Illuminating meningococcal diagnosis with LAMP.

Traditional polymerase chain reaction (PCR) based assays have allowed for relatively rapid detection of pathogens in clinical specimens with improved sensitivity compared to culture-based microbiology.1 Unfortunately actual utilization of PCR is limited by the requirements for lab personnel expertise, sophisticated lab equipment, and high cost of commercial PCR reagents, making PCR uncommon outside of urban medical centers in high-income countries.2 Thus, many PCR-based tests are only available at reference laboratories. The time dedicated to shipping, processing, and communicating results adds significant delay onto when the clinician can act upon the result. Clinicians thus have to rely on empiric treatment and often pursue a multitude of diagnostics, which had a definitive test result been promptly returned, would have been unnecessary. In this issue of the Lancet Infectious Diseases, Bourke and colleagues present a well-conducted, prospective clinical cohort study validating the use of loop mediated isothermal amplification (LAMP) for detection of meningococcal disease.3 LAMP is a nucleic acid amplification method that is iso-thermic in that the sample and assay reagents are able to rapidly duplicate the DNA of the condition for which the assay is targeted at a relatively constant temperature4. This allows for less laboratory infrastructure requirements. The results can be detected by turbidity or fluorescence4. Bourke and colleagues found that using LAMP as a near-patient test had a sensitivity of 89% and negative predictive value of 98% when tested on respiratory and blood specimens with 100% specificity and positive predictive value. Further the test was useful on CSF in patients in whom antibiotics had already been started, a common real world scenario where culture and Gram's stain have limited utility.5. The LAMP PCR performed roughly equivalent to traditional PCR and much better than culture. Perhaps one of the most interesting findings was that the median time to results was ∼90 minutes. Delay in effective treatment of meningitis or sepsis of any etiology is often highly detrimental leading to poor outcomes. A rapid test such as LAMP for meningococcal disease could vastly improve diagnostic capability, particularly in cases where empiric antibiotics have been started. LAMP has been investigated for a number of conditions, many of which are aimed at use in resource-limited settings.6,7 The technical requirements for LAMP are much less onerous than traditional PCR,7 and as shown here, LAMP for meningococcal disease is rapid and accurate. The relative simplicity of LAMP makes the test an attractive option. In middle and high-income countries, laboratory labor is a substantial component of an assay cost. Thus, LAMP may be an ideal test for detection of meningococcal disease in many settings. Yet, three cautions lay ahead. First, implementation of new conjugate meningococcal vaccines in Europe (serotype B) and in Africa (serotype A) may greatly diminish the need for meningococcal diagnostics as the disease prevalence greatly decreases. Second, the meningococcal LAMP is a single-plex test, yet we live in a “multiplex world” where the differential diagnosis of sepsis or meningitis is broad. Third, the path to commercialization is underway, but may be a challenge. Inexpensive, simple assays are excellent from public health and global health perspectives, but disruptive new technologies are not always adopted. Regardless of the path to commercialization, the authors have developed a novel, diagnostic test for Neisseria meningitidis which is an easy to perform, near-patient test with results in 90 minutes. In such a time frame, that results can lead to actionable decision-making, most likely to halt further diagnostic testing. The niche for LAMP in meningococcal disease remains to be determined, but allowing diagnostic confirmation at the treating hospital rather than a reference lab is a good start.