RESUMO
To investigate the effects of quinine on the electroretinograms (ERGs) of children with cerebral malaria (CM), we recruited subjects during a single malaria season in Blantyre, Malawi. Seventy ERG investigations were performed, on 34 children with CM. Time recorded from completion of the most recent quinine infusion was termed "quinine elapsed time" (QET). In a subgroup of 16 children, whole-blood quinine concentrations were estimated in a sample of capillary blood, for validation. A significant positive association was found between QET and both maximal-response A-wave amplitude (MRAWA; P=.03) and cone A-wave amplitude (P=.04). Longitudinal analysis demonstrated a significant trend of increasing MRAWA with increasing QET (P=.03). Parenteral quinine administered in therapeutic doses to a pediatric population appears to cause a transient depression in photoreceptor function. No evidence of ocular quinine toxicity was found at the therapeutic doses used.
Assuntos
Antimaláricos/farmacologia , Eletrorretinografia , Malária Cerebral/tratamento farmacológico , Quinina/farmacologia , Retina/efeitos dos fármacos , Retina/fisiopatologia , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Criança , Feminino , Humanos , Modelos Lineares , Malária Cerebral/complicações , Masculino , Quinina/administração & dosagem , Quinina/efeitos adversos , Quinina/uso terapêutico , Retina/patologia , Doenças Retinianas/complicações , Doenças Retinianas/patologia , Doenças Retinianas/fisiopatologia , Fatores de TempoRESUMO
We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya. We assessed the presence of mutations at codons 436, 437, 540, 581, and 613 of dhps. The results showed that the dhps genotype had a strong influence on the sensitivity to sulfadoxine and dapsone, but that the correlation was far from perfect. Eleven isolates carried a wild-type dhps allele, but were resistant to sulfadoxine (IC(50) values >10 microg/ml), and 4/28 isolates were classed as sensitive to sulfadoxine (IC(50) values <10 microg/ml), but carried a triple mutant (436/437/613) allele of dhps. These data show that in low folate medium in vitro, the dhps genotype alone did not account completely for sulfadoxine or dapsone resistance; other factors such as the utilisation of exogenous folate must also be considered.