Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Malone JL[original query] |
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Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial
Abreha T , Hwang J , Thriemer K , Tadesse Y , Girma S , Melaku Z , Assef A , Kassa M , Chatfield MD , Landman KZ , Chenet SM , Lucchi NW , Udhayakumar V , Zhou Z , Shi YP , Kachur SP , Jima D , Kebede A , Solomon H , Mekasha A , Alemayehu BH , Malone JL , Dissanayake G , Teka H , Auburn S , von Seidlein L , Price RN . PLoS Med 2017 14 (5) e1002299 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01680406. |
Field assessment of dried Plasmodium falciparum samples for malaria rapid diagnostic test quality control and proficiency testing in Ethiopia
Tamiru A , Boulanger L , Chang MA , Malone JL , Aidoo M . Malar J 2015 14 (1) 11 BACKGROUND: Rapid diagnostic tests (RDTs) are now widely used for laboratory confirmation of suspected malaria cases to comply with the World Health Organization recommendation for universal testing before treatment. However, many malaria programmes lack quality control (QC) processes to assess RDT use under field conditions. Prior research showed the feasibility of using the dried tube specimen (DTS) method for preserving Plasmodium falciparum parasites for use as QC samples for RDTs. This study focused on the use of DTS for RDT QC and proficiency testing under field conditions. METHODS: DTS were prepared using cultured P. falciparum at densities of 500 and 1,000 parasites/ inverted question markL; 50 inverted question markL aliquots of these along with parasite negative human blood controls (0 parasites/ inverted question markL) were air-dried in specimen tubes and reactivity verified after rehydration. The DTS were used in a field study in the Oromia Region of Ethiopia. Replicate DTS samples containing 0, 500 and 1,000 parasites/ inverted question markL were stored at 4 degrees C at a reference laboratory and at ambient temperatures at two nearby health facilities. At weeks 0, 4, 8, 12, 16, 20, and 24, the DTS were rehydrated and tested on RDTs stored under manufacturer-recommended temperatures at the RL and on RDTs stored under site-specific conditions at the two health facilities. Reactivity of DTS stored at 4 degrees C at the reference laboratory on RDTs stored at the reference laboratory was considered the gold standard for assessing DTS stability. A proficiency-testing panel consisting of one negative and three positive samples, monitored with a checklist was administered at weeks 12 and 24. RESULTS: At all the seven time points, DTS stored at both the reference laboratory and health facility were reactive on RDTs stored under the recommended temperature and under field conditions, and the DTS without malaria parasites were negative. At the reference laboratory and one health facility, a 500 parasites/ inverted question markL DTS from the proficiency panel was falsely reported as negative at week 24 due to errors in interpreting faint test lines. CONCLUSIONS: The DTS method can be used under field conditions to supplement other RDT QC methods and health worker proficiency in Ethiopia and possibly other malaria-endemic countries. |
A description of malaria sentinel surveillance: a case study in Oromia Regional State, Ethiopia
Yukich JO , Butts J , Miles M , Berhane Y , Nahusenay H , Malone JL , Dissanayake G , Reithinger R , Keating J . Malar J 2014 13 (1) 88 BACKGROUND: In the context of the massive scale up of malaria interventions, there is increasing recognition that the current capacity of routine malaria surveillance conducted in most African countries through integrated health management information systems is inadequate. The timeliness of reporting to higher levels of the health system through health management information systems is often too slow for rapid action on focal infectious diseases such as malaria. The purpose of this paper is to: 1) describe the implementation of a malaria sentinel surveillance system in Ethiopia to help fill this gap; 2) describe data use for epidemic detection and response as well as programmatic decision making; and 3) discuss lessons learned in the context of creating and running this system. CASE DESCRIPTION: As part of a comprehensive strategy to monitor malaria trends in Oromia Regional State, Ethiopia, a system of ten malaria sentinel sites was established to collect data on key malaria morbidity and mortality indicators. To ensure the sentinel surveillance system provides timely, actionable data, the sentinel facilities send aggregate data weekly through short message service (SMS) to a central database server. Bland-Altman plots and Poisson regression models were used to investigate concordance of malaria indicator reports and malaria trends over time, respectively. DISCUSSION: This paper describes three implementation challenges that impacted system performance in terms of: 1) ensuring a timely and accurate data reporting process; 2) capturing complete and accurate patient-level data; and 3) expanding the usefulness and generalizability of the system's data to monitor progress towards the national malaria control goals of reducing malaria deaths and eventual elimination of transmission. CONCLUSIONS: The use of SMS for reporting surveillance data was identified as a promising practice for accurately tracking malaria trends in Oromia. The rapid spread of this technology across Africa offers promising opportunities to collect and disseminate surveillance data in a timely way. High quality malaria surveillance in Ethiopia remains a resource intensive activity and extending the generalizability of sentinel surveillance findings to other contexts remains a major limitation of these strategies. |
In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia
Hwang J , Alemayehu BH , Reithinger R , Tekleyohannes SG , Takele Teshi , Birhanu SG , Demeke L , Hoos D , Melaku Z , Kassa M , Jima D , Malone JL , Nettey H , Green M , Poe A , Akinyi S , Udhayakumar V , Kachur SP , Filler S . PLoS One 2013 8 (5) e63433 BACKGROUND: In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used. METHODS AND FINDINGS: In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml. CONCLUSIONS: In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT01052584. |
In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia
Hwang J , Alemayehu BH , Hoos D , Melaku Z , Tekleyohannes SG , Teshi T , Birhanu SG , Demeke L , Gobena K , Kassa M , Jima D , Reithinger R , Nettey H , Green M , Malone JL , Kachur SP , Filler S . Malar J 2011 10 (1) 209 BACKGROUND: In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004. METHODS: Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively. RESULTS: Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/ vomiting being the most common adverse events. CONCLUSIONS: AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed. TRIAL REGISTRATION: NCT01052584. |
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