Is malaria becoming more drug-resistant?
In 2021, there were 247 million cases of malaria worldwide and 619,000 estimated deaths as a result of this disease. Malaria is one of the most severe public health problems we face, but in most cases it is easily treatable with antimalarial drugs.
Are these life-saving drugs becoming less effective against malaria? We asked 38 experts in medicine, biotechnology, statistics, chemistry and global health, ‘Is malaria becoming more drug-resistant?’, here is what they said…
Is malaria becoming more drug-resistant?
What is malaria?
Malaria is an infectious disease that causes fevers, headache and other flu-like symptoms. Children are particularly at risk of developing severe infection which can be life-threatening. Professor Shashi Pandey, an expert in biotechnology from Banaras Hindu University in India, says “Malaria is a serious, but preventable and treatable mosquito-borne disease. Malaria is predominant in areas with tropical and sub-tropical climates”.
Dr Eric Grist, an expert in statistics from Oxford University in the UK, adds that “Malaria is caused by a microscopic plasmodium parasite conveyed into humans by certain species of mosquito.” There are 5 species of Plasmodium parasites but most cases of the disease are caused by one called Plasmodium falciparum (P. falciparum for short).
What drugs are used combat malaria?
Professor Pandey says “WHO recommends artemisinin-based combination therapies (ACTs) for malaria which includes combination of two active antimalarial ingredients with different mechanisms of action, ACTs are the most effective antimalarial medicines available today. WHO currently recommends 5 ACTs for use against P. falciparum malaria. The choice of ACT should be based on therapeutic efficacy studies against local strains of P. falciparum malaria.”
ACTs are not the only tools we have against malaria, other drugs include chloroquine and mefloquine.
Is malaria becoming more drug-resistant?
37 out of 38 experts agreed that malaria is becoming more drug resistant. Professor Elizabeth Ashley, an expert in tropical medicine from Oxford University in the UK, says “Studies of patients with malaria in Cambodia, Vietnam and Thailand have shown increasing numbers of treatment failures in people treated with standard combination therapies.”
The level of drug-resistance depends on the drug in question and where in the world you are looking. Dr Grist says “In the case of long-established antimalarial drugs such as chloroquine, there is no doubt that antimalarial drug resistance to the drug exists in certain parts of the world and especially in some areas of Africa. The use of chloroquine in those areas now has virtually no effect as a treatment.”
When did malaria start becoming drug-resistant?
Drug-resistant malaria is not a new problem - it has been around for decades. Professor Timothy Egan, an expert in chemistry from Cape Town University in South Africa, said “Drug resistant strains .. have appeared over the last half century. Resistance to chloroquine appeared in the 1960s and became widespread in the 1980s, while resistance to the antifolate class of antimalarials appeared soon after.”
Professor Ashley, says “Two-drug combinations of an artemisinin compound (e.g. artesunate, artemether, dihydoartemisinin) plus a partner drug (e.g. mefloquine, piperaquine, lumefantrine) [also called ACTs] were introduced in the 1990s and early 2000s to try to overcome the problem of rapid resistance emergence in Plasmodium falciparum... This was very successful until around 2008-9 when scientists noticed that it took longer for the malaria parasite to be cleared from the blood in patients in Cambodia with the disease, related to decreased responsiveness to artemisinin. They were still cured eventually though. However, since then resistance of the parasite to at least 2 of the partner drugs commonly used (mefloquine and piperaquine) has followed.”
Why do parasites like malaria become drug-resistant?
Professor Egan said that resistance is “an inevitable result of natural selection. When any fast growing organism is exposed to a substance that is toxic to it, such as a drug, any individual organisms harbouring mutations that confer a degree of tolerance will be selected until they become dominant in the environment. Thus, the more drugs we expose the organism to, the more drugs it will ultimately become resistant to. This is what has happened in the case of malaria parasites.”
Professor Harin Karunajeewa, an expert in infectious diseases from the Walter and Eliza Hall Institute of Medical Research in Australia, adds: “whenever we come up with a new drug for malaria, drug resistance should always be considered a case of ‘when’ rather than ‘if’”.
Are we still able to treat malaria?
Malaria can still be effectively treated using ACTs. Professor Olivo Miotto, an expert in genomics and parasitology, adds that “it must be clarified that resistant to artemisinin is different from resistance to some of the other drugs mentioned, in that artemisinin still works and remains able to kill those parasites; however, it acts slower on the resistant parasites, such that they are sometimes able to survive the treatment. Artemisinin is always given in combination with another drug, so treatment failures happen when there is resistance to that partner drug. Unfortunately, in some Asian countries, this is happening, especially with the partner drug piperaquine- other combinations are more effective.”
What might happen in the future?
Professor Francois Nosten, an expert in medicine and global health from the Shoklo Malaria Research Unit in Thailand, says “Some argue that malaria is declining worldwide and that there is no reason to be concerned. Others observed that the decline in malaria has stalled, that artemisinin resistance can spread from South East Asia to Africa, like chloroquine resistance did in the past, causing millions of deaths, and that we cannot take the risk to see history repeats itself. They advocate rapid elimination of the parasites wherever they are.”
Professor Ashley adds that “If artemisinin resistance emerges in Africa and combination treatments start to fail there the prospects for successful containment are very limited and this could allow malaria to get out of control (~190 million of the estimated 207 million cases of malaria caused by P.falciparum in 2016 were in Sub-Saharan Africa). If this was to happen one of the likely outcomes would be a sharp increase in the number of child deaths from malaria (which is already high at >440,000 a year).”
How can we tackle drug-resistant malaria?
The spread of artemisinin resistance could be disastrous, so what can be done to avoid the worst case scenario?
Professor Karen Barnes, an expert in pharmacology from Cape Town University in South Africa, summarises a few things that can be done:
“In short, much is being done, and even more needs to be done better to address this problem, including:
Achieving high coverage with all effective malaria control tools (e.g. mosquito vector control measures, personal protection, single low dose primaquine, prompt malaria testing, treating and tracking), to reduce malaria transmission - particularly in areas threatened by drug resistance.
Using the malaria medicines that we currently have available better so that they can last as long as possible - always finishing the treatment, even if patients feel better sooner and always giving exactly the right number of tablets for each patient - bearing in mind that some types of patients (young children, pregnant women, people with other diseases such as malnutrition, obesity) may need more or less than the standard dose.
Using malaria treatments that combine medicines that have opposing mechanisms of drug resistance.
Enhanced surveillance for drug resistance to ensure prompt changes in treatment policy when needed.
Intensive efforts to develop new medicines to treat malaria, although these will still take years before they become widely available”
Malaria is becoming more drug-resistant, but multiple approaches are being taken to address the problem.
May the facts be with you!
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