**6. Conclusions**

time. The presence of *P. falciparum* gametocytes is positively associated with the absence of clinical symptoms and low asexual parasite densities; mosquitoes can become infected with gametocyte densities as low as 5 gametocytes/μl and theoretically as low as one gametocyte/μl—children with undetectable gametocytaemia by molecular methods were still observed to be infectious to mosquitoes [17]. To accelerate achieving malaria elimination, the human reservoir of infection needs to be tackled with new approaches. There is a growing interest in MDA of at-risk populations or in malaria hot-spot areas with an effective antimalarial to reduce the parasite reservoir in human host [18]. MDA aims to provide full post-treatment courses to the whole population to clear asymptomatic infections and provide posttreatment prophylaxis to prevent reinfection. The use of MDA is recommended in areas approaching interruption of transmission, with good access to treatment, effective vector control, and surveillance systems, ensuring a minimal risk of reintroduction of infection [19]. MDAs have been conducted using a variety of drug regimens at different dosages, timings, and frequency. There is evidence of substantial but short-lived reduction in *P. falciparum* parasite carriage [20]. In Zambia, a cluster-randomized control trial implemented in a population of 330,000 individuals, distributed in 56,000 households, compared MDA with DP (2 rounds), at the household level (DP to all members of household with at least a RDT-positive individual) and standard control measures (case management, LLIN, indoor residual spraying (IRS), and intermittent preventive treatment during pregnancy). MDA decreased significantly malaria prevalence and incidence in low (malaria prevalence <10%) but not in high (malaria prevalence ≥10%) transmission areas [21]. With the growing awareness of heterogeneity and clustering in transmission, MDA approaches have been modified by systematic (mass screening and treatment) or focused (focal screening and treatment) screening and treatment of populations in defined geographical areas. Reactive case detection, i.e., screening and treating positive contacts in response to a clinical event, has been tested and implemented in some countries [22–25]. However, its impact has been variable as it is affected by the sensitivity of the diagnostic tool and the radius of intervention around a

The antimalarial treatment administered during MDA campaigns could be complemented by single low-dose of primaquine, an 8-aminoquinoline that is able to clear mature *P. falciparum* gametocytes [30], and/or ivermectin, a systemic endectocidal drug that can be administered safely to both humans and animals but proven toxic to *Anopheles* mosquitoes when they take a blood meal from a host that has recently received the drug [31, 32]. Primaquine may cause a dose-dependent hemolysis, mainly in individuals with deficiency of the enzyme glucose 6-phosphate dehydrogenase (G6PD) in red blood cells [33], and this has slowed down its implementation. Nevertheless, a single low-dose of primaquine can significantly reduce gametocyte carriage in both symptomatic [33] and asymptomatic [34] individuals and reduces onward transmission from man to vector [35]. Ivermectin can be safely administered with an ACT [36, 37] and has been used widely against parasitic diseases in humans, with record of more than 2 billion doses in MDA campaigns against onchocerciasis and lymphatic filariasis. In Burkina Faso, Liberia, and Senegal, one round of MDA with ivermectin at the standard dose of 150 μg/kg decreased substantially *An. gambiae* survival for 6 days and reduced the proportion of sporozoite-positive (infectious) mosquitoes for 2 weeks [38]. However, evidence of ivermectin as an additional tool to decrease malaria transmission is limited and needs to be further quantified, possibly by a cluster randomized

clinical case [26–29].

6 Towards Malaria Elimination - A Leap Forward

In conclusion, achieving universal access to standard control interventions, namely, case management, LLIN, IRS, seasonal malaria chemoprevention, and intermittent preventive treatment for pregnant women, remains a priority. It is essential to contain emerging drug resistance in malarial parasite and insecticide resistance in mosquito vector species. There is a dire need of additional new interventions to accelerate interruption of transmission. These should be evaluated and rapidly integrated within the standard control activities. Most of these should be implemented at the community level, and it will be important to actively involve the local populations to reach high coverage. Finally, political and financial supports should be maintained and even increased; current financial support is less than half of that estimated to reach the 2030 targets of the WHO global technical strategy for malaria [1].
