Low-grade sulfadoxine–pyrimethamine resistance in Plasmodium falciparum parasites from Lubango, Angola

Autor: Filomeno Fortes, Maria de Fátima Ferreira-da-Cruz, Natália Ketrin Almeida-de-Oliveira, Bianca E Gama, Larissa Rodrigues Gomes, Elsa P. S. Kaingona-Daniel, Didier Menard, Cláudio Tadeu Daniel-Ribeiro
Přispěvatelé: Pesquisa em Malária [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centro de Pesquisa, Diagnóstico e Treinamento em Malária [Rio de Janeiro] (CPD-MAL), Hôpital Central António Agostinho Neto [Lubango, Angola], Health Progress and Investigation Network of the Portuguese-Speaking Countries Community [Lisbon] (RIDESMal/CPLP), Instituto Nacional de Câncer [Rio de Janeiro, Brésil], Angolan National Malaria Control Programme (NMCP), National Institute of Public Health [Angola] (NPHI-Angola), Ministério da Saúde [Luanda, Angola]-Ministério da Saúde [Luanda, Angola], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), CTDR and MFFC are recipients of a Research Productivity Fellowship from the National Brazilian Council for Scientific and Technological Development (CNPq) and from the Foundation for Research Support in the State of Rio de Janeiro (Faperj) as 'Cientistas do Nosso Estado'., We thank all the patients who voluntarily agreed in participate in this work, as well as the Angolan Ministry of Health and FESA (Eduardo dos Santos Foundation).
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
MESH: Sequence Analysis
DNA
medicine.medical_treatment
Drug Resistance
Protozoan Proteins
DHPS
MESH: Tetrahydrofolate Dehydrogenase
Gene mutation
Polymerase Chain Reaction
pfdhfr
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Genotype
Malaria
Falciparum
MESH: Dihydropteroate Synthase
MESH: Protozoan Proteins
MESH: Plasmodium falciparum
MESH: Malaria
Falciparum
3. Good health
MESH: Angola
Drug Combinations
Infectious Diseases
Pyrimethamine
MESH: Drug Resistance
medicine.drug
MESH: Mutation
Sulfadoxine
pfdhps
MESH: Pyrimethamine
Plasmodium falciparum
030231 tropical medicine
030106 microbiology
Biology
P. falciparum
Antimalarials
03 medical and health sciences
parasitic diseases
MESH: Polymorphism
Genetic
medicine
Humans
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
MESH: Drug Combinations
Dihydropteroate Synthase
Polymorphism
Genetic
MESH: Humans
Research
Haplotype
MESH: Polymerase Chain Reaction
Sequence Analysis
DNA
biology.organism_classification
Virology
MESH: Antimalarials
Sulfadoxine/pyrimethamine
Malaria
Tetrahydrofolate Dehydrogenase
Angola
Mutation
Parasitology
MESH: Sulfadoxine
Zdroj: Malaria Journal
Malaria Journal, BioMed Central, 2016, 15 (1), pp.309. ⟨10.1186/s12936-016-1358-7⟩
ISSN: 1475-2875
DOI: 10.1186/s12936-016-1358-7⟩
Popis: International audience; BACKGROUND: Malaria is a major parasitic disease, affecting millions of people in endemic areas. Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious. This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine-pyrimethamine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recommended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparum dhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively.METHODS: Blood samples from 52 falciparum patients were collected in Lubango, Angola and pfdhfr and pfdhps polymorphisms were analysed using nested-PCR and DNA sequencing.RESULTS: In the pfdhfr gene, the 108N mutation was almost fixed (98 %), followed by 59R (63 %), 51I (46 %), 50R and 164L (2 %, respectively). No 16V/S mutations were found. The most common double mutant genotype was CNRN (59 + 108; 46 %), followed by CICN (51 + 108; 29 %) whereas IRN (51 + 59 + 108; 15 %), CNRNVL (59 + 108 + 164; 2 %) and RICN (50 + 51 + 108; 2 %) triple mutant genotypes were detected. Investigations of the pfdhps gene showed that the 437G mutation was the most prevalent (97 %). Only two and one samples disclosed the 540E (7 %) and the 436A (3 %), respectively. Single mutant SGKAA (437; 86 %) was higher than SGEAA (437 + 540; 7 %) or AGKAA (436 + 437; 3 %) double mutants genotypes. No polymorphism was detected at codons 581G and 613T/S. Combining pfdhfr and pfdhps alleles two triple mutant haplotypes (double mutant in dhfr and single mutant in dhps) were observed: the ACICNVI/SGKAA in 14 (56 %) samples and the ACNRNVI/SGKAA in five (20 %) samples. One quadruple mutant haplotype was detected (ACIRNVI/SGKAA) in six (24 %) P. falciparum samples. No quintuple pfdhfr-pfdhps mutant was noted.CONCLUSION: pfdhfr and pfdhps gene mutations in isolates from Lubango are suggestive of a low-grade SP resistance and IPT for pregnant women and infant based on SP treatment could be effective. Routine molecular studies targeting polymorphism in these two genes need to be routinely conducted at country level.
Databáze: OpenAIRE
Externí odkaz: