Historical trends and new surveillance of Plasmodium falciparum drug resistance markers in Angola

Abstract

Background Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) has historically posed a major threat to malaria control throughout the world. The country of Angola officially replaced CQ with artemisinin-based combination therapy (ACT) as a first-line treatment in 2006, but malaria cases and deaths have recently been rising. Many classic resistance mutations are relevant for the efficacy of currently available drugs, making it important to continue monitoring their frequency in Angola. Methods Plasmodium falciparum DNA was sampled from the blood of 50 hospital patients in Cabinda, Angola from October-December of 2018. Each infection was genotyped for 13 alleles in the genes crt, mdr1, dhps, dhfr, and kelch13, which are collectively involved in resistance to six common anti-malarials. To compare frequency patterns over time, P. falciparum genotype data were also collated from studies published from across Angola in the last two decades. Results The two most important alleles for CQ resistance, crt 76T and mdr1 86Y, were found at respective frequencies of 71.4% and 6.5%. Historical data suggest that mdr1 N86 has been steadily replacing 86Y throughout Angola in the last decade, while the frequency of crt 76T has been more variable across studies. Over a third of new samples from Cabinda were ‘quintuple mutants’ for SP resistance in dhfr/dhps, with a sixth mutation at dhps A581G present at 9.6% frequency. The markers dhfr 51I, dhfr 108N, and dhps 437G have been nearly fixed in Angola since the early 2000s, whereas dhfr 59R may have risen to high frequency more recently. Finally, no non-synonymous polymorphisms were detected in kelch13, which is involved in artemisinin resistance in Southeast Asia. Conclusions Genetic markers of P. falciparum resistance to CQ are likely declining in frequency in Angola, consistent with the official discontinuation of CQ in 2006. The high frequency of multiple genetic markers of SP resistance is consistent with the continued public and private use of SP. In the future, more complete haplotype data from mdr1, dhfr, and dhps will be critical for understanding the changing efficacy of multiple anti-malarial drugs. These data can be used to support effective drug policy decisions in Angola.

High prevalence of Pfcrt 76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia

“…In countries like Ethiopia where CQ drug pressure persists for the treatment of vivax malaria, high frequency of the mutant allele is being reported from Yemen [ 31 ], Malaysia [ 22 ], Nigeria [ 32 ], India [ 33 ], Bangladesh [ 34 ] and Angola [ 35 ]. Conversely, progressive decrease in 76T allele and recovery of K76 allele were documented particularly in sub-Saharan African countries such as Malawi [ 16 ] Tanzania [ 36 ], Kenya [ 37 ] and Uganda [ 38 ], where AL is being implemented.…”

Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated Pfdhfr and Pfdhps Alleles

“…Because they synergistically affect the same biochemical pathway, these two drugs are generally used in combination and are referred to as monotherapy. Although the SP combination has been removed from the list of first-line treatments for malaria in the majority of African countries since 2008 ( 3 ), it is currently used for the intermittent preventive treatment of malaria in pregnancy (IPTp) and the intermittent preventive treatment of malaria in infants below 5 years of age (IPTi) in most central African countries to protect mothers during pregnancy and to protect against the consequences of malaria in newborns ( 1 , 4 – 8 ).…”

Potenciais aplicações medicinais de compostos 1,2,3-triazólicos: uma revisão

“…57 Compostos derivados de pamaquina, mepacrina e principalmente de cloroquina foram, por muito tempo, bem aceitos para o tratamento da malária. 58 No entanto, para superar a resistência dos plasmódios aos medicamentos usados, a hibridização molecular vem sendo uma alternativa atrativa e os 1,2,3-triazóis vem se mostrando bons grupos conectores. 15,59,60 No que diz respeito ao caso específico da leishmaniose, há derivados 1,2,3-triazólicos com potencial atividade antileishmanial quando combinados a outros grupos como eugenol, fenol, ácido cinâmico, e naftoquinona.…”