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|Title: ||Plasmodium falciparum histidine-rich protein 2 (PfHRP2) diversity in Ghana|
|Authors: ||Addai-Mensah, Otchere|
Ameke, Selassie Louis
Annani-Akollor, Max Efui
histidine-rich protein 2,
Rapid diagnostic test,
|Issue Date: ||3-Mar-2020|
|Publisher: ||Research Square|
|Abstract: ||Background: In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2
(PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum
malaria, particularly in endemic regions. However, genetic variability of the PfHRP2 gene threatens
the usefulness of the test. This study aimed to investigate the diversity of PfHRP2 in malaria cases
among children in Ghana.
Methods: A cross-sectional study was conducted at the Adidome Government Hospital in the Volta
Region of Ghana. A total of 50 children with mean age of 6.6±3.5 years and diagnosed of falciparum
malaria were included. Blood samples were collected for complete blood count, malaria parasite
identification and counting. DNA samples were amplified and sequenced. Nucleotide sequences were
translated in silico to corresponding amino acids and the deduced amino acids sequences were
analyzed for diversity.
Results: The number of repeats and number of each repeat within PfHRP2 varied between isolates.
Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this
study. Our HRP2 sequence shared high similarity with isolates from Kenya. Using Baker’s regression
model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes
recognized by PfHRP2-specific monoclonal antibodies (mAbs), we found the predominant motif to be
AHHAADAHH, which is recognized by the C1-13 mAbs.
Conclusion: This study reports diversity of P. falciparum histidine-rich proteins 2 in samples from
Ghanaian children with symptomatic malaria. We highlight the existence of extra amino acid repeat
types which adds to the PfHRP2 antigenic variability. The findings of this study will contribute to the
understanding of the performance of PfHRP2-based RDTs in the Ghanaian setting.
Malaria, which causes substantial morbidity and mortality, is a major public health problem in subSaharan
Africa, Asia, and Latin America . It claims the life of a child under five years every two
minutes in sub-Saharan Africa and has annual infection and mortality rates of 191 million and 395,000
individuals, respectively [2, 3]. In Ghana, malaria remains a major cause of loss of days of healthy life,accounting for not less than 20% of child deaths, 40% of child hospital admissions, and more than
50% of outpatient attendances [4-7].
Although, microscopic examination of stained blood smears remains the gold standard for malaria
diagnosis, its benefit is limited by the absence of adequate skilled personnel, and infrastructural and
logistic resources, particularly in resource-poor areas . To overcome this problem, the World Health
Organization (WHO) included rapid diagnostic tests (RDTs), a relatively less expensive and easily
accessible test, as one of the alternative testing systems for malaria diagnosis prior to the
prescription of antimalarial drugs.
Since its development in the 1990s, and with more than 200 currently available brands, there has
been consistent reports of observable increase in malaria RDT sales worldwide [9, 10]. Most of the
malaria RDTs exploit the presence of P. falciparum Histidine-Rich Protein-2 (PfHRP2) for the detection
of Plasmodium falciparum . The presence of repetitive epitopes, that enable their detection by
multiple antibodies, and their abundance in blood during the blood-stage of malaria infections has
made the PfHRP2 protein a common antigenic target for RDTs [12, 13].
In 2010, Ghana implemented the test-before-treat guideline for malaria where RDT use was promoted
to facilitate diagnosis . However, aside low parasite levels especially in asymptomatic cases,
improper interpretation of RDT results and/or the handling and storage of RDT kits, deletion of the
PfHRP2 gene and extensive antigen diversity has contributed to discrepancies in the RDT sensitivity
[15-20], threatening the future use of the test method, particularly in malaria-endemic regions such
as Ghana. Indeed, a recent study in Ghana reported PfHRP2 gene deletion in 33% and 36% of
microscopically-confirmed and PCR-confirmed RDT positive samples, respectively . Over the past
decade, several countries, especially in Africa, have reported cases of P. falciparum isolates with
deleted PfHRP2, and isolates with high PfHRP2 diversity [15-20, 22, 23], with potential negative
implications for malaria control and elimination programs. These notwithstanding, studies on PfHRP2
gene deletion and diversity of the PfHRP2 gene in Ghana, a malaria endemic country, are lacking.
This study thus aimed to investigate the diversity of PfHRP2 in malaria cases among children in
|Description: ||An article published by Research Square and also available at 10.21203/rs.3.rs-15776/v1|
|Appears in Collections:||College of Health Sciences|
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