Original article
Rapid and effective diagnosis of pulmonary tuberculosis with novel and sensitive loop-mediated isothermal amplification (LAMP) assay in clinical samples: A meta-analysis

https://doi.org/10.1016/j.jiac.2013.07.003Get rights and content

Abstract

In recent years, Loop-mediated isothermal amplification (LAMP) assay has been introduced for the diagnosis of pulmonary tuberculosis (TB). We performed the meta-analysis to establish the overall accuracy of LAMP assay for diagnosing pulmonary TB. Based on comprehensive searches of the pubmed, embase and cochrane databases, we identified outcome datas from all articles estimating diagnostic accuracy with LAMP assay until 1 October 2012. A summary estimation for sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the summary ROC curve (AUC) was calculated by using the bivariate random-effects approach. The meta-analysis included 10 studies (1920 suspected specimens). The summary estimate was 80.0% (95%CI, 78.0%–83.0%) for sensitivity, 96.0% (95%CI, 95.0%–97.0%) for specificity and 119.85/0.9633 for DOR/AUC in pulmonary TB. The findings in subgroup analysis were as follows: the accuracy of LAMP assay is higher in high quality level studies than moderate and low quality level studies. The pooled sensitivity for the diagnosis of pulmonary TB was 90.0% (95%CI, 86.0–93.0%) and 75.0% (95%CI, 71.0–78.0%) for high quality level studies and moderate combined low quality level studies, respectively, while the specificity was 99.0% (95%CI, 98.0–100.0%) and 91.0% (95%CI, 88.0–94.0%). Pulmonary TB can be rapidly and accurately diagnosed with LAMP assay.

Introduction

Tuberculosis (TB) remains a serious health problem worldwide with nearly 9 million new cases and 1.4 million deaths annually [1]. Several publications and international guidelines highlight the need for appropriate and accurate diagnosis for effective treatment. In this regard, the development of novel and accurate diagnostic tools which may supplement or replace existing methods becomes a necessity.

Rapid and effective diagnosis of patients suspected of having TB remains a challenge. The conventional TB diagnosis techniques, including methods based on direct microscopic examination by ZiehleNeelsen staining, culture, chest radiography and tuberculin skin testing have limitations and are thus not always helpful in diagnosing TB. Smear microscopy alone, although cheap and easy to perform, has both the problems of sensitivity and specificity [2]. Although the culture is more sensitive than the smear microscopy, the time required, automated liquid culture systems like BACTEC or Mycobacteria Growth Indicator Tube (MGIT) take 1–6 weeks for growth detection, and frequent negative results in paucibacillary specimens are important limitation [2], [3], [4] and need specialized laboratory personnel [5]. This leads to a diagnostic delay that impedes disease control, and increases healthcare costs [1]. In the last few years, since the discovery of the polymerase chain reaction(PCR), a large number of molecular techniques have been developed [6]. However, their sensitivity is greatly dependent on the efficiency of the sample preparation, DNA extraction and the presence of PCR inhibitors [7], [8] and such methods require expertise and highly sophisticated settings that are not cost-effective for the laboratory in low-resource countries. Therefore, a simple, rapid and effective method for TB diagnosis remains to be developed.

One of latest assay, loop-mediated isothermal amplification(LAMP, Eiken Chemical Co Ltd., Tokyo, Japan) assay has been developed as a novel technique for nucleic acid amplification [9] and was evaluated in large studies recently [10]. LAMP can amplify DNA with high specificity and efficiency under isothermal conditions. Unlike PCR, LAMP reaction does not require a denaturated DNA template and relies on auto cycling strand displacement DNA synthesis by a Bst DNA polymerase [11]. The large amount of DNA generated in less than an hour and positive LAMP reaction can be visualized with the naked eye, without need for gel electrophoresis [12].

The diagnostic performance of LAMP assay has been investigated in several studies, which have variable results. The aim of this meta-analysis is to establish the overall diagnostic accuracy of LAMP assay and identify potential confounders or effective modifiers of its value in pulmonary tuberculosis (TB), thus providing the important up-to-date information on LAMP assay for pulmonary TB diagnosis.

Section snippets

Search strategy

We identified studies that showed the evidence of using LAMP assay in order to diagnose pulmonary TB. Two investigators (Y.L. and L.Y.) independently performed a systematic electronic search of the pubmed, embase databases and the cochrane-controlled central register of controlled trials and included reports for original articles published until 1 October 2012 to identify potentially relevant articles and abstracts. The following search terms were used: “LAMP Assay” OR “LAMP” OR “loop-mediated

Literature search and study selection

A total of 135 studies were screened for analysis of patients with tuberculosis using the novel and sensitive LAMP assay. After full-text review, 10 studies eventually met the inclusion criteria (Fig. 1).

Characters of the selected studies

Overall, the selected 10 studies [18], [19], [20], [21], [22], [23], [24], [25], [26], [27] included 1920 suspected specimens of having pulmonary TB, which included 823 pulmonary TB specimens (Patients with microbiologically confirmed TB), and 1097 non-TB specimens (The samples of patients were

Discussion

In this study, we clarified the diagnostic accuracy of LAMP assay for pulmonary TB. In addition, the diagnostic accuracy in different quality levels of studies were also explored. To our knowledge, this is the first systematic review and meta-analysis to estimate the diagnostic accuracy of LAMP assay in pulmonary TB.

The results of these 10 studies showed that LAMP assay was accurate to diagnose pulmonary TB. Using the bivariate random-effects approach, we found a summary AUC of 0.9633, a

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

Conceived and designed the experiments:YL, LY. Performed the experiments:MW, WX, ZK. Analyzed the data:YL.Wrote the paper: YL, LY. This work was supported by a grant from the National Clinical Key Specialty Construction Projects to the Department of Clinical Laboratory of Renmin Hospital of Wuhan University.

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    These authors contributed equally to this work.

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