TY - JOUR
T1 - Clustering of malaria treatment failure (TF) in Daraweesh: hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs
AU - Giha, Hayder A
AU - ElGhazali, Gehad
AU - Nasr, Amre
AU - Iriemenam, Nnaemeka C
AU - Berzins, Klavs
AU - Troye-Blomberg, Marita
AU - Theander, Thor G
AU - Arnot, David
N1 - Keywords: Adolescent; Adult; Antibodies, Protozoan; Antimalarials; Chi-Square Distribution; Chloroquine; Cluster Analysis; Female; Genetic Predisposition to Disease; Host-Parasite Interactions; Humans; Immunoglobulin G; Malaria, Falciparum; Male; Plasmodium falciparum; Polymorphism, Single Nucleotide; Statistics, Nonparametric; Sudan; Treatment Failure
PY - 2010/5
Y1 - 2010/5
N2 - 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; FcγRIIA 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, FcγRIIA 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.
AB - 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; FcγRIIA 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, FcγRIIA 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.
U2 - 10.1016/j.meegid.2010.02.013
DO - 10.1016/j.meegid.2010.02.013
M3 - Journal article
C2 - 20215002
SN - 1567-1348
VL - 10
SP - 481
EP - 486
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
IS - 4
ER -
