PLoS Neglected Tropical Diseases (Mar 2024)

Analysis of diagnostic test outcomes in a large loiasis cohort from an endemic region: Serological tests are often false negative in hyper-microfilaremic infections.

  • Luzia Veletzky,
  • Kirsten Alexandra Eberhardt,
  • Jennifer Hergeth,
  • Daniel Robert Stelzl,
  • Rella Zoleko Manego,
  • Ruth Kreuzmair,
  • Gerrit Burger,
  • Johannes Mischlinger,
  • Matthew B B McCall,
  • Ghyslain Mombo-Ngoma,
  • Ayôla Akim Adegnika,
  • Selidji Todagbe Agnandji,
  • Pierre Blaise Matsiegui,
  • Bertrand Lell,
  • Peter Kremsner,
  • Benjamin Mordmüller,
  • Dennis Tappe,
  • Michael Ramharter

DOI
https://doi.org/10.1371/journal.pntd.0012054
Journal volume & issue
Vol. 18, no. 3
p. e0012054

Abstract

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BackgroundThe parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region.MethodsData and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis.ResultsELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively.ConclusionNone of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations.