SUDANESE JOURNAL OF PAEDIATRICS

2021; Vol 21, Issue No. 2

CASE REPORT

Antimalarial drug resistance in tropical countries: a solution towards decreasing mortality of children under 5 years of age

Idris Zubairu Sadiq (1)

(1) Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria

Correspondence to:

Idris Zubairu Sadiq

Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria

Email: izsadiq [at] abu.edu.ng

Received: 08 April 2021 | Accepted: 20 April 2021

How to cite this article:

Sadiq I Z. Antimalarial drug resistance in tropical countries: a solution towards decreasing mortality of children under 5 years of age. Sudan J Paediatr. 2021;21(2):228–231.

https://doi.org/10.24911/SJP.106-1617926256

Dear Editor,

Malaria affects one of the most vulnerable groups of people: children under the age of five. The World Health Organization (WHO) estimated that not less than 285,000 African children have died before reaching their fifth birthday in 2016 alone [1]. Antimalarial drug resistance coupled with the absence of a highly effective malaria vaccine forestalls international attempts to reduce malaria mortality and morbidity in endemic areas of sub-Saharan Africa, whereas significant protection to the malarial infection is gained in childhood throughout the endemic regions, the malarial complications have always been linked to death in young affected children who lack immune defence [1]. The symptoms of severe malaria, such as anaemia, seizures and hypoglycaemia seem to be more pronounced in children. Recently, six African countries, including Nigeria, the Democratic Republic of the Congo, the United Republic of Tanzania, Mozambique, Niger and Burkina Faso, accounted for approximately 51% of all malaria deaths worldwide in 2019, according to the World Malaria Report 2020 [2].

According to WHO, antimalarial drug resistance may be defined as a parasite strain’s ability to survive or multiply despite the administration and absorption of an antimalarial drug at doses equal to or higher than those normally prescribed, but within the subject’s tolerance [3]. This description can be broadened to include the ability of the active form of the parasite-fighting drug to gain access to the parasite or infected erythrocyte for the duration of the drug’s normal action. Artemisinin partial resistance occurs when parasite clearance is delayed after treatment with an artemisinin-based monotherapy or artemisinin-based combination therapy (ACT) [3].

The recently reported decline in the effectiveness of ACT in Southeast Asia [4] jeopardises global efforts to eliminate and eradicate the disease. Partial resistance to artemisinin in Plasmodium falciparum has emerged in a number of countries in The Greater Mekong Subregion which includes China, Myanmar, Thailand, Lao PDR, Cambodia and Viet Nam [5]. To contain this resistance from further spread to endemic areas, therapeutic efficacy studies (TES) that remain the gold standard used to inform treatment policies should be encouraged in malaria endemic regions. Information from TES can be supplemented with information on molecular markers of drug resistance to counteract partial or complete resistance as there is no treatment option should artemisinin-based combination therapy options fail in Africa [6]. A study of 287 children with severe malaria from Central, West and East Africa found that artemisinins currently to be highly effective for large malaria-endemic areas and the erstwhile resisted chloroquine sensitivity to be gradually returning likely as a result of reduced pressure on chloroquine [7]. While artemisinin derivatives are safe and well-tolerated in young children, the preference of ACT should be based primarily on the partner drug’s safety and tolerability. Antimalarial drugs should always be available in paediatric formulations, as dividing adult tablets could result in incorrect dosing which may trigger resistance. Several factors may affect the antimalarial therapeutic outcomes, for example, drug resistance, patient acquired immunity, initial parasite biomass, insufficient exposure of the parasite to the drug due to incorrect dosing, poor compliance, and vomiting of the administered drug and irregular pharmacokinetics (Figure 1).

A more contributing factor to the parasite resistance is its genetic diversity, which makes it possible for the parasite to adapt to a broad variety of malarial drugs, and hinder vaccine development. Besides, falciparum multidrug resistance gene 1 (Pfmdr1), for example, has been connected to parasite resistance to a variety of anti-malarial drugs. The 86Y and 1246Y mutations in Pfmdr1 have been linked to decreased chloroquine and amodiaquine sensitivity, as well as increased lumefantrine, mefloquine, and artemisinin sensitivity [8-12]. Although 184F mutations have been linked with lower susceptibility to lumefantrine [13], resistance to chloroquine and amodiaquine has been linked to mutations in the Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt), with the 76T point mutation being the most predictive of chloroquine resistance. Polymorphisms in the P. falciparum kelch 13 (Pfk13) propeller can also be used as markers to monitor and trace artemisinin-resistant parasites.

Measures to prevent the onset of artemisinin partial resistance and to make antimalarial effective in paediatrics can be achieved through the following: 1) the use of antimalarial drug combinations: as monotherapy treatment, such as intramuscular artemether injections for uncomplicated malaria cases, may lead to resistance. This is particularly the case in Sudan and other African countries. Also, if a severely ill patient is given parenteral artesunate for 24 hours, a complete course of ACT should be given as soon as possible. 2) In malaria case management, antimalarial drugs should be prescribed only after laboratory confirmation of malaria infection. 3) Compliance to a full course of therapy; sticking to medical advice helps to prevent drug resistance and often makes therapy effective. 4) Optimal antimalarial dosing, and the use of genuine, high-quality drugs with the appropriate formulation may all help to control the spread of drug resistance (Figure 2). 5) Antimalarial TES and surveillance using molecular markers of drug resistance should also be conducted among vulnerable children in endemic regions.

Figure 1. Factors affecting treatment outcomes.

Figure 2. Ways of preventing antimalarial drug resistance.

In most tropical countries with endemic malaria, drug resistance has become a growing concern. The spread of drug resistance emphasised the role of research efforts in identifying the underlying causes and the urgency to use the current effective treatments appropriately since there is no backup should these drugs fail. Nevertheless, malaria is still a treatable disease, despite the existence of drug resistance, and the value of prevention, early diagnosis and treatment are important for the overall success in saving the lives of children under 5 years of age.

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