pfhrp2 gene deletions

The vast majority of rapid diagnostic tests (RDTs) manufactured, procured and used around the world are based on detection of HRP2 either alone or in combination with other antigens (such as parasite lactate dehydrogenase or aldolase).

Since 2010, surveys in several settings in Africa and Asia have also found a varying proportion of P. falciparum parasites lacking the pfhrp2 gene. False negative RDT results due to pfhrp2/3 deletions can lead to incorrect or delayed diagnosis and threaten patient safety. The patient may also continue to be a source of malaria transmission until properly treated.

The prevalence of this genetic mutation reportedly varies between and within countries and, once confirmed, RDT procurement and case management practices need to be tailored accordingly. WHO has developed a global response plan to pfhrp2 gene deletions, surveillance protocols to estimate the proportion of the parasites carrying these gene deletions causing false negative P. falciparum diagnosis, and technical guidance for procurement and use of alternative non-HRP2 detecting RDTs. 

As of 2021, the WHO database includes pfhrp2/3 gene deletion data for 40 countries across 5 WHO regions, and the data are presented in the WHO malaria threat maps. An interactive model – Deletion Risk Explorer – has been developed to illustrate the level of risk of pfhrp2 deletions emerging and having a clinical impact in a country based on a set of key drivers that can be modified by the user to generate several possible scenarios.