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The New England Journal of MedicineRed-Cell Rosette Formation in Malaria

Mechanism of Red-Cell Rosette Formation in Malaria: Implications for Splenic Sequestration and Relapse Management

A 57-year-old woman with a history of recently treated Plasmodium vivax malaria presented with recurrent symptoms including fever, fatigue, and splenomegaly. Laboratory testing confirmed a relapse of P. vivax infection, characterized by red-cell rosette formation observed in peripheral blood smears. This piece illustrates the clinical presentation while discussing the diagnostic findings and treatment implications for managing relapsed malaria, with a focus on the underlying mechanisms that facilitate the evasion of splenic sequestration by infected erythrocytes.

Key Points:

  • Patient Presentation:
    • 57-year-old woman with a history of recently treated P. vivax malaria.
    • Symptoms: 2-week history of fatigue and anorexia, 2-day history of fever.
    • Physical findings: Temperature 39°C, blood pressure 98/50 mm Hg, splenomegaly.
  • Initial Treatment History:
    • Completed a course of piperaquine and dihydroartemisinin for P. vivax infection three months prior.
    • Returned to normal health post-treatment.
  • Laboratory Findings:
    • Hemoglobin level of 10.6 g/dL (reference range: 12.0 to 15.5 g/dL).
    • Peripheral-blood smear with May–Grünwald–Giemsa stain revealed:
      • Malaria gametocytes
      • Mature trophozoites surrounded by uninfected erythrocytes in rosette formations
    • Positive antigen test for P. vivax.
    • Parasite load less than 1% in red cells.
  • Red-Cell Rosette Formation:
    • Seen in P. vivax and P. falciparum infections.
    • Mechanism believed to help infected cells escape:
      • Splenic sequestration.
      • Phagocytosis.
      • Exposure to antimalarial agents.
  • Diagnosis and Treatment:
    • Diagnosed with relapsed P. vivax infection.
    • Administered another course of antimalarial agents.
    • Follow-up at 3 weeks showed the patient afebrile and asymptomatic.
  • Clinical Implications:
    • Importance of monitoring for relapse in P. vivax infections.
    • Consideration of red-cell rosette formation in diagnosis and treatment planning.
    • Potential need for prolonged or repeated courses of antimalarial therapy.
    • Recognition of splenomegaly as a significant clinical sign in relapsed malaria cases.

Plasmodium vivax is responsible for nearly half of all malaria cases outside sub-Saharan Africa, with an estimated 8.5 million cases annually. Its ability to form dormant liver stages (hypnozoites) contributes to its relapse potential.

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