---

Malaria in Children - Detailed Pediatric Notes

---

1. EPIDEMIOLOGY & BURDEN

• An estimated 249 million malaria cases occurred globally in 2022, across 85 endemic countries, causing 608,000 deaths (~1,660 per day)
• The vast majority of deaths - estimated >600,000 annually - are in young African children
• P. falciparum is the dominant lethal species, responsible for almost all pediatric deaths
• In holoendemic and hyperendemic areas (e.g., tropical sub-Saharan Africa, coastal New Guinea), children may sustain one or more infective mosquito bites per week
• Children in these areas experience intense morbidity and mortality in early childhood; if they survive, infections become progressively asymptomatic as immunity develops
• In areas of unstable transmission (low/erratic), full immunity is never acquired and symptomatic disease can occur at any age

---

2. CAUSATIVE SPECIES & LIFE CYCLE

Six Species in Humans

Life Cycle Summary

1. Female Anopheles mosquito injects sporozoites into bloodstream
2. Sporozoites travel to liver - intrahepatic schizogony: 1 sporozoite → up to 30,000 merozoites
3. In P. vivax and P. ovale: some become hypnozoites (dormant - cause of relapse)
4. Merozoites enter RBCs - become trophozoites then schizonts
5. Schizonts burst RBCs, releasing merozoites - erythrocytic cycle repeats every 24-72 h
6. Some become sexual gametocytes - mosquito takes up gametocytes and cycle continues
7. P. falciparum infects RBCs of ALL ages - hence capable of very high parasitemia (>1%, >10^5/µL)

---

3. PATHOGENESIS - PEDIATRIC FOCUS

Falciparum-Specific Pathomechanisms

• Cytoadherence: Infected RBCs express PfEMP1 protein (encoded by var genes), binding to endothelial receptors (ICAM-1, CSA, CD36) - causes sequestration in deep microcirculation
• Rosetting: Infected RBCs bind uninfected RBCs, further reducing microvascular flow
• High parasitemia: Because P. falciparum infects all RBC ages, parasitemia can exceed 20% in children
• Cytokines: Rupture of schizonts at high density → massive TNF-α release → fever, metabolic derangements

Why Children Are More Vulnerable

• No acquired immunity in early life in endemic areas
• Smaller blood volume → small absolute hemoglobin loss causes proportionally severe anemia
• Hypoglycemia risk higher (lower glycogen stores, quinine-induced insulin release)
• Seizure threshold lower
• Malnutrition exacerbates severity - malnourished children need higher weight-adjusted drug doses

---

4. CLINICAL FEATURES IN CHILDREN

Incubation Period

• P. falciparum: shortest (7-14 days); P. malariae: longest (up to 30+ days)
• Partially treated or prophylaxis: can delay symptoms weeks to months

Uncomplicated Malaria - Typical Presentation

• Prodrome: headache, fatigue, myalgia, anorexia, vomiting
• Classic fever paroxysm (less reliable in children than adults):
  • Cold stage (rigors)
  • Hot stage (high fever, 39-41°C)
  • Sweating stage (drenching sweat, temperature fall)
• Fever may be irregular or continuous in young children (no periodicity)
• Splenomegaly (tender initially, chronic later)
• Hepatomegaly is common in children
• Thrombocytopenia typical (platelet ~100,000/µL)
• Anaemia with pallor

Severe/Complicated Malaria in Children vs Adults

• Most common life-threatening complication in children
• Blantyre Coma Score used for children (vs Glasgow in adults)
• Unrousable coma (Blantyre ≤2), often with retinal changes
• CSF: opening pressure ~160 mmH2O; slight protein elevation; cells <20/µL
• Seizures: far more common in children than adults (+++); may be the presenting feature
• ~10% of children surviving cerebral malaria have neurologic sequelae (hemiplegia, cerebral palsy, cortical blindness, epilepsy), especially those with hypoglycemia, severe anemia, repeated seizures, or deep coma
• Adults: <3% have neurologic sequelae

• Hb <5 g/dL; the hallmark pediatric complication
• Multifactorial: RBC destruction, dyserythropoiesis, nutritional deficiencies
• Severely anemic children present with labored, deep ("Kussmaul-type") breathing - previously misdiagnosed as "anemic congestive cardiac failure" but actually metabolic acidosis

• Very frequent in children (+++)
• Causes: inadequate oral intake, high metabolic demands of infection, quinine/quinidine-stimulated hyperinsulinemia
• Can occur before or during treatment
• Treat with 10% dextrose IV (0.5 g/kg bolus); maintain glucose >4 mmol/L

• Lactic acidosis secondary to poor tissue perfusion and sequestration
• Manifests as "respiratory distress" in children
• Major determinant of mortality
• Check blood glucose + lactate in every child with severe malaria

• Common (+++), may be febrile or ictal
• Rule out hypoglycemia first before treating as seizure
• Treat with IV diazepam (0.3-0.5 mg/kg) or rectal diazepam (0.5 mg/kg) or IM midazolam

• Approximately 6% of children with severe malaria have concurrent bacteremia (especially Salmonella spp. with P. falciparum)
• Adults: <1%
• Therefore: broad-spectrum antibiotics should be considered in severely ill children when bacterial infection cannot be excluded

---

5. WHO CRITERIA FOR SEVERE MALARIA

---

6. DIAGNOSIS

Blood Film (Gold Standard)

• Thick film: 10x more sensitive; allows parasite concentration; used for detection; count parasites per 200 WBCs
• Thin film: species identification; parasite stage (prognostic); count per 1000 RBCs; less sensitive (<0.05% parasitemia)
• Repeat every 12-24 h for 72 h if initial smear negative but malaria suspected

Rapid Diagnostic Tests (RDTs)

• HRP2 dipstick: detects only P. falciparum; sensitivity comparable to thick film; remains positive for weeks after treatment; misses strains with HRP2/3 deletions
• pLDH dipstick: detects all species; two bands (genus-specific + P. falciparum-specific); becomes negative sooner after treatment clearance (more useful for monitoring)
• Always confirm with microscopy: RDT alone insufficient for management decisions
• False-negatives at low parasitemia; false-positives do occur

PCR

• Most sensitive (1000x more than microscopy); available in reference labs
• Best for species confirmation; too slow for acute decisions
• Particularly useful in artemisinin partial resistance areas

Laboratory Findings in Acute Malaria

• Anemia: normochromic normocytic
• Thrombocytopenia: platelet count typically ~100,000/µL (a normal platelet count should prompt consideration of alternative diagnosis)
• WBC: usually normal; slight monocytosis, lymphopenia, eosinopenia
• ESR, CRP: elevated
• Glucose: may be low (hypoglycemia)
• Lactate: elevated in severe cases (metabolic acidosis)
• BUN/creatinine: elevated in renal failure
• LFTs: may be deranged
• Coagulation: prolonged PT/aPTT in severe cases
• CSF (cerebral malaria): pressure ~160 mmH2O; minimal pleocytosis; slight protein elevation

---

7. MANAGEMENT - MADE EASY

Step 1: Classify Severity

Is the child able to take oral medication?
Has the child lost consciousness / having seizures?
Is there severe anemia, respiratory distress, or hypoglycemia?
→ YES to any = SEVERE MALARIA → parenteral treatment
→ NO to all = UNCOMPLICATED MALARIA → oral treatment

---

TREATMENT ALGORITHM

A. UNCOMPLICATED MALARIA (Oral Treatment)

1. Artemether-lumefantrine (AL) - most widely used globally; FDA-approved in the US
2. Artesunate-amodiaquine (ASAQ)
3. Dihydroartemisinin-piperaquine (DHA-PPQ)
4. Artesunate-mefloquine
5. Artesunate-sulfadoxine-pyrimethamine
6. Artesunate-pyronaridine

• Monitor for vomiting 1 hour after dose; repeat dose if vomiting occurs
• Give acetaminophen/paracetamol to reduce fever and thereby reduce vomiting
• Younger and malnourished children need higher weight-adjusted doses

• Chloroquine: 25 mg base/kg total dose over 3 days (10 mg/kg day 1 and 2; 5 mg/kg day 3)

• Primaquine: 0.5 mg/kg/day for 14 days (after checking G6PD status; contraindicated in severe G6PD deficiency)
• Tafenoquine: single dose 5 mg/kg (check G6PD; approved >16 years)

• Single low dose primaquine 0.25 mg/kg - safe even in G6PD deficiency at this dose; do not give in pregnancy

---

B. SEVERE MALARIA (Parenteral Treatment) - PRIORITY IN CHILDREN

• IV artesunate is FDA-approved for severe malaria
• Switch to oral ACT (artemether-lumefantrine preferred) once patient can tolerate oral medication

• Quinine dihydrochloride IV: 20 mg salt/kg loading dose over 4 h, then 10 mg salt/kg every 8-12 h (with ECG monitoring - QT prolongation risk); add doxycycline or clindamycin (children use clindamycin: 10 mg/kg BD)
• Artemether IM: 3.2 mg/kg loading dose, then 1.6 mg/kg daily

• Give IV artesunate PLUS IV quinine together
• Parasite clearance half-life >5 h is marker of partial resistance

• When parenteral treatment is not immediately available
• For children <6 years with severe malaria in remote settings
• Reduces mortality while arranging transfer; does not replace IV treatment

---

C. SUPPORTIVE CARE (Parallel to Antimalarial Treatment)

• No corticosteroids (proven harmful)
• No heparin (no benefit, increases bleeding risk)
• No mannitol (no proven benefit in children)

---

D. PROPHYLAXIS FOR CHILDREN (Travel / Chemoprevention)

• Monthly courses of SP + amodiaquine during peak malaria season
• WHO-recommended; dramatically reduces malaria deaths in this age group

• SP given at EPI immunization contacts (6, 10, 14 weeks; 9 months) in high-transmission areas

---

8. MONITORING RESPONSE TO TREATMENT

• Blood smear at 48 h and 72 h: expect >90% parasite reduction by 48 h with effective ACT
• Parasite clearance half-life >5 h = suspect artemisinin partial resistance
• Check blood glucose every 4-6 h (especially with quinine)
• Watch for post-artesunate delayed hemolysis (PADH) - can occur 2-3 weeks after IV artesunate in hyperparasitemia; check Hb weekly for 4 weeks after treatment

---

9. SPECIAL POPULATIONS

Neonates / Congenital Malaria

• Rare (<5% of infants born to infected mothers)
• Presents with fever, irritability, hepatosplenomegaly, anemia in first weeks of life
• Treatment: IV artesunate (pediatric dosing); avoid primaquine in neonates

Malnourished Children

• Paradoxically, severe malnutrition can partially protect against severe malaria (reduces parasite multiplication), BUT once infected, prognosis is worse
• Need higher weight-adjusted ACT doses
• Poor absorption of oral drugs - may require parenteral treatment even for "uncomplicated" disease

G6PD Deficiency

• Common in malaria-endemic populations (>400 million affected)
• ACTs, chloroquine, atovaquone-proguanil: safe
• Primaquine and tafenoquine: contraindicated in severe G6PD deficiency (hemolysis risk)
• Low-dose primaquine (0.25 mg/kg single dose) for gametocytocidal purpose is safe even in G6PD deficiency

---

10. COMPLICATIONS AND SEQUELAE

Neurological (Cerebral Malaria)

• ~10% of children surviving cerebral malaria develop long-term neurological deficits:
  • Hemiplegia, epilepsy, cerebral palsy, cortical blindness, cognitive impairment
• Risk factors for sequelae: hypoglycemia, severe anemia, repeated seizures, deep coma
• Compare: <3% in adults

Hyperreactive Malarial Splenomegaly (Tropical Splenomegaly Syndrome)

• Chronic exposure → massive splenomegaly, hepatomegaly, elevated IgM
• Pancytopenia due to hypersplenism
• Treat with long-term antimalarial chemoprophylaxis

Quartan Malarial Nephropathy

• Chronic P. malariae infection → immune complex glomerulonephritis → nephrotic syndrome
• Poor prognosis if fine-granular IF pattern; better if coarse-granular

---

QUICK SUMMARY TABLE

---