Improved diagnosis of active Schistosoma infection in travellers and migrants using the ultra-sensitive in-house lateral flow test for detection of circulating anodic antigen (CAA) in serum

Abstract

Schistosomiasis is a parasitic disease affecting over 250 million people in the tropics. In non-endemic regions, imported Schistosoma infections are commonly diagnosed by serology, but based on antibody detection an active infection cannot be distinguished from a cured infection and it may take more than 8 weeks after exposure before seroconversion occurs. In endemic populations, excellent results have been described in diagnosing low-grade active Schistosoma infections by the detection of the adult worm-derived circulating anodic antigen (CAA) utilising robust lateral flow (LF) assays combined with up-converting phosphor (UCP) reporter technology. The purpose of this study is to explore the diagnostic value of the UCP-LF CAA assay in a non-endemic setting. CAA concentrations were determined in 111 serum samples originating from 81 serology-positive individuals. In nine individuals, serum could be collected before travel and an additional five provided samples before and after seroconversion occurred. Based on detectable CAA levels, an active infection was seen in 56/81 (69%) of the exposed individuals, while the 10 controls and the 9 sera collected before travel were tested negative for CAA. Positive CAA levels were observed starting 4 weeks after exposure and in four cases CAA was detected even before Schistosoma-specific antibodies became positive. Higher serum CAA levels were seen in migrants than in travellers and CAA concentrations dropped sharply when testing follow-up samples after treatment. This explorative study indicates the UCP-LF CAA serum assay to be a highly accurate test for detecting active low-grade Schistosoma infections in a non-endemic routine diagnostic setting.

Circulating Anodic Antigen (CAA): A Highly Sensitive Diagnostic Biomarker to Detect Active Schistosoma Infections—Improvement and Use during SCORE

“…However, more recent clinical studies using the more sensitive UCP-LF CAA test indicated active infections in travelers with CAA serum levels even less than 1 pg/ mL. 11,15 We speculate that when infection intensities are very low, variation in CAA levels may be observed; circadian rhythms and feeding patterns as well as immune-mediated clearance mechanisms of the host may play a role. Current thinking is that a single worm pair might produce a minimum CAA level of 1 pg/mL serum (unpublished).…”

Refining Diagnosis of Schistosoma haematobium Infections: Antigen and Antibody Detection in Urine

“…In contrast to the detection of eggs and circulating worm antigens, the presence of host antibodies against Schistosoma derived biomolecules is not necessarily a measure for ongoing active infection, except in those who would not previously have been exposed to Schistosoma parasites [i.e., individuals from non-endemic settings or travelers; ( 46 )]. In the current small endemic cohort, antibody detection in urine could not contribute to resolving disputes regarding anodic antigen negatives and cathodic antigen positives or indecisive/trace results as the analytical sensitivity of the assay was not sufficient to identify all infected individuals.…”

DNA Diagnostics for Schistosomiasis Control

“…CAA-based lateral flow assays combined with up-converting phosphor reporter technology, work for both S. mansoni and S. haematobium . However, they have not as yet proven as effective with other schistosome species [ 20 , 21 , 22 ]. As a result, DNA, especially PCR-based parasite DNA detection assays, have stimulated much interest as alternative options due to their proven diagnostic accuracy, higher sensitivity, and wider range of applicability, including the ability to detect early pre-patent infections.…”