A major tool against malaria in Africa has been the use of rapid diagnostic tests, which are part of the “test-treat-follow” strategy in Ethiopia, Africa’s second most populous country. But researchers studying blood samples from more than 12,000 people in Ethiopia now estimate that these tests have failed nearly 10% of malaria cases caused by the parasite Plasmodium falciparum, the most common cause of malaria and malaria cases. death.

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

Jonathan Parr, MD, MPH

“This is a serious problem for malaria control efforts and a reminder that pathogens are very capable of adapting in order to survive,” said lead author Jonathan B. Parr, MD, assistant professor at the division of infectious diseases at the UNC School of Medicine. “Surveillance across the Horn of Africa and alternative approaches to diagnosing malaria in affected areas are urgently needed. “

Corresponding co-authors are Sindew M. Feleke, MSc, Ethiopian Institute of Public Health, Jane Cunningham, MD, WHO, and Dr Parr.

This research project was carried out in partnership with the Ethiopian Institute of Public Health and the World Health Organization. The research team recruited 12,572 participants along the Ethiopian border with Eritrea, Sudan and South Sudan, using RDTs, PCR diagnostics, a highly sensitive immunoassay for the detection of antigens and next-generation sequencing to find that P. falciparum lacks the histidine-rich protein 2 genes. (pfhrp2) and histidine-rich protein 3 (pfhrp3) escape detection by RDTs and appear to have spread rapidly.

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

“Our work indicates that prhrp3 deletions have occurred independently several times over the years,” said Parr, member of the UNC Institute for Global Health and Infectious Diseases. “We also found evidence that RDT-based testing and treatment is leading to a recent increase in the prevalence of the pfhrp2 deletion mutation, allowing parasites to escape detection.”

In the Nature Microbiology article, 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 difficult to answer. But the authors suggest several avenues of research in the article, although one thing is certain.

Parr said: “We have found clear evidence that parasites have recently evolved to escape detection by rapid diagnostic tests for malaria along Ethiopia’s borders with Sudan and Eritrea.

The Plasmodium falciparum parasite (Wikimedia commons)

False negative results were common at several sites and will lead to misdiagnoses and death from malaria without intervention.

“The results of this joint research effort have prompted us to change our policies from diagnostic testing from RDTs detecting HRP2 / 3 to untargeted HRP2 / 3 RDTs in the most affected areas of Ethiopia,” said Feleke.

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

Cunningham, said: “WHO recommends that all malaria-endemic countries initiate and maintain surveillance for pfhrp2 / 3 deletions and respond appropriately when confirmed, in order to prevent unnecessary morbidity and death and safeguard the progress made towards the elimination of malaria, particularly in sub-Saharan Africa.

The other authors of the Nature Microbiology article are Emily N. Reichert, Chris Hennelly, Madeline Denton, Corinna Keeler, and Jonathan J. Juliano of the UNC Institute for Global Health and Infectious Diseases; Ebba Abate, Hussein Mohammed, Bokretsion G. Brhane and Kalkidan Mekete, at the Ethiopian Institute of Public Health; Hassen Mamo and Beyene Petros at Addis Abada University in Ethiopia; Hiwot Solomon at the Ethiopian Ministry of Health; Nicholas J. Hathaway at the University of Massachusetts Medical School; Jeffrey A. Bailey and Ozkan Aydemir at Brown University; and Eric Rogier from the Centers for Disease Control and Prevention.

This work was funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria through Ethiopia’s Ministry of Health and the Bill and Melinda Gates Foundation through the World Health Organization. It was also partially supported by MSF Holland, which supported fieldwork in the Gambella region, the Doris Duke Charitable Foundation, the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Foundation and the US National Institutes of Health. -United.

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