Plasmodium falciparum evolving to escape malaria rapid diagnostics in
Africa

Date:
September 28, 2021
Source:
University of North Carolina Health Care
Summary:
A major tool against malaria in Africa has been the use of rapid
diagnostic tests, which have been part of the 'test-treat-track'
strategy in Ethiopia, the second most-populated country in
Africa. But researchers studying blood samples from more than 12,000
individuals in Ethiopia now estimate these tests missed nearly 10%
of malaria cases caused by the parasite Plasmodium falciparum,
the most common cause of malaria cases and deaths.



FULL STORY ==========================================================================
A major tool against malaria in Africa has been the use of rapid
diagnostic tests, which have been part of the "test-treat-track" strategy
in Ethiopia, the second most-populated country in Africa. But researchers studying blood samples from more than 12,000 individuals in Ethiopia
now estimate these tests missed nearly 10% of malaria cases caused by
the parasite Plasmodium falciparum, the most common cause of malaria
cases and deaths.


==========================================================================
The research, published in Nature Microbiology, showed that two genetic mutations to the parasite allow it to escape detection.

"This is a serious problem for malaria control efforts and a reminder that pathogens are very capable of adapting to survive," said senior author
Jonathan B. Parr, MD, assistant professor in the division of infectious diseases at the UNC School of Medicine. "Surveillance across the Horn of
Africa and alternative malaria diagnostic approaches in affected regions
are urgently needed." Co-corresponding authors are Sindew M. Feleke,
MSc, at the Ethiopian Public Health Institute, Jane Cunningham, MD,
at the WHO, and Dr. Parr.

This research project was conducted in partnership with the Ethiopian
Public Health Institute and the World Health Organization. The research
team enrolled 12,572 participants along Ethiopia's border with Eritrea,
Sudan, and South Sudan, using RDTs, PCR diagnostics, an ultrasensitive immunoassay for antigen detection, and next-generation sequencing to find
that P. falciparum lacking the genes histidine-rich protein 2 (pfhrp2)
and histidine-rich protein 3 (pfhrp3) escape detection by the RDTs and
appear to have spread rapidly.

In collaboration with Brown University's Jeffrey A. Bailey, MD, PhD,
and Ozkan Aydemir, PhD, the researchers applied a molecular sequencing
approach to pinpoint the particular deletion patterns of these genetic mutations. "Our method allowed us to study the rich genomic information surrounding these genes in fine detail and at scale, facilitating the identification of evolutionary origins of these deletions," Aydemir said.

"Our work indicates that prhrp3 deletions have arisen independently
multiple times over the course of years," said Parr, who is a member of
the UNC Institute for Global Health and Infectious Diseases. "We also
found signs that RDT-based testing and treatment are driving a recent
rise in pfhrp2 deletion mutation prevalence, allowing parasites to
escape detection." In the Nature Microbiology paper, the authors ask,
"What other advantages might pfhrp2/3-deleted parasites have over those
with intact genes? Our limited understanding of the biology of these
deletions makes this question hard to answer." But the authors posit
several lines of inquiry in the paper, though one thing is certain.

Parr said, "We found clear evidence that parasites have recently evolved
to escape detection by malaria rapid diagnostic tests along Ethiopia's
borders with Sudan and Eritrea. False-negative results were common in
multiple sites and will lead to misdiagnosis and malaria deaths without intervention." "The results of this joint research effort have prompted
us to change our diagnostic testing policies from HRP2/3-detecting RDTs
to non-HRP2/3 targeted RDTs in the most affected regions of Ethiopia,"
Feleke said.

Also, along with several other unpublished reports, this study prompted
the WHO to issue a statement of concern.

Cunningham, said, "The WHO recommends that all malaria endemic
countries start and maintain surveillance for pfhrp2/3 deletions and
respond appropriately when they are confirmed, in order to prevent
unnecessary morbidity and deaths and to safeguard inroads that have been
made towards malaria elimination, particularly in sub-Saharan Africa." ========================================================================== Story Source: Materials provided by
University_of_North_Carolina_Health_Care. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Sindew M. Feleke, Emily N. Reichert, Hussein Mohammed, Bokretsion G.

Brhane, Kalkidan Mekete, Hassen Mamo, Beyene Petros, Hiwot Solomon,
Ebba Abate, Chris Hennelly, Madeline Denton, Corinna Keeler,
Nicholas J.

Hathaway, Jonathan J. Juliano, Jeffrey A. Bailey, Eric Rogier,
Jane Cunningham, Ozkan Aydemir, Jonathan B. Parr. Plasmodium
falciparum is evolving to escape malaria rapid diagnostic
tests in Ethiopia. Nature Microbiology, 2021; 6 (10): 1289 DOI:
10.1038/s41564-021-00962-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210928171909.htm

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