Abstract

The rapid, accurate, and efficient identification of an infectious disease is critical to ensure timely clinical treatment and prevention in public health settings. In 2015, meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis was responsible for 379,200 (range: 322,700–444,700) deaths. Clinical features alone cannot determine whether bacterial meningitis is present; an analysis of cerebrospinal fluid (CSF) is essential. Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method offering an alternative to polymerase chain reaction (PCR). LAMP-based assays for detection of three leading bacteria in CSF for diagnosis of meningitis have been established. The typing assays using LAMP for detection of meningococcal serogroups A, B, C, W, X, and Y as well as H. influenzae serotypes a, b, c, d, e, and f were launched. In comparative analysis of the meningitis pathogen assays, LAMP assays did not yield false negative results, and the detection rate of LAMP assays was superior compared with PCR or conventional culture methods. LAMP assays provide accurate and rapid test results to detect major bacterial meningitis pathogens. Accumulating evidence suggests that LAMP assays have the potential to provide urgently needed diagnostics for bacterial meningitis in resource-limited settings of both developed and developing countries.

Highlights

  • Over the past several decades, the incidence of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae in children has declined due to widespread vaccination [1, 2]

  • Polymerase chain reaction (PCR)-based assays are relatively expensive and complex to perform in resource-limited laboratory settings

  • The pneumococcus Loop-mediated isothermal amplification (LAMP) method could detect as few as 10 copies of both purified DNA and spiked cerebrospinal fluid (CSF) specimens within 30 min with greater sensitivity than conventional polymerase chain reaction (PCR) [11]

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Summary

INTRODUCTION

Over the past several decades, the incidence of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae in children has declined due to widespread vaccination [1, 2]. Recent success in the introduction of the meningococcal conjugate serogroup A vaccine has underscored the importance of continued clinical and epidemiologic surveillance for invasive meningococcal disease across countries where the vaccine has been deployed [3]. The incidence of invasive diseases due to bacterial strains that were not included in the vaccines has increased [2, 4, 5]. Even with appropriate antimicrobial therapy, the burden of disease in adults and mortality both in adults and children remain high in several countries, resource-limited countries [6]

LAMP Assays for Bacterial Meningitis
LAMP SPECIFICITY
LAMP SENSITIVITY
LAMP PCR LAMP
LAMP ASSAY EVALUATION USING CLINICAL CSF SPECIMENS
Sample amount
CLINICAL APPLICATION
Findings
PUBLIC HEALTH PERSPECTIVES
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