Nigeria yet to detect resistance of malaria parasite to ACTs, says minister

*Study confirms some mosquitoes already have developed resistance to latest insecticide

Contrary to reports that Africa has for the first time identified resistance strain of the malaria parasite to the drug of choice, Artemisinin Combination Therapy (ACT), the Minister of Health, Dr. Osagie Emmanuel Ehanire, on Monday said a study conducted in three states of the country showed there is no such phenomenon in Nigeria.

Ehanire during a media briefing by the Presidential Task Force (PTF) on COVID-19 said: “Concerned about the growing resistance of the malaria parasite to ACTs especially in Asia and lately in Africa, we conducted some studies in three different states in different geopolitical zones. The result showed the recommended ACTs in Nigeria are still working optimally. This means there is no resistance to ACTs by the malaria parasite in Nigeria.

“However, we are still monitoring the situation. We insist that people should conduct a malaria test before using the drug of choice. This we hope will help prevent any kind of resistance of the malaria parasite to ACTs.”

Indeed, the hope to eliminate malaria just like smallpox has suffered a major setback with the discovery, for the first time of a drug-resistant strain of Plasmodium parasite in Rwanda.

The study, published in the journal Nature, found the parasites were able to resist treatment by artemisinin – a frontline drug in the fight against the disease.

This is the first time scientists have observed the resistance to the drug artemisinin in Africa.

The researchers warned that this “would pose a major public health threat” in the continent.

Scientists from the Institut Pasteur in collaboration with the National Malaria Control Programme in Rwanda (Rwanda Biomedical Centre), the World Health Organisation (WHO), Cochin Hospital, and Columbia University New York, United States of America (USA), analysed blood samples from patients in Rwanda. They found one particular mutation of the parasite, resistant to the drug-of-choice artemisinin, in 19 of 257 – or 7.4 per cent – of patients at one of the health centres they monitored.

According to the WHO, malaria is caused by Plasmodium parasites. The parasites are spread to people through the bites of infected female Anopheles mosquitoes, called “malaria vectors.” There are five parasite species that cause malaria in humans, and two of these species – P. falciparum and P. vivax – pose the greatest threat.

Until now, ACTs are the drugs recommended by the WHO for the treatment of malaria.

In the journal article the scientists warned that malaria parasites that developed a resistance to previous drugs are “suspected to have contributed to millions of additional malaria deaths in young African children in the 1980s”.

Meanwhile, an insecticide about to be widely deployed inside African homes to combat malaria-carrying mosquitoes is already losing its punch. Two years ago, the WHO gave the green light for clothianidin, long used in agriculture to kill crop pests, to be added to the current mainstays of indoor mosquito control, which are losing their effectiveness as the insects develop resistance. Since then, many African countries have been laying plans to spray the walls of homes with the pesticide—it would represent the first new class of chemicals adopted for such use in decades—and looking anxiously for evidence of pre-existing resistance.

Now, scientists at Cameroon’s Centre for Research in Infectious Diseases (CRID) have found it. They recently sampled mosquitoes from rural and urban areas around Yaoundé, the capital, including two key malaria carriers. In one standard susceptibility assay, exposure to clothianidin for one hour killed 100 per cent of Anopheles coluzzii. But in some A. gambiae samples as many as 55 per cent of the mosquitoes survived, the group reported in a preprint posted August 7 on the journal bioRxiv preprint server.

Corine Ngufor, a medical entomologist at the London School of Hygiene & Tropical Medicine, said this appears to be the first report of clear resistance to clothianidin in malaria-carrying insects. “It may spread very quickly and make this new class of insecticide almost useless for malaria vector control within a few years,” she warned.

Colince Kamdem, the CRID research scientist who led the study, said agricultural use of neonicotinoids—the class of chemicals to which clothianidin belongs—likely drove the emergence of the resistant mosquito strains. “WHO would never have recommended this insecticide if such data were available,” he contends.

Tiaan de Jager, director of the University of Pretoria Institute for Sustainable Malaria Control in South Africa, said the study shows it is crucial to test malaria vectors for resistance to an insecticide before deploying it. “It proves how important it is to tailor control methods to a region, such as an area of high agriculture, to ensure the success of the methods and overall program,” he said. “Other novel insecticide chemistries are urgently needed for malaria vector control,” Ngufor added.

Bed nets coated with long-lasting insecticides and indoor spraying have helped halve malaria mortality and morbidity in the past two decades. These programmes used insecticides from four classes but relied heavily on pyrethroids because they are cheap and non-toxic to mammals including humans, Kamdem said.

To combat the rise of pyrethroid-resistant mosquitoes, WHO added clothianidin to its “prequalified” list of chemicals acceptable for indoor spraying (and potentially nets). Neonicotinoids have become increasingly controversial as agricultural pesticides because of their impacts on pollinators; Europe has banned their use in agriculture. But farms in Cameroon and elsewhere in Africa rely heavily on them. In agricultural areas, Kamdem said, pesticide residues contaminate standing water that serves as breeding sites for mosquito larvae, favoring the evolution of neonicotinoid resistance.

The Cameroon finding doesn’t surprise German life science company Bayer AG, which manufactures one of the two formulations of clothianidin that malaria programs are considering for indoor spraying. “We supported some work in Côte d’Ivoire to also explore this and it seemed to suggest the same kind of finding, that there was already resistance to the family of insecticides that clothianidin belongs to,” said Sebastian Horstmann, Bayer’s product development manager for the clothianidin formulation. Horstmann said that to thwart, or at least slow, resistance, Bayer is developing new formulations with multiple insecticides for indoor spraying. But Kamdem noted those combinations have yet to be tested on resistant mosquitoes because none had been identified until now.

WHO has not reviewed the study because it has not yet been published in a peer-reviewed journal, said Deusdedit Mubangizi, who coordinates the agency’s “prequalification” assessments of active pharmaceutical products and medicines including insecticides used for mosquito control. But he thinks the chemical could still be an asset in mosquito control. “Resistance to clothianidin is much less prevalent than to other alternative insecticides in current use,” he said. But how long that will last is the great unknown—and concern.