80 research outputs found
Piloting CareStart⢠Rapid Diagnostic Test (RDT) to promote Glucose-6-phosphate dehydrogenase (G6PD) Screening in malaria endemic community in Cambodia
Background: Primaquine (PQ) is the only FDA-approved drug for radical cure of Plasmodium vivax (P.v) malaria, but treatment can result in life-threatening hemolysis if given to a glucose-6-phosphate dehydrogenase deficient (G6PDd) patient. Therefore, the G6PD status of the patient with P.v must be known prior to prescribing PQ. However, a patientâs G6PD status in rural malaria endemic settings is generally unknown, illuminating the need for reliable point of care G6PD diagnostic tests as a prerequisite to safely administer PQ. To increase community PQ access in Cambodia, performance of CareStart⢠G6PD rapid diagnostic tests (RDTs) needs to be evaluated in healthcare workers (HCWs) and village malaria workers (VMWs).
Methods: Training materials on G6PD and PQ were developed for HCWs and VMWs, and each trainee performed G6PD RDT test on 8-12 adult male volunteers, with pre- and post-training questionnaires completed by trainees and volunteers. The performance of CareStart⢠RDT for G6PDd screening was assessed against a quantitative G6PD test (Pointe Scientific, Inc. MI, USA). Descriptive and inferential statistics were used to analyze the data.
Results:94 trainees and 960 G6PD volunteers were recruited in Oddar Meanchey province, Cambodia from December 2017 to February 2018. Of the 960 volunteers, 146 (15%) were G6PD deficient based on a quantitative test activity threshold of 30%. The sensitivity, specificity, PPV and NPV of CareStart⢠RDT were 96.8%, 95.5%, 80.2%, 99.4% for HCW/VMW trainees vs. 96.2%, 97.2%, 86.7%, and 99.3% for trained study staff in the field and 94.2%, 98.8%, 93.6% and 98.92% for experienced laboratory staff, with no statistical difference among the groups. The mean knowledge score pre-training was 33.9% (VMWs) and 56.4% (HCWs), with improvement to 89% and 90% post training (p
Conclusions: With minimal training, CareStart⢠RDT seem highly specific, feasible and a practical option for the identification of G6PDd male patients and its use may enable safer prescribing of PQ to decrease the burden of P.v relapse
Evaluation of the CareStartTM Glucose-6-phosphate dehydrogenase (G6PD) Rapid Diagnostic test at Community and Health Center level, Cambodia
Background: Primaquine (PQ) is the only FDA-approved drug for radical cure of Plasmodium vivax (P.v) malaria, but treatment can result in life-threatening hemolysis if given to a glucose-6- phosphate dehydrogenase deficient (G6PDd) patient. Therefore, the G6PD status of the patient with P.v must be known prior to prescribing PQ. However, patient G6PD status in rural malaria endemic settings is generally unknown, illuminating the need for reliable point of care G6PD diagnostic tests as a prerequisite to safely administer PQ. To increase community PQ access in Cambodia, performance of CareStartTM G6PD rapid diagnostic tests (RDTs) needs to be evaluated in healthcare workers (HCWs) and village malaria workers (VMWs).
Methods: Training materials on G6PD and PQ were developed for HCWs and VMWs and each performed G6PD RDT test on 8-12 adult male volunteers, with pre- and post-training questionnaires completed by trainees and G6PD test volunteers. The performance of CareStartTM RDT for G6PDd screening was assessed against a quantitative G6PD lab test (Pointe Scientific, Inc. MI, USA). Descriptive and inferential statistics were used to analyze the data.
Results: 94 trainees and 960 G6PD volunteers were recruited in Oddar Meanchey province, Cambodia from December 2017 to February 2018. Of the 960 volunteers, 156 (16%) were G6PD deficient based on a quantitative test activity threshold of 30%. The sensitivity, specificity, PPV and NPV of CareStart⢠RDT were 96.8%, 95.5%, 80.2%, 99.4% for HCW/VMW trainees vs. 96.2%, 97.2%, 86.7%, and 99.3% for trained study staff in the field and 94.2%, 98.8%, 93.6% and 98.92% for experienced laboratory staff, with no statistical difference among the groups. The mean knowledge score pre-training was 33.9% (VMWs) and 56.4% (HCWs), with improvement to 89% and 90% post training (p
Conclusions: With minimal training, CareStart⢠RDT is highly specific, feasible and a practical option for the identification of G6PDd male patients and its use may enable safer prescribing of PQ to decrease the burden of P.v relapse
Influence of endovascular treatment on the vascular endothelium in patients with peripheral arterial disease: a systematic review
Peripheral arterial disease (PAD) is a major public health problem. Endothelial dysfunction represents an important mechanism in the development and progression of atherosclerosis, in part attributable to inflammation, platelet and smooth muscle activation, and arterial stiffening. The aim of this study was to explore the impact of lower limb revascularization on endothelial function in patients with PAD. We performed a comprehensive search of the academic literature using the PubMed and Embase databases to screen suitable records. Following the application of our search strategies, a total of eight studies were included in this review. Despite the limited available evidence, the dearth of academic literature suggests that revascularization has a positive effect on endothelial functioning. The effects of endovascular revascularization on endothelial functioning in patients with PAD are subject to further research
Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination
Background
In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response. Methods
A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (nâ=â72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the â1â3â7â reactive case detection approach among civilians alongside a pilot â1â3â7â study conducted by the Royal Thai Army (RTA). Results
Between MayâJuly 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (MayâJuly 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79â38.29]; pâ\u3câ0.001) and infected with P. vivax (OR=2.32 [1.27â4.22]; pâ=â0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTAâs â1â3â7â study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy). Conclusions
In 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond
Understanding work-related travel and its relation to malaria occurrence in Thailand using geospatial maximum entropy modelling
Estimating malaria risk associated with work locations and travel across a region provides local health officials with information useful to mitigate possible transmission paths of malaria as well as understand the risk of exposure for local populations. This study investigates malaria exposure risk by analysing the spatial pattern of malaria cases (primarily Plasmodium vivax) in Ubon Ratchathani and Sisaket provinces of Thailand, using an ecological niche model and machine learning to estimate the species distribution of P. vivax malaria and compare the resulting niche areas with occupation type, work locations, and work-related travel routes. A maximum entropy model was trained to estimate the distribution of P. vivax malaria for a period between January 2019 and April 2020, capturing estimated malaria occurrence for these provinces. A random simulation workflow was developed to make region-based case data usable for the machine learning approach. This workflow was used to generate a probability surface for the ecological niche regions. The resulting niche regions were analysed by occupation type, home and work locations, and work-related travel routes to determine the relationship between these variables and malaria occurrence. A one-way analysis of variance (ANOVA) test was used to understand the relationship between predicted malaria occurrence and occupation type. The MaxEnt (full name) model indicated a higher occurrence of P. vivax malaria in forested areas especially along the ThailandâCambodia border. The ANOVA results showed a statistically significant difference between average malaria risk values predicted from the ecological niche model for rubber plantation workers and farmers, the two main occupation groups in the study. The rubber plantation workers were found to be at higher risk of exposure to malaria than farmers in Ubon Ratchathani and Sisaket provinces of Thailand. The results from this study point to occupation-related factors such as work location and the routes travelled to work, being risk factors in malaria occurrence and possible contributors to transmission among local populations.https://doi.org/10.1186/s12936-023-04478-
Recent trends in digital text forensics and its evaluation
The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-40802-1_28This paper outlines the concepts and achievements of our evaluation lab on digital text forensics, PAN 13, which called for original research and development on plagiarism detection, author identification, and author profiling. We present a standardized evaluation framework for each of the three tasks and discuss the evaluation results of the altogether 58 submitted contributions. For the first time, instead of accepting the output of software runs, we collected the softwares themselves and run them on a computer cluster at our site. As evaluation and experimentation platform we use TIRA, which is being developed at the Webis Group in Weimar. TIRA can handle large-scale software submissions by means of virtualization, sandboxed execution, tailored unit testing, and staged submission. In addition to the achieved evaluation results, a major achievement of our lab is that we now have the largest collection of state-of-the-art approaches with regard to the mentioned tasks for further analysis at our disposal.This work was partially supported by the WIQ-EI IRSES project (Grant No. 269180) within the FP7 Marie Curie action.Gollub, T.; Potthast, M.; Beyer, A.; Busse, M.; Rangel Pardo, FM.; Rosso, P.; Stamatatos, E.... (2013). Recent trends in digital text forensics and its evaluation. En Information Access Evaluation. Multilinguality, Multimodality, and Visualization. Springer Verlag (Germany). 282-302. https://doi.org/10.1007/978-3-642-40802-1_28S282302Aleman, Y., Loya, N., Vilarino Ayala, D., Pinto, D.: Two Methodologies Applied to the Author Profiling TaskâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Argamon, S., Juola, P.: Overview of the International Authorship Identification Competition at PAN-2011. 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In: Proc. of ICWSM 2009 (2009)Haggag, O., El-Beltagy, S.: Plagiarism Candidate Retrieval Using Selective Query Formulation and Discriminative Query ScoringâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Holmes, J., Meyerhoff, M.: The Handbook of Language and Gender. Blackwell Handbooks in Linguistics. Wiley (2003)Inches, G., Crestani, F.: Overview of the International Sexual Predator Identification Competition at PAN-2012. In: Proc. of CLEF 2012 (2012)Juola, P.: Authorship Attribution. Found. and Trends in IR 1, 234â334 (2008)Juola, P.: Ad-hoc Authorship Attribution Competition. In: Proc. of ALLC 2004 (2004)Juola, P.: An Overview of the Traditional Authorship Attribution Subtask. In: Proc. of CLEF 2012 (2012)Koppel, M., Winter, Y.: Determining if Two Documents are by the Same Author. Journal of the American Society for Information Science and Technology (to appear)Koppel, M., Argamon, S., Shimoni, A.R.: Automatically Categorizing Written Texts by Author Gender. Literary and Linguistic Computing 17(4), 401â412 (2002)Koppel, M., Schler, J., Bonchek-Dokow, E.: Measuring Differentiability: Unmasking Pseudonymous Authors. Journal of Machine Learning Research 8, 1261â1276 (2007)Koppel, M., Schler, J., Argamon, S.: Authorship Attribution in the Wild. Language Resources and Evaluation 45, 83â94 (2011)Kong, L., Qi, H., Du, C., Wang, M., Han, Z.: Approaches for Source Retrieval and Text Alignment of Plagiarism DetectionâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Lim, W.Y., Goh, J., Thing, V.L.L.: Content-centric age and gender profilingâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Pastor Lopez-Monroy, A., Montes-Y-Gomez, M., Jair Escalante, H., Villasenor-Pineda, L., Villatoro-Tello, E.: INAOEâs participation at PANâ13: Author Profiling taskâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Meina, M., Brodzinska, K., Celmer, B., Czokow, M., Patera, M., Pezacki, J., Wilk, M.: Ensemble-based Classification for Author Profiling using Various FeaturesâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Nguyen, D., Gravel, R., Trieschnigg, D., Meder, T.: âHow Old Do You Think I Am?â; A Study of Language and Age in Twitter. In: Proc. of ICWSM 2013 (2013)Nguyen, D., Smith, N.A., RosĂŠ, C.P.: Author Age Prediction from Text Using Linear Regression. In: Proc. of LaTeCH at ACL-HLTGopal Patra, B., Banerjee, S., Das, D., Saikh, T., Bandyopadhyay, S.: Automatic Author Profiling Based on Linguistic and Stylistic FeaturesâNotebook for PAN at CLEF 2013. In: Forner, et al. (eds.) [15]Peersman, C., Daelemans, W., Van Vaerenbergh, L.: Predicting Age and Gender in Online Social Networks. In: Proc. of SMUC 2011 (2011)Pennebaker, J.W.: The Secret Life of Pronouns: What Our Words Say About Us. Bloomsbury, USA (2013)Pennebaker, J.W., Mehl, M.R., Niederhoffer, K.G.: Psychological Aspects of Natural Language Use: Our Words, Our Selves. Annual Review of Psychology 54(1), 547â577 (2003)Potthast, M., Stein, B., Eiselt, A., BarrĂłn-CedeĂąo, A., Rosso, P.: Overview of the 1st International Competition on Plagiarism Detection. In: Proc. of PAN at SEPLN 2009 (2009)Potthast, M., BarrĂłn-CedeĂąo, A., Eiselt, A., Stein, B., Rosso, P.: Overview of the 2nd International Competition on Plagiarism Detection. In: Proc. of CLEF 2010 (2010)Potthast, M., Stein, B., BarrĂłn-CedeĂąo, A., Rosso, P.: An Evaluation Framework for Plagiarism Detection. In: Proc. of COLING 2010 (2010)Potthast, M., Eiselt, A., BarrĂłn-CedeĂąo, A., Stein, B., Rosso, P.: Overview of the 3rd International Competition on Plagiarism Detection. 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Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008-2014
Gametocytes are the malaria parasite stages responsible for transmission from humans to mosquitoes. Gametocytemia often follows drug treatment, especially as therapies start to fail. We examined Plasmodium falciparum gametocyte carriage and drug resistance profiles among 824 persons with uncomplicated malaria in Cambodia to determine whether prevalent drug resistance and antimalarial use has led to a concentration of drug-resistant parasites among gametocyte carriers. Although report of prior antimalarial use increased from 2008 to 2014, the prevalence of study participants presenting with microscopic gametocyte carriage declined. Gametocytemia was more common in those reporting antimalarial use within the past year, and prior antimalarial use was correlated with higher IC50s to piperaquine and mefloquine, as well as to increased pfmdr1 copy number. However, there was no association between microscopic gametocyte carriage and parasite drug resistance. Thus, we found no evidence that the infectious reservoir, marked by those carrying gametocytes, is enriched with drug-resistant parasites
Cluster-randomized trial of monthly malaria prophylaxis versus focused screening and treatment: a study protocol to define malaria elimination strategies in Cambodia
Abstract
Background
Malaria remains a critical public health problem in Southeast Asia despite intensive containment efforts. The continued spread of multi-drug-resistant Plasmodium falciparum has led to calls for malaria elimination on the Thai-Cambodian border. However, the optimal approach to elimination in difficult-to-reach border populations, such as the Military, remains unclear.
Methods/design
A two-arm, cluster-randomized controlled, open-label pilot study is being conducted in military personnel and their families at focal endemic areas on the Thai-Cambodian border. The primary objective is to compare the effectiveness of monthly malaria prophylaxis (MMP) with dihydroartemisinin-piperaquine and weekly primaquine for 12Â weeks compared with focused screening and treating (FSAT) following current Cambodian national treatment guidelines. Eight separate military encampments, making up approximately 1000 military personnel and their families, undergo randomization to the MMP or FSAT intervention for 3Â months, with an additional 3Â monthsâ follow-up. In addition, each treatment cluster of military personnel and civilians is also randomly assigned to receive either permethrin- or sham (water)-treated clothing in single-blind fashion. The primary endpoint is risk reduction for malaria infection in geographically distinct military encampments based on their treatment strategy. Monthly malaria screening in both arms is done via microscopy, PCR, and rapid diagnostic testing to compare both the accuracy and cost-effectiveness of diagnostic modalities to detect asymptomatic infection. Universal glucose-6-phosphate dehydrogenase (G6PD) deficiency screening is done at entry, comparing the results from a commercially available rapid diagnostic test, the fluorescence spot test, and quantitative testing for accuracy and cost-effectiveness. The comparative safety of the interventions chosen is also being evaluated.
Discussion
Despite the apparent urgency, the key operational elements of proposed malaria elimination strategies in Southeast Asian mobile and migrant populations, including the Military, have yet to be rigorously tested in a well-controlled clinical study. Here, we present a protocol for the primary evaluation of two treatment paradigms â monthly malaria prophylaxis and focused screening and treatment â to achieve malaria elimination in a Cambodian military population. We will also assess the feasibility and incremental benefit of outdoor-biting vector intervention â permethrin-treated clothing. In the process, we aim to define the cost-effectiveness of the inputs required for success including a responsive information system, skilled human resource and laboratory infrastructure requirements, and quality management. Despite being a relatively low transmission area, the complexities of multi-drug-resistant malaria and the movement of vulnerable populations require an approach that is not only technically sound, but simple enough to be achievable.
Trial registration
ClinicalTrials.gov, ID:
NCT02653898
. Registered on 13 January 2016
Lung transplantation in patients with pulmonary arterial hypertension: The opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation
Pulmonary arterial hypertension is a rare but progressive disease that leads to death. Modern drug treatment slows the progression of the disease and prolongs patientsâ lives, but often, even maximal treatment with parenteral prostacyclin does not prevent deterioration. In the case of inadequate clinical response to drug treatment, lung transplantation (LTx) should be considered. This article aims to analyze thoroughly indications to refer a patient for consultation with a transplant center, the optimal timing of listing for LTx, contraindications for the procedure, bridging techniques, as well as tests needed before and after transplantation. We outline the technique of the procedurÄ and evaluate psychological aspects of LTx
Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia
Abstract Background While intensive Plasmodium falciparum multidrug resistance surveillance continues in Cambodia, relatively little is known about Plasmodium vivax drug resistance in Cambodia or elsewhere. To investigate P. vivax anti-malarial susceptibility in Cambodia, 76 fresh P. vivax isolates collected from Oddar Meanchey (northern Cambodia) in 2013â2015 were assessed for ex vivo drug susceptibility using the microscopy-based schizont maturation test (SMT) and a Plasmodium pan-species lactate dehydrogenase (pLDH) ELISA. P. vivax multidrug resistance gene 1 (pvmdr1) mutations, and copy number were analysed in a subset of isolates. Results Ex vivo testing was interpretable in 80% of isolates using the pLDH-ELISA, but only 25% with the SMT. Plasmodium vivax drug susceptibility by pLDH-ELISA was directly compared with 58 P. falciparum isolates collected from the same locations in 2013â4, tested by histidine-rich protein-2 ELISA. Median pLDH-ELISA IC50 of P. vivax isolates was significantly lower for dihydroartemisinin (3.4 vs 6.3Â nM), artesunate (3.2 vs 5.7Â nM), and chloroquine (22.1 vs 103.8Â nM) than P. falciparum but higher for mefloquine (92 vs 66Â nM). There were not significant differences for lumefantrine or doxycycline. Both P. vivax and P. falciparum had comparable median piperaquine IC50 (106.5 vs 123.8Â nM), but some P. falciparum isolates were able to grow in much higher concentrations above the normal standard range used, attaining up to 100-fold greater IC50s than P. vivax. A high percentage of P. vivax isolates had pvmdr1 Y976F (78%) and F1076L (83%) mutations but none had pvmdr1 amplification. Conclusion The findings of high P. vivax IC50 to mefloquine and piperaquine, but not chloroquine, suggest significant drug pressure from drugs used to treat multidrug resistant P. falciparum in Cambodia. Plasmodium vivax isolates are frequently exposed to mefloquine and piperaquine due to mixed infections and the long elimination half-life of these drugs. Difficulty distinguishing infection due to relapsing hypnozoites versus blood-stage recrudescence complicates clinical detection of P. vivax resistance, while well-validated molecular markers of chloroquine resistance remain elusive. The pLDH assay may be a useful adjunctive tool for monitoring for emerging drug resistance, though more thorough validation is needed. Given high grade clinical chloroquine resistance observed recently in neighbouring countries, low chloroquine IC50 values seen here should not be interpreted as susceptibility in the absence of clinical data. Incorporating pLDH monitoring with therapeutic efficacy studies for individuals with P. vivax will help to further validate this field-expedient method
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