MALARIA: Emergence of artemisinin-resistant malaria on the western border of Thailand:

Aung Pyae Phyo MD a b, Standwell Nkhoma PhD c, Kasia Stepniewska PhD a d e, Elizabeth A Ashley MD a b d, Shalini Nair MSc c, Rose McGready MD a b d, Carit ler Moo b, Salma Al-Saai MSc c, Arjen M Dondorp MD a d, Khin Maung Lwin MD b, Pratap Singhasivanon MD a, Nicholas PJ Day FRCP a d, Nicholas J White FRS a d, Tim JC Anderson PhD c, Prof François Nosten MD a b d

Summary

Background

Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand—Myanmar (Burma) border.

Methods

In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms.

Findings

3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5—2·7) in 2001, to 3·7 h (3·6—3·8) in 2010, compared with a mean of 5·5 h (5·2—5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010.

Interpretation

Genetically determined artemisinin resistance in P falciparum emerged along the Thailand—Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2—6 years.

Funding

The Wellcome Trust and National Institutes of Health.

MALARIA: Artemisinins and the biological basis for the PfATP6/SERCA hypothesis

Krishna, S., Pulcini, S., Fatih, F., Staines, H. Centre for Infection, Cellular and Molecular Medicine, St. George's University of London, Cranmer Terrace, London, SW17 0RE, United Kingdom

Abstract
With the advent of artemisinin resistance, it is timely to revisit the biological basis for the controversial suggestion that this class of antimalarial exerts its activity by inhibiting a calcium ATPase (PfATP6) that is most similar to sarcoplasmic endoplasmic reticulum calcium ATPases (SERCAs). Herein, evidence is discussed that relates to this hypothesis as alternative suggestions for how artemisinins might act have been reviewed elsewhere.

http://www.scopus.com/record/display.url?eid=2-s2.0-77957906346&origin=inward&txGid=ySsOrTI335qQwM-DKjDpUFD%3a2

MALARIA: Interview with Nicholas White, Professor of Tropical Medicine, Mahidol University, Bangkok

01 February 2011

Professor White is a recognised world authority on artemesinin combination therapy treatments for malaria, and on the development of artemesinin resistance. In a distinguished career he has received many awards, including last year the Canada Gairdner award, which recognised his “definitive clinical studies on the effectiveness of artemesinins in the treatment of malaria and elucidating the basis for the use of ACT to prevent resistance”.
MP3 format

http://www.malarianexus.com/articles/read/131/interview-with-nicholas-white-professor-of-tropical-medicine-mahidol-university-bangkok/

MALARIA: Stepping up to tackle drug-resistant malaria at the source

from: The Lancet 22 December 2010

 Flickr/DFID – UK Department for International Development
50 years ago, chloroquine-resistant malaria spread to Africa and killed millions of children.

Gains to control and eliminate malaria will be jeopardised by growing drug resistance in western Cambodia unless the global health community initiates a speedy, scientifically sound and coordinated response, says Nicholas J. White.
The emergence of resistance to artemisinin — a drug used to combat infections with the malaria parasite Plasmodium falciparum — mirrors the emergence of resistance to a different drug, chloroquine, which arose in the same part of Cambodia 50 years ago. It then spread quickly to Africa killing millions of children.
The only way to ensure that artemisinin-resistant malaria does not reach the rest of the tropical world might be to eliminate P. falciparum malaria at its source, at least temporarily, argues White. The affected part of Cambodia is geographically separated from other malarial areas, so this should prove possible, he says.
White pinpoints three questions to consider in deciding a course of action. Is enough being done to counter the threat, has artemisinin-resistant malaria spread already and is a truly radical approach to disease control justified?
If artemisinin resistance spreads widely, current strategies against malaria will be made redundant, he says.
The world has shown a limited ability to respond rapidly and effectively to global threats from infectious diseases. A 'passive model' of response — where individual countries make funding proposals to the Global Fund to Fight Aids, Tuberculosis and Malaria, for example — seems too "hit-and-miss", says White. He suggests that affected countries are involved in finding a solution, that the WHO takes a strong lead to tackle the problem and that high-level political backing for this effort is essential.
http://www.scidev.net/en/opinions/stepping-up-to-tackle-drug-resistant-malaria-at-the-source-1.html