Malaria treatment failure. Understand the enigma.

Malaria treatment failure. Understand the enigma.

Malaria remains a global public health threat – responsible for more than 75,000 infant deaths annually. Malaria treatment failure is an emerging entity of public health concern as it threatens the efficacy of the available antimalarial regimens on the market to date. There’s a distinction between antimalarial drug resistance and malaria treatment failure – and we ought to understand this rhetoric. It’s imperative to ascertain that no bedside tests currently exist to determine whether the malaria parasites are susceptible to a given drug or not. On sporadic occasions, clinicians switch from one antimalarial drug to another in the same patient because the previous one didn’t produce the desired therapeutic effect – in other words, it failed. Much as monitoring malaria treatment failure is a research-based endeavour, the thought of it emanates from day-to-day clinical practice that an antimalarial drug isn’t as effective as it ought to be. In today’s article, we explain why an antimalarial drug may fail to clear malaria in a given patient.

Malaria, tuberculosis, and HIV remain some of the most devastating infectious diseases globally. They have posed an existential threat to human beings since time immemorial. People from impoverished regions have tested the wrath of these diseases – yet the light at the end of the tunnel is obscure. Every two minutes, a child under five years in the (sub) tropical regions dies of malaria. The disease has some of the most efficacious chemotherapy to date – artemisinin derivatives like artesunate.

Artemisinin combination therapy (ACT) has revolutionised the way clinicians treat malaria. Unsurprisingly, it is the first-line treatment for malaria – both complicated and uncomplicated. Quinine follows suit as the second-line therapy. 

With the revolutionary artemisinin derivatives at full effect, some patients don’t improve on them. Clinicians then run towards antimalarials from a different class to treat malaria. We arbitrarily term the phenomenon – malaria treatment failure.

For malaria treatment failure to occur, the following happens. The administered drug fails to either clear malaria parasites from the body (parasitaemia), resolve the clinical symptoms, or both. Various reasons explain why such a catastrophe can ensue.

Drug resistance causes treatment failure. At appropriate doses, resistant parasite strains survive or even multiply – this defines antimalarial drug resistance. Drugs like chloroquine are no longer efficacious against Plasmodium falciparum malaria because this species is utterly resistant to the drug. So, when a clinician prescribes a regimen to which the said malaria parasite strain is not susceptible, the treatment will ultimately fail.

Not all treatment failure is due to drug resistance. Inappropriate ad incorrect dosing also culminates in malaria treatment failure – like a 60 kg patient with malaria who receives artemether-Lumefantrine (Co-Artem) once a day instead of twice a day. Such a patient’s malaria parasites won’t clear because the prescriber has subjected them to fewer drugs. Taking drugs at dosages lower than the recommended ones creates a selection pressure – whereby some parasites die, and others thrive, which may lead to uncalled for resistance patterns.

When the doses are correct, a patient may fail to adhere to the treatment. It is especially true for oral drug regimens that require a more than once-daily dosing. Several patients will deliberately leave out the third dose because they then feel better. Poor treatment adherence can complicate malaria to require hospital admission.

In the advent of correct doses, proper compliance, and lack of documented drug resistance, malaria treatment failure may occur because the clinicians prescribed a low-quality drug. It is no brainer that we hear a few medicines from certain manufacturers are less potent than others. Such drugs, when used, will provide a subpar treatment effect that will culminate if failure to resolve the malaria symptoms. So, it’s prudent to procure drugs to companies that manufacture high-quality medications to prevent unnecessary losses that result from failed treatment.

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In a few scenarios, a patient may be swallowing more than one drug for a completely different condition – and it so happens that the said drug affects the antimalarial drug the clinician has prescribed. The drug interactions that ensue afterwards may reduce the bioavailability of the antimalarial regimen. It negatively affects its efficacy. As such, the parasites won’t clear, and so malaria symptoms will not resolve. An example is the widely recognised interactions between antiretroviral drugs and antimalarial medications.

Even at the correct dosage, compromised drug absorption may occur. Antimalarial drugs like lumefantrine dissolve well in fats but not in water solvents. Others may be absorbed better when taken on an empty stomach. Doing the contrary may reduce the amount of the drug that the digestive system absorbs to avail to the parasite population in the body. Poor drug absorption leads to suboptimal parasite clearance, which eventually culminates in treatment failure. Clinicians can prevent such an apocalypse if they give correct instructions on how to swallow the prescribed drugs.

Lastly but not least, treatment failure can occur because the patient never had malaria in the first place. It was a misdiagnosis. Various ailments can present with fever, headache, abdominal pain, malaise, myalgias, nausea, vomiting, and loss of appetite – yet malaria isn’t one of them. It is a false failure since we were treating the wrong disease. It is imperative that clinicians only treat malaria that the laboratory has confirmed through microscopy or rapid antigen tests. Scenarios like these tend to occur in the remote villages where every drug shop is a ‘clinic’, and every elder is a ‘doctor.’ The only cause of fever they know in such a society is malaria.

In a nutshell, malaria treatment failure can result from any of the factors above. To prevent such, clinicians should engage with the community and all stakeholders to ensure proper drug use.

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