Table 1 Summary of the landscape of drug-resistant malaria in the DRC as of June 2023

Quinine

• Quinine-resistant malaria was not confirmed, since there is still no validated molecular marker; but it was only suspected given several isolates carrying PfCRT K76T and PfMDR-1 D1246Y mutations

Lumefantrine

• Lumefantrine-resistant malaria was suspected given isolates potentially carrying PfMDR1 the NFD haplotype which consists of N86, Y184F, and D1246 (but there is still no know validated marker for this resistance)

Mefloquine

• Mefloquine-resistant malaria was not detected as no isolate was detected with amplified copy numbers of pfmdr1 and pfmdr2 genes

Chloroquine

• Median 32.4% [IQR: 45.6] of isolates were chloroquine resistant as they carried a PfCRT K76T mutation predominately onto a background with CVIET haplotypes

• PfCRT K76T carriage by parasites substantially decreased from 2000 to 2020

• Wide geographic variations in the prevalence of PfCRT K76T parasites, however, was persisting in 2020 (1.8 to 89.5%) with increased risks of rebound due to the massive reintroduction and misuse of chloroquine for putative treatment or prevention of COVID-19

Amodiaquine

• Amodiaquine-resistant malaria was not confirmed as no parasite isolate carried a PfCRT SVMNT haplotype, but it was suspected, since up several isolates carried PfCRT N86Y and D1246Y mutations (and, therefore, possibly encoded the YYY haplotype consisting of N86Y, Y184 and D1246Y)

Piperaquine

• Piperaquine-resistant malaria was not explored (i.e., corresponding PfCRT mutations and gene amplification for PfPM2 and PfPM3 were not analyzed)

Artemisinin and derivatives

• Artemisinin-resistant malaria was not established as only a single isolate (sampled in 2013–2014) was detected with a R561H mutation that mediates for resistance. However, there is significant risk of local emergence or regional expansion of ART-resistant parasites from neighboring countries with reported emerging resistance (e.g., Uganda, Rwanda, and Tanzania) or from sites found with reduced levels of drug efficacy with ACTs

• Isolates harboring mutations that structurally mimic known molecular markers of artemisinin resistance need to be monitored and investigated

Pyronaridine

• Pyronaridine-resistant malaria was not explored, since corresponding mutations of the PfMRP1 were not analyzed

Proguanil

• The genetic background of the parasites suggests that proguanil-resistant malaria is very common (e.g., > 70% of parasites carry PfDHFR S108N, N51I, and C59R), suggesting caution in the use of a chemoprophylaxis including PRO (e.g., PRO–AV combination) when traveling to the DRC

Sulfadoxine–Pyriméthamine (S–P)

• S–P-resistant malaria was widespread at high frequencies but with a moderate molecular profile (PfDHPS A437G: 88.0% [IQR: 33.6]; PfDHPS K540E: 38.9% [IQR: 47.7])

• Quintuple mutants (i.e., IRN–GE) were identified in 13.1% of parasites with highest prevalence in areas located in East parts of the country