**4. Resistance of** *Anopheles* **mosquito vectors to insecticides**

efficacious antimalarial medicines, the rate of decline of both clinical cases and malaria deaths has stalled since 2014 and in some regions (the Americas mainly and marginally in the Southeast Asia, Western Pacific, and African regions) even reversed [1]. The World Health Organization (WHO) has estimated that to meet the 2030 targets of global malaria strategy, a minimum investment of US\$ 6.5 billion per year by 2020 is required [2]. In 2016, such investment was US\$ 2.7 billion, less than half of that required amount, and since 2014 in many high-burden countries, investments in malaria control have declined [1]. The call for malaria eradication launched at the Malaria Forum in October 2007 by the Bill & Melinda Gates Foundation and then supported by the WHO, Roll Back Malaria (RBM) Partnership,

The WHO currently considers malaria elimination at the national level as a continuum rather than the achievement of milestones for specific phases [2]. It is structured in 4 components (A–D), each of them to be implemented according to the malaria transmission intensity. Component "A" consists of enhancing and optimizing vector control and case management, which includes universal access to malaria preventions, diagnosis, and treatment for at-risk populations, and once elimination has been achieved, "focalized" vector control programs rather than scaling back these activities; component "B" aims at increasing the sensitivity and specificity of surveillance to detect, characterize, and monitor all cases (individual and in foci), namely, to transform malaria surveillance into a core intervention; component "C" aims at accelerating transmission reduction in which new interventions such as mass drug administration (MDA) or new vaccines are included; and component "D" is implemented when transmission intensity is low to very low, which includes the search for the few remaining infections and any foci of ongoing transmission, clearing them with appropriate treatment

and many other organizations and institutions seems to be at crossroads [3].

**3. Resistance of** *Plasmodium falciparum* **to anti-malaria drugs**

Resistance to first-line treatments for *Plasmodium falciparum* malaria and to the insecticides used for *Anopheles* vector control is threatening malaria elimination efforts [4]. Artemisinin and its derivatives provide the fastest parasite clearance among available antimalarial drugs and have been combined with an antimalarial drug of a different class in order to (i) enhance complete cure rates, (ii) shorten the duration of therapy for artemisinin monotherapies, and (iii) delay the selection and spread of resistant parasites [5, 6]. Artemisinin-based combination treatments (ACTs) are currently recommended for the management of uncomplicated malaria cases. In 2007, the first cases of delayed parasite clearance, suggesting artemisinin resistance, were observed at the Thailand-Cambodia border [7, 8]. Artemisinin resistance has now been reported in 5 countries of the Greater Mekong Subregion (GMS), which includes Cambodia, Myanmar, Laos, Thailand, and Vietnam, and delayed parasite clearance has been linked to

**2. Components of malaria elimination strategy**

4 Towards Malaria Elimination - A Leap Forward

and possibly additional vector control activities [2].

Resistance of malaria vectors to the 4 insecticide classes (pyrethroids, organochlorines, organophosphates, and carbamates) used for vector control interventions threatens malaria prevention and control efforts. Of the 76 malaria endemic countries that reported standard monitoring data from 2010 to 2016, resistance was detected in 61 countries to at least one insecticide in one malaria vector from one collection site, and 50 countries had resistance to 2 or more insecticides [1]. Resistance to pyrethroids, insecticides used in all long-lasting insecticidal nets (LLINs), is widespread though its impact on LLIN effectiveness is unclear [16]. There was no association between malaria disease burden and the level of resistance in a WHO-coordinated study implemented in 5 countries (Sudan, Kenya, India, Cameroon, and Benin) [1]. However, given the complexity in measuring the impact of insecticide resistance, it is not possible to equate lack of evidence of impact with evidence for no impact [16].
