Are antimalarial drugs still effective? Studies reveal emerging resistance to first–line treatments

Verah Okeyo: Sierra Leone: 29 May 2022:

Esther Ayuga knows all too well what to do when her four-year-old son Jeremy Otieno develops a fever: take him to the nearest health centre, Kaluo Health Centre immediately.

As a mother in the malaria-endemic Siaya county in Western Kenya, Esther takes the necessary precautions to keep her son safe from deadly mosquitoes — including ensuring he sleeps under an insecticide-treated mosquito bed net at night.

Whenever he is diagnosed with malaria, clinicians treat the boy with the medicine artemisinin, as per the guidelines in Kenya for his uncomplicated form of the disease.

2020 paper in the journal Nature, however, reported that researchers detected mutations associated with resistance to malaria parasites in another East African country Rwanda.

Another study in the New England Journal of Medicine confirmed that mutations are causing a drop in the ability of antimalarials, such as artemisinin, to treat people with the disease. The researchers found that it took longer than five hours for intravenous artesunate, a potent artemisinin derivative, to rid the body of more than half of the plasmodium falciparum, the malaria-causing parasite.

Less effective drugs

The declining effectiveness of these medicines could have catastrophic consequences if children like Jeremy do not get well after taking medication.

The latest World malaria report indicates that there were 241 million cases and 627,000 deaths of malaria in 2020. Ninety-five per cent of the cases and 96 per cent of deaths came from the World Health Organization Africa Region. Children under five years of age, like Jeremy, accounted for about 80 per cent of all malaria deaths in Africa.

According to Dr. George Githuka, the head of the Division of the National Malaria Control Programme (DNMP) at the Ministry of Health of Kenya, the country uses the medication Artemether-Lumefantrine (AL), an artemisinin derivative, for uncomplicated malaria. If the malaria were severe, the clinicians would administer the second-line Dihydroartemisinin-piperaquine (DHP) treatment.

Dr. Githuka says that these medications are still effective in Kenya. Yet, in Asia, scientists are raising the alarm about a “super malaria” parasite that is resistant to the recommended first-line treatment for malaria, the artemisinins.

Malaria gets into the bloodstream through an infected mosquito bite and incubates there for about two weeks. Later, it multiplies and infects the body’s red blood cells, causing fever and chills, headaches, and nausea, among other symptoms. With no treatment, the disease kills.

There are four types of malaria parasites. The most virulent type, responsible for more than 90 percent of infections and deaths in Kenya, is Plasmodium falciparum.

The malaria community has battled with resistance for a while. During World War II, an anti-malarial drug called ‘chloroquine’ treated malaria effectively until resistance rendered it useless.

Now, clinicians prescribe artemisinin and its derivatives and “partner” drugs in what are called artemisinin-combination therapies (ACTs), which is a treatment that has been effective so far.

The Kenya Malaria Indicator Survey (KMIS), published last year, showed that the country had recorded a slight decrease in malaria prevalence, from 8 per cent of the population in 2015 to less than 6 per cent in 2020.

As part of global efforts to eradicate malaria, agencies such as the United States Agency for International Development (USAID) are funding the prevention and control of malaria and tracking how it responds to medication through a monitoring activity known as Therapeutic Efficacy Studies (TES).

Since 2021, the ministry has worked with the John Hopkins University affiliate Jhpiego through the US President’s Malaria Initiative (PMI) Impact Malaria project, the Centers for Disease Control and Prevention, and USAID to determine if the medicines clinicians use to treat patients in Kenya are effective.

Dr. Githuka explained: “We have used the drugs Artemether-Lumefantrin and Dihydroartemisinin-piperaquine since 2006. Globally, there are areas we are already seeing the malaria parasite becoming resistant, meaning the drugs are becoming less effective. But we have not seen that in the country yet, and we continue monitoring to ensure the drugs we are using are effective.”

Young Jeremy is one of the children enrolled in the TES study in Siaya County. Each week for a month and a half, his mother takes him to the hospital for a blood sample that is analysed and tested to determine whether or not he still has the parasites. If results show that parasites are present, Jeremy will undergo molecular testing to determine whether they represent a new infection or whether the antimalarials failed to clear them from his system.

Jeremy’s mother was happy to allow him to participate in the study.

“The health workers told me that this study may tell them whether they should drop the medicine we are using or not and that the study results would later help all children like my son in Kenya,” Esther said.

Dickson Mwakangalu, a malaria specialist at the John Hopkins Affiliate Jhpiego and Chief of Party for the country team in Kenya for the U.S. President’s Malaria Initiative (PMI) Impact Malaria project, said that while Kenya has not recorded artemisinin resistance like those seen in the Mekong region, he and his colleagues continue to monitor the effectiveness of the antimalarials.

“Results from these TES studies will guide the country to decide whether it will seek alternatives or continue with AL,” said Dr. Mwakangalu.

In 2020, the Ministry of Health and PMI Impact Malaria Kenya tested lab technologists’ knowledge to identify the malaria parasite and narrow it down to what species and quantity of were in the blood.

The survey found that 69 per cent of the lab specialists could pick malaria out of other parasites, while another 42 per cent could identify the species, and only 13 could quantify how many parasites were in a microliter of blood.

“So apart from the study, we train the lab personnel to conduct microscopic tests properly,” Dr. Mwakangalu.

The Centers for Disease Control and Prevention in the United States (CDC) is still analysing the results of the study, but the Ministry of Health of Kenya is counting on it for its next course of action.

“If and when we notice there is an emergence of resistance, then we can appropriately change our treatment guidelines and have more effective medication,” said Dr. Githuka.

Africa Renewal

 

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