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(green), or, in some circumstances, the slope changes or the maximum achievable effect

(Emax) is reduced (purple). The effect measured in vivo is parasite killing (reflected by re-

duction in parasite density), and that in vitro is usually a measure of parasite development

[15].

Resistance to antimalarial agents arises because of the selection of parasites with ge-

netic changes (mutations or gene amplifications) that confer reduced susceptibility. To date,

parasite resistance to antimalarial medicines has been documented in 3 of the 5 malaria

species known to affect humans: P. falciparum, P. vivax and P. malariae. Resistance has

also been documented to all classes of antimalarial medicines, including the artemisinin

derivatives, and it is a major threat to malaria control. The main consequence of antimalar-

ial drug resistance is treatment failure [19].

Widespread inappropriate use of antimalarial drugs exerts a strong selective pressure

on malaria parasites to develop high levels of resistance. Resistance can be prevented, or

its onset slowed considerably by combining antimalarial drugs with different mechanisms

of action and ensuring high cure rates through full adherence to correct dose regimens. If

different drugs with different mechanisms of resistance are used together, the emergence

and spread of resistance should be slowed.

Artemisinin based combination therapies (ACTs) are a combination of an artemisinin

component and a partner drug which is currently the main strategy to combat resistance

to antimalarial medicines. However, in the WHO Western Pacific Region and in the WHO

South-East Asia Region, partial resistance to artemisinin and resistance to a number of the

ACT partner drugs has been confirmed in Cambodia, Lao People’s Democratic Republic,

Myanmar, Thailand, and Viet Nam through studies conducted between 2001 and 2019. In

Africa, evidence has recently been published showing emergence of mutations linked to

partial artemisinin resistance in Rwanda. A summary of worldwide data on antimalarial

drug efficacy and drug resistance is available on GMP website.^10.3

In 2015, the WHO World Health Assembly endorsed a global plan of action against

antimicrobial resistance. The goal of the draft global action plan is to ensure, for as long

as possible, continuity of successful treatment and prevention of infectious diseases with

effective and safe medicines that are quality-assured, used in a responsible way, and acces-

sible to all who need them [20]. To achieve this goal, the global action plan sets out five

strategic objectives:

• to improve awareness and understanding of antimicrobial resistance;

• to strengthen knowledge through surveillance and research;

• to reduce the incidence of infection;

• to optimize the use of antimicrobial agents; and

10.3https://www.who.int/malaria/areas/drug_resistance/drug_efficacy_

database/en/