Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials

Abstract

The efficacies of 3-day regimens of artemether-lumefantrine (AL), artesunate-amodiaquine (AA), and dihydroartemisinin-piperaquine (DHP) were evaluated in 910 children < 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan-Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature > 38°C, enrollment parasitemia > 75,000 μL, and PRRD1 < 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction-corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1-100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.

Artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers

“…The study also revealed PCR corrected AL cure rate of 100% observed in the study sites demonstrate that AL remained highly efficacious. In contrast to the results of the current study, ASAQ has maintained its high efficacy in neighbouring [ 42 – 44 ] and other West African countries [ 45 – 50 ] with cure rates of 98% and above. Similar high cure rates (96% and above) with the AL treatment have also been reported in the sub-region [ 42 – 51 ].…”

Artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers

“…The study also revealed PCR corrected AL cure rate of 100% observed in the study sites demonstrate that AL remained highly efficacious. In contrast to the results of the current study, ASAQ has maintained its high efficacy in neighbouring [ 42 – 44 ] and other West African countries [ 45 – 50 ] with cure rates of 98% and above. Similar high cure rates (96% and above) with the AL treatment have also been reported in the sub-region [ 42 – 51 ].…”

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana

“…Day 3 parasitaemia was detected following AL treatment in only two of 85 participants, and this is consistent with rapid ART clearance in the studied parasite population. This largely agrees with findings from under 5 years children with uncomplicated malaria in studies from Ghana and Nigeria which all reported day 3 positive parasitaemia below 5% [ 31 , 32 ]. WWARN earlier proposed a day 3 positive parasitaemia of 5% threshold as more suitable in keeping track of ART resistance in SSA instead of the currently recommended 10% by the WHO due to high acquired immunity against the parasite in African populations and its contribution to faster parasite clearance [ 33 ].…”

Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021

“…The study also assessed, for the first time, the efficacy of DP, a second-line treatment introduced in 2016, and demonstrated high efficacy (PCR corrected cure rates of 100% in Kouvé and Anié on day 28 and 98.9% in Kouvé and 100% in Anié on day 42, respectively). These results are similar to those reported in neighboring countries such as Ghana [ 45 ] and Benin [ 46 ], but also as well as other West African countries [ 47 – 54 ], and Central and East African countries [ 55 – 57 ]. This contrasts with recent reports of the reduced PCR-corrected cure rates of AL (< 90%) found, in the absence of a Pfkelch13 validated variants, in Burkina Faso [ 58 ], Angola [ 59 ], and the Democratic Republic of Congo [ 60 ], suggesting lumefantrine resistance.…”

Artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers

“…The study also revealed PCR corrected AL cure rate of 100% observed in the study sites demonstrate that AL remained highly efficacious. In contrast to the results of the current study, ASAQ has maintained its high efficacy in neighbouring [ 42 – 44 ] and other West African countries [ 45 – 50 ] with cure rates of 98% and above. Similar high cure rates (96% and above) with the AL treatment have also been reported in the sub-region [ 42 – 51 ].…”

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana

“…Day 3 parasitaemia was detected following AL treatment in only two of 85 participants, and this is consistent with rapid ART clearance in the studied parasite population. This largely agrees with findings from under 5 years children with uncomplicated malaria in studies from Ghana and Nigeria which all reported day 3 positive parasitaemia below 5% [ 31 , 32 ]. WWARN earlier proposed a day 3 positive parasitaemia of 5% threshold as more suitable in keeping track of ART resistance in SSA instead of the currently recommended 10% by the WHO due to high acquired immunity against the parasite in African populations and its contribution to faster parasite clearance [ 33 ].…”

Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021

“…The study also assessed, for the first time, the efficacy of DP, a second-line treatment introduced in 2016, and demonstrated high efficacy (PCR corrected cure rates of 100% in Kouvé and Anié on day 28 and 98.9% in Kouvé and 100% in Anié on day 42, respectively). These results are similar to those reported in neighboring countries such as Ghana [ 45 ] and Benin [ 46 ], but also as well as other West African countries [ 47 – 54 ], and Central and East African countries [ 55 – 57 ]. This contrasts with recent reports of the reduced PCR-corrected cure rates of AL (< 90%) found, in the absence of a Pfkelch13 validated variants, in Burkina Faso [ 58 ], Angola [ 59 ], and the Democratic Republic of Congo [ 60 ], suggesting lumefantrine resistance.…”

Artesunate–amodiaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia: in vivo efficacy and frequency of molecular markers

“…The study also revealed PCR corrected AL cure rate of 100% observed in the study sites demonstrate that AL remained highly efficacious. In contrast to the results of the current study, ASAQ has maintained its high efficacy in neighbouring [ 42 – 44 ] and other West African countries [ 45 – 50 ] with cure rates of 98% and above. Similar high cure rates (96% and above) with the AL treatment have also been reported in the sub-region [ 42 – 51 ].…”

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana

“…Day 3 parasitaemia was detected following AL treatment in only two of 85 participants, and this is consistent with rapid ART clearance in the studied parasite population. This largely agrees with findings from under 5 years children with uncomplicated malaria in studies from Ghana and Nigeria which all reported day 3 positive parasitaemia below 5% [ 31 , 32 ]. WWARN earlier proposed a day 3 positive parasitaemia of 5% threshold as more suitable in keeping track of ART resistance in SSA instead of the currently recommended 10% by the WHO due to high acquired immunity against the parasite in African populations and its contribution to faster parasite clearance [ 33 ].…”

Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine and prevalence of molecular markers of anti-malarial drug resistance in children in Togo in 2021

“…The study also assessed, for the first time, the efficacy of DP, a second-line treatment introduced in 2016, and demonstrated high efficacy (PCR corrected cure rates of 100% in Kouvé and Anié on day 28 and 98.9% in Kouvé and 100% in Anié on day 42, respectively). These results are similar to those reported in neighboring countries such as Ghana [ 45 ] and Benin [ 46 ], but also as well as other West African countries [ 47 – 54 ], and Central and East African countries [ 55 – 57 ]. This contrasts with recent reports of the reduced PCR-corrected cure rates of AL (< 90%) found, in the absence of a Pfkelch13 validated variants, in Burkina Faso [ 58 ], Angola [ 59 ], and the Democratic Republic of Congo [ 60 ], suggesting lumefantrine resistance.…”