Effectiveness of interventions in surveillance programs and monitoring therapy response in clinical management: use of traditional and investigational tools.
Schistosoma infection is a poverty-related parasitic infection, being the second most important neglected tropical disease in the world after malaria. Schistosomiasis is caused by five distinct Schistosoma species distributed in tropical and subtropical areas. But, imported cases can also be seen in non - endemic areas. Human populations acquire infection after exposure to contaminated water collections. Schistosoma infection falls on a large spectrum of clinical manifestations that ranges from absence of signs and symptoms to severe forms of disease. Although morbidity and mortality have been reduced along the years after use of mass drug administration (MDA) in endemic areas, large populations are still at risk of disability-related outcomes on daily basis. Recently, a great deal of debate has been done over two main issues in schistosomiasis management in endemic and non-endemic areas: how to accurately diagnosis Schistosoma infections pre and post-therapy in addition to assess morbidity level. Adoption of promising new diagnostic tools and development of new markers of disease progression might change the current scenario by improving schistosomiasis clinical management in both community and institutional settings.
- diagnostic tests
- markers of therapy response
- community settings
- institutional settings
Recently, a great deal of debate has been done over two main issues in schistosomiasis management in endemic and nonendemic areas: how to accurately diagnosis
The diagnosis of active
2. New diagnostic tools in both community and institutional settings
The laboratory investigation of
Traditionally, egg detection by microscopy is the major criteria for active
Other parasitological methods such as sedimentation, centrifugation, flotation techniques, and miracidium hatching were developed and had improved the diagnosis of light infections by increasing sensitivity [26, 32]. In institutional settings, tissue biopsy such as rectal snips and liver biopsy are largely used to diagnose active infection in non-egg excretors despite its invasiveness . Eventually, surgical specimens reveal previously undiagnosed schistosomiasis. Except for rectal snips, histological examination is not quantitative, lack of information on parasite burden does not preclude clinical assistance.
Albeit the availability of diverse parasitological methods and tissue biopsies as alternatives to the reference test (Kato-Katz), nonparasitological methods were also developed to overcome microscopy false-negative results. This is the case of immunological tests, which have become more useful for showing active infections in recently exposed individuals, such as travelers or chronically infected immigrants residing in nonendemic areas . In areas of transmission, immunodiagnosis is a suitable tool for surveillance in low endemic areas . Several immunodiagnostic tests were developed, but currently the ELISA-based assays using egg antigen, cercarial, or adult worm antigens have been extensively used . In addition, recombinant proteins and peptides have been potential targets [34-36]. Despite its infrequent use in National Programs for Schistosomiasis Control, serology is a potent auxiliary diagnostic approach that permits the diagnosis of non-egg excretors. However, the presence of active infection may be undermined by persistent reactivity despite successful treatment [13, 29]. Although immunoreactivity does not correlate with the intensity of infection, data have demonstrated that isotypic immunoresponse may reflect morbidity levels [37, 38].
Moreover, rapid tests (RDT) for the detection of
3. Assessment of morbidity and drug response in community and institutional settings
Sanitation and community health education in addition to chemotherapeutic intervention are measures that effectively contribute to the control and/or elimination of
||Light Exposure Test
(Cercarial shedding detection)
|For determination of transmission control, elimination or erradication. Inaccurate. no
||Antigen Detection||Detection in 2nd week post-infection (pi); secretion by live larvae; group specific. Not commercially available assays.|
|DNA- based assays||Detection in 1st week pi; quantitation of parasite load (real -time PCR; specie-specific identification. Mapping foci of vector snails and monitoring transmission. In house assays.|
|Traditional methods which are simple, cheap and effective for
(urine lateral flow test)
|Detection of active infection independent of patent egg-excretion in primate non-humans. Only determination of genus but not species.
Defines exposure to
Comercial available test.
Sanitation / Education
|Questionnaries are applied to identify high - risk populations and permits assessment of
||DNA- based assays1||Identification and mapping of
DNA based assays are powerful tools for detection of
Mostly tested in “small” studies.
|Microscopy is highly sensitive and specific to detect egg-patent infections. Day-to-day variations on egg excretion is a limitation. Absence of egg excretion post-treatment may not represent response to therapy. Cure rates determined in different
||DNA-based assays1||DNA detection has higher sensitivity after use of chemotherapy. Persistent DNA amplification in both egg excretors and non-egg excretors strongly suggest no response to therapy. Presents good performance compared to parasitological methods to determine effect of MDA. Cure rates calculated by different DNA - based assays in distinct populations and by different Schistosoma species may varie from 21.1 - 30.7 to 75.6% [55, 15].
Persistence of DNA amplification until 6 months and post- 6 months after treatment might suggest incomplete infection and reinfection, respectively DNA-based assays for
|Serology||Loss of sensitivity of microscopy has been replaced in some control programs by serology which may remain reactive for extended periods post effective drug use. In areas submitted to several rounds of chemotherapy, low and/or absence of reactivity might represent control of infection.Long periods of obsevation are necessary to determine
||Rapid Test||POC-CCA maintains higher sensitivity than parasitological methods after PZQ use. However, specificity may be compromised by the presence of persistent low reactivity ( trace positive samples) post-chemotherapy.Cure rates may vary from 23.3 - 26.1 to 40.7- 47.8% [42, 54]
|Assessment of post-therapy response by parasitological methods in clinical wards has similar advantages and limitations as in community settings. In immigrants (long gone from endemic areas) and recently exposed travelers, absence of egg excretion pre-therapy represent an obstacle. Ova detection is inappropriate to determine therapy response in these groups. See above other coments.||DNA-based assays1||DNA-based assays are a reliable tool to detect response to therapy in distinct clinical specimens. Absence of DNA amplification correlates with response to therapy in individuals treated in Travel Medicine Clinics
.In case of therapy failure, maintained DNA amplification correlate with persistence of clinical signs, symptoms and pathological abnormalities associated to therapy failure . Usefulness of DNA-based assays to detect past infection incomplete cure for non re-exposed individuals has to be established with large studies .
|Tissue Biopsy||No viable eggs in rectal snips show good correlation with response to therapy. However, tissue biopsy (rectal snips, liver biopsies) are invasive procedures. And, lack of ova detection may not represent absence of active infection .|
|Serology||Immunoreactivity persistence for years after effective therapy is the major limitation. Negative seroconversion representes response to therapy and it is observed in some individuals . But, assessment of therapy failure is mostly difficult .|
||Tissue Biopsy||Donnor and organ-recipients from endemic areas with /without transaminase alterations can be screened by tissue biopsy . But, negative tissue samples do not rule out active infection.||DNA- based assays1||Further studies are necessary.|
RDTs for antigen detection have been largely used for population studies to evaluate posttherapy response and efficacy [42, 43]. In areas of moderate and high endemicity, therapy response represented by decrease or disappearance of antigen detection may represent cure. However, in light infections, rapid test accuracy is reduced with maintained antigen detection in individuals without infection. The use of antigen detection assays is a debatable matter to measure posttherapy response. In contrast, DNA assays seem to be a suitable marker of drug response. Cure is determined by the absence of DNA amplification postchemotherapy use, while persistent DNA amplification correlates with nonresponse to therapy .
Schistosomiasis presents as a large spectrum of manifestations and disease severity during acute and chronic phases. Usually, imaging tests and/or biological markers are required to confirm diagnosis, to assess morbidity, and to stage disease progression [21, 22]. Image tests such as ultrasonography became revolutionary to assess urogenital
In community settings, concerns have been increasing on the effectiveness of schistosomiasis control interventions like MDA over the years. The low accuracy of the reference test to detect active
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