What are the clinical features, diagnosis, and treatment of malaria in infants and adults?

Clinical Features, Diagnosis, and Treatment of Malaria in Infants and Adults

Clinical Features

Malaria presents with fever, myalgias, and thrombocytopenia in both adults and infants, but severe disease manifestations differ significantly between age groups, with adults more commonly developing cerebral malaria and multi-organ failure, while infants may present with subtle seizures and respiratory distress. 1

Adults

• Uncomplicated malaria: Fever (often cyclical), diffuse myalgias, headache, mild anemia, thrombocytopenia (typically <150,000/mL), and elevated bilirubin 1
• Severe malaria criteria: Impaired consciousness (Glasgow Coma Scale <11), multiple seizures (>2 in 24 hours), shock (systolic BP <80 mmHg), pulmonary edema/ARDS, severe anemia (hemoglobin <7 g/dL), hypoglycemia (<40 mg/dL), acidosis (lactate >5 mmol/L), acute renal failure (creatinine >3 mg/dL), jaundice (bilirubin >3 mg/dL with parasitemia >100,000/mL), and hyperparasitemia (>2-5% depending on immune status) 1

Infants and Children

• Seizures are common (occurring in approximately 25% of cases), with 25% being subtle or subclinical, manifesting as eye deviation, irregular respiratory pattern, or drooling 1
• Brain swelling is a major feature in fatal pediatric cases, with unilateral sluggish or absent pupillary responses being the only reliable sign of raised intracranial pressure 1
• Early vomiting is frequently associated with treatment administration and has been cited as a possible cause of treatment failure 1

Diagnosis

Blood smear microscopy remains the gold standard for malaria diagnosis, requiring identification of parasite species and quantification of parasitemia to guide treatment decisions. 1

• Peripheral blood smear: Two independent microscopists should examine thick and thin blood films to identify species and quantify parasitemia 1
• Rapid diagnostic tests (RDTs): Can be used as adjunct but should not replace microscopy when available 2
• Molecular testing (PCR): Useful for species confirmation and distinguishing recrudescence from reinfection, but not for acute diagnosis 1
• Essential laboratory monitoring: Complete blood count, glucose, creatinine, bilirubin, lactate dehydrogenase, and blood gas analysis (if severe disease suspected) 1

Treatment

Uncomplicated P. falciparum Malaria

For uncomplicated P. falciparum malaria in both adults and children, artemether-lumefantrine is the first-line treatment, with cure rates of 96-100%. 1, 3, 4

Adults (>35 kg)

• Artemether-lumefantrine (AL): 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3 (total 24 tablets over 72 hours) 1, 3
• Critical requirement: Must be taken with a fatty meal or drink to ensure adequate absorption; failure to do so results in subtherapeutic levels and treatment failure 1, 3, 4
• Alternative first-line: Dihydroartemisinin-piperaquine (DHA-PPQ): 3-4 tablets daily for 3 days (dose based on weight), taken in fasting condition 1, 3

Infants and Children

• Weight-based dosing for AL:
  • 5-<15 kg: 1 tablet per dose
  • 15-<25 kg: 2 tablets per dose
  • 25-<35 kg: 3 tablets per dose
  • Given at 0,8,24,36,48, and 60 hours 1
• Tablets may be crushed and suspended in water, milk, or other beverage for infants unable to swallow whole 5
• Safety note: AL is approved for infants ≥5 kg and has efficacy and safety profiles comparable to other ACTs in children 6, 7

Second-Line Options

• Atovaquone-proguanil: 4 tablets daily for 3 days (>40 kg), taken with fatty meal; relatively slow-acting regimen 1, 4
• Mefloquine: Day 1: 750 mg salt followed by 500 mg salt after 8-12 hours; reserved for third-line due to neuropsychiatric effects 1
• Quinine plus doxycycline: Quinine 750 mg salt three times daily for 7 days plus doxycycline 100 mg twice daily for 7 days (adults only; doxycycline contraindicated in children <8 years) 1

Uncomplicated P. vivax, P. ovale, P. malariae, P. knowlesi

Chloroquine remains first-line treatment for non-falciparum malaria in chloroquine-sensitive regions, but P. vivax and P. ovale require additional radical cure with primaquine to eliminate liver hypnozoites. 1, 3, 4

Initial Treatment

• Chloroquine: 1000 mg salt initially, then 500 mg salt at 6,24, and 48 hours 1, 4
• Alternative (chloroquine-resistant regions): DHA-PPQ or AL using same dosing as for P. falciparum 1, 4

Radical Cure (P. vivax and P. ovale only)

• Primaquine: 30 mg base daily for 14 days, started after blood schizontocidal treatment 1, 3, 4
• Mandatory G6PD testing before primaquine administration to prevent severe hemolytic anemia 3, 4, 8
• Alternative: Tafenoquine 300 mg single dose (requires G6PD activity >70%; not available outside US/Australia) 1, 4
• Absolute contraindication: Both primaquine and tafenoquine are contraindicated in pregnancy and infants <6 months 1, 4

Severe Malaria (All Ages)

Intravenous artesunate is the first-line treatment for severe malaria and should be administered immediately as a medical emergency, with mortality reduction compared to quinine. 1, 3, 4

Treatment Protocol

• Artesunate IV: 2.4 mg/kg at 0,12, and 24 hours, then 2.4 mg/kg daily until parasitemia <1% and patient can tolerate oral medication 1, 3
• Transition to oral therapy: Once parasitemia <1% and patient clinically improved, complete treatment with full course of oral ACT (preferably AL or DHA-PPQ) 1, 3
• Alternative (if artesunate unavailable): Quinine dihydrochloride 20 mg salt/kg IV over 4 hours (loading dose), then 10 mg/kg over 4 hours every 8 hours 1
• Omit quinine loading dose if patient received mefloquine in previous 24 hours or treatment dose within 3 days 1

Monitoring Requirements

• Parasitemia: Check every 12 hours until <1%, then every 24 hours until negative 1, 3
• Laboratory monitoring: Daily complete blood count, hepatic function, renal function, glucose, and blood gas analysis 1
• Post-artemisinin delayed hemolysis (PADH): Monitor on days 7,14,21, and 28 after treatment (occurs in 37.4% of patients) 1, 4

Seizure Management in Children

Seizures in pediatric malaria require immediate airway management and oxygen before anticonvulsant administration, following standard Advanced Pediatric Life Support protocols. 1

• First-line: Lorazepam 0.1 mg/kg IV/intraosseous; may repeat once after 10 minutes 1
• Second-line (if IV access unavailable): Paraldehyde 0.4 mg/kg rectally (0.8 mL/kg of prepared solution) 1
• Third-line: Phenytoin 18 mg/kg IV over 20 minutes OR phenobarbital 15-20 mg/kg IV over 10 minutes 1
• Critical warning: Prophylactic phenobarbital increased mortality in African children with cerebral malaria, particularly when combined with diazepam, likely due to respiratory depression in unventilated settings 1
• Hypoglycemia check: Always check glucose as hypoglycemia may precipitate seizures 1

Special Populations

Pregnancy

• Artemether-lumefantrine can be used in all trimesters of pregnancy as indicated by WHO and CDC, with no increased risk of teratogenic effects or adverse pregnancy outcomes in >700 first-trimester exposures 1, 3, 4
• Quinine remains an option for all trimesters if ACTs contraindicated 1
• Primaquine and tafenoquine are absolutely contraindicated in pregnancy due to hemolysis risk 4

Infants <6 months

• Safety and effectiveness of mefloquine for treatment not established in infants <6 months 5
• Limited experience with AL in infants <5 kg 1

Critical Pitfalls to Avoid

• Delayed diagnosis: P. falciparum malaria is frequently overlooked initially in non-endemic settings, leading to preventable deaths; maintain high index of suspicion in any febrile patient with travel history 1, 2
• Inadequate fat intake with AL: Failure to take artemether-lumefantrine with fatty meal results in subtherapeutic drug levels and treatment failure 1, 3, 4
• Early vomiting in children: If vomiting occurs <30 minutes after dose, repeat full dose; if 30-60 minutes after dose, give half-dose; monitor closely for treatment failure 1, 5
• QTc prolongation risk: Both AL and DHA-PPQ prolong QTc interval; avoid in patients with baseline QTc prolongation or taking QTc-prolonging medications 1, 3, 4
• G6PD testing omission: Never administer primaquine or tafenoquine without documented G6PD testing to prevent life-threatening hemolysis 3, 4, 8
• Incomplete treatment of P. vivax/P. ovale: Failure to provide radical cure with 8-aminoquinoline results in high relapse rates 1, 3, 4
• Misdiagnosis of raised intracranial pressure: In children, pupillary signs and consciousness level may be misleading in peri-ictal state; unilateral sluggish or absent pupillary responses are the only reliable signs 1