scholarly journals Confirmed Plasmodium vivax Resistance to Chloroquine in Central Vietnam

2015 ◽  
Vol 59 (12) ◽  
pp. 7411-7419 ◽  
Author(s):  
Pham Vinh Thanh ◽  
Nguyen Van Hong ◽  
Nguyen Van Van ◽  
Melva Louisa ◽  
Kevin Baird ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Cumulative Risk ◽  
Artemisinin Resistance ◽  
Blood Levels ◽  
Radical Cure ◽  
Blood Concentrations ◽  
Content Type ◽  
Central Vietnam ◽  
Almost All ◽  
First Time

ABSTRACTPlasmodium vivaxresistance to chloroquine (CQ) is currently reported in almost all countries whereP. vivaxis endemic. In Vietnam, despite a first report onP. vivaxresistance to chloroquine published in the early 2000s,P. vivaxwas still considered sensitive to CQ. Between May 2009 and December 2011, a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine (0.5 mg/kg/day) together with 3 days of CQ (25 mg/kg). Here we report the results of the first 28-day follow-up estimating the cumulative risk ofP. vivaxrecurrences together with the corresponding CQ blood concentrations, among other endpoints. Out of 260 recruitedP. vivaxpatients, 240 completed treatment and were followed up to day 28 according to the WHO guidelines. Eight patients (3.45%) had a recurrentP. vivaxinfection, at day 14 (n= 2), day 21 (n= 1), and day 28 (n= 5). Chloroquine blood concentrations, available for 3/8 recurrent infections (days 14, 21, and 28), were above the MIC (>100 ng/ml whole blood) in all of these cases. Fever and parasitemia (both sexual and asexual stages) were cleared by day 3. Anemia was common at day 0 (35.8%), especially in children under 10 years (50%), and hemoglobin (Hb) recovery at day 28 was substantial among anemic patients (median change from day 0 to 28, +1.7 g/dl; interquartile range [IQR], +0.7 to +3.2). This report, based on CQ blood levels measured at the time of recurrences, confirms for the first timeP. vivaxCQ resistance in central Vietnam and calls for further studies using standardized protocols for accurately monitoring the extent and evolution ofP. vivaxresistance to chloroquine in Vietnam. These results, together with the mounting evidence of artemisinin resistance in central Vietnam, further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam.

scholarly journals Therapeutic Responses of Plasmodium vivax Malaria to Chloroquine and Primaquine Treatment in Northeastern Myanmar

2014 ◽  
Vol 59 (2) ◽  
pp. 1230-1235 ◽  
Author(s):  
Lili Yuan ◽  
Ying Wang ◽  
Daniel M. Parker ◽  
Bhavna Gupta ◽  
Zhaoqing Yang ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Cumulative Incidence ◽  
Therapeutic Efficacy ◽  
Cumulative Risk ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Radical Cure ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTChloroquine-primaquine (CQ-PQ) continues to be the frontline therapy for radical cure ofPlasmodium vivaxmalaria. Emergence of CQ-resistant (CQR)P. vivaxparasites requires a shift to artemisinin combination therapies (ACTs), which imposes a significant financial, logistical, and safety burden. Monitoring the therapeutic efficacy of CQ is thus important. Here, we evaluated the therapeutic efficacy of CQ-PQ forP. vivaxmalaria in northeast Myanmar. We recruited 587 patients withP. vivaxmonoinfection attending local malaria clinics during 2012 to 2013. These patients received three daily doses of CQ at a total dose of 24 mg of base/kg of body weight and an 8-day PQ treatment (0.375 mg/kg/day) commencing at the same time as the first CQ dose. Of the 401 patients who finished the 28-day follow-up, the cumulative incidence of recurrent parasitemia was 5.20% (95% confidence interval [CI], 3.04% to 7.36%). Among 361 (61%) patients finishing a 42-day follow-up, the cumulative incidence of recurrent blood-stage infection reached 7.98% (95% CI, 5.20% to 10.76%). The cumulative risk of gametocyte carriage at days 28 and 42 was 2.21% (95% CI, 0.78% to 3.64%) and 3.93% (95% CI, 1.94% to 5.92%), respectively. Interestingly, for all 15 patients with recurrent gametocytemia, this was associated with concurrent asexual stages. Genotyping of recurrent parasites at the merozoite surface protein 3α gene locus from 12 patients with recurrent parasitemia within 28 days revealed that 10 of these were the same genotype as at day 0, suggesting recrudescence or relapse. Similar studies in 70 patients in the same area in 2007 showed no recurrent parasitemias within 28 days. The sensitivity to chloroquine ofP. vivaxin northeastern Myanmar may be deteriorating.

scholarly journals Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam

2014 ◽  
Vol 58 (12) ◽  
pp. 7049-7055 ◽  
Author(s):  
Kamala Thriemer ◽  
Nguyen Van Hong ◽  
Anna Rosanas-Urgell ◽  
Bui Quang Phuc ◽  
Do Manh Ha ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clearance Rate ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Sensitivity Testing ◽  
Content Type ◽  
Parasite Clearance Time ◽  
Central Vietnam

ABSTRACTReduced susceptibility ofPlasmodium falciparumtoward artemisinin derivatives has been reported from the Thai-Cambodian and Thai-Myanmar borders. Following increasing reports from central Vietnam of delayed parasite clearance after treatment with dihydroartemisinin-piperaquine (DHA-PPQ), the current first-line treatment, we carried out a study on the efficacy of this treatment. Between September 2012 and February 2013, we conducted a 42-dayin vivoandin vitroefficacy study in Quang Nam Province. Treatment was directly observed, and blood samples were collected twice daily until parasite clearance. In addition, genotyping, quantitative PCR (qPCR), andin vitrosensitivity testing of isolates was performed. The primary endpoints were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates, qPCR clearance profiles,in vitrosensitivity results (for chloroquine, dihydroartemisinin, and piperaquine), and genotyping for mutations in the Kelch 13 propeller domain. Out of 672 screened patients, 95 were recruited and 89 available for primary endpoint analyses. The median parasite clearance time (PCT) was 61.7 h (interquartile range [IQR], 47.6 to 83.2 h), and the median parasite clearance rate had a slope half-life of 6.2 h (IQR, 4.4 to 7.5 h). The PCR-corrected efficacy rates were estimated at 100% at day 28 and 97.7% (95% confidence interval, 91.2% to 99.4%) at day 42. At day 3, theP. falciparumprevalence by qPCR was 2.5 times higher than that by microscopy. The 50% inhibitory concentrations (IC50s) of isolates with delayed clearance times (≥72 h) were significantly higher than those with normal clearance times for all three drugs. Delayed parasite clearance (PCT, ≥72 h) was significantly higher among day 0 samples carrying the 543 mutant allele (47.8%) than those carrying the wild-type allele (1.8%;P= 0.048). In central Vietnam, the efficacy of DHA-PPQ is still satisfactory, but the parasite clearance time and rate are indicative of emerging artemisinin resistance. (This study has been registered at ClinicalTrials.gov under registration no. NCT01775592.)

Determinants of Islamic banks’ profitability: international evidence

2017 ◽  
Vol 10 (3) ◽  
pp. 331-350 ◽  
Author(s):  
Ahmad T. Alharbi
Keyword(s):  
Fixed Effects ◽  
Deposit Insurance ◽  
Islamic Banks ◽  
Content Type ◽  
Operating Income ◽  
Real Gdp ◽  
Time Deposit ◽  
Fixed Effects Regression ◽  
Almost All ◽  
First Time

Purpose The purpose of this paper was to investigate the determinants of Islamic banks’ profitability using longitudinal data from 1992 to 2008 of almost all Islamic banks in the world. Design/methodology/approach An unbalanced panel data fixed-effects regression model was used. Findings The results of the study indicate that capital ratio, other operating income, GDP per capita, bank size, concentration and oil prices affected Islamic banks positively. Insurance schemes, foreign ownership and real GDP growth affected Islamic banks negatively. Research limitations/implications This study did not include data beyond 2008 (the financial crisis), which can be considered a limitation to this study. However, evidence suggests that including data beyond 2008 would not have changed the outcome of the study[1]. Originality/value The paper adds to the literature on the determinants of Islamic banks’ profitability for the reasons mentioned above. In addition, this study used a purified sample of Islamic banks (see the Data section for details). Furthermore, to the author’s knowledge, this is the first time deposit insurance has been included in a study related to Islamic banks’ profitability.

Mapping lean experiences and emerging connections with clinical risk management in Italian context

2015 ◽  
Vol 21 (5) ◽  
pp. 1091-1116 ◽  
Author(s):  
Maria Crema ◽  
Chiara Verbano
Keyword(s):  
Risk Management ◽  
Web Sites ◽  
Clinical Risk Management ◽  
Content Type ◽  
Clinical Risk ◽  
Multiple Challenges ◽  
Italian Context ◽  
Almost All ◽  
First Time

Purpose – The purpose of this paper is to describe the Italian state of art of Health Lean Management (HLM) and to analyze the Italian projects that connect this approach with clinical risk management (CRM). Design/methodology/approach – After introducing Italian healthcare system and its main challenges, relevant Italian experiences have been searched investigating regional health plans (RHPs), managerial reports, books, workshops, conference proceedings and hospital web sites. The degree of experience of each Italian region has been first studied. Further, field of applicability, objectives, tools, practices and results of the projects with first signs of HLM and CRM integration have been analyzed. Findings – Although interest in new managerial approaches is spreading in almost all the territory and new managerial solutions are fostered in many RHPs, HLM projects are implemented patchy in Italy. For what regards HLM projects with CRM connections, the Italian context seems aligned with the international one, apart from few features. First indications for the implementation of HLM projects with CRM connections emerged. Originality/value – Healthcare systems are facing multiple challenges in a context where public funds decrease but quality of care must be guaranteed. Combining different managerial approaches could solve these issues. In this research, for the first time, a map about Italian HLM adoption has been drawn, and Italian HLM projects with CRM connections have been analyzed. The results constitute one of the first contributions useful to develop guidelines for the implementation of projects pursuing efficiency, quality and safety objectives.

scholarly journals Limited Polymorphism of the Kelch Propeller Domain in Plasmodium malariae and P. ovale Isolates from Thailand

2016 ◽  
Vol 60 (7) ◽  
pp. 4055-4062 ◽  
Author(s):  
Supatchara Nakeesathit ◽  
Naowarat Saralamba ◽  
Sasithon Pukrittayakamee ◽  
Arjen Dondorp ◽  
Francois Nosten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Severe Malaria ◽  
Malaria Control ◽  
Artemisinin Resistance ◽  
Plasmodium Malariae ◽  
The Other ◽  
Content Type ◽  
Functional Consequences ◽  
First Time

ABSTRACTArtemisinin resistance inPlasmodium falciparum, the agent of severe malaria, is currently a major obstacle to malaria control in Southeast Asia. A gene named “kelch13” has been associated with artemisinin resistance inP. falciparum. The orthologue of thekelchgene inP. vivaxwas identified and a small number of mutations were found in previous studies. Thekelchorthologues in the other two human malaria parasites,P. malariaeandP. ovale, have not yet been studied. Therefore, in this study, the orthologouskelchgenes ofP. malariae,P. ovale wallikeri, andP. ovale curtisiwere isolated and analyzed for the first time. The homologies of thekelchgenes ofP. malariaeandP. ovalewere 84.8% and 82.7%, respectively, compared to the gene inP. falciparum.kelchpolymorphisms were studied in 13P. malariaeand 5P. ovaleisolates from Thailand. There were 2 nonsynonymous mutations found in these samples. One mutation was P533L, which was found in 1 of 13P. malariaeisolates, and the other was K137R, found in 1 isolate ofP. ovale wallikeri(n= 4). This result needs to be considered in the context of widespread artemisinin used within the region; their functional consequences for artemisinin sensitivity inP. malariaeandP. ovalewill need to be elucidated.

scholarly journals Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax

2015 ◽  
Vol 83 (8) ◽  
pp. 3083-3095 ◽  
Author(s):  
Bo Wang ◽  
Feng Lu ◽  
Yang Cheng ◽  
Jun-Hu Chen ◽  
Hye-Yoon Jeon ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protein Microarray ◽  
Expression System ◽  
Membrane Structures ◽  
Igg Antibody ◽  
Content Type ◽  
Seropositive Rate ◽  
A Cell ◽  
The Mean ◽  
First Time

Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rodent malaria parasites. TRAgs have been proposed as candidate antigens for potential vaccines. ThePlasmodium vivaxTRAg (PvTRAg) family includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C-terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluorescence analysis suggest that PvTRAgs are, at least in part, associated with caveola-vesicle complexes, a unique structure ofP. vivax-infected erythrocytes. The mechanism of formation and the function of these abundant membrane structures are not known. Further investigation aimed at determining the functions of these proteins would lead to a better understanding of the blood-stage biology ofP. vivax.

scholarly journals KAI407, a Potent Non-8-Aminoquinoline Compound That Kills Plasmodium cynomolgi Early Dormant Liver Stage ParasitesIn Vitro

2013 ◽  
Vol 58 (3) ◽  
pp. 1586-1595 ◽  
Author(s):  
Anne-Marie Zeeman ◽  
Sandra M. van Amsterdam ◽  
Case W. McNamara ◽  
Annemarie Voorberg-van der Wel ◽  
Els J. Klooster ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Inhibitory Concentration ◽  
Radical Cure ◽  
Malaria Prophylaxis ◽  
Activity Profile ◽  
Liver Stage ◽  
Content Type ◽  
Plasmodium Cynomolgi ◽  
Malaria Eradication

ABSTRACTPreventing relapses ofPlasmodium vivaxmalaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay ofin vitro-cultured hypnozoite forms ofPlasmodium cynomolgi(an excellent and accessible model forPlasmodium vivax). In this assay, primary rhesus hepatocytes are infected withP. cynomolgisporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class forP. vivaxmalaria prophylaxis and potentially a radical cure.

scholarly journals Novel Insights into Plasmodium vivax Therapeutic Failure: CYP2D6 Activity and Time of Exposure to Malaria Modulate the Risk of Recurrence

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Ana Carolina Rios Silvino ◽  
Flora Satiko Kano ◽  
Marcelo Azevedo Costa ◽  
Cor Jesus Fernandes Fontes ◽  
Irene Silva Soares ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Risk Ratio ◽  
Recurrence Risk ◽  
Therapeutic Failure ◽  
Radical Cure ◽  
Cyp2d6 Activity ◽  
Content Type ◽  
Risk Of Recurrence ◽  
Malaria Exposure ◽  
Recurrence Risk Ratio

ABSTRACT Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination.

scholarly journals Exposure-Response Analyses for Tafenoquine after Administration to Patients with Plasmodium vivax Malaria

2015 ◽  
Vol 59 (10) ◽  
pp. 6188-6194 ◽  
Author(s):  
David Tenero ◽  
Justin A. Green ◽  
Navin Goyal
Keyword(s):  
Plasmodium Vivax ◽  
Regression Tree ◽  
Classification And Regression Tree ◽  
Radical Cure ◽  
Pivotal Phase ◽  
Time Curve ◽  
Content Type ◽  
Cart Analysis ◽  
Exposure Response ◽  
Time To Relapse

ABSTRACTTafenoquine (TQ), a new 8-aminoquinoline with activity against all stages of thePlasmodium vivaxlife cycle, is being developed for the radical cure of acuteP. vivaxmalaria in combination with chloroquine. The efficacy and exposure data from a pivotal phase 2b dose-ranging study were used to conduct exposure-response analyses for TQ after administration to subjects withP. vivaxmalaria. TQ exposure (i.e., area under the concentration-time curve [AUC]) and region (Thailand compared to Peru and Brazil) were found to be statistically significant predictors of clinical response based on multivariate logistic regression analyses. After accounting for region/country, the odds of being relapse free at 6 months increased by approximately 51% (95% confidence intervals [CI], 25%, 82%) for each 25-U increase in AUC above the median value of 54.5 μg · h/ml. TQ exposure was also a significant predictor of the time to relapse of the infection. The final parametric, time-to-event model for the time to relapse, included a Weibull distribution hazard function, AUC, and country as covariates. Based on the model, the risk of relapse decreased by 30% (95% CI, 17% to 42%) for every 25-U increase in AUC. Monte Carlo simulations indicated that the 300-mg dose of TQ would provide an AUC greater than the clinically relevant breakpoint obtained in a classification and regression tree (CART) analysis (56.4 μg · h/ml) in more than 90% of subjects and consequently result in a high probability of being relapse free at 6 months. This model-based approach was critical in selecting an appropriate phase 3 dose. (This study has been registered at ClinicalTrials.gov under registration no. NCT01376167.)

Do hospitals earn their nonprofit status? Evidence from New Hampshire in 2012

2018 ◽  
Vol 30 (1) ◽  
pp. 69-85
Author(s):  
Catherine Plante ◽  
Linda Ragland
Keyword(s):  
Best Interest ◽  
Charity Care ◽  
Nonprofit Hospitals ◽  
Content Type ◽  
The Difference ◽  
Almost All ◽  
First Time ◽  
True Measure ◽  
Practical Implications ◽  
Hospital Research

Purpose The purpose of this paper is to add to the stream of research examining the difference between the amount of taxes waived for nonprofit hospitals and the amount of charity care they provide. Design/methodology/approach The study is an archival study. Findings Almost all nonprofit hospitals in the sample provide enough charity care to cover their waived taxes. Almost none provide enough charity care at the level that has been proposed to the federal government for hospitals to maintain their nonprofit status. Research limitations/implications As with most hospital research, a limitation is this study’s focus on a single state to control for regulatory differences among states. Practical implications The data on the new Form 990 allow better measurement and transparency regarding a nonprofit hospital’s charity care. For legislators, regulators, and taxpayers, the results from this study raise questions about: the large variations in the amount of charity care provided among nonprofit hospitals and whether enough is being done in terms of providing charity care. Social implications There is great variation among nonprofit hospitals as to the amount of charity care provided. Relying upon a nonprofit hospital’s altruistic nature may not be enough to ensure that they act in the best interest of society. Originality/value This study is unique because, for the first time, a true measure of taxes waived is used in the analysis. All previous research has had to proxy taxes.

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