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Tackling malaria drug resistance in Uganda

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A bite from an infected female anopheles mosquito is the common way through which malaria is transmitted. PHOTO/FILE/COURTESY

Malaria remains one of the leading causes of morbidity, and mortality in Uganda. Sub-Saharan Africa bears nearly the entire global burden of malaria, accounting for an estimated 96 percent of malaria cases and deaths in 2020; approximately four in five of these deaths were among children under the age of five.

The World Health Organisation (WHO) currently recommends six different artemisinin-based combination therapies (ACTs) as first- and second-line treatment for uncomplicated P. falciparum malaria. 

ACTs combine an artemisinin derivative (artesunate, artemether, or dihydroartemisinin) with a partner drug.

The role of the artemisinin compound is to reduce the number of parasites during the first three days of treatment, while the role of the partner drug is to eliminate the remaining parasites and cure the infection.

However, on a global scale, parasite resistance to artemisinin has been identified in several areas in Africa; notably Eritrea, Rwanda, and Uganda. While artemisinin resistance alone rarely leads to treatment failure, resistance to both artemisinin and the partner drug within ACT drug regimens can lead to high rates of treatment failure according to WHO.

What is drug resistance?
The WHO defines antimalarial drug resistance as the ability of a parasite strain to survive and multiply despite the administration and absorption of medicine given in doses equal to or higher than those usually recommended.

According to Eric Okek, a research fellow at Makerere University in Kampala, drug resistance develops through a complex process involving genetic mutations, natural selection, and environmental pressures. Some of the factors contributing to drug resistance include overuse and misuse of drugs, inadequate treatment, dosing and poor infection control practices. 

“Malaria drug resistance occurs when the parasite that causes malaria adapts to drugs that are meant to kill it, making the drugs ineffective. This occurs due to genetic mutations in the parasite, which can be accelerated by the misuse of antimalarial drugs and poor adherence to treatment guidelines,” he says.

Drugs. Some parts of Africa have recently reported a drug resistant malaria. 

Given the heavy reliance on ACTs in Africa, full-blown treatment failure could have very serious consequences. 

“We do not have that many options for malaria drugs,” notes Dr Dorothy Achu, WHO’s new Team Lead for Tropical and Vector-Borne Diseases for the WHO African Region.  As it stands, we just have artemisinin-based combination therapies for uncomplicated malaria. So, any threat to these drugs could lead to lots of cases and deaths, which we want to avoid,” she says.

Why resistance?
Dr Moses Ocan, a senior lecturer at Makerere University's College of Health Sciences specialising in Pharmacology and therapeutics, also emphasises that malaria parasites are developing resistance to drugs that are currently used in treatment.

According to the research, the level of malaria drug resistance in Uganda is at about 15 percent and if nothing is done, the prevalence is going to increase sharply. 

In a bid to find out the drivers of this resistance, research revealed that many people are unable to complete their malaria treatment doses because the drugs are expensive such as chloroquine which is cheaper. 

“Many people who are taking malaria medication have shown persistent symptoms even after completing the dose. About 70 percent of the people in Uganda cannot afford to buy a full dose of antimalarial drugs and 30 percent of the patients come to private facilities having experienced persistent symptoms of malaria following treatment.”

“Although antimalarial drug resistance is a serious cause for concern, artemisinin-based combination therapies (ACTs) remain the best available treatment for uncomplicated P. falciparum malaria,” notes Dr Pascal Ringwald, lead author of the new strategy and a Coordinator in the WHO Global Malaria Programme. 

Following guidelines
One of the leading factors driving resistance according to Okek is treatment behaviours such as self-medication, and over or under-use of medicines. 

"Many people go and buy medicines from pharmacies even before they are diagnosed," she says.  
He recommends that all patients suspected to have malaria must first get tested for proper diagnosis of the disease before they are given treatment. 

“This is essential for the effective management of the disease and reduces the risks of resistance. When one takes antimalarial medicines at a time the body does not need them, it may take some time before the body expels them completely. If the person then suffers malaria, the parasites learn to live in the presence of these medicines, hence resistance.”

Such a person then needs a stronger dose or a completely different medicine, probably second line, which is usually more expensive. One may also stay in the hospital longer and hence lose out on productivity.  

Quality assurance 
Another driver of resistance according to Dr Ocan is poor quality of drugs. Quality-assured artemisinin-based combination therapies are not common in private drug outlets in selected districts in Uganda. 

“We found that about 20 percent of the medicines being sold in the private pharmacies have no active ingredients that they claim to contain and are of an unacceptable quality. We notified the National Drug Authority (NDA) and the drugs were withdrawn from the market because they were substandard,” he remarks.

In a cross-sectional survey of anti-malarial agents in private drug outlets in selected moderate-to-high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings, it was found that the majority of treatments are combination but only one in seven antimalarial agents in these private drug outlets were quality-assured artemisinin-based combination therapies. 

Co-payment mechanism 
A large proportion of malaria-symptomatic patients in Uganda seek healthcare in the private sector. However, availability and affordability are major barriers to access to effective treatment and a driver of resistance.

It is against this background that the government, under the private sector malaria treatment programme, started the co-payment mechanism to avail affordable medicines facilities for malaria.

The co-payment programme has been in existence since 2011 but nearly all private healthcare workers and other people are not aware of it so they do not stock the medicine using the mechanism.

In the co-payment mechanism, the government pays between 50 to 70 percent of the cost of the medicine to the manufacturing companies in India, Asia and China and by the time the consumer buys it, they get it at a subsidised cost. 

Such medicines, Dr Ocan says, are marked by a Green leaf and when one is buying them, they are supposed to be cheaper. However, research suggests that the cost of ACT antimalarial agents is higher at about Shs5,000 for Artemether-Lumefantrine, and about Shs47,000 for Dihydroartemisinin-Piperaquine, which are the first-line and second-line agents respectively, for treatment of uncomplicated malaria.