Abstract

Recent findings suggest that changes in human odors caused by malaria infection have significant potential as diagnostic biomarkers. However, uncertainty remains regarding the specificity of such biomarkers, particularly in populations where many different pathological conditions may elicit similar symptoms. We explored the ability of volatile biomarkers to predict malaria infection status in Kenyan schoolchildren exhibiting a range of malaria-like symptoms. Using genetic algorithm models to explore data from skin volatile collections, we were able to identify malaria infection with 100% accuracy among children with fever and 75% accuracy among children with other symptoms. While we observed characteristic changes in volatile patterns driven by symptomatology, our models also identified malaria-specific biomarkers with robust predictive capability even in the presence of other pathogens that elicit similar symptoms.

Highlights

  • Recent findings suggest that changes in human odors caused by malaria infection have significant potential as diagnostic biomarkers

  • In addition to examining differences in the volatile profiles of malaria-infected and uninfected children presenting any symptom, we made similar comparisons for non-exclusive subsets of children exhibiting the two most commonly observed symptoms in our dataset: fever and diarrhea. For each of these three symptom categories, discriminant analysis of principal components (DAPC) revealed clear separation in the overall volatile composition between individuals with and without malaria infection (Fig. 1, S1), with a permutational analysis of variance resulting in significant differences in both arms and feet

  • These results indicate that the effect of malaria infection on volatile profiles is apparent even when directly compared to other conditions that produce similar symptoms

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Summary

Introduction

Recent findings suggest that changes in human odors caused by malaria infection have significant potential as diagnostic biomarkers. To the extent that Plasmodium parasites, or other vector-borne pathogens, alter host odors in ways that consistently influence vector attraction, they may generate unique patterns of effects on host volatile profiles—possibly tailored to the olfactory responses of particular vector species—distinct from more general changes in volatile emissions that arise as mere byproducts of pathology The presence of such unique signatures of infection might, in turn, facilitate the identification of pathogen-specific biomarkers capable of reliably predicting infection status even in populations where numerous pathological conditions elicit similar symptoms. We reported differential up and down regulation of specific volatile organic compounds in both symptomatic and asymptomatic schoolchildren in K­ enya7 While these characteristic changes were highly predictive of malaria infection, the specific processes by which the presence of malaria parasites alter human volatiles remain almost entirely unknown. One recent study reported that a malaria-derived isoprenoid increases the production of several monoterpenes and aldehydes in vitro, but this does not account for the majority of volatile alterations observed by our and other s­ tudies suggesting that the underlying mechanisms are likely to be complex

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