Abstract
BackgroundBoth chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are failing drugs in much of sub-Saharan Africa. Previous findings suggest an association between resistance to CQ and to SP in vivo, in vitro, and on the molecular level.MethodsIn 126 Ghanaian children with uncomplicated malaria, associations between mutations conferring resistance in the Plasmodium falciparum dihydrofolate reductase (dhfr; SP) and chloroquine resistance transporter (crt; CQ) genes, concentrations of residual antimalarial drugs, and gametocyte carriage were examined.ResultsMutant dhfr alleles and the CQ-resistance allele crt T76 were strongly associated with each other. Isolates exhibiting the dhfr triple mutation seven times more likely also contained crt T76 parasites as compared to isolates without the dhfr triple variant (P = 0.0001). Moreover, both, isolates with the dhfr triple mutation (adjusted OR, 3.2 (95%CI, 1.0–10.4)) and with crt T76 (adjusted OR, 14.5 (1.4–150.8)) were associated with an increased likelihood of pre-treatment gametocytaemia. However, crt T76 did not correlate with gametocytaemia following SP treatment and no selection of crt T76 in SP treatment failure isolates was observed.ConclusionThese results confirm an association between CQ and SP resistance markers in isolates from northern Ghana. This could indicate accelerated development of resistance to SP if CQ resistance is already present, or vice versa. Considering the enhanced transmission potential as reflected by the increased proportion of isolates containing gametocytes when resistant parasites are present, co-resistance can be expected to spread in this area. However, the underlying mechanism leading to this constellation remains obscure.
Highlights
Both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are failing drugs in much of sub-Saharan Africa
These results confirm an association between CQ and SP resistance markers in isolates from northern Ghana
Considering the enhanced transmission potential as reflected by the increased proportion of isolates containing gametocytes when resistant parasites are present, co-resistance can be expected to spread in this area
Summary
Both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are failing drugs in much of sub-Saharan Africa. Previous findings suggest an association between resistance to CQ and to SP in vivo, in vitro, and on the molecular level. In several East African countries where SP was introduced in response to intense CQ-resistance, the drug has gradually lost efficacy the pace of this development is subject to controversy [5,6]. Studies in murine models [11] and in vitro [12,13] support this hypothesis. If this was true, the spread of CQ resistance could pave the way for an accelerated development of SP resistance, and bear substantial importance to the health systems of affected regions. Transmission potential may be increased in both SP and CQ resistant parasites [14,15]
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