Systematic review and meta-analysis of the interaction between Plasmodium falciparum and Plasmodium vivax in humans

Abstract

Objectives: This study aimed to quantify the interaction between Plasmodium falciparum and P. vivaxand the sources of heterogeneity between studies.Methods: We systematically reviewed three databases: Medline (1966–2001), Embase (1980–2001)and CAB-health (1976–2001). Random effects meta-analysis was applied to the data of 62 selectedpopulations. Meta-regression was used to assess the following potential sources of heterogeneity: agegroup,presence of fever, continent, temporal and spatial span of studies, and endemicity level.Results: The summary odds ratio (OR) between P. falciparum and P. vivax was 0.6 (95% CI: 0.49–0.79). The minimum and maximum observed ORs were 0.01 and 10.9, respectively, and theheterogeneity test was highly significant (τ2= 0.92, p<0.0001)—the ORs varied over a very wide range.The ORs in longer studies and in those from areas with higher prevalence yielded smaller, morestrongly negative association. This is consistent with the idea that any difference in the species’temporal patterns should decrease the OR, and more so over longer periods of time.Interpretation & conclusion: Although such odds ratios between Plasmodium species may be partlydue to missed mixed infections when reading blood slides, the negative association between the ORand prevalence supports the existence of biological interactions such as suppression or cross-immunitybetween species.

Keywords

• Meta-analysis
• Plasmodium
• species interactions
• systematic review