A 28-year-old pregnant woman (6 months gestation) from a malaria-endemic district in Madhya Pradesh presents with fever and chills for 4 days. She has no prior malaria history. Blood smear microscopy shows *Plasmodium vivax* trophozoites. She is treated with chloroquine. On follow-up at 2 weeks, she reports recurrent fever with similar symptoms. What is the most likely reason for this clinical relapse?

Explanation

## Understanding Malaria Relapse in *Plasmodium vivax* This case highlights a critical epidemiological feature of *P. vivax* malaria: the existence of dormant liver stages (hypnozoites) that cause relapse. ### Clinical Presentation **Initial Episode:** - *P. vivax* trophozoites on blood smear - Fever, chills (typical tertian pattern) - Chloroquine-sensitive (responds initially) **Relapse (2 weeks later):** - Recurrent fever with identical symptoms - Timing: within weeks to months of initial infection - Blood smear again positive for *P. vivax* ### Key Point: The Hypnozoite Cycle **Key Point:** *Plasmodium vivax* (and *P. ovale*) have a unique feature: **hypnozoites**—dormant parasites in hepatocytes that can reactivate weeks to months (or even years) after the initial blood-stage infection is cleared. **High-Yield:** Chloroquine kills only the **erythrocytic (blood) stage** parasites. It does NOT eliminate hypnozoites. Therefore: - Chloroquine alone cures the acute attack but leaves hypnozoites intact - Relapse occurs when hypnozoites spontaneously reactivate and enter the blood - **Primaquine** (8-aminoquinoline) is the only drug that eliminates hypnozoites (true causal prophylaxis) ### Why Primaquine Was Not Given **Clinical Pearl:** Primaquine is **contraindicated in pregnancy** because: 1. It is teratogenic (Category X in older classifications) 2. It can cause haemolysis in G6PD-deficient individuals (risk to fetus) 3. Safety data in pregnancy are insufficient Therefore, this pregnant patient was treated with chloroquine alone—standard practice to avoid fetal harm—but this leaves her vulnerable to relapse from hypnozoites. ### Relapse vs. Recrudescence | Feature | Relapse | Recrudescence | |---------|---------|---------------| | **Cause** | Hypnozoite reactivation | Inadequate drug clearance of blood parasites | | **Parasite source** | Liver | Blood | | **Timing** | Weeks to months (or years) | Days to weeks | | **Associated parasites** | *P. vivax*, *P. ovale* | *P. falciparum*, *P. malariae* | | **Drug sensitivity** | Responds to primaquine | May indicate drug resistance | **Mnemonic: VIVAX RELAPSE = HYPNO** - **HYP**nozoites in liver - **NO** chloroquine effect on liver stage - Requires **primaquine** for true cure ### Management in This Case **During Pregnancy:** - Continue chloroquine for acute episodes - Do NOT give primaquine - Counsel on risk of relapse **Postpartum (after delivery and if breastfeeding, after weaning):** - Administer primaquine 15 mg daily × 14 days (or 45 mg weekly × 8 weeks in some regimens) - First check G6PD status - This will eliminate hypnozoites and prevent future relapses [cite:Park 26e Ch 10; WHO Malaria Treatment Guidelines 2023]