{"id":6522,"date":"2026-04-01T09:38:08","date_gmt":"2026-04-01T09:38:08","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/eleanor-ochodo\/"},"modified":"2026-04-01T09:38:14","modified_gmt":"2026-04-01T09:38:14","slug":"eleanor-ochodo","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/eleanor-ochodo\/","title":{"rendered":"Eleanor Ochodo"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":6525,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-6522","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Strengthening Methods of Diagnostic Accuracy Studies","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/eleanor-ochodo\/\">hier<\/a>.","summary":"In studies with mixed post-treatment evaluations of 1 year (n=6), 6 months (n=1) and 1 month (n=1), King\u2019s review produced a lower estimate of sensitivity (72%) in the subgroup of treated populations as compared to the overall analysis (81%). King considered treatment evaluations with praziquantel and metrifonate whereas we focused on studies that evaluated the effect of praziquantel treatment as this is the current drug of choice. Due to studies with varied time intervals between treatment and retesting, we opted not to pool the estimates of the studies as this would likely produce biased overestimates of sensitivity and specificity. Studies with long time intervals were likely to have more participants reinfected compared to studies carried out at shorter time intervals, as well as potentially being confounded by repeated treatments by country programmes.\n\nA recently published multi-centre evaluation of CCA POC tests done in five African countries (49) recommended the CCA POC test for S. mansoni (evaluated with a positivity threshold of = trace positive) as a sufficiently sensitive and specific tool for mapping intestinal schistosomiasis in moderate to high prevalence areas and therefore as a viable alternative to microscopy (92). Acknowledging the absence of a gold standard, this multi-centre study used latent class analysis (modeling results from CCA POC, Kato Katz and PCR) to generate an overall estimate of 86% sensitivity and 72% specificity of CCA POC based on data from 4405 school age children. Using microscopy only (KK) as the reference standard, our review, which incorporated all of their results with additional studies, produced a comparable summary estimate of 87% sensitivity but a lower summary estimate of 61% specificity at a threshold of trace positive. The differences in specificity could be explained by the reference standard and indicates that some of the false positives identified by CCA POC are indeed likely to be true infections, which are not detected by standard microscopy.\n\nFew studies exist that fully evaluate the accuracy of the circulating antigen ELISA tests (CCA\/CAA). The serum CAA ELISA test is currently being developed into a point of care format for S. mansoni (95) and S. haematobium (96) with promising results of analytical sensitivity and specificity. In our review, the sensitivity of the included studies evaluating the serum CAA ELISA test for S. mansoni ranged widely from 47% to 94% and specificity ranged widely from 8% to 100%. The sensitivity of the included studies evaluating serum CAA ELISA test for S. haematobium ranged from 55% to 97% and specificity was low and ranged from 24% to 57%. However, the studies included in our review were carried out before the year 2000 with in-house tests. The tests currently being developed are most likely improved versions and therefore more current studies analysing the clinical sensitivity and specificity of the serum ELISA tests are needed to conclusively know if they are suitable for the diagnosis of active schistosomiasis.\n\n8.6.4 Strengths and limitations of the review\n\n8.6.4.1 Strengths\n\nWe have evaluated the accuracy of POC tests currently being used and also tests that have recently transformed into POC tests for detection of active schistosomiasis in endemic areas. This makes our review relevant to current practice. To avoid missing studies we did not use a search filter and we did not limit our search by publication year or language and to limit bias, two people performed data extraction independently.\n\n8.6.4.2 Weaknesses\n\na. Choice of the reference standard\n\nIn light of the absence of a suitable gold standard for active schistosomiasis and the presence of other proposed alternative reference standards, evaluating index tests with only microscopy as the reference standard may be considered a shortcoming of our review. However because microscopy remains the most commonly used test and therefore reference test, we wanted our review to be applicable to current practice. Our review gives a better insight on the proportion of cases detected and proportion of cases misclassified by urine reagent strips and CCA POC tests when microscopy is used as the reference standard. A more reliable way of evaluating if an index test can replace microscopy would be to compare the accuracy of microscopy, urine reagent strips and circulating antigen tests against other proposed reference standards in the same set of participants (direct comparison studies). A few studies have compared the accuracies of one or more KK smears and CCA POC against a reference standard comprising six or more KK smears (85, 87, 90) or against PCR as the reference test (92). All these studies have shown CCA POC test to be more sensitive but less specific than single or double KK. More direct comparative studies and reviews are needed to reliably confirm this finding and identify sources of variation in results.\n\nb. Quality of included studies\n\nPoor and inconsistent reporting of patient characteristics such as clinical status of participants, intensity of infection, administration of praziquantel treatment and the conduct of the study limited our investigations of sources of heterogeneity and risk of bias assessment.\n\nIn our review, the reporting of intensity of infection was unclear (reported in different ways: arithmetic mean or range of infection or geometric mean or range of infection or proportions with light\/moderate\/heavy infections; or not reported at all) for a large proportion of the included studies (Microhaematuria (44%), Proteinuria (42%) and CCA POC (45%)). It was therefore difficult to effectively investigate its influence on the accuracy of the evaluated tests. It was also a challenge to fully investigate the effect of praziquantel treatment on the accuracy of the evaluated tests because 82% of the studies did not report the treatment status of the participants prior to the study. The effect of intensity of infection and effect of praziquantel treatment on the accuracy of diagnostic tests for schistosomiasis is currently an important concern for national control programmes, particularly as praziquantel treatments progress, with subsequent decreases in infection intensities. Indeed, in areas where the force of infection and associated morbidity has been greatly reduced, some programmes are beginning to focus on elimination; it is therefore of vital importance that highly sensitive tests are used for monitoring, and that highly sensitive and specific tests are used in efficacy studies pre and post treatment.\n\n8.6.5 Applicability of findings to the review question\n\nOur concern about the applicability of the included studies to our review question was low as assessed by QUADAS 2. As all but one study were carried out in Africa and all but one study were done in field settings making our results highly applicable for use in endemic communities where disease control programs are often targeted. However, one area that may limit the applicability of our findings to the review question is our investigations into the sources of heterogeneity such as effect of praziquantel treatment and risk of bias assessment on the accuracy estimates of the evaluated tests. As discussed earlier, poor and inconsistent reporting limited this investigation. In light of the ongoing disease control programs it would be useful to policymakers to fully show any variation of test accuracy with effect of praziquantel treatment. Knowing the risk of bias of included studies would also help in objectively assessing the strength of the evidence. Authors are therefore encouraged to use the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines (97) in reporting the design and conduct of their studies.\n\n8.7 Authors' conclusions\n\n8.7.1 Implications for practice\n\nAmong the evaluated tests for S. haematobium infection, microhaematuria detected the largest proportion of infections and non-infections identified by microscopy. This test could continue to serve as a replacement test for microscopy for initial mapping or estimation of S. haematobium infection, particularly in endemic areas with a moderate to high prevalence of infection.\n\nThe CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy but misclassifies many microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection. This may be because the test is potentially more sensitive than microscopy. Nevertheless, health workers should interpret the results with care, when using the test for initial mapping or estimation of S. mansoni infection, as some of the positives may still be false positives.\n\nBesides the accuracy of a test the choice of a suitable diagnostic test should be made in light of cost and logistical considerations. Costs for microscopy (USA per examination, 0.3 for a single thick KK smear) (26), and the reagent strips for microhaematuria (USA 0.32) (98) are comparable but the strips are easier to use and interpret and are therefore not logistically challenging in field settings. The CCA POC tests are more costly (USA 2.6 per examination) (26), but are still rapid and easy to use and interpret, highly portable and require less technical personnel than microscopy and are therefore also suitable for field screening and diagnosis.\n\n8.7.2 Implications for research\n\nAs control programmes progress with expected subsequent decrease in prevalence and intensity of infection, we highlight the importance of more primary research identifying a suitable clinical reference standard for active schistosomiasis.\n\nAdditional studies comparing the accuracy of microscopy, circulating antigen tests and urine reagent strips to other proposed reference standards are needed to reliably recommend a suitable replacement for microscopy in practice.\n\nFurther studies to identify other sensitive tests to detect active S. haematobium and S. mansoni infections and further evaluations of the CAA test as a future POC test for serum or urine are also needed.\n\nTo reliably recommend suitable tests for monitoring effects of praziquantel treatment in disease control programs more follow up studies are required to evaluate the effects of praziquantel treatment on the intensity of infection and accuracy of urine reagent strips and circulating antigen tests.\n\nFurther research on cost-effectiveness of diagnostic tests in areas of different endemicity is also needed as cost is a key deciding factor in resource-limited settings.\n\nFinally authors of primary test accuracy studies need to be encouraged to use the STARD guidelines in reporting the design and conduct of their studies. This will enable systematic reviewers to better synthesize the data and draw conclusions on the risk of bias in studies of test accuracy.\n\nSummary of findings table for tests to detect S. haematobium\n\nWhat is the diagnostic accuracy of circulating antigen tests and biochemical urine reagent strips for S. haematobium infection?\n\nPatients\/Population: People residing in areas endemic for S. haematobium infection (71 out of 86 studies)\n\nPrior treatment with praziquantel before baseline study: Yes (6 studies), No (8 studies), Unclear (57 studies)\n\nPrior testing: None\n\nSettings: Field settings (Villages & schools) and one outpatient clinic in Africa\n\nIndex tests:\nCirculating cathodic antigen test (CCA)\nCirculating anodic antigen test (CAA)\nUrine reagent strips to detect microhaematuria, proteinuria and leukocyturia","auteur":"Eleanor Ochodo","auteur_slug":"eleanor-ochodo","publicatiedatum":"19 juni 2014","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/eleanorochodo?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604010934","isbn":"978908891 9046","doi_nummer":"","naam_universiteit":"Universiteit van Amsterdam","afbeeldingen":6526,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit van Amsterdam","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/6522","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=6522"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/6522\/revisions"}],"predecessor-version":[{"id":6523,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/6522\/revisions\/6523"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/6525"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=6522"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=6522"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}