Accuracy of point-of-care testing for circulatory cathodic antigen in the detection of schistosome infection: systematic review and meta-analysis

Bull World Health Organ 2016;94:522–533A | doi: http://dx.doi.org/10.2471/BLT.15.158741 Systematic reviews 522 Accuracy of point-of-care testing for circulatory cathodic antigen in the detection of schistosome infection: systematic review and meta- analysis Anthony Danso-Appiah,a Jonathan Minton,b Daniel Boamah,c Joseph Otchere,d Richard H Asmah,e Mark Rodgers,f Kwabena M Bosompem,d Paolo Eusebig & Sake J De Vlash Introduction Schistosomiasis is common in low-income tropical and sub- tropical countries, especially where it is difficult to provide basic care at the peripheral level.1 Almost a billion people are estimated to be at risk of schistosome infection and over 200 million are infected.2–5 As there is a high risk of reinfection after treatment, repeated screening and treatment are important.6,7 Schistosoma mansoni and S. japonicum cause most cases of intestinal schistosomiasis while S. haematobium causes uro- genital schistosomiasis. Although the World Health Organization’s (WHO’s) strategy for schistosomiasis control was largely based on active case detection and treatment with praziquantel, mass treat- ment – with no prior diagnosis – is now increasingly employed in areas with high endemicity.5 Most diagnosis is based on Kato–Katz thick smears8 for intestinal schistosomiasis and urine filtration for urogenital schistosomiasis. The sensitivity of both of these diagnostic techniques depends on the severity of infection and often falls below 30% for mild infections.9,10 Although repeated sampling – e.g. the taking of several stool specimens on different days, from each subject, for Kato–Katz testing – can increase sensitivity, it also increases costs and the risk of false-positive results. Since the introduction of mass drug administration within the preventive chemotherapy strategy, the prevalence and intensity of schistosome infection has fallen substantially in most settings and, in consequence, such infection has become harder to detect.5 Better but low-cost diagnostic tests are now needed to increase sensitivity without compromising speci- ficity. It is possible to detect some schistosome infections by testing for either of two of the parasites’ secretory metabolites that have been linked with active infection: circulatory anodic antigen and circulatory cathodic antigen.11–18 A cassette assay for the point-of-care testing of urine samples for the latter antigen has been developed.19 When validated in settings in Africa, this assay was generally found to be much more sensitive – in the detection of S. mansoni infection – than the Kato–Katz test, although it appeared to suffer the same limita- tion when intensities of infection were low.20–24 Systematic reviews are widely regarded as providing the best evidence to inform health-care decisions.25,26 The systematic review and meta-analysis described below was commissioned by WHO to assess the diagnostic accuracy of point-of-care testing for circulatory cathodic antigen – here- after called antigen testing. A Cochrane review was recently published on the same topic.27 The main aim of the review and meta-analysis was to evaluate the accuracy of antigen testing in the detection of all schistosome infections. We generally used the examination of two Kato–Katz thick smears of stools per subject as the refer- ence standard in the detection of S. mansoni and S. japonicum Objective To assess the accuracy of point-of-care testing for circulatory cathodic antigen in the diagnosis of schistosome infection. Methods We searched MEDLINE, EMBASE, LILACS and other bibliographic databases for studies published until 30 September 2015 that described circulatory cathodic antigen testing compared against one to three Kato–Katz tests per subject – for Schistosoma mansoni – or the filtration of one 10-ml urine sample per subject – for S. haematobium. We extracted the numbers of true positives, false positives, true negatives and false negatives for the antigen testing and performed meta-analyses using a bivariate hierarchical regression model. Findings Twenty-six studies published between 1994 and 2014 met the inclusion criteria. In the detection of S. mansoni, a single antigen test gave a pooled sensitivity of 0.90 (95% confidence interval, CI: 0.84–0.94) and a pooled specificity of 0.56 (95% CI: 0.39–0.71; n = 7) when compared against a single Kato–Katz test. The corresponding values from comparisons with two to three Kato–Katz tests per subject were 0.85 (95% CI: 0.80–0.88) and 0.66 (95% CI: 0.53–0.76; n = 14), respectively. There appeared to be no advantage in using three antigen tests per subject instead of one. When compared against the results of urine filtration, antigen testing for S. haematobium showed poor sensitivity and poor specificity. The performance of antigen testing was better in areas of high endemicity than in settings with low endemicity. Conclusion Antigen testing may represent an effective tool for monitoring programmes for the control of S. mansoni. a Department of Epidemiology and Disease Control, School of Public Health, University of Ghana, PO Box LG13, Legon, Ghana. b School of Social and Political Sciences, University of Glasgow, Glasgow, Scotland. c Department of Microbiology, Centre for Plant Medicine Research, Mampong, Ghana. d Department of Parasitology, University of Ghana, Legon, Ghana. e School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana. f Centre for Reviews and Dissemination, University of York, York, England. g Health Planning Service, Regional Health Authority of Umbria, Perugia, Italy. h Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, Netherlands. Correspondence to Anthony Danso-Appiah (email: tdappiah@yahoo.co.uk). (Submitted: 23 June 2015 – Revised version received: 19 December 2015 – Accepted: 26 January 2016 – Published online: 22 April 2016 ) Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 523 Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. and the filtration of 10 ml of urine per subject as the corresponding standard for S. haematobium. Methods Search methods We searched MEDLINE, EMBASE and LILACS for relevant articles, in any language, recorded between the incep- tion of each database and 30 September 2015. We also searched BIOSIS, Web of Science, Google Scholar, the Rapid Medical Diagnostics database, African Journals Online, Cochrane Infectious Diseases Group Specialized Register, the Cochrane Library 2015 and the metaRegister of Controlled Trials. We maximized the sensitivity of our search by using free texts based on the index test and target condition – i.e. antigen testing and schistosome infection, re- spectively. We also hand-checked the reference lists of relevant articles and textbooks and contacted experts in the field to see if they had any relevant but unpublished data. Inclusion criteria We considered a study for inclusion if, for the detection of schistosome infec- tion, it compared antigen testing with Kato–Katz tests and/or urine filtration, the pre-control infection status of the participants was not known, the same participants were checked using anti- gen tests and at least one reference test, and data on diagnostic accuracy were reported. The data included in our review had to come from study participants whose stools had been checked for S. man- soni and/or S. japonicum eggs using the Kato–Katz test8 or whose urine had been checked for S. haematobium eggs using filtration of a 10 ml sample and microscopical examination of the filter. Diagnostic thresholds Stool samples found to contain fewer than 100, 100–399 and more than 399 eggs per gram of faeces when examined as Kato–Katz smears were considered to come from participants with light, mod- erate and heavy infections, respectively. Urine that contained fewer than 51 or more than 50 eggs per 10-ml sample was considered to come from partici- pants with light and heavy infections, respectively. All of the included results of antigen testing had been classifying qualitatively as: trace as negative, trace as positive or single, double or triple positive. Study selection One author conducted the initial wide- ranging search of the literature. Two other authors then screened the results to identify those studies that were po- tentially relevant and useful. Full study reports were then obtained and checked to see if they satisfied several predefined inclusion criteria. Any discrepancies were resolved through discussion be- tween the authors. Data extraction and management Using a standardized form, two authors extracted study characteristics such as the country and year in which the study was conducted and the study design and the methods. Information on diagnostic criteria – e.g. the number of stool and urine samples examined per participant and the diagnostic thresholds employed – and epidemiological and demographic data – e.g. endemicity status, region where the study was conducted, par- ticipants’ prior treatment status, target population, sex, age and number of participants and whether diagnosis was delivered at the point of care – were also extracted. We extracted the numbers of true positives, false positives, true negatives and false negatives for the antigen test- ing – using the results of a reference test as the gold standard. When necessary, we contacted the authors of the pub- lished articles on included studies to see if they could clarify or supplement the published results or provide raw data that we could use. If two or more communities were involved in a study, data were extracted for each community – with a link to the parent study. Data synthesis Data were analysed and presented as sensitivities, specificities and false- positive rates, with their 95% confidence intervals (CIs). The meta-analyses were performed using the bivariate model specified by Reitsma et al.28 and the mada package in the R program- Fig. 1. Selection of studies included in the systematic review and meta-analysis on the accuracy of point-of-care testing for circulatory cathodic antigen in the detection of schistosome infection 4578 citations retrieved 4513 records screened 123 full text articles assessed for eligibility 20 published articles on 26 studies included in the systematic review and meta-analyses 65 duplications excluded 4390 records excluded 97 articles excluded: • Not primary data (n = 57) • Inappropriate reference standard (n = 17) • Inappropriate participants (n = 11) • Insufficient data to populate the 2 x 2 contingency table (n = 9) • Case–control study (n = 3) Schistosoma mansoni (n = 24) Schistosoma haematobium (n = 2) Schistosoma japonicum (n = 0) 4500 records identified through database search 78 additional records identified through other sources Note: Some reported articles were conducted in settings of low, moderate and high endemicity. We treated each of these articles as a report on three studies. Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741524 Systematic reviews Accuracy of antigen testing in detecting schistosome infection Anthony Danso-Appiah et al. Ta bl e 1. Ch ar ac te ris tic s o f t he st ud ie s i nc lu de d in th e sy st em at ic re vi ew a nd m et a- an al ys is on th e ac cu ra cy o f p oi nt -o f-c ar e te st in g fo r c irc ul at or y c at ho di c a nt ig en in th e de te ct io n of sc hi st os om e in fe ct io n St ud y Co un tr y Ye ar No . o f s tu dy co m m un iti es In iti al sa m pl e siz e Pa rt ici pa nt s Ag es (y ea rs ) Pr ev al en ce (% )a CC A te st in ve st ig at ed , a nd n o. of sa m pl es p er p ar tic ip an t No . o f s to ol sa m pl es p er pa rt ici pa nt b Kr em sn er , 1 99 41 7 Ca m er oo n N R 1 14 8 Sc ho ol ch ild re n 4– 13 N R EI A (1 ) 1 D e Cl er cq , 1 99 73 6 M al i N R 2 N Rc Ad ul ts a nd c hi ld re n N R 99 .0 EL IS A (1 ) 2 D e Cl er cq , 1 99 73 7 M al i 19 93 4 N Rd Ad ul ts a nd c hi ld re n N R N R EL IS A (1 ) 1 Le ge ss e, 2 00 73 8 Et hi op ia 20 07 1 25 1 Ad ul ts a nd c hi ld re n > 5 90 .0 (s ch oo lc hi ld re n) Re ag en t s tri p (1 ) 1 Ay el e, 2 00 83 9 Et hi op ia N R 1 20 6 Sc ho ol ch ild re n 4– 21 47 .6 Re ag en t s tri p (1 ) N A Le ge ss e, 2 00 84 0 Et hi op ia 20 07 1 18 4 Sc ho ol ch ild re n 5– 22 36 .4 Re ag en t s tri p (1 ) 1 M id zi , 2 00 94 1 Zi m ba bw e 20 06 1 26 5 Pr es ch oo l c hi ld re n an d sc ho ol ch ild re n 2– 19 40 .4 Re ag en t s tri p (1 ) 1 St ot ha rd , 2 00 94 2 U ga nd a 20 09 1 24 2 In fa nt s a nd pr es ch oo l c hi ld re n < 6 > 5 0. 0 Re ag en t s tri p (1 ) 2 So us a- Fi gu ei re do , 20 10 43 U ga nd a 20 07 a nd 20 09 N R 60 8 Pr es ch oo l c hi ld re n an d m ot he rs < 7 e 16 .0 a nd 4 3. 3 (c hi ld re n) , 29 .2 a nd 6 0. 0 (m ot he rs ) fro m e ith er L ak e Vi ct or ia o r La ke A lb er t Ca ss et te (1 ) 2 St an dl ey , 2 01 04 4 Ke ny a, U ni te d Re pu bl ic o f Ta nz an ia 20 09 11 17 1 Sc ho ol ch ild re n 6– 17 68 .6 Re ag en t s tri p (1 ) 1 Co ul ib al y, 20 11 20 (s tu dy 1 )f Cô te d ’Iv oi re 20 10 1 14 6 Ch ild re n 8– 12 32 .9 Ca ss et te (1 , 2 o r 3 ) 1, 2 o r 3 Co ul ib al y, 20 11 20 (s tu dy 2 )f Cô te d ’Iv oi re 20 10 1 13 0 Ch ild re n 8– 12 53 .1 Ca ss et te (1 , 2 o r 3 ) 1, 2 o r 3 Co ul ib al y, 20 11 20 (s tu dy 3 )f Cô te d ’Iv oi re 20 10 1 17 0 Ch ild re n 8– 12 91 .8 Ca ss et te (1 , 2 o r 3 ) 1, 2 o r 3 Sh an e, 2 01 14 5 Ke ny a 20 07 1 48 4 Ch ild re n 1– 15 38 .8 D ip st ic k (1 ) 3 Tc hu em Tc hu en té , 20 12 21 (s tu dy 1 )f Ca m er oo n 20 10 /2 01 1 1 76 5 Sc ho ol ch ild re n 8– 12 21 .0 Ca ss et te (1 ) a nd d ip st ic k (N R) 3 Tc hu em Tc hu en té , 20 12 21 (s tu dy 2 )f Ca m er oo n 20 10 /2 01 1 1 76 5 Sc ho ol ch ild re n 8– 12 41 .8 Ca ss et te (1 ) a nd d ip st ic k (N R) 3 Tc hu em Tc hu en té , 20 12 21 (s tu dy 3 )f Ca m er oo n 20 10 /2 01 1 1 76 5 Sc ho ol ch ild re n 8– 12 31 .4 Ca ss et te (1 ) a nd d ip st ic k (N R) 3 Co lle y, 20 13 22 Ca m er oo n, Cô te d’ Iv oi re , Et hi op ia , Ke ny a, U ga nd a 20 10 5 43 05 Sc ho ol ch ild re n 9– 12 15 .1 (K en ya ), 25 .0 (U ga nd a) , 38 .4 (C am er oo n) , 4 3. 0 (E th io pi a) a nd 4 7. 9 (C ôt e d’ Iv oi re ) Ca ss et te (1 ) 1 (c on tin ue s. . . ) Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 525 Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. ming environment (R Foundation, Vienna, Austria).29 The model we used is equivalent to the hierarchical regres- sion approach described by Rutter and Gatsonis.30,31 In the model, variance components are estimated by restricted maximum likelihood. To remove the need to adjust for confounders, we restricted our analyses to data from studies in which both index and refer- ence standard tests were evaluated in the same participants. Subgroup effects were investigated by stratifying the analyses by age – categorized as preschool chil- dren and infants, school-aged children or adults – as well as the sensitivity of the reference standard and the background endemicity of either the intestinal schis- tosomiasis investigated – categorized as low, moderate or high – or the urinary schistosomiasis investigated – catego- rized as low or high. Heterogeneity and subgroup analysis We assessed heterogeneity by inspecting forest plots for overlapping confidence intervals and outlying data. Although we generally considered a P-value below 0.05 to indicate statistical significance, we used a more sensitive threshold32,33 – i.e. a P-value below 0.10 – to indicate statistically significant heterogeneity. Where such significant heterogeneity was detected, we carried out subgroup analyses based on clinical and method- ological differences. We applied an exploratory analysis based on a latent class bivariate model34 to investigate the performance of anti- gen testing – compared with Kato–Katz tests used as the reference standard. For this analysis, Latent GOLD version 5.0 (Statistical Innovations Inc., Belmont, United States of America)35 was used to capture the between-study heterogeneity in sensitivity and specificity – assuming that our included studies belonged to one of several latent classes.34 Results We retrieved 4578 records in the ini- tial search. The data in 20 published articles on the 26 studies that met all of our inclusion criteria were included in the review (Fig. 1 and Table 1). In this article we present our main findings on the performance of antigen testing com- pared with Kato–Katz smears and urine filtration. More details on this topic and St ud y Co un tr y Ye ar No . o f s tu dy co m m un iti es In iti al sa m pl e siz e Pa rt ici pa nt s Ag es (y ea rs ) Pr ev al en ce (% )a CC A te st in ve st ig at ed , a nd n o. of sa m pl es p er p ar tic ip an t No . o f s to ol sa m pl es p er pa rt ici pa nt b Co ul ib al y, 20 13 46 Cô te d ’Iv oi re 20 11 2 24 2 Pr es ch oo l c hi ld re n < 6 23 .1 Ca ss et te (2 ) 2 D aw so n, 2 01 34 7 U ga nd a 20 11 N R 82 Pr es ch oo l c hi ld re n < 6 45 .0 Ca ss et te (1 ) 2 Er ko , 2 01 34 8 Et hi op ia 20 10 /2 01 1 2 62 0 Sc ho ol ch ild re n 8– 12 34 .0 Ca ss et te (1 , 2 o r 3 ) 1, 2 o r 3 Ko uk ou na ri, 2 01 34 9 U ga nd a 20 05 1 44 6 Ch ild re n an d ad ul ts 7– 16 a nd 17 –7 6 N R Ca ss et te (1 ) 3 So us a- Fi gu ei re do , 20 13 23 (s tu dy 1 ) f U ga nd a 20 09 N R 33 3 Pr es ch oo l c hi ld re n < 7 7. 2 D ip st ic k (1 ) 1 So us a- Fi gu ei re do , 20 13 23 (s tu dy 2 ) f U ga nd a 20 09 N R 33 7 Pr es ch oo l c hi ld re n < 7 16 .9 D ip st ic k (1 ) 1 So us a- Fi gu ei re do , 20 13 23 (s tu dy 3 ) f U ga nd a 20 09 N R 25 5 Pr es ch oo l c hi ld re n < 7 38 .8 D ip st ic k (1 ) 1 Ad rik o, 2 01 42 4 U ga nd a N R 5 50 0 Sc ho ol ch ild re n 7– 13 8. 0, 2 3. 0 an d 36 .0 fr om lo w , m od er at e an d hi gh en de m ic a re as , r es pe ct iv el y Ca ss et te (1 ) 1, 2 o r 3 CC A: c irc ul at or y ca th od ic a nt ig en ; E IA : e nz ym e im m un oa ss ay ; E LI SA : e nz ym e- lin ke d im m un os or be nt a ss ay ; N A: n ot a pp lic ab le ; N R: n ot re po rte d. a O f i nf ec tio n w ith th e sc hi st os om e sp ec ie s o f i nt er es t, as in di ca te d by th e re su lts o f t he re fe re nc e te st . b Ea ch e xa m in ed a s a d up lic at e Ka to –K at z s m ea r. c O ve ra ll, 35 2 se ru m , 1 34 st oo l a nd 3 37 u rin e sa m pl es w er e in ve st ig at ed d O ve ra ll, 34 8 bl oo d, 3 24 st oo l a nd 4 31 u rin e sa m pl es w er e in ve st ig at ed . e R ep or te d ag e of c hi ld re n. f Th e ar tic le w as c on du ct ed in se tti ng s o f l ow , m od er at e an d hi gh e nd em ic ity . W e tre at ed th e pu bl ic at io n as a re po rt on th re e st ud ie s, w hi ch w e de sig na te d st ud ie s 1 , 2 a nd 3 . (. . . co nt in ue d) Anthony Danso-Appiah et al.Accuracy of antigen testing in detecting schistosome infection Systematic reviews 526 Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 on other parts of the meta-analysis we conducted are available from the cor- responding author. All of the included studies were conducted in Africa – i.e. in East Afri- ca,23,24,38–40,42–45,47–49 West Africa17,20,21,36,37,46 southern Africa41 or five countries scat- tered across Africa.22 Most were cross- sectional and none was a randomized control trial. Three of the studies were conducted in the 1990s and used the older version of the test for circulatory cathodic antigen.17,36,37 The rest were conducted after 2000. All but two of the included studies involved the de- tection of S. mansoni. Two involved the detection of S. haematobium (Fig. 2) and none investigated S. japonicum infections. Each of two publications20,21 re- ported studies conducted in settings of low, moderate and high endemicity. We treated each of these publications as a report on three studies, which we designated studies 1, 2 and 3. As another investigation49 had both adult and child participants and reported data separately for these two age groups, we were able to analyse its data as if they came from two studies. Since one publication22 included some data from primary research represented by other articles included in our analysis, we had to be careful to avoid duplicate analyses. When contacted, the authors of three included articles23,24,44 provided useful unpublished data. One antigen test per participant Versus single Kato–Katz The accuracy of single antigen test- ing compared with single Kato–Katz reference testing – i.e. the examination of two smears of a single stool sample per participant – for the detection of S. mansoni infection had been inves- tigated in seven studies,21,20,48,44,45,23,24 in Cameroon, Côte d’Ivoire, Ethiopia, Kenya and Uganda. Our meta-analysis of the data from these studies indicated that the antigen test had a high pooled sensitivity (0.90; 95% CI: 0.84–0.94) but a low pooled specificity (0.56; 95% CI: 0.39–0.71; Fig. 3). The area under the corresponding receiver-operating characteristic curve indicated that the antigen test had an accuracy of 0.86 (Fig. 4; available at: http://www.who. int/bulletin/volumes/94/7/15-158741). The same curve indicated that there had been wide variation in the antigen test’s false-positive rate when the test had been used to detect S. mansoni infection. Versus triple Kato–Katz In 14 studies on the detection of S. mansoni infection – described in nine articles20,21,24,32,38,40,46,48,49 – single antigen testing had been compared with triple Kato–Katz reference testing – i.e. the examination of two smears of each of three consecutive stool samples per participant. When pooled, these comparisons indicated that the antigen test had a sensitivity of 0.85 (95% CI: 0.80–0.88) and a specificity of 0.66 (95% CI: 0.53–0.76). The wide CIs of some of the studies indicated the ef- fects of small sample sizes. While the estimates of the antigen test’s sensitivity showed some consistency, there was huge variation in the corresponding estimates of specificity (Fig. 5). Fig. 2. Single point-of-care testing for circulatory cathodic antigen in the detection of Schistosoma haematobium infection: summary receiver-operating characteristic curve Se ns iti vi ty 1.0 0.8 0.6 0.4 0.2 0 False-positive rate 0.2 0.4 0.6 0.8 1.0 AUC: area under the curve. Notes: The analysed data came from two studies39,41 in which, for each participant, filtration of a 10-ml urine sample served as the reference standard. Each participant was tested once for antigen, using reagent strips. In the antigen testing, all positive results – including trace positives – were considered indicative of infection. The graph contains six separate types of information, represented by six separate types of graphical feature. Hollow circles represent the point estimates for the sensitivity and specificity of each study. Each of these circles is surrounded by a light grey oval, which presents the 95% credible region associated with that particular study. Similarly, the summary models – produced by pooling the estimates from each of the studies using a standard bivariate model – are presented both as a point estimate, represented by a solid green circle, and an associated 95% credible region, represented by the black oval. In addition to this, the best estimate for how the sensitivity and specificity vary with the diagnostic threshold adopted is represented by a line which runs from the bottom left to the top right portion of the graph. The solid section of this line represents interpolated estimates – which fill in the gaps between the studies available – whereas the dashed parts of this line are extrapolated from the data and are therefore more dependent on the modelling assumptions. Both the interpolated and the extrapolated parts of this line are needed to estimate the AUC, which is a measure of the antigen test’s diagnostic accuracy. Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 527 Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. Versus combined antigen test and Kato–Katz One of the studies we included in our analysis24 had used the combined results of single antigen testing with single Kato–Katz reference testing in evaluat- ing the performance of the antigen test when detecting S. mansoni infection. In this study, single antigen testing had been found to have a high sensitivity (90%) and optimal specificity (100%). Three antigen tests per participant Versus combined antigen test and Kato–Katz In the study just described,24 the use of three antigen tests per participant led to slightly higher sensitivity (96%) and left specificity unchanged (100%). Versus triple Kato–Katz In eight of the studies we included in our analysis – i.e. three from Cameroon,21 four from Côte d’Ivoire20,46 and one from Ethiopia48 – triple antigen testing for the detection of S. mansoni infection Fig. 3. Accuracy of single point-of-care testing for circulatory cathodic antigen in the detection of Schistosoma mansoni infection Study TP FP FN TN Sensitivity Specificity Standley 2010 105 38 1 9 0.99 (0.95–1.00) 0.19 (0.10–0.33) Coulibaly 2011 230 42 38 249 0.86 (0.81–0.89) 0.86 (0.81–0.89) Shane 2011 231 664 35 833 0.87 (0.82–0.90) 0.56 (0.53–0.58) Tchuem Tchuenté 2012 247 208 27 231 0.90 (0.86–0.93) 0.53 (0.48–0.57) Erko 2013 251 158 16 195 0.94 (0.90–0.96) 0.55 (0.50–0.60) Sousa-Figuereido 2013 133 316 37 429 0.78 (0.71–0.84) 0.58 (0.54–0.61) Adriko 2014 114 119 11 176 0.91 (0.85–0.95) 0.60 (0.54–0.65) Pooled effect 0.90 (0.84–0.94) 0.56 (0.39–0.71) Sensitivity 0 0.2 0.4 0.6 0.8 1 Specificity 0 0.2 0.4 0.6 0.8 1 FN: false negatives; FP: false positives; TN: true negatives; TP: true positives. Notes: The analysed data came from seven studies20,21,23,24,44,45,48 in which, for each participant, examination of duplicate Kato–Katz smears of a single stool sample served as the reference standard. In the antigen testing, all positive results – including trace positives – were considered indicative of infection. Data points for two studies21,24 were extracted from a report22 that included primary data from a multi-country study in Africa. Although reagent strips were used as the antigen tests in two of the studies,44,45 most of the data came from studies in which cassette assays had been used. Fig. 5. Accuracy of single point-of-care testing for circulatory cathodic antigen in the detection of Schistosoma mansoni infection Study TP FP FN TN Sensitivity Specificity Legesse 2007 130 59 21 41 0.86 (0.80–0.91) 0.41 (0.32–0.51) Legesse 2008 60 60 18 46 0.77 (0.66–0.85) 0.43 (0.34–0.53) Coulibaly 2011 (study 1) 27 6 21 92 0.56 (0.42–0.69) 0.94 (0.87–0.97) Coulibaly 2011 (study 2) 48 5 21 56 0.70 (0.58–0.79) 0.92 (0.82–0.96) Coulibaly 2011 (study 3) 138 2 16 11 0.90 (0.84–0.94) 0.85 (0.58–0.96) Tchuem Tchuenté 2012 (study 1) 41 31 9 57 0.82 (0.69–0.90) 0.65 (0.54–0.74) Tchuem Tchuenté 2012 (study 2) 145 26 31 43 0.82 (0.76–0.87) 0.62 (0.51–0.73) Tchuem Tchuenté 2012 (study 3) 136 37 19 50 0.88 (0.82–0.92) 0.57 (0.47–0.67) Coulibaly 2013 52 104 4 82 0.93 (0.83–0.97) 0.44 (0.37–0.51) Dawson 2013 37 14 7 22 0.84 (0.71–0.92) 0.61 (0.45–0.75) Erko 2013 306 103 23 188 0.93 (0.90–0.95) 0.65 (0.59–0.70) Koukounari 2013 (study 1) 148 2 17 2 0.90 (0.84–0.93) 0.50 (0.15–0.85) Koukounari 2013 (study 2) 189 7 41 37 0.82 (0.77–0.87) 0.84 (0.71–0.92) Adriko 2014 155 140 21 153 0.88 (0.82–0.92) 0.52 (0.47–0.58) Pooled effect 0.85 (0.80–0.88) 0.66 (0.53–0.76) Sensitivity 0 0.2 0.4 0.6 0.8 1 Specificity 0 0.2 0.4 0.6 0.8 1 FN: false negatives; FP: false positives; TN: true negatives; TP: true positives. Notes: The analysed data came from 14 studies20,21,24,32,38,40,46,48,49 in which, for each participant, examination of duplicate Kato–Katz smears of three or, in one study,32 two consecutive stool samples – in two studies,38,40 combined with the results of formol–ether concentration – served as the reference standard. In the antigen testing, all positive results – including trace positives – were considered indicative of infection. Although reagent strips were used as the antigen tests in two of the studies,38,40 most of the data came from studies in which cassette assays had been used. The data in one report49 that presented separate results for children aged 7–16 years and adults older than 16 years were treated as if they came from two independent studies. Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741528 Systematic reviews Accuracy of antigen testing in detecting schistosome infection Anthony Danso-Appiah et al. was compared with triple Kato–Katz reference testing. The meta-analysis of the data from these studies showed that triple antigen testing gave a pooled sensitivity of 0.91 (95% CI: 0.84–0.95) and a pooled specificity of 0.56 (95% CI: 0.39–0.72) (Fig. 6). Although the sensitivities of the triple antigen test- ing appeared to be fairly consistent across the studies, the corresponding specificities showed wide CIs and much between-study variability. Latent class analysis We analysed 32 data points from studies included in this review and identified two latent classes for the antigen testing (Table 2). Discussion In this review, we were disappointed by the lack of a relevant randomized controlled trial. Most of the data we analysed came from cross-sectional studies. Despite the variability in the design of the studies we investigated, including variation in the format of the antigen tests employed, the studies gave fairly consistent results. An independent study found no batch-to-batch variation in the cassette version of the antigen test we investigated, negligible intra-reader variability (2%) and substantial agree- ment in the inter-reader reliability of the test.50 As all the studies we included in our analysis were conducted in Africa and most only assessed the perfor- mance of antigen testing for detecting S. mansoni infection, there needs to be much caution in generalizing our findings to other endemic areas and other schistosome species. Additional studies – on the detection of S. mansoni beyond Africa and on the detection of other schistosome species throughout the tropics and subtropics – are en- couraged.51 The finding that the antigen test performed better when endemicity was high than when it was low has both practice and control implications. As schistosome control becomes more successful, antigen testing may have no advantage over Kato–Katz smears or urine filtration. As there is no test for schistosome infection that has 100% sensitivity and 100% specificity, the ap- parent performance of any index test is partially dependent on the performance and other characteristics of the reference test or tests. Microscopy performed on multiple stool or urine samples – as ap- propriate – might be considered to be an effective parasitological gold standard.52 Researchers have suggested that a use- ful gold standard might be created by combining the results of the index and reference tests.52 However, the combined results of antigen and Kato–Katz testing might be adversely affected by false- positive antigen tests, false-negative Kato–Katz tests and interdependence in the two sets of results. When investigat- ing the performance of antigen testing, it may be better to use a test with a low false-positive rate as the reference for sensitivity – e.g. Kato–Katz testing of multiple stool samples collected on dif- ferent days from each participant – and to evaluate the test’s specificity using participants from non-endemic areas. An alternative approach would be to use a predicted gold standard at population level – like the pocket chart described Table 2. Latent class analysis of the studies on the accuracy of point-of-care testing for circulatory cathodic antigen in the detection of schistosome infection included in the meta-analysis Latent class and study CCA test investigated, and no. of samples per participant No. of stool samples per participanta Latent class 1 Coulibaly, 2011 Cassette (1) 1 Coulibaly, 2011 (study 1) Cassette (1) 3 Coulibaly, 2011 (study 1) Cassette (3) 3 Coulibaly, 2011 (study 2) Cassette (1) 3 Coulibaly, 2011 (study 2) Cassette (3) 3 Coulibaly, 2011 (study 3) Cassette (1) 3 Koukounari, 2013 (study 2) Cassette (1) 3 Latent class 2 Legesse, 2007 Cassette (1) 1b Legesse, 2008 Reagent strip (1) 1b Standley, 2010 Cassette (1) 1 Shane, 2011 Cassette (1) 1 Coulibaly, 2011 (study 3) Cassette (3) 3 Tchuem Tchuenté, 2012 Cassette (1) 1 Tchuem Tchuenté, 2012 (study 1) Cassette (1) 3 Tchuem Tchuenté, 2012 (study 1) Cassette (3) 3 Tchuem Tchuenté, 2012 (study 2) Cassette (1) 3 Tchuem Tchuenté, 2012 (study 2) Cassette (3) 3 Tchuem Tchuenté, 2012 (study 3) Cassette (1) 3 Tchuem Tchuenté, 2012 (study 3) Cassette (3) 3 Coulibaly, 2013 Cassette (1) 3 Coulibaly, 2013 Cassette (2) 2 Dawson, 2013 Cassette (1) 2 Erko, 2013 Cassette (1) 1 Erko, 2013 Cassette (1) 3 Erko, 2013 Cassette (3) 3 Koukounari, 2013 (study 1) Cassette (1) 3 Sousa-Figueiredo, 2013 Cassette (1) 1 Sousa-Figueiredo, 2013 (study 1) Cassette (1) 1 Sousa-Figueiredo, 2013 (study 2) Cassette (1) 1 Sousa-Figueiredo, 2013 (study 3) Cassette (1) 1 Adriko, 2014 Cassette (1) 1 Adriko, 2014 Cassette (1) 3 CCA: circulatory cathodic antigen. a Each examined as a duplicate Kato–Katz smear. b Stool samples were also checked by formol–ether concentration. Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 529 Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. by researchers.53 Although the combined results of antigen and Kato–Katz testing are not being employed in any current control programme, they may become a diagnostic option in the future. The absence of a clear and accurate reference standard creates additional uncertainty in the meta-analysis of results data from any diagnostic test. After investigating heterogeneity pat- terns through latent class bivariate analysis,34 we identified two latent classes (Table 2). As the substantial variation we observed in the diagnostic accuracy of the antigen test could not be entirely explained by a threshold ef- fect, we conducted subgroup analyses. The results indicated that the number of urine samples tested per participant had little effect on the antigen test’s sen- sitivity and specificity (data available from corresponding author). When we attempted to relate latent class to several background factors, we found that the number of urine samples tested per participant and the study year and country had little effect on the antigen test’s accuracy (data available from corresponding author). Several other factors that could not be thoroughly explored at this stage – e.g. age, ende- micity and effect of treatment – require further investigation. If not fully cured, most individu- als covered by mass administrations of praziquantel will have light infections that can easily be missed by insensitive tests. Although we made no comparison of the antigen test’s performance before and after treatment, we evaluated the ef- fect of endemicity on the performance of antigen testing with the specific aim of determining how the test would perform in settings with generally low intensities of infection. We appreciate the fact that important additional evidence could have come from post-treatment stud- ies and – given that our meta-analysis involved mostly cross-sectional stud- ies – there may have been unknown confounding factors. We are also aware that our analysis was limited to data from Africa recorded in 20 articles. Despite these limitations, the findings of the studies included in our analysis seem fairly consistent. Although the quality of the included studies was not formally assessed, potential sources of heterogeneity were explored. Our main conclusions are consistent with the available evidence shown and are likely to be reliable. In conclusion, the antigen testing we evaluated appears to represent an effective, easy and low-cost tool for map- ping and monitoring programmes for the control of S. mansoni and, possibly, S. haematobium. Well-designed studies involving head-to-head comparisons of the cost and cost–effectiveness of anti- gen testing and either Kato–Katz smears or urine filtration and evaluations of the performance of antigen testing post- treatment are recommended. ■ Acknowledgements We thank WHO for commissioning and supporting the preparation of this study. We thank L Chitsulo, D Engels, G Biswas, A Garba and M Vonlanthen (all currently or formerly of WHO), G Van Dam and the School of Public Health, University of Ghana, Legon, Ghana. Funding: This study was commissioned and supported by WHO. Competing interests: None declared. Fig. 6. Accuracy of double or triple point-of-care testing for circulatory cathodic antigen in the detection of Schistosoma mansoni infection Study TP FP FN TN Sensitivity Specificity Coulibaly 2011 (study 1) 32 17 16 80 0.67 (0.53–0.78) 0.82 (0.74–0.86) Coulibaly 2011 (study 2) 51 9 15 48 0.77 (0.66–0.86) 0.84 (0.73–0.91) Coulibaly 2011 (study 3) 138 3 13 10 0.91 (0.86–0.95) 0.77 (0.50–0.92) Tchuem Tchuenté 2012 (study 1) 46 40 4 48 0.92 (0.81–0.97) 0.55 (0.44–0.65) Tchuem Tchuenté 2012 (study 2) 160 45 16 24 0.91 (0.86–0.94) 0.35 (0.25–0.47) Tchuem Tchuenté 2012 (study 3) 149 60 6 27 0.96 (0.92–0.98) 0.31 (0.22–0.41) Coulibaly 2013 53 132 3 54 0.95 (0.85–0.98) 0.29 (0.23–0.36) Erko 2013 313 126 16 165 0.95 (0.92–0.97) 0.57 (0.51–0.62) Pooled effect 0.91 (0.84–0.95) 0.56 (0.39–0.72) Sensitivity 0 0.2 0.4 0.6 0.8 1 Specificity 0 0.2 0.4 0.6 0.8 1 FN: false negatives; FP: false positives; TN: true negatives; TP: true positives. Notes: The analysed data came from eight studies20,21,24,46 in which, for each participant, examination of duplicate Kato–Katz smears of three – or, in one study,46 two – consecutive stool samples served as the reference standard. Each participant was tested three times – or, in one study,46 twice – for antigen, using cassette assays. In the antigen testing, all positive results – including trace positives – were considered indicative of infection. Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741530 Systematic reviews Accuracy of antigen testing in detecting schistosome infection Anthony Danso-Appiah et al. 摘要 血吸虫感染检测中循环阴极抗原即时检测的准确性 ： 系统评价和元分析 目的 旨在评估血吸虫感染诊断中循环阴极抗原即时检 测的准确性。 方法 我们搜索了截止 2015 年 9 月 30 日前在美国联 机医学文献分析和检索系统 (MEDLINE)、荷兰医学 文摘数据库 (EMBASE)、拉丁美洲和加勒比健康科学 文献库 (LILACS) 和其他书目数据库中发表的研究， 这 些研究对每位研究对象的循环阴极抗原检测与一至三 次加藤氏厚涂片检测进行对比描述——以检测曼氏血 吸虫——或对每位研究对象的循环阴极抗原检测与一 份 10ml 尿液样本过滤进行对比描述——以检测埃及 血吸虫。 我们归纳整理了抗原检测中真阳性、假阳性、 真阴性和假阴性结果的数量，并且利用多变量分层回 归模型进行了元分析。 结果 在 1994 年到 2014 年间发表的研究中，有二十六 项符合纳入标准。 曼氏血吸虫检测中，与单次加藤氏 厚涂片检测相比，单次抗原检测的汇总灵敏度为 0.90 （95% 置信区间，CI: 0.84–0.94），且汇总特异度为 0.56 （95% 置信区间 : 0.39–0.71;n = 7）。 与每位研究对象 的两至三次加藤氏厚涂片检测相比，相应数值分别 为 0.85（95% 置信区间 : 0.80-0.88）和 0.66（95% 置信 区间 : 0.53–0.76;n = 14）。 与一次抗原检测相比，对每 位研究对象进行三次抗原检测后，并未发现明显优势。 当与尿液过滤相比，埃及血吸虫抗原检测表现出较差 的灵敏度和特异度。 在高发地区，抗原检测的表现优 于低发环境中的表现。 结论 抗原检测可用作一种控制曼氏血吸虫的有效监测 措施。 Résumé Précision des tests de détection de l’antigène cathodique circulant réalisés sur les lieux des soins pour le diagnostic des schistosomiases: revue systématique et méta-analyse Objectif Évaluer la précision des tests de détection de l’antigène cathodique circulant pratiqués sur les lieux des soins pour le diagnostic des schistosomiases. Méthodes Nous avons fait des recherches dans MEDLINE, EMBASE, LILACS et d’autres bases de données bibliographiques pour trouver des études publiées jusqu’au 30 septembre 2015 décrivant les résultats de tests de détection de l’antigène cathodique circulant comparativement à ceux obtenus avec un, deux ou trois tests Kato-Katz réalisé(s) pour chaque sujet (pour le dépistage d’une infection à Schistosoma mansoni) ou comparativement aux résultats de l’examen par filtration d’un échantillon de 10 ml d’urine par sujet (pour le dépistage d’une infection à S. haematobium). Nous avons extrait les nombres de vrais positifs, de faux positifs, de vrais négatifs et de faux négatifs associés à la technique de détection antigénique et nous avons réalisé des méta-analyses en employant un modèle de régression hiérarchique bivarié. Résultats Vingt-six études publiées entre 1994 et 2014 ont respecté les critères d’inclusion. Pour le dépistage des infections à S. mansoni, avec un test unique de détection antigénique, nous avons obtenu une sensibilité combinée de 0,90 (intervalle de confiance -IC- de 95%: 0,84–0,94) et une spécificité combinée de 0,56 (IC de 95%: 0,39–0,71; n = 7) par comparaison avec les résultats d’un seul test Kato-Katz. Par comparaison avec les résultats de deux ou de trois tests Kato-Katz صخلم :ايسراهلبلا ىودع فاشتكا في نيارودلا يطبهلما دضتسملل ةيريسرلا ةياعرلا نكامأ تارابتخا ةقد يولَت ليلتحو ةيجهنم ةعجارم ةيريسرلا ةياعرلا نكامأ في متت يتلا تارابتخلاا ةقد مييقت ضرغلا .ايسراهلبلا ىودع فاشتكا في نيارودلا يطبهلما دضتسملل ،MEDLINE تايطعم دعاوق في ثحب ءارجإب انمق ةقيرطلا ةيفارغويلببلا دعاوقلا نم اهيرغو LILACS و ،EMBASE و لوليأ/برمتبس 30 ىتح تشرن تاسارد لىع روثعلل ىرخلأا يطبهلما دضتسلما رابتخا فصو الهلاخ نم مت يتلاو 2015 Kato‑Katzةينقتب تارابتخا ةثلاث لىإ دحاو عم ةنراقلماب نيارودلا ةدحاو ةنيع يرطقت وأ – ةينوسنلما ايسراهلبلا ىودعل – ةلاح لكل .ةيومدلا ايسراهلبلا ىودعل – ةلاح لكل لوبلا نم لم 10 رادقمب ،ةيقيقلحا ةيبايجلإا جئاتنلا لىإ ةيرشلما ماقرلأا جارختساب انمقو جئاتنلاو ،ةيقيقلحا ةيبلسلا جئاتنلاو ،ةبذاكلا ةيبايجلإا جئاتنلاو يولَت ليلتح ءارجإب انمقو ،دضتسلما رابتخلا ةبذاكلا ةيبلسلا .جودزلما ليسلستلا فوحتلا جذومن مادختساب ينب ةترفلا في ةروشنم ةسارد نوشرعو تس كانه تناك جئاتنلا فاشتكا ةلاح في .رايتخلاا يرياعلم ةمئلام 2014و 1994 يماع اًرادقم دضتسملل دحاو رابتخا رهظأ ،ةينوسنلما ايسراهلبلا ىودع :% 95 اهرادقم ةيحجرأ ةبسنب( 0.90 غلبي ةيعمالجا ةيساسلحا نم ةيحجرأ ةبسنب( 0.56 رادقمب ةيعاجم ةيعونو )0.94–0.84 عم هتنراقم متت امدنع )7 = ددعلا ؛0.39–0.71 95% اهرادقم نع ةتجانلا ةلباقلما ميقلا تناكو .Kato‑Katz ةينقتب دحاو رابتخا لكل Kato‑Katz ةينقتب تارابتخا ةثلاث لىإ يننثا عم تانراقلما )0.88–0.80 :% 95 اهرادقم ةيحجرأ ةبسنب( 0.85 غلبت ةلاح = ددعلا ؛0.76–0.53 :% 95 اهرادقم ةيحجرأ ةبسنب( 0.66و ةثلاث مادختسا في ةزيم ةيأ دجوت لا هنأ ادب دقل .لياوتلا لىع ،)14 .دحاو رابتخا مادختسا نم ًلادب ةلاح لكل دضتسملل تارابتخا ةيساسح ةيومدلا ايسراهلبلا ىودعل دضتسلما رابتخا رهظأ دقل ناكو .لوبلا يرطقت جئاتن عم هتنراقم دنع ةفيعض ةيعونو ةفيعض ينطوت بسن ابه دجوي يتلا قطانلما في لضفأ دضتسلما رابتخا ءادأ ينطوت بسن ابه دجوي يتلا نكاملأا نم رثكأ ىودعلل ةعفترم .ىودعلل ةضفخنم جمابرلا ةبقارلم ةلاعف ةادأ دضتسلما رابتخا لثمي دق جاتنتسلاا .ةينوسنلما ايسراهلبلا ىودع ةحفاكلم ةصصخلما Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 531 Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. pour un même sujet, ces valeurs ont été estimées à 0,85 (IC de 95%: 0,80-0,88) et 0,66 (IC de 95 % : 0,53–0,76; n = 14) respectivement. La réalisation de trois tests de détection antigénique plutôt que d’un seul ne semble apporter aucun avantage. Pour le dépistage des infections à S. haematobium, les tests de détection antigénique se sont révélés peu sensibles et peu spécifiques par comparaison avec les résultats des examens d’urine par filtration. Les tests de détection antigénique ont été plus performants dans les régions à forte endémicité que dans les régions à faible endémicité. Conclusion Les tests de détection antigénique peuvent constituer des outils efficaces pour le suivi des programmes de lutte contre S. mansoni. Резюме Точность тестирования на циркулирующий катодный антиген по месту лечения при диагностике шистосомоза: систематический обзор и метаанализ Цель Дать оценку точности тестирования на циркулирующий катодный антиген по месту лечения при диагностике шистосомоза. Методы Был осуществлен поиск в базах данных MEDLINE, EMBASE, LILACS и других библиографических базах данных на предмет исследований, опубликованных до 30 сентября 2015 года, в которых результаты тестирования на циркулирующий катодный антиген сравнивались бы с результатами от 1 до 3 анализов проб, взятых у одного пациента, по методу Като-Кац для обнаружения Schistosoma mansoni или с результатами фильтрования одного образца мочи (10 мл), взятого у одного пациента, для обнаружения S. haematobium. Было подсчитано количество истинно положительных, ложно положительных, истинно отрицательных и ложно отрицательных результатов тестирования на антитела, и были проведены метаанализы с конструированием двумерной иерархической регрессии. Результаты Двадцать шесть исследований, опубликованных в период между 1994 и 2014 годами, соответствовали критериям включения. При диагностике S. mansoni объединенная чувствительность метода при проведении одного теста на антитела составила 0,90 (95%-й доверительный интервал, ДИ: 0,84–0,94), а объединенная специфичность — 0,56 (95%-й ДИ: 0,39–0,71; n = 7) в сравнении с одним анализом по методу Като- Кац. Соответствующие значения, в сравнении с результатами от 2 до 3 анализов по методу Като-Кац для каждого пациента, были равны 0,85 (95%-й ДИ: 0,80–0,88) и 0,66 (95%-й ДИ: 0,53–0,76; n = 14) соответственно. Было установлено, что проведение трех тестов на антитела вместо одного не является целесообразным. В сравнении с результатами фильтрования мочи чувствительность и специфичность метода при тестировании на антитела для диагностики S. haematobium были неудовлетворительными. Эффективность тестирования на антитела была выше в зонах с высокой эндемичностью, чем в условиях с низкой эндемичностью. Вывод Тестирование на антитела может послужить эффективным способом для программ мониторинга по борьбе с S. mansoni. Resumen Exactitud de las pruebas en el punto de atención en busca de antígenos catódicos circulantes en la detección de infección por esquistosomas: una revisión sistemática y un metaanálisis Objetivo Evaluar la exactitud de las pruebas en el punto de atención en busca de antígenos catódicos circulantes en el diagnóstico de infección por esquistosomas. Métodos Se realizaron búsquedas en MEDLINE, EMBASE, LILACS y otras bases de datos bibliográficas para encontrar estudios publicados hasta el 30 de septiembre de 2015 que describiesen las pruebas de antígenos catódicos circulantes en comparación con entre una y tres pruebas de Kato–Katz por sujeto (para encontrar Schistosoma mansoni) o la filtración de 10 ml. de muestra de orina por sujeto (para encontrar S. haematobium). Se extrajeron las cifras de positivos, falsos positivos, negativos y falsos negativos para las pruebas de antígenos y se realizaron metaanálisis mediante un modelo bivariante de regresión jerárquica. Resultados Entre 1994 y 2014 se publicaron veintiséis estudios que cumplían los criterios de inclusión. Para detectar S. mansoni, una sola prueba de antígenos ofreció una sensibilidad combinada de 0,90 (intervalo de confianza, IC, del 95%: 0,84–0,94) y una especificidad combinada del 0,56 (IC del 95%: 0,39–0,71; n = 7) en comparación con una única prueba de Kato–Katz. Los valores correspondientes derivados de las comparaciones con entre dos y tres pruebas de Kato–Katz por sujeto fueron del 0,85% (IC del 95%: 0,80–0,88) y del 0,66 (IC del 95%: 0,53–0,76; n = 14), respectivamente. No parecía haber ventaja alguna a la hora de utilizar tres pruebas de antígenos por sujeto en lugar de una. En comparación con los resultados de la filtración de orina, las pruebas de antígenos de S. haematobium mostraron una sensibilidad y especificidad bajas. Los resultados de las pruebas de antígenos fueron mejores en zonas de alta endemicidad que en lugares de baja endemicidad. 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PMID: 22129037 53. de Vlas SJ, Gryseels B, van Oortmarssen GJ, Polderman AM, Habbema JD. A pocket chart to estimate true Schistosoma mansoni prevalences. Parasitol Today. 1993 Aug;9(8):305–7. doi: http://dx.doi.org/10.1016/0169- 4758(93)90132-Y PMID: 15463790 Bull World Health Organ 2016;94:522–533A| doi: http://dx.doi.org/10.2471/BLT.15.158741 533A Systematic reviews Accuracy of antigen testing in detecting schistosome infectionAnthony Danso-Appiah et al. Fig. 4. Single point-of-care testing for circulatory cathodic antigen in the detection of Schistosoma mansoni infection: summary receiver-operating characteristic curve Se ns iti vi ty 1.0 0.8 0.6 0.4 0.2 0 False-positive rate 0.2 0.4 0.6 0.8 1.0 AUC: area under the curve. Notes: The analysed data came from seven studies20,21,23,24,44,45,48 in which, for each participant, examination of duplicate Kato–Katz smears of a single stool sample served as the reference standard. In the antigen testing, all positive results – including trace positives – were considered indicative of infection. Data points for two studies21,24 were extracted from a report22 that included primary data from a multi-country study in Africa. Although reagent strips were used as the antigen tests in two of the studies,44,45 most of the data came from studies in which cassette assays had been used. The graph contains six separate types of information, represented by six separate types of graphical feature. Hollow circles represent the point estimates for the sensitivity and specificity of each study. Each of these circles is surrounded by a light grey oval, which presents the 95% credible region associated with that particular study. Similarly, the summary models – produced by pooling the estimates from each of the studies using a standard bivariate model – are presented both as a point estimate, represented by a solid green circle, and an associated 95% credible region, represented by the black oval. In addition to this, the best estimate for how the sensitivity and specificity vary with the diagnostic threshold adopted is represented by a line which runs from the bottom left to the top right portion of the graph. The solid section of this line represents interpolated estimates – which fill in the gaps between the studies available – whereas the dashed parts of this line are extrapolated from the data and are therefore more dependent on the modelling assumptions. Both the interpolated and the extrapolated parts of this line are needed to estimate the AUC, which is a measure of the antigen test’s diagnostic accuracy.