Submicroscopic malaria infection is not associated with fever in cross-sectional studies in Malawi

Background: Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. In this study we evaluated whether participants with submicroscopic P . falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi. Methods: We enrolled a total of 16,650 children and adults in the course of six cross-sectional surveys during the dry season (October - November) and after the rainy season (April - May) between 2012 - 2014 in three districts in southern Malawi. Demographic and socioeconomic data were collected in conjunction with data on clinical histories, use of malaria preventive measures, and antimalarial medication taken within two weeks of the survey. Axillary temperatures were measured, and blood samples were collected for P. falciparum detection by microscopy and PCR. Participants without malaria parasites detected on microscopy but with a positive PCR for P. falciparum were defined as having submicroscopic infection. Fever was defined as having any one of: reported fever in the past two weeks, reported fever in the past 48 hours, or a temperature of ≥37.5 °C measured at the time of interview. Results: Submicroscopic P. falciparum infections and fever were both detected in 9% of the study population. In the final analysis adjusted for clustering within household and enumeration area, having submicroscopic P. falciparum infection was associated with reduced odds of fever in the dry season (odds ratio = 0.52; 95% CI: 0.33 – 0.82); the association in the rainy season did not achieve statistical significance (odds ratio = 1.20; 95% CI: 0.91 – 1.59). The association between submicroscopic infection and fever was consistent across all age groups. When we limited the definition of fever to temperature of ≥37.5 °C measured at the time of interview, the association was not statistically significant in either the rainy or dry season. Conclusions: In this series of cross-sectional studies in southern Malawi, submicroscopic P. falciparum infection was not associated with increased risk of fever. Submicroscopic detection of the malaria parasite is important in efforts to decrease transmission but is not essential for the clinical recognition of malaria disease.