Faculty of Medicine, Imperial College London, London, UK.
Medical Research Council Centre for Global Infections Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Malar J. 2020 Dec 9;19(1):453. doi: 10.1186/s12936-020-03520-1.
In clinical trials of therapy for uncomplicated Plasmodium falciparum, there are usually some patients who fail treatment even in the absence of drug resistance. Treatment failures, which can be due to recrudescence or re-infection, are categorized as 'clinical' or 'parasitological' failures, the former indicating that symptoms have returned. Asymptomatic recrudescence has public health implications for continued malaria transmission and may be important for the spread of drug-resistant malaria. As the number of recrudescences in an individual trial is often low, it is difficult to assess how commonplace asymptomatic recrudescence is, and with what factors it is associated.
A systematic literature review was carried out on clinical trials of artemether-lumefantrine (AL) in patients seeking treatment for symptomatic uncomplicated falciparum malaria, and information on symptoms during treatment failure was recorded. Only treatment failures examined by polymerase chain reaction (PCR) were included, so as to exclude re-infections. A multivariable Bayesian regression model was used to explore factors potentially explaining the proportion of recrudescent infections which are symptomatic across the trials included in the study.
Across 60 published trials, including 9137 malaria patients, 37.8% [95% CIs (26.6-49.4%)] of recrudescences were symptomatic. A positive association was found between transmission intensity and the observed proportion of recrudescences that were asymptomatic. Symptoms were more likely to return in trials that only enrolled children aged < 72 months [odds ratio = 1.62, 95% CIs (1.01, 2.59)]. However, 84 studies had to be excluded from this analysis, as recrudescences were not specified as symptomatic or asymptomatic.
AL, the most widely used treatment for uncomplicated P. falciparum in Africa, remains a highly efficacious drug in most endemic countries. However in the small proportion of patients where AL does not clear parasitaemia, the majority of patients do not develop symptoms again and thus would be unlikely to seek another course of treatment. This continued asymptomatic parasite carriage in patients who have been treated may have implications for drug-resistant parasites being introduced into high-transmissions settings.
在治疗无并发症恶性疟原虫的临床试验中，通常会有一些患者即使没有耐药性也会治疗失败。治疗失败可归因于复发或再感染，分为“临床”或“寄生虫学”失败，前者表明症状已经恢复。无症状复发对持续疟疾传播具有公共卫生意义，并且可能对耐药性疟疾的传播很重要。由于个体试验中的复发数量通常较低，因此难以评估无症状复发的普遍程度以及与哪些因素相关。
对寻求治疗有症状的无并发症恶性疟原虫的患者使用青蒿琥酯-甲氟喹（AL）的临床试验进行了系统文献回顾，并记录了治疗失败期间的症状信息。仅包括通过聚合酶链反应（PCR）检查的治疗失败，以排除再感染。使用多变量贝叶斯回归模型探索了可能解释研究中包括的试验中复发感染中出现症状的比例的因素。
在 60 项已发表的试验中，包括 9137 名疟疾患者，37.8%（95%CI（26.6-49.4%））的复发是有症状的。在传染性较高的地区，观察到的无症状复发比例较高。在仅招募年龄<72 个月的儿童的试验中，症状更有可能恢复[比值比=1.62，95%CI（1.01，2.59）]。然而，由于未指定复发是有症状还是无症状，因此有 84 项研究必须从该分析中排除。
AL 是非洲最广泛用于治疗无并发症恶性疟原虫的药物，在大多数流行地区仍然是一种非常有效的药物。然而，在 AL 不能清除寄生虫血症的少数患者中，大多数患者不会再次出现症状，因此不太可能寻求另一种疗程。在已接受治疗的患者中持续无症状携带寄生虫可能会对将耐药性寄生虫引入高传播环境产生影响。
