Asymptomatic Malaria Gametocyte levels in Kenya: An observational survey

肯尼亚无症状疟疾配子体水平：一项观察性调查

• 批准号: 8860724
• 负责人: Brian T. Grimberg
• 金额: $ 39.78万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8860724
• 关键词: Acute; Address; Adult; Aftercare; Antimalarials; Beds; Biomedical Engineering; Blood; Blood specimen; Cells; Clinic; Clinical; Communicable Diseases; Communities; Complex; Country; Data; Data Analyses; Detection; Developing Countries; Development; Devices; Diagnosis; Diagnostic; Disease; Economics; Epidemiology; Goals; Health; Hospitals; Incidence; Individual; Infection; Insecticides; Intervention; Kenya; Laboratory Study; Lead; Life; Light; Linear Models; Magnetism; Malaria; Measures; Medical Research; Metabolic Clearance Rate; Methodology; Methods; Microscopy; Mission; Modeling; Monitor; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Noise; Observational Study; Optics; Parasitemia; Parasites; Patient Self-Report; Patients; Polymerase Chain Reaction; Population; Population Surveillance; Prevalence; Property; Public Health; Recommendation; Reporting; Research Institute; Reverse Transcription; Sampling; Seasons; Sensitivity and Specificity; Signal Transduction; Site; Staining method; Stains; Surveys; Symptoms; Testing; Time; Work; artemether; base; benflumetol; cost effective; data modeling; hemozoin; improved; insight; light microscopy; magnetic field; malaria transmission; member; mortality; multidisciplinary; novel strategies; point of care; prevent; programs; public health relevance; screening; tool; transmission process; vector

 DESCRIPTION (provided by applicant): More than three billion people live with the threat of malaria throughout the world, which results in a significant impact on the economic stability of developing countries and subsequently on the global economy. While improvements in terms of morbidity, mortality, and transmission have been achieved in the past 5 years, malaria parasites continue to evade elimination. Our long term goal is to aid global malaria elimination efforts through improved detection, diagnosis, and treatment. We hypothesize that the issue of ongoing malaria transmission can be addressed through better assessment of total malaria prevalence (overall) and a more accurate determination of gametocyte prevalence (specific). Without this kind of information many elimination efforts will fail. Our multidisciplinary team of malariologist, physicists, and biomedical engineers exploited the magnetic properties of malaria pigment, hemozoin, to develop a device that utilizes magneto-optical detection (MOD) of hemozoin thereby avoiding staining and microscopy-based examination of patient blood. This inexpensive, portable MOD device uses alternating magnetic fields to align hemozoin so that it blocks transmitted light in proportion to parasitemia (R2=0.9997). Laboratory studies of the MOD device have optimized signal to noise ratios to detect parasitemia < 0.00002% (<1 parasitized cells/µL) with a sensitivity of 94% in less than 1 minute. Further, to determine the levels of gametocytemia we will perform quantitative reverse transcription polymerase chain reaction (qRT-PCR) on samples which are positive for malaria by MOD. In accordance with the malERA Consultative Group on Diagnosis and Diagnostics recommendations, we will use our methodology (MOD) to conduct population surveillance for active case detection of very low levels of Plasmodium infection to help identify asymptomatic individuals contributing to malaria transmission. Evaluating large numbers of asymptomatic individuals over time will provide the first opportunity to assess the levels of gametocytes in a large population. In conjunction with clinical malaria prevalence and vector intervention we will be able to more effectively model the potential for ongoing malaria transmission. Therefore, this proposal will provide insights needed to predict the potential for resurgence of malaria transmission in endemic regions, which, ultimately, may lead to improved treatment and eradication efforts.

 描述(申请人提供)：全世界有30多亿人生活在疟疾的威胁下，这对发展中国家的经济稳定以及随后对全球经济造成了重大影响。虽然在过去5年中在发病率、死亡率和传播率方面取得了改善，但疟疾寄生虫仍在逃避消灭。我们的长期目标是通过改进检测、诊断和治疗来帮助全球消除疟疾的努力。我们假设，可以通过更好地评估疟疾总流行率(总体)和更准确地确定配子体流行率(具体)来解决持续的疟疾传播问题。如果没有这种信息，许多消除努力将失败。我们由疟疾专家、物理学家和生物医学工程师组成的多学科团队利用疟疾色素血球蛋白的磁性开发了一种设备，该设备利用血球蛋白的磁光检测(MOD)，从而避免了对患者血液的染色和基于显微镜的检查。这种价格低廉的便携式MOD设备使用交变磁场来对准血球蛋白，从而按照寄生虫血症的比例阻挡透射光(R2=0.9997)。对MOD设备的实验室研究优化了信噪比，在不到1分钟的时间内检测出寄生虫血症&lt；0.00002%(&lt；1个寄生细胞/µL)，灵敏度为94%。此外，为了确定配子细胞症的水平，我们将对MOD检测呈疟疾阳性的样本进行定量逆转录聚合酶链式反应(qRT-PCR)。根据马雷拉诊断和诊断咨询小组的建议，我们将使用我们的方法(MOD)进行人口监测，以发现极低水平的疟疾感染的活跃病例，以帮助识别导致疟疾传播的无症状个人。随着时间的推移，评估大量无症状个体将提供第一次机会来评估大量人群中配子细胞的水平。结合临床疟疾流行和病媒干预，我们将能够更有效地模拟疟疾持续传播的可能性。因此，这项提案将提供必要的见解，以预测疟疾传播在流行地区死灰复燃的可能性，这最终可能导致改善治疗和根除努力。