Evidence-based diagnosis of toxoplasma infection Evans R, Ho-Yen D O

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1 Evidence-based diagnosis of toxoplasma infection Evans R, Ho-Yen D O Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology Four commercially available toxoplasma assays and one in-house IgG enzyme immunoassay (EIA) for the diagnosis of toxoplasma infection were under evaluation. The commercial assays were AxSym IgG (Abbot Laboratories), Captia Select Toxo-G (Trinity Biotech), Toxoreagent "Eiken" (Eiken Chemical) and Toxolatex (Fumouze Laboratories). The in-house IgG EIA was from the Scottish Toxoplasma Reference Laboratory. Type of intervention Diagnosis. Economic study type Cost-effectiveness analysis. Study population The study population comprised patients who had a toxoplasmosis sera assay performed at the Scottish Toxoplasma Reference Laboratory (i.e., pregnant women, immunocompromised patients, patients suffering from ocular disease, patients with a transplant, and so on). Setting The setting was secondary care (a laboratory). The economic study was performed in Inverness, Scotland, UK. Dates to which data relate The effectiveness data were collected between June and December The resource use data related to the same time period. The price year appears to have been Source of effectiveness data The effectiveness data were derived from a single study. Link between effectiveness and cost data The staff costs were estimated prospectively from the same sample of sera that was used in the effectiveness analysis. The equipment costs were estimated from a sub-sample of five sera, although it was not reported whether this estimation was prospective or retrospective. Study sample Power calculations, to assure a certain power, were not reported in the planning phase of the study. One hundred and fifty-seven sera were randomly selected from all sera received at the Scottish Toxoplasma Reference Laboratory during the study period. All the tests considered at analysis were applied to them. The study sample included 53 pregnant Page: 1 / 5

2 women, 26 lymphadenopathy patients, 22 patients with a positive toxoplasmosis screening test, 14 with other symptoms, 10 transplanted patients, 9 patients with tiredness or fatigue, 8 with jaundice, 6 with ocular disease, 5 with fever, 2 babies, one patient with human immunodeficiency virus 1, and one with malignancy. Twenty potential crossreactive sera were tested to assess the specificity of the tests. The samples tested were reported not to differ significantly from those of the study population in terms of their antibody levels. Study design This was a diagnostic study that was performed at a single centre. The sera were randomly selected and four staff members assessed the outcomes blind. Analysis of effectiveness The diagnostic outcomes assessed were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the numbers-needed-to-diagnose (NND) one case of toxoplasma infection. These were assessed for each test under evaluation. A negative result was obtained when: the IgG was less than 2 IU/mL for the AxSym assay; the optical density was less than the cut-off value (2 IU/mL) minus 10% of this value for the Captia assay; there was less than 50% agglutination with the Eiken assay; and there was no agglutination with the Fumouze assay. For the purposes of the study, any other value was considered a positive result. Effectiveness results The following results were obtained in comparison with the dye test: for the IgG EIA, the sensitivity was 89.6%, the specificity 92.9%, the PPV 94%, the NPV 87.8%, and the NND 1.21; for the AxSym assay, the sensitivity was 87.4%, the specificity 94.3%, the PPV 95%, the NPV 85.7%, and the NND 1.22; for the Captia assay, the sensitivity was 78.2%, the specificity 97.1%, the PPV 97.1%, the NPV 78.2%, and the NND 1.33; for the Eiken assay, the sensitivity was 89.6%, the specificity 91.4%, the PPV 92.9%, the NPV 87.7%, and the NND 1.24; and for the Fumouze assay, the sensitivity was 86.2%, the specificity 94.3%, the PPV 94.9%, the NPV 84.6%, and the NND The number of false negative sera were: 9 with the in-house IgG EIA, 11 with the AxSym assay, 19 with the Captia assay, 9 with the Eiken assay, and Page: 2 / 5

3 12 with the Fumouze assay. The AxSym assay was the only one that produced false-positive results with the 20 potential cross-reactive sera used to assess the specificity of the tests. Clinical conclusions The in-house EIA and Eiken assays were the most sensitive and had specificities higher than 90%. The AxSym and Fumouze assays were less sensitive, but had better specificity values. The Captia EIA was the least sensitive, but it had the highest specificity. The NNDs were very similar across the four assays, with a higher value being obtained for the Captia assay. Methods used to derive estimates of effectiveness The authors made assumptions to derive the estimates of effectiveness. Estimates of effectiveness and key assumptions All the results of the effectiveness analysis were based on the assumption that the Sabin-Feldman dye test was the 'gold' standard. Therefore, it was assumed to have 100% sensitivity and specificity. Measure of benefits used in the economic analysis The summary measure of benefit used was the NND. This measure of benefit was obtained directly from the effectiveness analysis. Direct costs The costs considered in the economic analysis were those of the hospital. These were for the assays, manpower and equipment. The costs were obtained from the study sample and from the list prices for each assay. Some of the cost sources (e.g. for equipment and manpower) were not clearly specified, therefore it could not be assessed whether all the costing was based on current data. The time required for each assay was reported separately from the costs, and also the equipment costs associated with performing each test. Discounting was not carried out and neither were there any further adjustments for inflation, although these would not have been relevant given the short time (7 months) considered at analysis. No total costs or average costs were reported, only the cost per positive diagnosis. Statistical analysis of costs No statistical analyses of the costs were performed. Indirect Costs No indirect costs were estimated. Currency UK pounds sterling () and US dollars ($). The exchange rate used appears to have been 1 = $1.6. Sensitivity analysis No sensitivity analyses were performed. Estimated benefits used in the economic analysis See the 'Effectiveness Results' section. Page: 3 / 5

4 Cost results See the 'Synthesis of Costs and Benefits' section. Synthesis of costs and benefits The estimated benefits and costs were combined through cost-effectiveness ratios (CERs), calculated as the cost per positive diagnosis detected. The estimated CERs were: 0.57 ($0.91) per positive diagnosis detected with the IgG EIA assay; 7.06 ($11.30) per positive diagnosis detected with the AxSym assay; 2.79 ($4.46) per positive diagnosis detected with the Captia assay; 1.81 ($2.90) per positive diagnosis detected with the Eiken assay; and 1.42 ($2.27) per positive diagnosis detected with the Fumouze assay. Authors' conclusions The most cost-effective assay was the in-house enzyme immunoassay (EIA). This was followed by the Fumouze latex assay, which was the most cost-effective of the commercial assays. CRD COMMENTARY - Selection of comparators The authors reported that there is a wide range of assays on the commercial market for the diagnosis of toxoplasmosis infection. A positive point of this economic evaluation was that it considered five assays that were currently available in the UK. The comparator chosen was the Sabin-Feldman dye test, which was assumed to be the 'gold standard'. You should consider which toxoplasma assay is the most commonly used in your own setting. Validity of estimate of measure of effectiveness This was a diagnostic cohort study. Sera were randomly selected from all those received at the laboratory, which decreased the risk of selection bias. Moreover, the authors reported that the selected sera were representative of the sera from the study population in terms of their antibody levels. Validity of estimate of measure of benefit The summary measure of benefit used in the economic analysis was the NND. This measure of benefit was obtained directly from the effectiveness analysis. Validity of estimate of costs The perspective adopted was that of the hospital and, as such, all the relevant cost categories were included. Some of the resource quantities were reported separately from the costs. However, not all the sources of the cost data were reported. Moreover, no statistical analyses of the costs were performed. All these factors introduce uncertainty into the reliability of the conclusions. The authors did not report the total costs for each test, only the CERs. The total costs associated with performing each assay were not reported, although this would have been useful in order to perform an incremental analysis. Other issues The authors made appropriate comparisons of the study results with those from other studies, finding lower sensitivities and specificities for all the assays in this study. The results of this study would not be easily generalisable to other Page: 4 / 5

5 Powered by TCPDF ( settings because the study sample was not homogeneous. Implications of the study The authors recommended the use of in-house reagents for those specialist laboratories that are able to produce tachyzoites. Among the commercially available assays, they recommended the use of the Eiken latex kit because of its wide use across the UK, even though the Fumouze assay had a lower CER. Because of the heterogeneity of the study sample, and the different consequences that false-positive and false-negative results may have depending on the type of disease, it would have been useful to limit the study to specific sub-groups of patients with similar characteristics. That way, the results could have been extrapolated to other contexts. Source of funding None stated. Bibliographic details Evans R, Ho-Yen D O. Evidence-based diagnosis of toxoplasma infection. European Journal of Clinical Microbiology and Infectious Diseases 2000; 19(11): Other publications of related interest Lapplalainen M, Sintonen H, Koskiniem M. Cost-benefit analysis of screening for toxoplasmosis during pregnancy. Scandinavian Journal of Infectious Diseases 1995;27: Guerina NG, Ho-Wen H, Messner HC. Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. New England Journal of Medicine 1994;330: Indexing Status Subject indexing assigned by NLM MeSH Animal Population Groups; Antibodies, Protozoan /blood; Coloring Agents /metabolism; Comparative Study; Evidence- Based Medicine; Humans; Immunoenzyme Techniques /methods; Reagent Kits, Diagnostic /economics; Sensitivity and Specificity; Toxoplasma /immunology; Toxoplasmosis /diagnosis AccessionNumber Date bibliographic record published 31/01/2005 Date abstract record published 31/01/2005 Page: 5 / 5