Can we use human odors to diagnose malaria?

Abstract

After declining steadily during the early part of the twenty-first century, the worldwide incidence of malaria has recently reached a plateau [1]. Further progress toward the eradication of this devastating disease will likely require overcoming a number of serious challenges, including a need for improved methods of detecting asymptomatic infections, which currently often go undetected and untreated. Infected individuals who do not present symptoms remain capable of transmitting malaria parasites and in fact may account for 20–50% of onward transmission [1,2]. Identifying and treating these asymptomatic individuals is therefore a key goal for eradication efforts, but currently available methods for diagnostic screening of human populations, including microscopy and antibody-based rapid diagnostic tests (RDTs), have significant limitations. A significant proportion of asymptomatic malaria cases are caused by incipient or otherwise low-level infections that are not readily detectable via microscopy [3]. RDTs may produce high rates of false negatives for these submicroscopic infections [4] and can also be unreliable for the detection of parasite species other than Plasmodium falciparum [5]. Furthermore, widely used RDTs based on the detection of PfHRP-2 are exhibiting increasing rates of false negatives for P. falciparum in some regions of Africa, India and Peru due to parasite gene deletions [5,6], raising concerns about the evolution of diagnostic resistance. A further drawback of both RDTs and microscopy-based detection methods is the need to collect blood droplets for testing, which can pose health risks in areas where blood-borne infections, such as HIV, are widespread [5]. These and other limitations of existing diagnostic methods have led to calls for the development of new detection methods that are reliable and noninvasive, and which can be easily and affordably deployed for screening of human populations [5]. Volatile compounds are an under-explored class of potential diagnostic biomarkers that could conceivably be employed for population screening to detect malarial infection. It is possible, for example, to envision the development of an easy-to-use portable device for detecting malaria-specific biomarkers that could be readily deployed in areas with limited medical infrastructure. Recently, several studies have explored the ability to detect human malaria infections via volatiles from the skin and breath, and their results suggest that volatile biomarkers may hold significant potential for the reliable detection of infected people, including those with asymptomatic infections. These promising results make a volatile diagnostic for malaria a realistic option, particularly with regard to population-wide diagnostic screening and monitoring aimed at malaria eradication.