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Elizabeth Ashley

Publications and source records attributed to Elizabeth Ashley.

3 recordsLinked to original sources
PubMed2004

Seasonal variation in hyperparasitaemia and gametocyte carriage in patients with Plasmodium falciparum malaria on the Thai-Burmese border.

Between January 2000 and December 2002 monthly rainfall was correlated with the proportion of patients with hyperparasitaemic Plasmodium falciparum malaria and with the proportion of patients with P. falciparum gametocytes. During the observation period 6953 cases of P. falciparum malaria were treated at the Shoklo Malaria Research Unit in Maela refugee camp on the Thai-Burmese border. Three hundred and seventy-five of these patients had >/=4% of parasitized red blood cells. Although there were more monthly malaria cases in the rainy season, rainfall was negatively correlated with the proportion of patients with hyperparasitaemia (Spearman's rho = -0.59, P < 0.001 ), and the proportion of gametocyte carriers among P. falciparum cases, (Spearman's rho = -0.39, P = 0.018). After controlling for age and the origin of the patient, the odds ratio for developing hyperparasitaemia during the dry season was 1.6 (95% CI 1.14-2.2; P = 0.006). The adjusted odds ratio for gametocyte carriage during the dry season was 1.3 (95% CI 1.03-1.6; P = 0.02). Migrations, changes in transmission patterns, the haematological burden of cumulative infections, and ultraviolet immunosuppression are discussed as potential explanations for these observations.

Adolescent↗
PubMedDate not supplied

Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.

BACKGROUND: The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. METHODS: The relation between polymorphisms in the P falciparum multidrug resistant gene 1 (pfmdr1) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 samples from patients with falciparum malaria studied prospectively over 12 years. pfmdr1 copy number was assessed by a robust real-time PCR assay. Single nucleotide polymorphisms of pfmdr1, P falciparum chloroquine resistance transporter gene (pfcrt) and P falciparum Ca2+ ATPase gene (pfATP6) were assessed by PCR-restriction fragment length polymorphism. FINDINGS: Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine, and also to reduced artesunate sensitivity in vitro. In a Cox regression model with control for known confounders, increased pfmdr1 copy number was associated with an attributable hazard ratio (AHR) for treatment failure of 6.3 (95% CI 2.9-13.8, p<0.001) after mefloquine monotherapy and 5.4 (2.0-14.6, p=0.001) after artesunate-mefloquine therapy. Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro, but not in vivo. INTERPRETATION: Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria. RELEVANCE TO PRACTICE: Multidrug resistant P falciparum malaria is common in southeast Asia, but difficult to identify and treat. Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance. In this study we show that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with mefloquine. Increase in pfmdr1 copy number predicts failure even after chemotherapy with the highly effective combination of mefloquine and 3 days' artesunate. Monitoring of pfmdr1 copy number will be useful in epidemiological surveys of drug resistance in P falciparum, and potentially for predicting treatment failure in individual patients.

ATP-Binding Cassette Transporters↗