AST/ALT) go up

• Cold, clammy extremities
• Rapid, weak pulse
• Narrowed pulse pressure (≤20 mmHg) - e.g., BP = 100/80 instead of 120/70
• Hypotension
• Decreased urine output

🔑 The paradox: The fever drops, the patient and family feel relieved - but this is actually the most dangerous moment. A patient who "improves" on day 4 can collapse into shock on day 5.

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🟢 Phase 3 - RECOVERY PHASE (Days 7-10)

• Fever gone, patient feels better
• Good urine output returns
• Appetite comes back
• Platelet count starts rising (recovery sign)
• Hematocrit falls as fluid returns to vessels

• If the patient was given too much IV fluid during the critical phase, the fluid that returns to the vessels can cause pulmonary edema (fluid in the lungs) and breathing difficulty
• Bradycardia (slow heart rate) can occur
• A new rash may appear: the classic "white islands in a sea of red" - islands of normal skin surrounded by red flush

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7. The Classic Dengue Rash

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8. Bleeding in Dengue

1. Thrombocytopenia - low platelets = poor clotting
2. Vasculopathy - leaky damaged vessels allow red cells to escape
3. DIC (Disseminated Intravascular Coagulation) - in severe cases, clotting factors are consumed

• Petechiae (tiny red dots under skin from capillary bleeding)
• Easy bruising (ecchymoses)
• Nosebleeds (epistaxis)
• Bleeding gums
• Heavy periods in women (menorrhagia)
• Blood in vomit (hematemesis) or stool (melena)
• Internal bleeding (rare, severe)

• Inflate BP cuff to midpoint between systolic and diastolic for 5 minutes
• Positive: ≥10 petechiae per 2.5×2.5 cm area
• In DHF: usually ≥20 petechiae
• It shows the fragility of blood vessels

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9. Severe Dengue (DHF/DSS) - The Dangerous Form

Who Gets Severe Dengue?

• People with second dengue infection (different serotype) - most common reason
• Infants of dengue-immune mothers (maternal ADE)
• Young children
• Patients infected with DEN-2 serotype (most virulent)
• People with certain genetic factors

Grades of DHF (Old WHO Classification)

Severe Dengue (2009 WHO Classification) includes:

• Severe plasma leakage causing shock or fluid accumulation with breathing difficulty
• Severe bleeding (clinician-assessed)
• Severe organ involvement:
  • Liver: AST or ALT ≥1000 IU/L
  • Brain: altered consciousness, encephalitis
  • Heart: myocarditis, arrhythmia
  • Kidneys: acute kidney injury

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10. Unusual/Expanded Dengue Manifestations

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11. Diagnosis (How Is Dengue Confirmed?)

Day-by-Day Testing Strategy

NS1 Antigen Test

• Detects the Non-Structural Protein 1 (NS1) of dengue virus
• Positive in first 5 days
• Quick result (15-30 minutes)
• Sensitivity ~80-90% in primary infection, slightly lower in secondary (ADE clears NS1 faster)

IgM/IgG ELISA

• IgM rises from day 5, peaks at 2 weeks
• IgG: low in primary infection; rises rapidly (within 1-2 days of fever) in secondary infection
• High IgG with low IgM = secondary dengue (higher risk of severe disease)

Important Lab Monitoring (Not Diagnostic But Essential)

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12. Management (How Is It Treated?)

🔑 There is NO specific antiviral drug for dengue. Treatment is entirely supportive.

Group A - Dengue Without Warning Signs (Home Management)

• Rest
• Paracetamol (acetaminophen) for fever and pain - doses every 6 hours
• Oral hydration - drink plenty of fluids (oral rehydration salts, coconut water, fruit juice, soup)
• DO NOT give: Aspirin, ibuprofen, or any NSAID - they thin blood and can cause serious bleeding
• Monitor at home: Watch for warning signs. Return to hospital immediately if any appear.
• Daily platelet check if falling

Group B - Dengue With Warning Signs (Hospital Admission Required)

• Start with isotonic fluids (Normal Saline or Lactated Ringer's)
• Give cautiously - just enough to maintain circulation
• Monitor urine output (target: 0.5-1 mL/kg/hour)
• Check hematocrit every 4-6 hours - if rising, increase rate; if falling with clinical improvement, slow down

• Platelet transfusion: Only for platelets <10,000 with active bleeding (NOT just for a low number alone in a stable patient)
• Fresh Frozen Plasma (FFP): For DIC or coagulopathy with bleeding
• Packed Red Cells: If significant hemorrhage

Group C - Severe Dengue / Shock (ICU)

1. Immediate IV fluid resuscitation - 10-20 mL/kg isotonic fluid bolus over 1 hour
2. Reassess: If improved, reduce rate gradually
3. If not improved: repeat bolus, consider colloids (Dextran 40, HES)
4. AVOID fluid overload - this is as dangerous as the shock itself
5. Monitoring: BP, pulse, urine output, hematocrit every 1-2 hours
6. Treat complications (hypoglycemia, metabolic acidosis, organ failure)

• During recovery, the leaked fluid re-enters the vessels
• Stop IV fluids early in recovery phase to avoid pulmonary edema
• Patient may develop bradycardia (slow heart rate) - usually benign

What NOT to Do

• ❌ No aspirin or NSAIDs (increases bleeding risk)
• ❌ No prophylactic platelets (in absence of bleeding)
• ❌ No antibiotics (it's viral - antibiotics do nothing)
• ❌ No steroids (not proven to help; may cause harm)
• ❌ Don't over-hydrate (fluid overload causes pulmonary edema in recovery)

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13. Differential Diagnosis (What Can Look Like Dengue?)

Quick "Dengue vs Others" Cheat Sheet

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14. Prevention

Personal Protection

• Use mosquito repellents containing DEET, picaridin, or IR3535
• Wear long sleeves and pants during daytime (Aedes bites during the day!)
• Use window screens and air conditioning
• Sleep under bed nets (especially for daytime naps in children)

Eliminating Breeding Sites (Most Important)

• Tip out water from flower pots, tyres, buckets
• Toss or cover any container that can hold water
• Turn over unused containers
• Treat water tanks with larval insecticide (Temephos/Bacillus thuringiensis)
• Change water in flower vases weekly
• Clean blocked gutters

Vaccines

• First dengue vaccine, approved in ~17 countries
• 3-dose schedule (0, 6, 12 months)
• Only approved for ages 9-45 years
• Critical point: Only for people who have had dengue before (seropositive)
• Giving it to someone who has never had dengue can make their first infection MORE severe (the vaccine mimics a first infection, so subsequent real infection behaves like a dangerous second infection)
• FDA-approved in the USA for ages 9-16 in endemic areas with confirmed prior dengue

• Releasing Aedes mosquitoes infected with Wolbachia bacteria reduces viral replication inside the mosquito
• Trials in Colombia showed 95-97% reduction in dengue cases in treated areas - revolutionary approach

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15. Quick Summary Card

DENGUE IN A NUTSHELL
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Caused by:     Dengue Virus (4 serotypes: DEN-1,2,3,4)
Spread by:     Aedes aegypti mosquito (day-biting)
Incubation:    4-7 days
3 Phases:      Febrile → Critical → Recovery
Key symptoms:  Sudden fever + breakbone pain + retro-orbital
               pain + rash + low WBC + low platelets
Danger signs:  Abdominal pain, persistent vomiting,
               mucosal bleeding, restlessness, ↑ hematocrit
Labs:          Thrombocytopenia + leukopenia + ↑ hematocrit
Diagnosis:     NS1 antigen (early) / IgM antibody (late)
Treatment:     Paracetamol + fluids (NO aspirin/NSAIDs!)
Severe dengue: IV fluids carefully; treat shock; no steroids
Prevention:    Remove stagnant water + repellent + vaccine
               (only if prior dengue)
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• Harrison's Principles of Internal Medicine 22E (2025), Ch. on Emerging Infectious Diseases
• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th Ed.)
• Tintinalli's Emergency Medicine, Ch. 162
• Red Book 2021 (AAP Committee on Infectious Diseases)
• Park's Textbook of Preventive and Social Medicine