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

Abstract

Background: Submicroscopic Plasmodium falciparum infections are widespread in many areas. However, the contribution of these infections to symptomatic malaria is not well understood. This study evaluated whether participants with submicroscopic P. falciparum infections have higher prevalence of fever than uninfected participants in southern Malawi. Methods: A total of 16,650 children and adults were enrolled in the course of six cross-sectional surveys during the dry season (October-November) and after the rainy season (April-May) between 2012 and 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 anti-malarial medication taken within 2 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 2 weeks, reported fever in the past 48 h, 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 the definition of fever was limited 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.

Accuracy of diagnosis among clinical malaria patients: comparing microscopy, RDT and a highly sensitive quantitative PCR looking at the implications for submicroscopic infections

“…In high transmission areas in sub-Saharan Africa, there are conflicting reports on the clinical relevance of submicroscopic infections. A cross-sectional survey in Malawi found no association between submicroscopic infection and clinical manifestation of malaria [ 54 ] whereas a recent study in Bagamoyo, Tanzania, was inconclusive on the contribution of submicroscopic infections to malaria transmission [ 55 ]. Meanwhile, longitudinal studies in Uganda found significant association between submicroscopic infections and febrile/non-febrile illnesses in younger children but not in adults [ 56 ].…”

Statistical haemoglobin thresholds to define anaemia across the lifecycle

“…36 Explanations for these heterogenous thresholds are uncertain, but may relate to undetected current or recent inflammatory disease. For example, asymptomatic submicroscopic Plasmodium parasitaemia is highly prevalent in sub-Saharan African children, 65,66 while in India the incidence of acute respiratory infections in children under 3 years is 2766 per 1000 child years, 67 and about 22% of Bangladeshi infants receive some form of health care due to illness (usually fever, vomiting or diarrhoea) over a three month period. 68 We found evidence for heterogeneity of both common and rare genetic effects on haemoglobin across different ancestries, including two variants proximal to the alpha-thalassaemia genes (HBA1/ HBA2) which show larger effect sizes than might be expected given their frequency within individuals of African ancestry.…”

Understanding the Intransigence of Malaria in Malawi

“…The majority of infections detected in community-based surveillance are submicroscopic, and these low-density infections are not associated with fever. 8 However, a small proportion of infections causes clinical disease. Through a longitudinal cohort of adults and children at a rural health center, we demonstrated that asymptomatic parasitemia was present in 23% of all visits.…”