Enevold A., Nkya W.M.M.M., Theisen M., Vestergaard L.S., Jensen A.T., Staalsoe T., Theander T.G., Bygbjerg I.C., Alifrangis M.
Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Mbeya Referral Hospital (MRH), Mbeya, Tanzania; Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark; Department of Epidemiology, Statens Serum Institute, Copenhagen, Denmark
Enevold, A., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Nkya, W.M.M.M., Mbeya Referral Hospital (MRH), Mbeya, Tanzania; Theisen, M., Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark; Vestergaard, L.S., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, Department of Epidemiology, Statens Serum Institute, Copenhagen, Denmark; Jensen, A.T., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Staalsoe, T., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Theander, T.G., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Bygbjerg, I.C., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Alifrangis, M., Centre for Medical Parasitology, Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
Background. In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant Plasmodium falciparum. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of P. falciparum in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP) or amodiaquine (AQ). Methods. One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA), and IgG antibody responses to a panel of P. falciparum antigens were assessed and related to treatment outcome. Results. Parasitological or clinical treatment failure (TF) was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR) compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP)-specific IgG antibodies were significantly higher (P < 0.001), while prevalence of parasite haplotypes associated with SP and AQ resistance was lower (P = 0.02 and P = 0.07, respectively). Interestingly, anti-GLURP-IgG antibodies were more strongly associated with treatment outcome than parasite resistant haplotypes, while the IgG responses to none of the other 11 malaria antigens were not significantly associated with ACPR. Conclusion. These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity. © 2007 Enevold et al; licensee BioMed Central Ltd.
amodiaquine; fansidar; immunoglobulin G; protein antibody; glutamate rich protein, Plasmodium; glutamate-rich protein, Plasmodium; protozoal protein; protozoon antibody; pyrimethamine; sulfadoxine; sulfadoxine-pyrimethamine; unclassified drug; alpha thalassemia; antibody response; article; clinical trial; controlled clinical trial; controlled study; enzyme linked immunosorbent assay; female; gene mutation; haplotype; human; infant; major clinical study; malaria falciparum; male; oligonucleotide probe; parasite immunity; Plasmodium falciparum; polymerase chain reaction; preschool child; prevalence; randomized controlled trial; sickle cell trait; Tanzania; treatment failure; treatment outcome; animal; blood; drug combination; drug effect; drug resistance; genetics; immunocompetence; immunology; methodology; Amodiaquine; Animals; Antibodies, Protozoan; Child, Preschool; Drug Combinations; Drug Resistance; Female; Humans; Immunocompetence; Immunoglobulin G; Infant; Malaria, Falciparum; Male; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Pyrimethamine; Sulfadoxine; Tanzania; Treatment Outcome