Malaria breath biomarkers across the spectrum of malaria disease severity
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Date
2022-05-12
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Abstract
Type of study: Observational cohort study
The Problem: The need for rapid, accurate, affordable, and non-invasive diagnostic
methods for malaria remains urgent, particularly in peripheral health centers.
Methodology: The study population of interest will be children aged 4-8 years drawn
from two ongoing COMREC-approved studies at Queen Elizabeth Central Hospital in
Blantyre. Fifty children in the ongoing “Treatment of brain swelling in pediatric cerebral
malaria” study (P. 09/16/2024, PI: Taylor) with cerebral malaria will be matched with
fifty children with asymptomatic parasitemia from the “Malaria pathogenesis:
Progression cohort and extremes, case control study” (P.11/18/2530, PI: Seydel). Fifty
children with no evidence of malaria infection in the “Malaria pathogenesis” study will
be used as uninfected controls. After obtaining informed consent from their primary
caretaker, a brief medical history and demographic information will be collected.
For children with cerebral malaria (CM), breath will be collected through a mask with
two one-way valves – allowing for inspiration through one valve and exhalation through
a separate valve. Asymptomatic children and children confirmed to not have malaria
by qPCR (controls) will provide exhaled breath gas samples after 5 minutes of sitting
or lying quietly. A full breath will be exhaled into a small plastic device attached to an
inflatable plastic bag. Once the exhaled breath is collected, the sample will be filter
concentrated into a sorbet trap that absorbs nonpolar organic molecules. These
samples can then be stored refrigerated and shipped at 4-6°C.
A finger prick blood sample will be taken on a filter paper at the same time to be used
for PCR quantification of asexual parasites and gametocytes.
A nasopharyngeal swab will be taken from the children with CM to test for viral and
bacterial respiratory pathogens.
Following sample collection, children with CM will receive routine medical care for their
malaria, including usual antimalarial therapy as warranted. The asymptomatic children
will be tested for malaria with a mRDT and treated with standard anti-malarial therapy
(LA) if found to be positive. The children with no evidence of malaria will also be tested
by mRDT and treated with LA if found to be positive.
The breath samples will be analyzed for VOCs by thermal desorption (TD) mass
spectrometry. The mass spectrometry resource facility at Children’s Hospital of
Philadelphia (CHOP) has successfully detected VOCs emitted by cultured malaria
parasites (1) and in breath of Malawian children (2) and will again be engaged to seek
these compounds in the breath from patient specimens.
Objectives:
To develop a novel non-invasive, rapid, accurate, reusable, and affordable malaria
diagnostic method capable of detecting P. falciparum even at sub-mRDT
parasitemias. This will be achieved through two specific aims:12-May-2022
Breath malaria biomarkers
COMREC submission
Version 1.2, 26 Feb 2022
Page 5 of 22
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a) To collect and analyze breath from fifty children with asymptomatic
malaria and fifty children without malaria infection to determine the
possible presence of biomarkers able to distinguish these
populations
b) To collect and analyze breath from fifty children with cerebral
malaria and simultaneously evaluate these children for the presence
of respiratory pathogens, allowing us to characterize the possible
role of respiratory pathogens in altering the malaria breathprint.
Expected Findings: We hypothesize that VOCs will be detected in the breath of children
with malaria even at the very low levels of parasite infection seen in many
asymptomatically infected children. Furthermore, we hypothesize that co-infection with
respiratory pathogens will shift the VOC profile – but that an underlying ‘breathprint’
can be identified that is malaria specific. These core VOCs can then be explored as
novel biomarkers of malaria infection that could be used to screen for asymptomatic
infection serving as the basis for future non-invasive malaria diagnostic devices. It is
the hope that, in addition to being non-invasive, these devices could be portable,
reusable, affordable, and accurate so that they could be used in rural health facilities
and communities to identify the population of children who are asymptomatically
infected and thus serving as a transmission reservoir.
Dissemination: Results will be disseminated to the medical community through peer-
reviewed publications and presentations at relevant scientific conferences. Results will
also be shared with KUHeS at the annual Research Dissemination Conference. We
will also report our findings and publications to COMREC
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Research Subject Categories::MEDICINE