Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial

Background: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. Methods and findings: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%–10.4%) after CQ treatment and 0% (95% CI 0%–4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%–20.6%) following AL alone and 2.3% (95% CI 0.6%–9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%–28.0%) after CQ, 1.2% (95% CI 0.2%–8.0%) after CQ+PQ, 29.9% (95% CI 21.6%–40.5%) after AL, and 5.9% (95% CI 2.4%–13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0–3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9–9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6–11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia. Conclusions: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y

Assessing the preferences of plant breeders for utilization, benefit sharing and priorization of conservation of wild rice relatives in Sri Lanka

The purpose of this study was to assess empirically the preferences of plant breeders for utilization, benefit sharing and conservation of the genetic resources of Wild Rice Relatives (WRR) in Sri Lanka. The “Choice Experiment Models” (CEM), i.e. stated preference method uses to obtain Option Values for non-market goods by exploring the individuals’ stated behavior in a hypothetical setting, were employed with the primary data collected from a panel of reputed plant breeders (n = 30) work at the administrative capacity in various reputed academic and research institutions in Sri Lanka. The data collection process was characterized by a face-to-face interview with each breeder during March to May 2009, which was supported by a structured questionnaire designed specifically for the CEM. The outcome of analysis shows that, from the breeders’ point of view, the benefit for an individual, in general, for conserving WRR for the future is nearly Rs. 10. Given the facts that there are not much significant direct uses of WRR revealed to date; there exists yet unrevealed benefits to the society (e.g. use of favorable genes in WRR to improve the quality of cultivated rice varieties), and the outcome of previous studies divulge that the gene sequence of different WRR populations belong to different geographical area varies significantly, the option value derived through this analysis implies that conservation of WRR can be done in-situ effectively, if people reside close to the areas where they are growing predominately would like to contribute more than the value that the scientists expected. The results highlight the importance of carrying out extensive economic research program focusing of the people adjacent to the areas where WRR growing to estimate such values as so would facilitate setting up alternative institutional arrangements (i.e. public / private) work for effective conservation of CWR, in general, and WRR, in particular

Economic valuation of conservation of genetic resources of wild rice relatives : Assessing the preferences of adjacent community for conserving Oryza granulata in the Wavulpane area

This study was aimed to achieve the specific objective of assessing the preferences of adjacent communities for utilization, benefit sharing and conservation of the genetic resources of Wild Rice Relatives (WRR) in Sri Lanka and to explore the capability of setting the priorities for conservation and management of WRR based on these preferences. The “Wavulpane” village located in the Rathnapura district was selected as the case as: (a) it was reported to be one of the growing areas for the WRR of Oriza granulata, and (b) there were no weedy rice problems prevailing in this village. The “Choice Experiment Models” (CEM) [i.e. stated preference method used to obtain Option Values for non-market goods by exploring the individuals’ stated behavior in a hypothetical setting] were applied. The data were collected from 50 individuals who were well aware of the presence and potential importance of this particular WRR through a Participatory Community Appraisal (PCA) carried out with the support of a structured questionnaire designed specifically for the CEM. Outcome of the Choice Experiment, which used a Fractional Factorial Design to array four attributes and three levels in the choice sets orthogonally, shows that an individual in an adjacent community was Willing-To-Pay nearly Rs. 82 per year for in-situ conservation of WRR. The need of the hour is, therefore, to develop appropriate policy and institutional framework that works for this task to which both short and long term policies as well as stakeholder participation should be guaranteed (i.e. research stations, universities, NGOs

Correction: Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002299.]

Hazard ratios and incidence rate ratios.

<p>Hazard ratios and incidence rate ratios.</p

Cumulative risk of <i>P</i>. <i>vivax</i> recurrence in all four treatment arms over the entire follow-up time.

<p>AL, artemether-lumefantrine; AL+PQ, artemether-lumefantrine + primaquine; CQ, chloroquine; CQ+PQ, chloroquine + primaquine.</p

Baseline characteristics of the study population.

<p>Baseline characteristics of the study population.</p

CONSORT flowchart of patient allocation for the day 42 outcome.

<p>AL, artemether-lumefantrine; AL+PQ, artemether-lumefantrine + primaquine; CQ, chloroquine; CQ+PQ, chloroquine + primaquine; G6PD, glucose-6-phosphate dehydrogenase; Lost, lost to follow-up.</p

Treatment failure and risk and incidence of recurrent parasitaemia.

<p>Treatment failure and risk and incidence of recurrent parasitaemia.</p

Parasite and fever clearance by treatment arm.

<p>Parasite and fever clearance by treatment arm.</p