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The potential of various quantitative lateral flow (LF) based assays utilizing up-converting phosphor (UCP) reporters for the diagnosis of schistosomiasis is reviewed including recent developments. Active infections are demonstrated by screening for the presence of regurgitated worm antigens (genus specific polysaccharides), whereas anti-Schistosoma antibodies may indicate ongoing as well as past infections. The circulating anodic antigen (CAA) in serum or urine (and potentially also saliva) is identified as the marker that may allow detection of single-worm infections. Quantitation of antigen levels is a reliable method to study effects of drug administration, worm burden and anti-fecundity mechanisms. Moreover, the ratio of CAA and circulating cathodic antigen (CCA) is postulated to facilitate identification of either Schistosoma mansoni or Schistosoma haematobium infections. The UCP-LF assays allow simultaneous detection of multiple targets on a single strip, a valuable feature for antibody detection assays. Although antibody detection in endemic regions is not a useful tool to diagnose active infections, it gains potential when the ratio of different classes of antibody specific for the parasite/disease can be determined. The UCP-LF antibody assay format allows this type of multiplexing, including testing a linear array of up to 20 different targets. Multiple test spots would allow detection of specific antibodies, e.g. against different Schistosoma species or other pathogens as soil-transmitted helminths. Concluding, the different UCP-LF based assays for diagnosis of schistosomiasis provide a collection of tests with relatively low complexity and high sensitivity, covering the full range of diagnostics needed in control programmes for mapping, screening and monitoring.

Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas 1 . Novel medicines and vaccines are urgently needed 2 , 3 . An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324 ), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3–10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4 + T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis. A new human challenge model of schistosomiasis, which affects more than 290 million people globally, will aid development of novel therapies and vaccines for this neglected tropical disease.

Cystic echinococcosis (CE) or hydatidosis is a parasitic disease affecting both humans and animals. The present study aimed to evaluate the efficacy of the ELISA test in diagnosis of human hydatidosis using crude protoscolices antigens. Echinococcus granulosus protoscolices were isolated from the human liver hydatid cyst (local strain G1). Their crude antigen was prepared by the sonication technique. One hundred and eight sera samples were collected from patients with hydatid cyst ( n  = 21), individuals with other infections ( n  = 27) and sheep breeders ( n  = 60). These sera were evaluated using the ELISA assay. The predictable rate of sensitivity for the ELISA using the crude antigens was 100% depending on the cut-off. Additionally, the estimated values of specificity, positive and negative predictive values and accuracy were 97.4%; 87.3%; 100% and 97.8%, respectively. Crud E . granulosus protoscolices antigens are considered suitable candidates for the sero-diagnosis of human CE. To identify a single antigen and increase its effectiveness in serologic diagnostic testing, more research on these antigens is needed.

Taenia solium neurocysticercosis is a zoonotic neglected tropical disease, for which adequate diagnostic management is paramount, especially in patients with active cysts for whom improved and timely management could prove beneficial. Immunodiagnosis can potentially partially mitigate the necessity for neuroimaging, shortening the diagnostic -and treatment- pathway. An up-to-date review of immunological test performance is however lacking. Searches were performed in PubMed, EMBASE, Web of Science, and Scopus (up to January 2024), with included records fitting the review scope, i.e. accuracy evaluation of an antibody-/or antigen-detecting immunological test, using serum or urine of humans confirmed via reference standard (i.e. neuroimaging or surgery/biopsy). Record data was assessed, with classification of descriptive data on cyst localization and stage according to a developed confidence scale, and with selection of tests evaluated on a sufficiently high sample size. A QUADAS-2 risk of bias assessment was performed. After screening, 169 records were included for data collection, with 53 records-corresponding to 123 tests- selected for analysis. Absence of data and large data heterogeneity complicated result interpretation. The lentil lectin-bound glycoprotein enzyme-linked immunoelectrotranfser blot seems to fulfill high accuracy standards regarding detection of parenchymal active multiple cysts; also antigen-detecting tests on serum and urine performed well, additionally in detection of extraparenchymal neurocysticercosis. A novel multi-antigen print immunoassay is highly promising, with sensitivity for detection of extraparenchymal and parenchymal active single and multiple cysts of 100.0%, and specificity of 98.5%. Point-of-care tests showed promising results, however require further evaluation in targeted resource-poor settings. The review highlights the importance of transparent and unambiguous data reporting. With promising immunological tests in development, the challenge before usage in targeted settings will be to perform large-scale evaluations whilst holding into account both optimized test performance and ease of use. Accessibility to validated tests and feasibility of implementation should also be considered.

The success of mass drug administration at reducing the prevalence of lymphatic filariasis in endemic areas has led to an increased need for highly sensitive and specific diagnostic assays. To be useful in post-elimination surveillance in areas with low to zero prevalence, high test performance characteristics are required to enable the early detection of infection recrudescence. As current testing suffers from either sensitivity or specificity levels that fail to meet adopted target product profiles, additional targets that could be used as confirmatory tests or in multiplexed assays could overcome these issues. To this end, bioinformatic analyses coupled with stage-specific expression data for W. bancrofti (Wb) and/or B. malayi (Bm) resulted in the identification of 12 targets that were: 1) present in Wb and/or Bm; 2) had very little to no homology with proteins from other filariae; and 3) were enriched in the microfilarial or L3 stages. Screening of these 12 antigens by a Luciferase Immunoprecipitation System assay for IgG with serum from Wb-infected and uninfected individuals identified a single antigen, termed Wb5, that was specific for Wb infections only. Recombinant Wb5 proteins were generated in multiple expression systems for use in a variety of IgG4-based immunoassays. To assess if Wb5 could provide additional sensitivity to assays using IgG4 antibodies to Wb123, head-to-head comparisons were performed using serum from 466 samples (231 Wb-infected, 235 controls). Using IgG4-based immunoassays at 100% specificity against uninfected controls and other helminth species ( O. volvulus, L. loa, S. stercoralis, M. perstans ), Wb5 and Wb123 had individual sensitivities of 53.7% and 75.3%, respectively, while a combination resulted in 81.0% sensitivity. Moreover, kinetic studies of patients that were treated and followed up longitudinally suggest that Wb5 titers may decline more sharply than those of Wb123, thus paving the way for Wb5 as a complementary tool to Wb123.

Detection of circulating antigen of Dirofilaria immitis has been a mainstay of identifying heartworm infection in clinical practice for the past three decades. Several validated commercial antigen tests have very good sensitivity, specificity, and positive predictive values, especially when used in patients for which heartworm infection is likely. In some dogs and cats infected with heartworm, antigen may not be available for detection although present in the patient sample; heat pretreatment of these samples reveals the antigen, changing the false negative to positive. This phenomenon was documented in the literature in the 1980s but subsequently overlooked by the heartworm research community for many years. In this review, we provide a summary of the current understanding of the role of heat reversal in diagnosing heartworm infection. This additional diagnostic step is most important for patients in which heartworm infection is likely, such as dogs or cats in an endemic area with an inconsistent history of heartworm preventive use, or dogs with a prior diagnosis of heartworm infection that were recently treated. To illustrate the concept, we share a summary of results from canine samples tested at the state veterinary diagnostic laboratory in Oklahoma, USA in 2017 by modified Knott test and by commercial antigen test before and after heat treatment of samples; in this sample set, heat treatment changed all D. immitis microfilaria-positive but antigen-negative samples to antigen-positive. Pet dogs with a history of consistent preventive use are unlikely to become positive with heat pretreatment; for that reason, routine pretreatment of all samples tested in a veterinary practice is not recommended. We also review known causes of false negative and false positive results on heartworm antigen tests that, although uncommon, can complicate accurate diagnosis in individual patients. Together, this review provides a primer to aid understanding of strategies that can enhance accurate diagnosis of heartworm infection in veterinary practice and clinical research.

The present study compares the immunogenic patterns of muscle larvae excretory-secretory proteins (ML E-S) from T . spiralis and T . britovi recognized by Trichinella -infected human sera. Samples were analyzed using two-dimensional electrophoresis (2-DE) coupled with 2D-immunoblot and liquid chromatography-tandem mass spectrometry LC-MS/MS analysis, two ELISA procedures and a confirmatory 1D-immunoblot test. Sera were obtained from nine patients with a history of ingestion of raw or undercooked meat who presented typical clinical manifestations of trichinellosis and from eleven healthy people. Specific anti- Trichinella IgG antibodies were detected in all samples tested with the Home-ELISA kits, but in only four samples for the commercially-available kit. The 1D-immunoblot results indicated that all nine serum samples were positive for T . spiralis ML E-S antigens, expressed as the presence of specific bands. In contrast, eight of the serum samples with T . britovi E-S ML antigens were positive, with one serum sample taken from a patient at 33dpi (days post infection) being negative. To identify immunoreactive proteins that are specifically recognized by host antibodies, both species of ML E-S proteins were subjected to 2D-immunoblotting with human serum taken at 49 dpi. The sera recognized 22 protein spots for T . spiralis and 18 for T . britovi in 2D-immunoblot analysis. Their molecular weights (MW) ranged from 50 to 60 kDa. LC-MS/MS analysis identified both common and specifically-recognized immunoreactive proteins: transmembrane serine protease 9, serine protease, antigen targeted by protective antibodies and Actin-1 partial were shared for both Trichinella species; hypothetical protein T01_7775 and P49 antigen, partial those specific to T . spiralis ; deoxyribonuclease-2-alpha and hypothetical protein T03_17187/T12_7360 were specific to T . britovi . Our results demonstrate the value of 2-DE and 2D-immunblot as versatile tools for pinpointing factors contributing to the parasite-host relationship by comparing the secretomes of different Trichinella species.

Before the 1990s, human fascioliasis diagnosis focused on individual patients in hospitals or health centres. Case reports were mainly from developed countries and usually concerned isolated human infection in animal endemic areas. From the mid-1990s onwards, due to the progressive description of human endemic areas and human infection reports in developing countries, but also new knowledge on clinical manifestations and pathology, new situations, hitherto neglected, entered in the global scenario. Human fascioliasis has proved to be pronouncedly more heterogeneous than previously thought, including different transmission patterns and epidemiological situations. Stool and blood techniques, the main tools for diagnosis in humans, have been improved for both patient and survey diagnosis. Present availabilities for human diagnosis are reviewed focusing on advantages and weaknesses, sample management, egg differentiation, qualitative and quantitative diagnosis, antibody and antigen detection, post-treatment monitoring and post-control surveillance. Main conclusions refer to the pronounced difficulties of diagnosing fascioliasis in humans given the different infection phases and parasite migration capacities, clinical heterogeneity, immunological complexity, different epidemiological situations and transmission patterns, the lack of a diagnostic technique covering all needs and situations, and the advisability for a combined use of different techniques, at least including a stool technique and a blood technique.

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.

The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood. This study aimed to identify the potential impact of HIV coinfection in CC and NCC patients. A nested study within a cross-sectional analysis in two Tanzanian regions was performed and 234 participants (110 HIV+ and 124 HIV-) were tested for cysticercosis antibodies, antigens, CD4 counts and serum Th1 and Th2 cytokines via multiplex bead-based immunoassay. 127 cysticercosis seropositive individuals underwent cranial computed tomography (CCT) and clinical symptoms were assessed. Multiple regression analyses were performed to identify factors associated with cytokine modulation due to HIV in CC and NCC patients. Serologically, 18.8% tested positive for cysticercosis antibodies, with no significant difference HIV+ and HIV+. A significantly higher rate of cysticercosis antigen positivity was found in HIV+ individuals (43.6%) compared to HIV- (28.2%) (p = 0.016). CCT scans revealed that overall 10.3% had active brain cysts (NCC+). Our study found no significant changes in the overall cytokine profiles between HIV+ and HIV- participants coinfected CC and NCC, except for IL-5 which was elevated in HIV+ individuals with cysticercosis. Furthermore, HIV infection in general was associated with increased levels of pro-and some anti-inflammatory cytokines e.g. TNF-α, IL-8, and IFN-γ. However, based on the interaction analyses, no cytokine changes were observed due to HIV in CC or NCC patients. In conclusion, while HIV infection itself significantly modulates levels of key cytokines such as TNF-α, IL-8, and IFN-γ, it does not modulate any cytokine changes due to CC or NCC. This underscores the dominant influence of HIV on the immune system and highlights the importance of effective antiretroviral therapy in managing immune responses in individuals coinfected with HIV and CC/NCC.