Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study.
Influence of rapid malaria diagnostic tests on treatment and health outcome in fever patients, Zanzibar: a crossover validation study.
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快速疟疾诊断测试对发烧患者治疗和健康结果的影响，桑给巴尔：一项跨界验证研究。
DOI：
10.1371/journal.pmed.1000070
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发表时间：
2009-04-28
期刊：
影响因子：
15.8
通讯作者：
Björkman A
中科院分区：
文献类型：
--
作者：
Msellem MI;Mårtensson A;Rotllant G;Bhattarai A;Strömberg J;Kahigwa E;Garcia M;Petzold M;Olumese P;Ali A;Björkman A
安德斯·比约克曼及其同事报告了在桑给巴尔进行的一项评估疟疾快速诊断检测的交叉试验结果。
在非洲的基层医疗环境中，有人建议使用恶性疟原虫疟疾快速诊断检测（RDT）来提高诊断效率。这种改进的诊断方法对于尽量减少过度使用抗疟药物，从而延缓青蒿素类复方疗法（ACTs）耐药性的产生至关重要。我们的目的是研究RDT辅助疟疾诊断对基层医疗环境中的药物处方、健康结果和成本的影响。
我们在桑给巴尔的四个基层医疗单位进行了一项交叉验证临床试验。过去48小时内有发热报告的所有年龄段患者均符合条件，并每隔一周交替分配到RDT辅助疟疾诊断组或仅基于症状的临床诊断（CD）组。随访时间为14天。两组中被诊断为疟疾的患者都要使用ACT治疗。采用多层模型进行统计分析。2005年2月至8月期间，共有1887名患者入组。与仅采用临床诊断相比，RDT与更低的抗疟治疗处方率相关，RDT组为361/1005（36%），临床诊断组为752/882（85%）（优势比[OR]为0.04，95%置信区间[CI]为0.03 - 0.05，p < 0.001）。RDT组使用抗生素的处方比仅临床诊断组更高，即分别为372/1005（37%）和235/882（27%）（OR为1.8，95%CI为1.5 - 2.2，p < 0.001）。RDT组因感觉临床治疗未成功而再次就诊的比例为25/1005（2.5%），低于仅临床诊断组的43/882（4.9%）（OR为0.5，95%CI为0.3 - 0.9，p = 0.005）。每位患者的总平均成本相似：RDT组和仅临床诊断组分别为2.47美元和2.37美元。
RDTs在不增加每位患者成本的情况下，提高了适当治疗水平和健康结果。RDTs可能是基层医疗环境中改善发热患者管理的一种工具。
Clinicaltrials.gov NCT00549003
请查看文章后面的编辑摘要
每年，近100万人（主要是生活在撒哈拉以南非洲的儿童）死于疟疾，这是一种亚热带和热带寄生虫病。虽然有几种寄生虫会导致疟疾，但恶性疟原虫是造成大多数死亡的原因。实际上，如果不治疗，恶性疟原虫感染可能在数小时内致命。在过去的50年里，恶性疟原虫疟疾的主要治疗方法是氯喹和磺胺多辛/乙胺嘧啶。不幸的是，寄生虫对这两种“单一疗法”的耐药性现在已经很普遍，撒哈拉以南非洲和其他地区由恶性疟原虫引起的疾病和死亡人数一直在增加。为了应对这种增长，世界卫生组织现在建议在所有有耐药性疟疾的地区，对恶性疟原虫疟疾采用青蒿素复方疗法（ACT）。在ACT中，青蒿素衍生物（新型、速效抗疟药物）与另一种抗疟药物联合使用，以降低恶性疟原虫对任何一种药物产生耐药性的可能性。
通过只给确定患有疟疾的人使用ACT，也应该降低恶性疟原虫对ACT产生耐药性的可能性。不幸的是，许多没有疟疾的人也被给予了ACT，因为基于症状（临床）的诊断并不总是能够区分发热是由疟疾引起的患者和那些患有其他感染、因此从其他治疗中获益更多的患者。血液涂片显微镜检测寄生虫会大大提高疟疾诊断的准确性，但这种检测在发展中国家的农村诊所很少能进行。针对恶性疟原虫的最近开发的“快速诊断检测”（RDTs）是否可以提供一种替代方法来改善疟疾诊断，从而减少ACT的过度使用呢？在这项“交叉试验”中，研究人员调查了在桑给巴尔（坦桑尼亚联合共和国的一部分，是撒哈拉以南非洲最早引入ACT的地区之一）的四个基层医疗诊所中，常规使用RDT诊断疟疾对ACT处方、健康结果和成本的影响。
每个诊所每隔一周交替使用RDT辅助的基于症状的疟疾临床诊断（试验的RDT组）和基于症状的临床诊断（临床诊断组）来确定发热就诊患者是否患有疟疾。被诊断为疟疾的患者都要使用ACT治疗；在使用RDT的周，只有RDT结果呈阳性的患者才使用ACT治疗。在试验期间，RDT组的1005名患者中有36%被开具了ACT处方，而临床诊断组的882名患者中有85%被开具了ACT处方。RDT组和临床诊断组分别有37%和27%的患者被开具了抗生素处方，而且RDT组返回诊所的患者比临床诊断组少，因为他们仍然感觉不适。两组每位患者的总体成本相似。研究人员还报告说，RDT组患者接受的抗疟治疗中有23%，临床诊断组患者接受的抗疟治疗中有80%是给予了血液中显微镜下未检测到寄生虫的人。重要的是，RDT组中26名涂片呈阳性但因RDT结果为阴性而未接受抗疟药物治疗的患者中，没有一人发展为重症疟疾。
这些发现表明，用RDT辅助诊断取代仅临床诊断可能会减少没有疟疾却被开具ACT处方的人数，并可能在不增加成本的情况下增加因非疟疾疾病而使用抗生素的患者人数。然而，虽然参与这项研究的医护人员只给RDT组中RDT结果呈阳性的患者开具ACT（按照试验方案的规定），但其他研究的证据表明，医护人员经常给RDT结果为阴性的患者使用抗疟药物。因此，这些发现可能不适用于其他诊所。不过，令人欣慰的是，那些通过血液涂片检测到疟疾但被RDT漏诊的患者中，没有一人后来发展为重症疟疾。如果这一发现得到重复验证，可能会说服医护人员相信RDT结果，而不是给每个发热患者都开具ACT“以防万一”。
请通过本摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.1000070
泽诺·比索菲及其同事在《公共科学图书馆·医学》的一篇观点文章中进一步讨论了这项研究
MedlinePlus百科全书包含一个关于疟疾的页面（有英语和西班牙语版本）
世界卫生组织提供了关于疟疾（多种语言）和疟疾快速诊断检测的信息。他们的2008年《世界疟疾报告》包括全球控制疟疾的努力以及坦桑尼亚联合共和国疟疾的最新信息
美国疾病控制与预防中心提供关于疟疾的信息（有英语和西班牙语版本）
疟疾防治伙伴关系提供了其全球控制疟疾的方法以及青蒿素类复方疗法的相关信息
Anders Bjorkman and colleagues report results from a cross-over trial evaluating rapid diagnostic testing for malaria diagnosis in Zanzibar. The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria is being suggested to improve diagnostic efficiency in peripheral health care settings in Africa. Such improved diagnostics are critical to minimize overuse and thereby delay development of resistance to artemisinin-based combination therapies (ACTs). Our objective was to study the influence of RDT-aided malaria diagnosis on drug prescriptions, health outcomes, and costs in primary health care settings. We conducted a cross-over validation clinical trial in four primary health care units in Zanzibar. Patients of all ages with reported fever in the previous 48 hours were eligible and allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Statistical analyses with multilevel modelling were performed. A total of 1,887 patients were enrolled February through August 2005. RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%) (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03–0.05, p<0.001). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5–2.2, p<0.001), respectively. Reattendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3–0.9, p = 0.005). Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD alone, respectively. RDTs resulted in improved adequate treatment and health outcomes without increased cost per patient. RDTs may represent a tool for improved management of patients with fever in peripheral health care settings. Clinicaltrials.gov NCT00549003 Please see later in the article for Editors' Summary Every year, nearly one million people (mainly children living in sub-Saharan Africa) die because of malaria, a subtropical and tropical parasitic disease. Although several parasites cause malaria, Plasmodium falciparum is responsible for most of these deaths. Indeed, infection with P. falciparum can be fatal within hours if left untreated. For the past 50 years, the main treatments for P. falciparum malaria have been chloroquine and sulfadoxine/pyrimethamine. Unfortunately, parasitic resistance to both of these “monotherapies” is now widespread and the illness and death caused by P. falciparum in sub-Saharan Africa and elsewhere has been increasing. To combat this increase, the World Health Organization now recommends artemisinin combination therapy (ACT) for P. falciparum malaria in all regions with drug-resistant malaria. In ACT, artemisinin derivatives (new, fast-acting antimalarial drugs) are used in combination with another antimalarial to reduce the chances of P. falciparum becoming resistant to either drug. The chances of P. falciparum becoming resistant to ACT should also be reduced by giving ACT only to people who definitely have malaria. Unfortunately, many people who do not have malaria are given ACT because symptom-based (clinical) diagnosis cannot always distinguish between patients whose fever is caused by malaria and those who have a different infection and who would, therefore, gain more benefit from other treatments. Microscopic detection of parasites in blood smears would greatly improve the accuracy of malaria diagnosis, but this test is rarely available in rural clinics in developing countries. Might the recently developed “rapid diagnostic tests” (RDTs) for P. falciparum provide an alternative way to improve malaria diagnosis and thus reduce the overuse of ACT? In this “cross-over trial,” the researchers investigate the effect of the routine use of an RDT for the diagnosis of malaria on ACT prescribing, health outcomes, and costs in four primary health-care clinics in Zanzibar (part of the United Republic of Tanzania), one of the first regions in sub-Saharan Africa to introduce ACT. Each clinic used RDT-aided symptom-based clinical diagnosis of malaria (the RDT arm of the trial) and symptom-based clinical diagnosis (the CD arm) in alternate weeks to decide whether patients attending with fever had malaria. ACT was prescribed to everyone diagnosed with malaria; during RDT weeks only patients with positive RDT results were prescribed ACT. During the trial, 36% of the 1,005 patients in the RDT arm were prescribed ACT compared to 85% of the 882 patients in the CD arm. 37% and 27% of the RDT and CD arm patients, respectively, were prescribed antibiotics and fewer RDT-arm patients than CD-arm patients returned to the clinic because they still felt ill. The overall cost per patient was similar in both arms. The researchers also report that 23% of the antimalarial treatments given to patients in the RDT arm and 80% of those given to patients in the CD arm were given to people with no microscopically detectable parasites in their blood. Importantly, none of the 26 patients in the RDT group who had positive smears but who were not treated with antimalarial drugs because of a negative RDT result developed severe malaria. These findings suggest that the replacement of clinical diagnosis alone with RDT-aided diagnosis may reduce the number of people prescribed ACT who do not have malaria and may increase the number of patients given antibiotics for nonmalarial illnesses without increasing costs. However, while the health-care workers involved in this study only prescribed ACT to those patients in the RDT arm who had a positive RDT result (as stipulated in the trial protocol), evidence from other studies suggests that health-care workers often give antimalarials to patients with negative RDT results. Consequently, these findings may not be generalizable to other clinics. Nevertheless, it is reassuring that none of the patients who had malaria that was detected by blood smear but that was missed by RDT subsequently developed severe malaria. This finding, if replicated, might persuade health-care workers to trust RDT results rather than prescribing ACT to everyone with a fever “just in case.” Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000070. This study is further discussed in a PLoS Medicine Perspective by Zeno Bisoffi and colleagues The MedlinePlus encyclopedia contains a page on malaria (in English and Spanish) Information is available from the World Health Organization on malaria (in several languages) and on rapid diagnostic tests for malaria. Their 2008 World Malaria Report includes information about global efforts to control malaria and the latest information on malaria in the United Republic of Tanzania The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish) Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria and on artemisinin-based combination therapies
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影响因子：
3.3
作者：
Bojang, KA;Obaro, S;Greenwood, BM
通讯作者：
Greenwood, BM
影响因子：
2.7
作者：
Björkman, AB;Bhattarai, A
通讯作者：
Bhattarai, A
影响因子：
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作者：
Reyburn, Hugh;Mbakilwa, Hilda;Whitty, Christopher J. M.
通讯作者：
Whitty, Christopher J. M.
影响因子：
3.3
作者：
Murray, CK;Bell, D;Wongsrichanalai, C
通讯作者：
Wongsrichanalai, C
影响因子：
120.7
作者：
Hamer, Davidson H.;Ndhlovu, Micky;Snow, Robert W.
通讯作者：
Snow, Robert W.