title: Chloroquine resistant P. falciparum prevalence is low and unchanged between 1990 and 2005 in Guinea-Bissau: an effect of high chloroquine dosage?
abstract: Chloroquine resistant malaria was first reported in Guinea-Bissau in 1990 but chloroquine remains the most commonly used antimalarial in the country. Since 1990, we have conducted nearly annual standardized WHO in vitro micro-tests to assess chloroquine resistance. We have identified pfcrt 76T and other genetic polymorphisms in samples from 1992, 1993, 1995, 2004 and 2005. We have also monitored drug prescriptions for febrile illnesses. The mean proportion of in vitro tests indicating chloroquine resistance was 33% (range 14-54%) with the exception of an outlying value year 2000. The proportion of chloroquine resistant P. falciparum detected by in vitro testing did not increase over time. Pfcrt 76T was associated with chloroquine resistance but pfmdr1 86Y was not. The mean pfcrt 76T prevalence varied between 13% and 38%. The prevalence of SNPs at Pfcrt positions 76, 271, 326 and pfmdr1 position 86 did not change significantly between 1992 and 2005. In a health centre the median chloroquine dose prescribed for febrile illnesses between 1994 and 2003 was 63mg/kg. The genetic basis of chloroquine resistance appears to be the same in Guinea-Bissau as in other countries. Despite that, the prevalence of chloroquine resistant P. falciparum has not gradually increased between 1990 and 2005 in Guinea-Bissau. Chloroquine is commonly prescribed at more than double the normal dose in Guinea Bissau. It has previously been hypothesized that treatment with high doses of chloroquine may be effective. We discuss the possibility that the delayed spread of chloroquine resistant P. falciparum in Guinea-Bissau is the result of treatment with high and effective doses of chloroquine.
authors.affiliation: Malaria Research Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. johan.ursing@ki.se
authors.forename: Johan
authors.initials: J
authors.lastname: Ursing
authors.forename: Berit Aydin
authors.initials: BA
authors.lastname: Schmidt
authors.forename: Marianne
authors.initials: M
authors.lastname: Lebbad
authors.forename: Poul-Erik
authors.initials: PE
authors.lastname: Kofoed
authors.forename: Fransisco
authors.initials: F
authors.lastname: Dias
authors.forename: José Pedro
authors.initials: JP
authors.lastname: Gil
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology; D002738:Chloroquine / Q000008:administration & dosage* / Q000494:pharmacology*; D004351:Drug Resistance; D006169:Guinea-Bissau / Q000453:epidemiology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D013997:Time Factors
chemical_list: D000962:Antimalarials; D002738:Chloroquine