Strategies for improving radical cure in P. vivax malaria

Thesis

Plasmodium vivax can no longer be considered a benign cause of malaria with increasing reports of severe vivax malaria emphasising the importance of tackling this neglected parasite globally. Important differences in the lifecycle of P. vivax, in particular, its ability to relapse at varying periods after the primary infection make its control more difficult than P. falciparum. Prevention of relapse is dependent upon effective radical cure of blood and liver stage parasites with primaquine being the only current licensed drug effective against P. vivax hypnozoites.

Despite half a century of its use in malaria treatment, there is still no consensus on how primaquine can be deployed safely and effectively. The aims of this thesis were to review the efficacy of different primaquine regimens in preventing P. vivax relapse, to quantify the risk of recurrence of P. vivax following P. falciparum infection and to determine risk factors for representation with P. vivax. Analyses of primaquine clinical trials conducted till date reveal the inadequacy of data for the recommendation of a uniform high dose regimen across the world. A review of clinical studies using artemether-lumefantrine (AL) for P. falciparum malaria conducted in P. vivax endemic regions demonstrated that P. vivax was paradoxically responsible for the majority of recurrent parasitaemia within 63 days of treatment. AL is highly active against both P. falciparum and P. vivax and hence these recurrences are likely to reflect relapse triggered by activation of dormant liver stages.

To test the hypothesis that febrile illnesses other than malaria may be triggering relapses, risk factors for representation were assessed in Timika, Indonesia, an area endemic to the four main malarial species. The risk of representation with P. vivax was increased in patients initially presenting with non-malarial febrile illnesses (Adjusted Hazards Ratio 1.02-1.14). However, the odds were similar for representation with P. falciparum, suggesting an inherent risk of the patient population to cause representation rather than febrile illnesses. Patients presenting with P. falciparum and severe anaemia were at greatest risk of P. vivax representation. Further clinical studies are needed to ensure more pragmatic treatment regimens and reliable point of care testing for G6PD status to avoid haemolysis due to primaquine. In the interim, the target of primaquine radical cure should be widened to include these high risk groups.

Authors: John, G

• Publication date: 2012
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: Plasmodium vivax; Malaria; radical cure; relapse
• Subjects: Infectious diseases; Medical sciences; Malaria; Tropical medicine; Public Health