A 32-year-old woman from Odisha presents with fever, chills, and sweating for 3 days. Blood smear shows P. vivax trophozoites. She is started on chloroquine 600 mg base stat, followed by 300 mg at 6, 24, and 48 hours. On day 5 of treatment, fever recurs with similar parasitaemia. What is the most appropriate next step in management?

Explanation

## Clinical Context The patient has recurrent fever and parasitaemia on **day 5** despite a complete, adequate chloroquine course — this is the classic presentation of **chloroquine-resistant P. vivax (CRPV)**, not a simple relapse from hypnozoites. ## Key Distinction: Resistance vs. Relapse **High-Yield:** A relapse from hypnozoites typically occurs **weeks to months** after the initial attack, not within days of completing chloroquine. Recurrence of parasitaemia within 28 days of adequate chloroquine therapy (≥25 mg/kg total base) is the WHO definition of **chloroquine treatment failure / resistance**. - **Relapse** (hypnozoite reactivation): occurs weeks–months later → treated with primaquine after chloroquine - **Chloroquine resistance / treatment failure**: parasitaemia persists or recurs within days of chloroquine → requires switch to ACT ## Why ACT Is the Correct Next Step **Key Point:** WHO guidelines (2015, updated 2022) and NVBDCP India recommend **artemisinin-based combination therapy (ACT)** — specifically artesunate + sulfadoxine-pyrimethamine (AS+SP) or artemether-lumefantrine — for chloroquine-resistant P. vivax. ACTs are effective against erythrocytic stages of CRPV and are the standard of care when chloroquine fails. - Odisha is a high-transmission, high-resistance zone in India where CRPV is well-documented - Switching to ACT addresses the acute resistant infection - Primaquine for radical cure can be added **after** the acute attack is controlled with ACT, once G6PD status is assessed ## Why Other Options Are Wrong - **Option A (Primaquine now):** Primaquine targets hypnozoites, not erythrocytic schizonts. It does not treat the active chloroquine-resistant blood-stage infection. Adding it without first controlling the acute parasitaemia is inappropriate. - **Option B (Double-dose chloroquine):** Doubling chloroquine in a patient who has already failed a full course is ineffective and potentially toxic. Not recommended by any guideline. - **Option D (G6PD testing before any further therapy):** While G6PD testing is important before primaquine, it should NOT delay treatment of an active, drug-resistant malaria infection. The immediate priority is controlling parasitaemia with ACT. **Clinical Pearl:** In chloroquine-resistant P. vivax, the sequence is: (1) ACT for acute blood-stage infection → (2) G6PD testing → (3) Primaquine for radical cure if G6PD normal. [cite: WHO Guidelines for the Treatment of Malaria, 3rd ed. 2015; NVBDCP National Drug Policy on Malaria 2013; KD Tripathi 8e Ch 52]