Lumefantrine-resistant and Piperaquine-resistant Plasmodium berghei show cross-resistance to Primaquine but not to Atovaquone

Abstract

Background: Malaria affects 300-500 million people annually and kills more than 1 million, with majority of the clinical cases and deaths occurring in Sub-Saharan Africa. Rapid development of drug resistance remains a major challenge in malaria control and has lead to use of combined antimalarial therapies. Resistance to an antimalarial drug may however, be selected for by another drug in which the mechanism of resistance is similar.

Objective: This study sought to establish cross-resistance patterns between four antimalarials namely atovaquone (ATQ), primaquine (PMQ), lumefantrine (LM) and piperaquine (PQ) using murine malaria models.

Method: The activities of ATQ and PMQ against drug sensitive, PQ and LM-resistant Plasmodium berghei lines was assessed using the 4-day test and 90% index of resistance (I₉₀) determined.

Results: Analysis of cross-resistance patterns showed a significant decrease in PMQ sensitivity (I₉₀ of 6.39), and a slight but not significant decrease in ATQ (I₉₀ of 1.19) activity towards the LM-resistant P.berghei ANKA.

Conclusion: PQ-resistance in P. berghei is associated with a significant resistance of PMQ (I₉₀ of 12.22) and a slight, though not significant reduction in ATQ (I₉₀ of 1.27) efficacy.

Key words: Plasmodium berghei, resistance, piperaquine, lumefantrine, primaquine, atovaquone