What is the role of chloroquine (hydroxychloroquine) in treating malaria?

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Role of Chloroquine in Treating Malaria

Chloroquine is the first-line treatment for uncomplicated malaria due to susceptible strains of Plasmodium species, particularly effective against P. vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum. 1

Treatment Regimens for Uncomplicated Malaria

Standard Dosing

  • For adults: Total dose of 1,500 mg chloroquine base (approximately 25 mg/kg body weight) administered over 3 days as 600 mg, 600 mg, and 300 mg at 0,24, and 48 hours, respectively 2
  • For children: Total dose of 25 mg/kg body weight chloroquine administered over 3 days as 10 mg/kg, 10 mg/kg, and 5 mg/kg at 0,24, and 48 hours, respectively 2
  • For pregnant women: Same regimen as adults, as chloroquine is considered safe during pregnancy 2

P. vivax and P. ovale Treatment

  • Chloroquine alone does not prevent relapses in P. vivax or P. ovale infections as it is not effective against hypnozoite liver stages 1
  • Supplementation with primaquine is necessary for radical cure of P. vivax and P. ovale infections 3:
    • Adults: Primaquine 15 mg daily for 14 days 2
    • Children: Primaquine 0.3 mg/kg/day for 14 days 2
  • G6PD testing is mandatory before primaquine administration to prevent hemolytic reactions 3
  • In populations with high prevalence of G6PD deficiency (especially among Asians), primaquine should not be administered for more than 5 days 2

Management of Chloroquine Resistance

  • In areas with chloroquine resistance, alternative treatments should be considered 2:
    • If symptoms persist after 48-72 hours of chloroquine treatment, second-line drugs should be administered 2
    • Alternative options include sulfa drugs with pyrimethamine (Fansidar), tetracycline, quinine, or newer drugs like mefloquine 2
    • Artemisinin-based combination therapy (ACT) is recommended for chloroquine-resistant areas, with dihydroartemisinin-piperaquine preferred due to its longer half-life 3

Prophylaxis

  • Chloroquine can be used for malaria prophylaxis in geographic areas where resistance is not present 1
  • For expatriates in endemic areas: Weekly chloroquine (300 mg base) during exposure and for 6 weeks after leaving the area 2
  • During high transmission seasons, chemoprophylaxis should be considered for high-risk groups 2:
    • Children under 5 years, especially those with malnutrition or anemia 2
    • Pregnant women 2
    • Individuals with compromised health status 2

Monitoring and Follow-up

  • The first dose of chloroquine should be administered when blood smear is taken 2
  • Patients should return the next day for smear results; if positive, continue treatment 2
  • If symptoms persist beyond 3 days, repeat blood smear and consider alternative therapy if parasitemia has not markedly diminished 2
  • Monitor for clinical improvement within 48 hours and confirm parasite clearance with follow-up blood smears 3

Important Considerations and Precautions

  • Chloroquine resistance is widespread in P. falciparum and has been reported in P. vivax 1
  • Some regions have observed the return of chloroquine sensitivity after discontinuation of chloroquine use for several years 4
  • Minor side effects may include gastrointestinal disturbance, headache, dizziness, blurred vision, and pruritus 2
  • Serious side effects are rare with prophylactic doses 2
  • Chloroquine may exacerbate psoriasis and interfere with antibody response to intradermal rabies vaccine 2

Treatment of Severe Malaria

  • For severe malaria, intravenous artesunate is the first-line treatment 3
  • If using parenteral chloroquine in areas without resistance, modified dosing regimens can improve safety profile:
    • Continuous infusion (0.83 mg base/kg/hour for 30 hours) or smaller, more frequent injections (3.5 mg base/kg every 6 hours) produce smoother blood concentration profiles with fewer adverse effects 5

Chloroquine remains a valuable antimalarial medication when used appropriately in regions without significant resistance, but its use must be guided by local resistance patterns and combined with primaquine for complete treatment of P. vivax and P. ovale infections.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment Guidelines for P. vivax Malaria

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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