Last Updated: 15/02/2023
The impact of a malaria infection on G6PD activity (MAGY)
Objectives
To measure G6PD activity, before infection and repeatedly after infection so that any change in G6PD activity across the course of a malaria infection can be monitored.
G6PD deficiency is the most common hereditary enzymopathy, affecting more than 400 million people worldwide. In most cases these enzyme deficiencies are not clinically relevant, however in some individuals they can cause drug or food induced hemolysis. Globally 2.5 billion people are at risk of vivax malaria. In contrast to most other malaria types, vivax malaria can relapse weeks to months after the first episode, causing significant morbidity and mortality among affected populations.
Primaquine and tafenoquine are the only available drugs that effectively remove the vivax parasite from the human host. While safe in most recipients, primaquine can lead to severe side effects in G6PD deficient individuals. The WHO therefore recommends testing for G6PD deficiency prior to treatment, assuming that G6PD activity is stable within the human host. Preliminary data from clinical trials in Bangladesh, Indonesia, and Ethiopia suggest that G6PD activity may be altered during a malaria infection. We found significantly less G6PD deficient cases when patients were measured during a malaria episode, compared to a second measurement when the same patients were free of malaria.
In the course of a human volunteer infection studies with malaria undertaken at QIMR Berghofer Medical Research Institute in Brisbane, Australia, volunteers will be infected with the malaria parasite and treated on day at onset of target parasitemia. The sample size of the challenge trial is small and the study will be designed as a proof of concept study. Any observed change in G6PD activity will need to be verified by subsequent larger field trials that may ultimately result in an altered global test and treat strategy for the treatment of vivax malaria.
A total of eight participants will be enrolled into the challenge study. Venous blood will be collected from all participants for G6PD measurement prior to malaria inoculation, as well as on days 4, 5, 6, 7, 9, 11, 14, 22 and 49 post-inoculation (total = 10 measurements). Full blood count, reticulocyte count and parasite count will be done at the same time points. All participants will also be asked to record any food and drug ingested in the 24 hours prior to sample collection. 11 Sample analysis G6PD activity will be measured within 4 hours by UV-spectrophotometry on a ThermoFischer Indiko Plus (ThermoFischer, Waltham, USA) using kits from Randox Laboratories (Crumlin, UK) and controls from Trinity Biotech (Wicklow, Ireland).
All results from the spectrophotometer will be normalized by a red blood cell count done on the same sample. Blood parameters will be collected from the same sample in the course of a full blood count. Data management and analysis All generated data will be fed into a custom-made database and will be analyzed using standard methods for trend analysis such as regression analysis, Mann-Kendall test and others as appropriate. Correlations will be done following standard procedures. Analysis will be done using STATA (USA) and R (Austria).
May 2019 — Oct 2023
$15,000
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