Malaria drug beats resistant parasite
•New non-artemisinin combination shows promise in Phase 2b study in children
•Parasite evolving to escape rapid tests in Africa as diagnostics miss 10% of malaria cases
•WHO seeks surveillance across Africa, alternative diagnostic approaches in affected regions
Scientists have recorded major breakthrough on resistance of malaria parasite to current treatment, Artemisinin-based Combination Therapies (ACTs), with the discovery of a new non-artemisinin combination in a Phase 2b study.
They, however, warned that the malaria parasite, Plasmodium falciparum, is evolving to escape rapid diagnostics and treatments in Africa.
Plasmodium falciparum malaria is primarily treated with ACTs such as artemether-lumefantrine.
ACTs are still highly effective and well tolerated. However, the increased observation of parasites with a slower response to artemisinin in Africa points to an increasingly urgent need to develop a new non-artemisinin class of anti-malarials to avoid a return to the high levels of childhood mortality last seen in the 1990s.
To this end, Novartis and Medicines for Malaria Venture (MMV) have reported positive results of a new non-artemisinin combination in a Phase 2b study.
The study tested ganaplacide, a novel agent with an entirely new mechanism of action, in combination with a new formulation of lumefantrine that is optimised for once daily dosing. This combination has the potential not only to clear malaria infection, including artemisinin resistant strains, but also to block the transmission of the malaria parasite.
These positive results support the future progression of the combination in patients with acute uncomplicated malaria.
The results are timely given the recent publication of a study in the New England Journal of Medicine that found decreased sensitivity to artemisinin in Uganda, a year after the publication of similar research in Rwanda.
The Phase 2b study was an open label randomised controlled study conducted in two parts and which enrolled more than 500 patients with acute uncomplicated malaria due to Plasmodium falciparum infection. After successful evaluation of the treatment in 349 patients older than 12 years in Part A of the study, Part B enrolled 175 patients under 12 years of age in seven countries that suffer from endemic malaria (Burkina Faso, Côte d’Ivoire, Gabon, Kenya, Mali, Uganda and India).
The ganaplacide/lumefantrine solid dispersion formulation combination met the primary objective in Part B of the study in children with acute uncomplicated malaria. The primary objective of adequate clinical and parasitological response (ACPR) at Day 29 with polymerase chain reaction (PCR) correction was considered to be met if the lower limit of the two-sided 95 per cent exact confidence interval for PCR corrected ACPR) rate was greater than 80 per cent.
In children with acute uncomplicated malaria, response to treatment with ganaplacide/lumefantrine was similar to the rate observed in patients who received artemether-lumefantrine control therapy. Ganaplacide/lumefantrine also demonstrated similar median parasite-clearing times compared to the control therapy. The combination of ganaplacide/lumefantrine solid dispersion formulation was generally well tolerated in the children.
Meanwhile, according to a research published in the journal Nature Microbiology, tests missed nearly 10 per cent of malaria cases caused by parasite Plasmodium falciparum, most common cause of malaria cases and deaths.
The study concluded that two genetic mutations in the parasite allow it to escape detection.
To address the situation, the researchers from the Ethiopian Public Health Institute and the World Health Organisation (WHO) want urgent surveillance across Africa and alternative malaria diagnostic approaches in affected regions.
Until now, 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.
The research team enrolled 12,572 participants along Ethiopia’s border with Eritrea, Sudan, and South Sudan, using Rapid Diagnostic Tests (RDTs), Polymerase Chain Reaction (PCR) diagnostics, an ultrasensitive immunoassay for antigen detection, and next-generation sequencing to find that Plasmodium 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.
Senior author, Dr. Jonathan B. Parr, assistant professor in the division of infectious diseases at the University of North Carolina (UNC) School of Medicine, United States (U.S.), said: “This is a serious problem for malaria control efforts and a reminder that pathogens are very capable of adapting to survive.
“Surveillance across the Horn of Africa and alternative malaria diagnostic approaches in affected regions is urgently needed.”