In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C<T<A) and Hb AA/AS, polymorphisms. Results revealed that all treatment failures were experienced by 37 individual (TF-prone-individuals, TFPi), while the remaining donors were treated for 182 malaria episodes without TF (treatment responders, TR). In 7 households, all malaria patients were TFPi, while in 19 households all patients were TR. The TFPi compared with matched TR individuals (TRi), had significantly higher IgG1 levels (p=0.021), while IgG3/IgG1 ratio was significantly higher in the TRi (p=0.016). However, the frequencies of all tested polymorphisms (GM/KM, FcgammaRIIA 131, CRP 286 and Hb AA/AS), were comparable between the study groups. In conclusion, there was clustering of TF at level of individuals and households with differences in base-line immunity between the TFPi and TRi. Together, the results suggest an immune-mediated genetic susceptibility to TF, as some of the tested polymorphisms showed trends but no significant association with TF.
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