Chloroquine susceptibility phenotype and virulence of Plasmodium falciparum
Abstract number: P748
Saliba G., Kamouh W., Fontanet A., Lebras J.
Objective: In order to study the relation between Plasmodium falciparum's virulence and phenotype, Chloroquine® resistant or susceptible, we postulated, based on the Fitness concept, that the susceptible phenotype would be more virulent in-vivo than the resistant one and thus more predictive of severe malarial episodes.
Methods: A case-control study on severe malaria imported into metropolitan France over the period of January 1st 1996 and September 30th 2006. Cases and controls were defined as subjects manifesting severe and non severe malarial episodes respectively.
The world health organisation classification, 2000, was used to assess the severity of malarial episodes. The criterion of >4% of peripheral parasitism in non-immune patients was excluded among the above criteria. All patients fulfilling this condition, solely, were regarded as manifesting non severe malaria. Using a bilateral 80% statistically powered test to detect a minimum odds ratio (OR) of 2.0, the number of subjects required was estimated to be 91 severe and 364 non severe cases. Independent risk factors of severe malaria, and subsequently virulence assessment of Plasmodium falciparum's phenotypes, were determined using multiple logistic regression models.
Results: Our study population consisted of 81 severe and 840 non severe cases. The threshold of 80% statistical power required for an appropriate analysis was respected by recruiting 921 subjects thus increasing the case-control ratio to ~1/10. Regarding severe falciparum malaria, the Chloroquine® susceptible phenotype turned to be a protective factor compared to the Chloroquine® resistant phenotype. After controlling for age, level of parasitism, continent of infection and native zone, the resistant phenotype was significantly associated with an increased risk of severe malaria with an OR of 1.85 (95% CI: 1.093.1). This result was controlled and consistently confirmed in several logistic regression models including and excluding missing data.
Conclusion: Virulence and Fitness do not seem to correlate. The adaptive advantage of the Chloroquine® susceptible phenotype, according to the Fitness concept, does not result in more enhanced in-vivo virulence. This is the first study to address this subject without any restrictions of age or of aetiology of severe malaria.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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