Trends in Parasitology
ReviewSchistosomiasis in areas of low endemicity: a new era in diagnosis
Section snippets
Diagnosis in low endemicity areas: facing a new challenge
Schistosomiasis is a neglected tropical disease caused by a trematode of the genus Schistosoma. This helminthiasis is highly prevalent in subtropical regions of Africa, the Americas, and Asia. The parasitological detection (PD) of Schistosoma is extensively used in schistosomiasis diagnosis because this method is both efficacious and cost-effective (Table 1). However, the role of PD in diagnosis, response to chemotherapy, and measurement of transmission control or elimination is limited.
Assessment of Schistosoma infection by specific immunoreactivity
Schistosoma infection elicits specific immunoglobulin-dependent responses against several parasite antigens [23]. Most AbD assays measure serum immune reactivity to soluble adult worm antigen (SWA) and soluble egg antigen (SEA) preparations for diagnostic purposes, using mostly crude extracts, but also other parasite fractions, such as Schistosoma tegument proteins. Whereas several antigens are available for diagnostic purposes, sera-reactivity studies show variable results even when
AbD is a valuable strategy in LEAs
Active, current S. mansoni infections may occur in the presence of low parasite loads with undetectable eggs as determined by coproscopy. Because of their high sensitivity and ease of use, AbD assays became extensively used in the NPs of several countries experiencing decreased prevalence. AbD has been used as a tool to support schistosomiasis surveillance and control/elimination strategies 11, 21, 34. Community-based studies in LEAs using both PD and AbD demonstrate that diagnosis of
The dark side of AbD: major criticisms
Despite the high sensitivity of AbD assays, the specificity is usually low 41, 42. Frequently, cross-reactivity with some antigens from soil-transmitted helminthiasis compromises the specificity 15, 21, 42. Nonetheless, the antigens used in immunoassays prove to be a crucial element in test sensitivity and specificity. In community-based studies, assays for antibody reactivity against S. haematobium HAMA (see Glossary) present with 99% specificity and 99% sensitivity [34]. Furthermore,
AgD opens new avenues in diagnosis
In addition to egg detection by microscopy, another direct approach for schistosomiasis diagnosis is the detection of schistosome-derived antigens in the circulation and stool [25]. In the 1960s, schistosomal antigens were further characterized as circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) [25]. A later study revealed the potential of antigen detection in schistosomiasis diagnosis by using a monoclonal antibody against the CCA of S. japonicum [42]. CAA detection in
Use of AgD in LEAs
Discrimination of schistosome-infected from non-infected individuals, current and past infection, and determination of infection intensity are the strengths of the direct diagnosis of schistosomiasis performed by the coproscopy and AgD assays [54]. However, both approaches differ when applied to samples with low parasite loads and in areas of low prevalence. In a study conducted in Ugandan and Zanzibari sentinel schools to evaluate a commercial AgD assay in areas of low and high endemicity,
Pros and cons of AgD
AgD has been used as an alternative for egg excretion detection by microscopy to diagnose intestinal and urinary schistosomiasis 52, 53. In areas of coinfection with S. haematobium, the AgD assay results do not interfere with S. mansoni diagnosis [52]. Ease of use, rapid results, and large-scale sample testing have favored the use of AgD assays 15, 16, 20. In addition, AgD can be used to determine the intensity of infection 2, 57. Nonetheless, contrasting sensitivities and specificities are
DNA detection as a promising tool for Schistosoma infection diagnosis
Although egg-excretion detection methods have proved to be inadequate as a gold standard, advances in the development of antibody and antigen detection assays were not sufficient to allow their use either universally or as reliable single detection approaches in schistosomiasis diagnosis, particularly in areas of low endemicity. Recently, the availability of DNA detection assays may allow these tests to become potentially valuable as a supplementary tool in schistosomiasis diagnosis. DNA-based
Molecular diagnosis: the cutting edge of schistosomiasis diagnosis
Antigen detection by PCR-based methods has shown superior accuracy, sensitivity and specificity in areas with a low intensity of infection. Real-time PCR detects active S. japonicum and S. haematobium infection in areas of low endemicity and is 100% specific and 89% sensitive for the latter. Moreover, real-time PCR also permits the determination of infection intensity in samples with a low parasite burden 14, 53. PCR assays also have a high accuracy in the diagnosis of S. mansoni infection by
Applications and limitations of DNA-detection assays
PCR-based methods seem to be a diagnostic alternative with high sensitivity and specificity, and could have a role in the diagnostic algorithm for schistosomiasis management that is suitable for decision-making in eradication settings. Nonetheless, PCR remains an expensive method, although reduced costs can be obtained by methodological modifications, such as the improvement of DNA extraction methods [69]. Recently, DNA detection by new technologies such as LAMP promises to be the most
LEAs: searching for a (new) gold standard?
The immediate impact of widespread therapy in schistosomiasis endemic areas was clearly related to a decrease of the more severe morbid forms, the maintenance of infection with lower parasite loads, and the appearance of LEAs. Because transmission remains persistent, new cases occur but with a notable characteristic: they are undetectable by gold-standard tests. Hence, the detection of ‘truly’ infected hosts is crucial for disease surveillance in Schistosoma eradication settings. In addition,
Concluding remarks
A new era in the diagnosis of schistosomiasis comes with the fall of parasitological diagnosis as the gold-standard test in LEAs. As a tool for surveillance, the association of antibody and antigen detection by DNA-based assays potentiates the diagnosis of low-intensity infection in areas of low transmission and endemicity. Improved AbD and AgD assays include point-of-care test systems that reduce costs and permit large-scale studies in transmission areas. In Schistosoma elimination settings,
Glossary
- Antibody detection (AbD)
- indirect methods for parasitic infection diagnosis using immunoassays for the detection of anti-Schistosoma spp. antibodies.
- Antigen detection (AgD)
- diagnostic assays for detection of Schistosoma intestinal polysaccharide antigens known as circulating anodic antigen and circulating cathodic antigen.
- Circulating anodic antigen (CAA)
- gut-associated proteoglycan schistosome compounds.
- Circulating cathodic antigen (CCA)
- soluble glycoprotein found in adult worms of S. mansoni.
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