Non-invasive detection of malaria parasites in vitro and in Cameroonian adults

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Project Summary Malaria remains the leading infectious cause of morbidity and mortality by a single pathogen in sub-Saharan African children despite great progress in the past two decades. While the advent of rapid diagnostic tests has been a major stride, these tests suffer from similarly inadequate sensitivity as the gold standard, microscopy, and require a blood sample for testing. Newer molecular methods offer enhanced sensitivity, but most require significantly higher levels of laboratory infrastructure, cost more, and take longer to perform than microscopy and rapid diagnostic tests. Photoaccoustic flow cytometry (PAFC) is a technique that allows for the non- invasive detection of various cell types based on photoaccoustic signals generated following laser absorption. The device is being used currently in melanoma trials in humans and has demonstrated excellent safety. We have pioneered its use for the non-invasive detection of malaria in laboratory settings, as well as in animal models, and have demonstrated safety in early human studies using a portable prototype. As a follow-up, we propose to rigorously assess the in vivo analytical performance of this portable prototype for the detection of uncomplicated Plasmodium falciparum malaria in adults in Cameroon. PAFC results will be compared to highly sensitive and specific molecular assays, alongside standard diagnostic methods. Importantly, participants will be studied longitudinally, and rigorous safety assessments will be conducted. As a second aim, we will determine the ability of PAFC to detect and distinguish human malaria species in vitro and ex vivo through the use of stored blood from infected individuals, in vitro culture, and microscopy slides. Overall, the proposed studies aim to demonstrate the rapid, safe, and highly sensitive capability of PAFC for the non-invasive detection of malaria in non-pregnant adults. Data will lay the groundwork for expanded studies by our group in children, pregnant women, severe malaria patients, screening of asymptomatic individuals, and additional pharmacodynamic studies.