ArticleJournal of clinical microbiology2014
Loop-mediated isothermal amplification for Rickettsia typhi (the causal agent of murine typhus): problems with diagnosis at the limit of detection.
Article in Journal of clinical microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The diagnostic accuracy of point-of-care nucleic acid-based isothermal amplification assays for scrub typhus: a systematic review and meta-analysis.Frontiers in microbiology · 2024Pooled it
- A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Comparison ofMicrobiology spectrum · 2026Article
- Targeting surface cell antigen 2 increases sensitivity of Rickettsia typhi detection.PLoS neglected tropical diseases · 2026Article
- Murine Typhus: A Review of a Reemerging Flea-Borne Rickettsiosis with Potential for Neurologic Manifestations and Sequalae.Infectious disease reports · 2023Review
- Development and validation of a novel detection method forFrontiers in microbiology · 2023Article
- Detection and significance of neuronal autoantibodies in patients with meningoencephalitis in Vientiane, Lao PDR.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2022Article
- Moving towards improved surveillance and earlier diagnosis of aquatic pathogens: From traditional methods to emerging technologies.Reviews in aquaculture · 2022Review
- Visual closed dumbbell-mediated isothermal amplification (CDA) for on-site detection of Rickettsia raoultii.PLoS neglected tropical diseases · 2022Article
- Genetic typing of isolates of Rickettsia typhi.PLoS neglected tropical diseases · 2022Article
- Loop-Mediated Isothermal Amplification as a Promising Method for Mass COVID-19 Diagnostics.Applied biochemistry and microbiology · 2021Article
- History, Rats, Fleas, and Opossums. II. The Decline and Resurgence of Flea-Borne Typhus in the United States, 1945-2019.Tropical medicine and infectious disease · 2020Review
- The Isolation of Orientia tsutsugamushi and Rickettsia typhi from Human Blood through Mammalian Cell Culture: a Descriptive Series of 3,227 Samples and Outcomes in the Lao People's Democratic Republic.Journal of clinical microbiology · 2020Review
- Performance of molecular and serologic tests for the diagnosis of scrub typhus.PLoS neglected tropical diseases · 2020Article
- Development and evaluation of loop-mediated isothermal amplification for detection of Yersinia pestis in plague biological samples.PloS one · 2020Article
- The Rickettsioses: A Practical Update.Infectious disease clinics of North America · 2019Review
- Article
- Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic Landscape.The American journal of tropical medicine and hygiene · 2017Review
- State of the art of diagnosis of rickettsial diseases: the use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus.Current opinion in infectious diseases · 2016Review
- Development and Diagnostic Evaluation of Loop-Mediated Isothermal Amplification Using a New Gene Target for Rapid Detection of Helicobacter pylori.Jundishapur journal of microbiology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Murine typhus is a flea-borne disease of worldwide distribution caused by Rickettsia typhi. Although treatment with tetracycline antibiotics is effective, treatment is often misguided or delayed due to diagnostic difficulties. As the gold standard immunofluorescence assay is imperfect, we aimed to develop and evaluate a loop-mediated isothermal amplification (LAMP) assay. LAMP assays have the potential to fulfill the WHO ASSURED criteria (affordable, sensitive, specific, user friendly, robust and rapid, equipment free, deliverable to those who need them) for diagnostic methodologies, as they can detect pathogen-derived nucleic acid with low technical expenditure. The LAMP assay was developed using samples of bacterial isolates (n=41), buffy coat specimens from R. typhi PCR-positive Lao patients (n=42), and diverse negative controls (n=47). The method was then evaluated prospectively using consecutive patients with suspected scrub typhus or murine typhus (n=266). The limit of detection was ∼40 DNA copies/LAMP reaction, with an analytical sensitivity of <10 DNA copies/reaction based on isolate dilutions. Despite these low cutoffs, the clinical sensitivity was disappointing, with 48% (95% confidence interval [95% CI], 32.5 to 62.7%) (specificity, 100% [95% CI, 100 to 100%]) in the developmental phase and 33% (95% CI, 9.2 to 56.8%) (specificity, 98.5% [95% CI, 97.0% to 100%]) in the prospective study. This low diagnostic accuracy was attributed to low patient R. typhi bacterial loads (median, 210 DNA copies/ml blood; interquartile range, 130 to 500). PCR-positive but LAMP-negative samples demonstrated significantly lower bacterial loads than LAMP-positive samples. Our findings highlight the diagnostic challenges for diseases with low pathogen burdens and emphasize the need to integrate pathogen biology with improved template production for assay development strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.