Ethiopia: Parasite mutations are responsible for a large percentage of malaria cases that cannot be diagnosed quickly in Ethiopia. Credit: UNC School of Medicine
Rapid diagnostic tests have been a key tool in fighting malaria in Africa. They are part of the "test–treat-track” strategy in Ethiopia, Africa's second-most-populated country. However, researchers who examined blood samples from over 12,000 people in Ethiopia have found that these tests missed almost 10% of cases of malaria caused by Plasmodium falciparum. This parasite is the leading cause of death and cases.
Nature Microbiology published the research that showed two genetic mutations in the parasite were able to hide detection.
Jonathan B. Parr MD, senior author, said that this is a problem for malaria control efforts. He also noted that the UNC School of Medicine assistant professor in infectious diseases, the Division of Infectious Diseases, stated that "this is a serious issue for malaria control efforts." "Surveillance in the Horn of Africa is urgently required, as well as alternative diagnostic methods for malaria in affected areas.
Sindew M.Feleke, MSc at the Ethiopian Public Health Institute; Jane Cunningham MD at the WHO; and Dr. Parr are co-corresponding authors.
The World Health Organization and Ethiopian Public Health Institute collaborated on this research project. The research team recruited 12,572 participants at Ethiopia's border to Eritrea, Sudan and South Sudan using RDTs,PCR diagnostics, an ultrasensitive immuneassay for antigen detection and next-generation sequencing. They discovered that P. falciparum, which is devoid of the genes histidine rich protein 2 (pfhrp2), and histidine rich protein 3 (pfhrp3), had escaped detection by RDTs and appeared to have rapidly spread.
The researchers worked with Jeffrey A. Bailey, MD, Ph.D. of Brown University and Ozkan Aydemir. Ph.D. to identify the specific deletion patterns for these genetic mutations. Aydemir stated that their method allowed them to examine the rich genomic information surrounding these genetic mutations in fine detail and at large, which enabled them to identify the evolutionary origins.
Plasmodium falciparum, parasite causing malaria. Credit: Dr. Mae Melvin (CDC/Wikimedia commons)
Parr, a member the UNC Institute for Global Health and Infectious Diseases said that "our work indicates prhrp3 mutations have arisen independently multiple time over the course of the years." We also discovered signs that RDT-based treatment and testing are contributing to a recent increase in the prevalence of pfhrp2 mutations, which allows parasites escape detection.
The Nature Microbiology paper asks: "What other benefits might pfhrp2/3 deleted parasites have over their intact genes?" This question is difficult to answer because of our limited knowledge of the biology behind these deletions. The paper contains several lines of inquiry, but one thing is certain.
Parr stated, "We found clear evidence to show that parasites recently evolved to evade detection by malaria rapid diagnostic test along Ethiopia's border with Sudan and Eritrea." False-negative results are common at multiple locations and can lead to malaria deaths and misdiagnosis without intervention.
Feleke stated that the results of this joint research project have led to a change in our diagnostic testing policies, from HRP2/3-detecting to non-HRP2/3 targeted tests RDTs in most affected areas of Ethiopia.
This study, together with other unpublished reports, prompted WHO to issue a statement concerning the situation.
Cunningham stated, "The WHO recommends all malaria-endemic countries to start and maintain surveillance for the pfhrp2/3 mutations and respond appropriately when confirmed. This is to prevent unnecessary morbidity, deaths, and safeguard progress made towards eliminating malaria, especially in sub-Saharan Africa."
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More information: Sindew, M. Feleke, et al. Plasmodium falciparum evolves to escape malaria rapid diagnostic test in Ethiopia, Nature Microbiology (2021). Information from Nature Microbiology Sindew M. Feleke and colleagues, Plasmodium Falciparum is evolving in order to escape malaria rapid diagnostic testing in Ethiopia (2021). DOI: 10.1038/s41564-021-00962-4
