A Novel, Highly Sensitive Nucleic Acid Amplification Test Assay for the Diagnosis of Loiasis and its Use for Detection of Circulating Cell-Free DNA

J Infect Dis. 2023 Oct 3;228(7):936-943. doi: 10.1093/infdis/jiad186.

Abstract

Mass drug administration programs targeting filarial infections depend on diagnostic tools that are sensitive and specific. The coendemicity of Loa loa with other filarial species often hampers the control programs. LL2634 was identified as the most promising target among several highly repeated targets, with sensitivity between 500 ag and 1 fg of genomic DNA. Using DNA from infected individuals, LL2643 quantitative polymerase chain reaction (qPCR) was positive in all individuals. LL2643 was detected in plasma-derived circulating cell-free DNA (ccfDNA) from 48 of 53 microfilariae-positive patients. Detection of ccfDNA in urine was possible, but it occurred rarely among those tested. Importantly, LL2643 ccfDNA became undetectable within 1 month following diethylcarbamazine (DEC) treatment and remained negative for at least a year. LL2643 offers a more sensitive and specific target for detection of L. loa infection and would be easily configurable to a point-of-contact assay. Clinical Trials Registration. NCT00001230 and NCT00090662.

Keywords: ccfDNA; circulating cell-free DNA; diagnosis; filaria; loiasis; qPCR.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • DNA
  • Diethylcarbamazine
  • Humans
  • Loa / genetics
  • Loiasis* / diagnosis
  • Nucleic Acid Amplification Techniques

Substances

  • Diethylcarbamazine
  • DNA

Associated data

  • ClinicalTrials.gov/NCT00001230
  • ClinicalTrials.gov/NCT00090662