Drug Resistant Malaria

Definition: Antimalarial drug resistance is defined as the ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended, but within the limits of tolerance of the patient.
Distinction from Treatment Failure: Resistance is a specific property of the parasite. However, "treatment failure" in a clinical setting can also result from inadequate drug exposure due to vomiting, non-compliance (poor adherence), substandard medicines, or incorrect dosing,,.
Mechanisms: Resistance often arises due to genetic mutations in the parasite that reduce the drug's binding affinity or increase its efflux from the cell. In the absence of combination therapy, these mutant parasites are selected and propagate.

Global Hotspots: Southeast Asia, particularly the Greater Mekong Subregion (Cambodia, Thailand, Myanmar, Laos, Vietnam), is the epicenter for multidrug-resistant P. falciparum, including resistance to mefloquine and artemisinin derivatives,,.
Indian Scenario:
- P. falciparum: Resistance to Chloroquine is widespread. Resistance to Sulfadoxine-Pyrimethamine (SP) is also prevalent,.
- P. vivax: Generally sensitive to Chloroquine, but resistance is emerging. Anecdotal reports of Artemisinin resistance (delayed parasite clearance) have surfaced in East India.
- North-Eastern States: Due to high resistance levels, the National Vector Borne Disease Control Programme (NVBDCP) mandates different treatment regimens (Artemether-Lumefantrine) for this region compared to the rest of India,.

Chloroquine Resistance:
- P. falciparum: Widespread globally and in India. Chloroquine is no longer the first-line drug for P. falciparum,.
- P. vivax: High prevalence of chloroquine-resistant P. vivax exists in Indonesia and Papua New Guinea,. Rare cases are reported in India, Myanmar, and Central/South America,.
Sulfadoxine-Pyrimethamine (SP) Resistance: Widespread in many endemic areas, leading to its removal as a monotherapy. It is now used only in combination (e.g., with Artesunate) in specific regions where efficacy is preserved,.
Mefloquine Resistance: Significant problem in the Thailand-Cambodia and Thailand-Myanmar border regions. Use of mefloquine is restricted in these areas,.
Artemisinin Resistance:
- Manifests as delayed parasite clearance (parasites remaining detectable on day 3 of treatment) rather than complete treatment failure,.
- Documented in Southeast Asia and anecdotally in East India,.
- To combat this, Artemisinin is always used in Artemisinin-based Combination Therapy (ACT), never as a monotherapy,.

Treatment depends on the species and the resistance pattern of the geographic area of acquisition.

First-Line (India - General): Artemisinin-based Combination Therapy (ACT-SP).
- Artesunate (3 days) + Sulfadoxine-Pyrimethamine (1 day) + Single dose Primaquine (Day 2),.
First-Line (India - North East): ACT-AL.
- Artemether-Lumefantrine (co-formulated) for 3 days + Single dose Primaquine (Day 2),.
Alternative Regimens (e.g., for travelers or second-line):
- Atovaquone-Proguanil.
- Quinine sulfate + Doxycycline (or Tetracycline/Clindamycin).
- Mefloquine (only if no other options and not acquired in mefloquine-resistant areas),.

Suspected Resistance: If a patient does not respond to Chloroquine (worsening symptoms or no decrease in parasite density), resistance should be suspected.
Treatment:
- Artemether-Lumefantrine.
- Atovaquone-Proguanil.
- Quinine + Doxycycline/Clindamycin.
- Note: Anti-relapse therapy with Primaquine (14 days) is still required.

Drug of Choice: IV Artesunate is the first-line treatment for severe malaria (including resistant strains) due to its rapidity of action and lower mortality compared to Quinine,.
Follow-up: Must be followed by a full course of an oral ACT (e.g., Artemether-Lumefantrine) once the patient can tolerate oral medication to clear any remaining parasites and prevent recrudescence,.

Therapeutic Efficacy Studies (TES): The NVBDCP conducts regular TES at sentinel sites to monitor the efficacy of first-line antimalarials (ACTs and Chloroquine). A failure rate of >10% triggers a change in drug policy,.
Rational Drug Use:
- Ban on Monotherapy: Use of oral artemisinin monotherapy is banned in India to prevent the development of resistance.
- Compliance: Ensuring patients complete the full course of treatment (especially Primaquine for 14 days) is critical.
Surveillance: Monitoring for "Late Treatment Failure" (Recrudescence) within 28 days of treatment is essential to identify resistant cases,.