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IgM ELISA for leptospirosis diagnosis: a systematic review and meta-analysis/ ELISA IgM para diagnostico de leptospirose: revisao sistematica e meta-analise.


Leptospirosis is a neglected infectious disease caused by spirochetes from the genus Leptospira. It constitutes the most widespread zoonosis and is emerging as a major public health problem with outcomes ranging from subclinical infections to fatal pulmonary hemorrhage and Weil's syndrome (1).

Leptospirosis has a broad geographical distribution, occurring in both rural and urban areas of tropical, subtropical and temperate regions. The disease outbreaks in developed countries are usually associated with occupational exposure, tourism or sporting events (1).

Leptospirosis is transmitted by contact of abraded skin or mucous membranes with water or soil contaminated with urine from reservoir animals, such as rodents (2). More than 500.000 cases of severe leptospirosis are reported each year, with mortality rates exceeding 10% (3). A new global estimate estimates that the overall annual incidence is 1 million cases and 60,000 deaths (4).

The microscopic agglutination test (MAT) is most often used as a reference test (5). Standard tests are tedious, laborious and require well-equipped laboratories with experienced staff and are therefore restricted to a few centers. Because the initial presentation of leptospirosis may be difficult to discern from other infectious diseases, rapid and accurate diagnosis is essential to prevent the progression of the more severe form of the disease, particularly in developing countries (2).

Traditional serological methods, such as the ELISA, are widely used to diagnose leptospirosis. Antileptospires IgM may be detected 4 to 5 days after the onset of symptoms, before detection of IgG and agglutinating antibodies, and persist at least 5 months in patients (6). ELISA can be performed with minimal training and typically provides results in 2-4 hours. The aim of this study was to perform a systematic review and meta-analysis of the literature to verify the accuracy of the IgM ELISA for leptospirosis diagnosis.


All methods for analysis, inclusion/exclusion criteria, data extraction and quality assessment were specified in advance. It was performed a systematic review according to a prospective protocol using PRISMA-statement guidelines (7,8). The review protocol is registered at PROSPERO (International prospective register of systemic reviews,; CRD42014 009784).

The electronic databases Medline via Pubmed, Lilacs (through Scielo interface), Cochrane Central Register of Controlled Trials, Embase and Grey literature (Google Scholar and British Library) were searched for papers published from January 1969 to July 2014. The following terms were used, both as text words and, as appropriate, Medical Subjects Heading (MeSH), or equivalent subject heading/thesaurus terms: Leptospirosis, Human Leptospirosis and IgM ELISA.

This sensitive filter was created by combining three filters to identify diagnostic studies via the Boolean operators "OR" and "AND". The search was limited to human studies and had no language restrictions. Reference lists of all available primary studies were reviewed to identify additional relevant citations. The complete search strategy is available on request.

Abstracts/titles identified from the search were screened by two reviewers. Disagreements about study inclusion or exclusion were initially solved by consensus, and if agreement was not possible, they were arbitrarily resolved by a third reviewer.

Cross-sectional and cohort studies, prospective and retrospective, which evaluated IgM enzyme-linked immunosorbent assay (Elisa) in Leptospirosis diagnosis were included. Studies that used the index test IgM Elisa to diagnose leptospirosis in patients were analyzed. The diagnostic reference standard was the result of the MAT with confirmation based on the result on the same serum sample as used for the index test. Therefore, the primary outcome analyzed was the presence of Leptospirosis.

It was extracted data on the studies, patients and test characteristics using a standardized form. Data were abstracted as 2 x 2 tables regarding IgM Elisa vs MAT in leptospirosis diagnosis (positive vs negative by cut-off). It was also calculated the sensitivities, specificities, and Odds Ratio diagnostic (DOR). Studies that lacked the data needed to construct 2 x 2 contingency tables were excluded. The assessment of non-English-language articles was performed independently following translation (if necessary). Any disagreement was resolved by consensus for studies published in all languages. Final inclusion or exclusion was made with reference to a selection criteria checklist.

Disagreements about study inclusion or exclusion were initially solved by consensus, and if agreement was not possible, they were arbitrarily resolved by another reviewer. The agreement statistics among reviewers were computed.

The methodological quality assessment for diagnostic accuracy was performed according to criteria from the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) (9). QUADAS-2 is designed to assess the quality of primary diagnostic accuracy studies, and it consists of four domains: patient selection, index test, reference standard, and flow of patients through the study and timing of the index tests(s) and reference standard "flow and timing". Signaling questions are included to help judge the risk of bias (8). The Quality assessment of studies was independently performed using the Review Manager 5.2 software (10).

The rates were calculated as true positive (TPR, sensitivity), false positive (FPR, 1--specificity), true negative (TN) and false negative (FN) (11). If any cell containing "0" was present in the contingency table, 0,5 was added to each cell to facilitate the calculations; if the study contained two cells with "0", the study was excluded from the analysis (12).

Bivariate analysis was used to calculate pooled estimates of sensitivity, specificity, and DOR in addition to 95% confidence intervals (CIs) for the summary estimates (13). The bivariate model preserves the 2-dimensional nature of diagnostic data by analyzing the logit transformed sensitivity and specificity of each study in a single model and considers both within-study and between-study variability, in contrast to the Littenberg and Moses method that departs from a fixed effects model (14). To detect cut-off threshold effects, the relationship between sensitivity and specificity was evaluated by the Spearman's correlation coefficient. Pooled estimates were only calculated for studies showing sufficient clinical and statistical homogeneity. [I.sup.2] or Q tests (commonly used in meta-analysis) are not recommended for assessing statistical homogeneity in diagnostic reviews because they do not consider the association between sensitivity and specificity (15). The DOR can relate to different combinations of sensitivities and specificities and describes the odds of the positive test resulting in participants with the disease compared with the odds of a positive test resulting in those without disease. A single diagnostic odds ratio corresponds to a set of sensitivities and specificities depicted by the SROC. It can change according to the threshold and to the ROC curve used to define an abnormal examination resulted in the expected trade-off between sensitivity and specificity.

A summary receiver operating characteristic curve was generated using data from all thresholds using the Littenberg and Moses method. Additionally, the area under the curve (AUC) can summarize the inherent capacity of a test for discriminating a diseased from a non-diseased subject. Accurate tests usually have AUCs close to 1, and poor tests usually have AUCs close to 0.5 (16). Sensitivity analyses were performed to assess excluding studies with a high risk of verification bias according to QUADAS 2. To analyze publication bias, inverted funnel plots of the logarithmic odds ratio (OR) of individual studies were plotted against sample size (15).

The statistical analysis was performed with the software Stata 1117, Meta-DiSc[R] (18) (version 1.4), and Review Manager 5.210.


A total of 545 studies were identified: 510 studies were identified using the database search and 35 additional records were identified through other sources. Seventy-nine full-text articles were retrieved; 27 were excluded after further scrutiny. Fifty-two primary studies, including 10,775 serum samples, met the criteria for inclusion and were included in the meta-analysis 19-69 (Figure 1).

Details of the participants and interventions are summarized in Table 1 (18-69). Most studies were prospective, except for two (41,44).

The quality assessment results are presented in Figure 2 (19-69). Thirteen studies fulfilled all criteria of QUADAS 2 (19-20-27-28-36-41-52-56-57-59-61-63-70). In five studies, the risk of bias was in the patient selection (31,44,55,58,62). Two studies showed unclear risk of bias in the reference standard (22,44) and two studies showed unclear risk of bias in the flow timing (39,45). Two studies have indicated high risk of bias in the patient selection in the applicability criteria (50,51), and two studies demonstrated a high risk of bias in evaluating the index test (48,65). In the other studies, there were some unclear applicability criteria in the index test and reference standard (19,21,23-26,29,30,32,34,35,38,40,42,43,46,47,49,53,54,57,64,67-69)

The robustness of the results was tested by repeating the analysis using a different statistical model (random effects model). Some studies were identified as outliers, and one re-analysis was performed without them. However, no significant difference was found in the sensitivity or specificity; therefore, those papers were not excluded from the meta-analysis.

All 52 studies selected were included in the meta-analysis. Statistical analyses were performed on both the acute and unspecific phase and only the acute phase. Analysis with excluding particular studies with high risk of bias (48,65) in relation to the index test were conducted, and because there was no significant change they were maintained the meta-analysis.

IgM ELISA for the diagnosis of human Leptospirosis had a pooled sensitivity in all studies of 0.86 (95% CI, 0.85-0.87). The pooled specificity in all studies was 0.90 (95% CI, 0.89-0.91). The estimates for heterogeneity were highly consistent across studies: sensitivity: QT = 914.77, P-value < 0.0001; inconsistency [I.sup.2] = 94.4%; and specificity: QT = 738.48, P-value < 0.0001; inconsistency [I.sup.2] = 93.1% (Figure 3).

IgM ELISA for the diagnosis of human leptospirosis had a pooled sensitivity in the acute phase of 0.84 (95% CI, 0.82-0.85), and the specificity of Leptospirosis in the acute phase was 0.91 (95% CI, 0.90-0.91). The estimates for heterogeneity were highly consistent across studies: sensitivity: QT = 764.77, P-value < 0.0001; [I.sup.2] = 95.3%; and specificity: QT = 435.55, P-value < 0.0001; [I.sup.2] = 91.7% (data not shown).

The DOR was 82.06 (95% CI, 45.77-147.12), QT=595.94, P-value = 0.001 in all studies and 67.11 (95% CI, 33.53-134.29), QT = 426.33, P-value = 0.001 in the acute phase (data not shown).

SROC curves were constructed due to heterogeneity in the DOR. The AUC for the ROC curve was estimated by a trapezoidal rule 95. The resulting summary ROC curves are shown with operating points for sensitivity and specificity. The AUC was 0.960 in all studies and 0.952 in the acute phase respectively (Figure 4).

Covariable-type studies were separated into prospective and retrospective design, and the meta-regression analysis indicated no association between type of studies and outcome (P = 0.32).

Begg's funnel plot and Egger's test were performed to assess the publication bias of the literature in all comparison models. The shape of the funnel plot reveals any evidence of obvious asymmetry. Then, the Egger's test was used to provide statistical evidence of funnel plot symmetry for total phase (P for bias = 0.001) and acute phase (P for bias = 0.008), indicating publication bias (data not shown).


In summary, this systematic review showed that IgM ELISA in all phases had a sensitivity of 0.86 and specificity of 0.84, whereas the acute phase had a sensitivity of 0.90 and specificity of 0.91.

The results showed that IgM ELISA could be useful as a screening and a confirmatory test, especially in regions with small laboratories that have difficulty performing other techniques such as MAT.

A recent systematic review included 35 studies up to 2010 and analyzed ELISA (IgM, IgG and IgA). In the present study, 55 studies with IgM only were included and analyzed the accuracy of IgM in the acute phase of the disease. We found a higher sensitivity compared to IgM results Signorini et al. (71), 86 versus 80%, respectively.

It was found high heterogeneity between studies. It is expected in meta-analyses of diagnostic test accuracy because it comes from observational studies, study designs and different cutoff points. This high heterogeneity was also observed in the meta-analysis performed by Signorini et al. (71).

A rapid diagnostic test provides a quick test result but does not indicate an early test. The ideal rapid test should have high accuracy, be easy to perform, interpret, inexpensive, and stable and give the result within 2 hours (70).

There are two phases of Leptospira infection: (1) between 3-7 days or acute septicemic phase with nonspecific symptoms such as myalgia and headache. The leptospires are detectable in the blood stream, decrease until 15 days (72) and (2) the start in the second week after the onset of symptoms, and the antibodies usually persist for several months (6). During this phase, leptospires are eliminated from the blood stream as IgM antibodies increase (73).

The rapid test depends on the detectable presence of anti-Leptospira antibodies already presented during the acute phase of the disease (74). Molecular tests that detect the causative agent can be confirmed during the first 5 days after the onset of the disease (75). It is very important that a test be rapid and sensitive, because the earlier the diagnosis the faster the treatment decision.

Whereas molecular tests, such as the polymerase chain reaction (PCR), that demonstrate the presence of the causative agent in a clinical sample mainly during the first 5 days after the onset of the disease (DPO), serological tests depend on the accumulation of detectable amounts of anti-Leptospira antibodies in the late acute to convalescent samples (74-76).

Rapid diagnostic tests should ideally be accurate, simple to use, relatively inexpensive, easy to interpret, stable under extreme conditions, require little or no processing, and give the results within 1-2 hours (70). Again, it is very important that a test be rapid and sensitive, because the earlier the diagnosis the faster the treatment decision.

Often, an early diagnosis or reference standard is employed in referral centers where confirmation is performed by experts. The rapid diagnosis is highly useful at the peripheral facilities and might be integral for early outbreak warning and useful for monitoring outbreaks if a rapid unusual accumulation of cases might provide an early alert, provided that specimens are collected, transported, and stored in an adequate manner (76).

This review, which included retrospective and prospective studies, had the following limitations: i) high heterogeneity found between studies; ii) use of selected samples and the choice of case definition may be a source of bias; and iii) it is a misunderstanding that rapid tests are easy and therefore do not require experience; iv) it may reflect population-related differences, such as past exposure to leptospirosis, exposure to environmental leptospires, or infection with other infectious agents.

In conclusion, in the meta-analysis, the diagnosis of leptospirosis was ascertained by definite clinical criteria and standard MAT criteria. Also, IgM ELISA is sufficiently sensitive for use as an initial screen for leptospiral infections. The IgM ELISA showed higher sensitivity (84%) and specificity (91%) in the diagnosis of acute leptospiral infection and can be used as a rapid test for the detection of the disease, therefore improving the prognosis of patients and decreasing the lethality of leptospirosis.

DOI: 10.1590/1413-812320172212.14112016


MI Rosa was responsible for the literature review, results analysis, data interpretation, and writing of the final article. MF Reis, C Simon, E Dondossola, MC Alexandre, and T Colonetti conducted the data interpretation and writing of the final article. FO Meller contributed with the writing and critic review of the manuscript.


The study was supported by the University of Extremo Sul Catarinense.


(1.) Pappas G, Papadimitriou P, Siozopoulou V, Christou L, Akritidis N. The globalization of leptospirosis: worldwide incidence trends. Int J Infect Dis 2008;12(4):351-357.

(2.) Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM; Peru-United States Leptospirosis Consortium. Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 2003;3(12):757-771.

(3.) World Health Organization (WHO). Report of the Second Meeting of the Leptospirosis Burden Epidemiology Reference Group (LERG).WHO: Geneva; 2011.

(4.) Hagan JE, Costa J, Calcagno M, Kane M, Torgerson P, Martinez-Silveira MS, Stein C, Abela-Ridder B, Ko AI. Global morbidity and mortality of leptospirosis: a systematic review. PLoS Negl Trop Dis 2015; 9(9):e0003898

(5.) Limmathurotsakul D, Turner EL, Wuthiekanun V, Thaipadungpanit J, Suputtamongkol Y, Chierakul W, Smythe LD, Day NP, Cooper B, Peacock SJ.FooPs gold: why imperfect reference tests are undermining the evaluation of novel diagnostics: a re-evaluation of 5 diagnostic tests for leptospirosis. Clin Infect Dis 2012;55(3):322-331.

(6.) Silva MV, Camargo ED, Batista L, Vaz AJ, Brandao AP, Nakamura PM, Negrao JM. Behaviour of specific IgM, IgG and IgA class antibodies in human leptospirosis during the acute phase of the disease and during convalescence. J Trop Med Hyg 1995;98(4):268-272.

(7.) Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analysis of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700.

(8.) Medeiros LR, Rosa MI, Silva BR, Reis ME, Simon CS, Dondossola ER, Cunha Filho JS. Accuracy of magnetic resonance in deeply infiltrating endometriosis: a systematic review and meta-analysis. Arch Gynecol Obstet 2015;291(3):611-621.

(9.) Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM; QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155(8):529-536.

(10.) Review Manager (RevMan) [computer program]. Version 5.2. 2012 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration.Altman DG. Some common problems in medical research. In: Altman DG, editor. Practical statistics for medical research. 9a ed. London: Chapman; 1999. p. 396-439.

(11.) Altman DG. Some common problems in medical research. In: Altman DG (eds). Practical statistics for medical research, 9 ed. London: Chapman; 1999. p. 396-439.

(12.) Irwig L, Tosteson AN, Gatsonis C, Lau J, Colditz G, Chalmers TC, Mosteller F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med 1994; 120(8):667-676.

(13.) Reitsma JB, Glas AS, Rutjes AWS, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produce informative summary measures in diagnostic reviews. J Clin Epidemiol 2005; 58(10):982-990.

(14.) Gatsonis C, Paliwal P. Meta-analysis of diagnostic and screening test accuracy evaluations: methodologic primer. AJR Am J Roentgenol 2006; 187(2):271-281.

(15.) Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 2005; 58(9):882-893.

(16.) Stata Corporation. Stata Statistical Software version 11: College Station, TX/ Stata Corporation; 2009.

(17.) Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006; 6:31.

(18.) Terpstra WJ, Ligthart GS, Schoone GJ. Serodiagnosis of human leptospirosis by enzyme-linked-immunosorrbent-assay (ELISA). Zentralbl Bakteriol A 1980; 247(3):400-405.

(19.) Pappas MG, Ballou WR, Gray MR, Takafuji ET, Miller RN, Hockmeyer WT. Rapid serodiagnosis of leptospirosis using the IgM-specific Dot-ELISA: comparison with the microscopic agglutination test. Am J Trop Med Hyg 1985; 34(2):346-354.

(20.) Da Silva MV, Camargo ED, Vaz AJ, Souza, AMC, Ueda M, Sakata, EE. Teste imunoenzimatico (ELISA) para deteccao de anticorpos circulantes da classe IgM na leptospirose humana. Rev Inst Med Trop Sao Paulo [online] 1988; [acessado 2017 Ago 25];30(2):95-100. Disponivel em:

(21.) Da Silva MV, Camargo ED, Vaz AJ, Souza AMC, Chieffi PP, Sakata EE. Imunodiagnostico da leptospirose humana atraves do teste ELISA-IgM, empregando-se diferentes preparacoes antigenicas a partir de sorotipos prevalentes de Leptospira interrogans. Rev Inst Med Trop Sao Paulo [online] 1990 [acessado 2017 Ago 25]; 32(4):233-239. Disponivel em: scielo.php?pid=S0036-46651990000400001&script=sci_abstract&tlng=pt

(22.) Silva MV, Camargo ED. Enzyme-linked immunosorbent assay ELISA for the detection of antibodies in the human leptospirosis. Rev Inst Med Trop Sao Paulo [online]. 1992[acessado 2017 Ago 25]; 34(3):239-242. Disponivel em:

(23.) Cinco M, Balanzin A, Banfi DAE. Evaluation of an immunoenzimatic test (ELISA) for the diagnosis of leptospirosis in Italy. Eur J of Epidemiology 1992;8(5):677682.

(24.) Cumberland P, Everard CO, Levett PN. Assessment of the efficacy of anIgM-elisa and microscopic agglutination test (MAT) in the diagnosis of acute leptospirosis. Am J Trop Med Hyg 1999;61(5):731-734.

(25.) Ribeiro MA, Souza CC, Almeida SH. Dot-ELISA for human leptospirosis employing immunodominant antigen. J Trop Med Hyg. 1995;98(6):452-456.

(26.) Ribeiro MA, Brandao AP, Romero EC. Evaluation of diagnostic tests for human leptospirosis. Braz J Med Biol Res 1996;29(6):773-777.

(27.) Polanco J, Aguirre L, Marcano E, Pantoja A. Diagnostico de la Leptospirosis Humana Mediante el uso de la tecnica dot-ELISA. Veterinaria Tropical 1997;22(1):65-75.

(28.) Winslow WE, Merry DJ, Pirc ML, Devine PL. Evaluation of a commercial enzyme-linked immunosorbent assay for detection of immunoglobulin M antibody in diagnosis of human leptospiral infection. J Clin Microbiol 1995;35(8):1938-1942.

(29.) Da Silva MV, Nakamura PM, Camargo ED, Batista L, Vaz AJ, Romero EC, Brandao AP. Immunodiagnosis of human leptospirosis by dot-ELISA for the detection of IgM, IgG, and IgA antibodies. Am J Trop Med Hyg 1997;56(6):650-655.

(30.) Brandao AP, Camargo ED, da Silva ED, Silva MV, Abrao RV. Macroscopic agglutination test for rapid diagnosis of human leptospirosis. J Clin Microbiol 1998;36(11):3138-3142.

(31.) Yersin C, Bovet P, Smits HL, Perolat P. Field evaluation of a one-step dipstick assay for the diagnosis of human leptospirosis in the Seychelles. Trop Med Int Health 1999;4(1):38-45.

(32.) Smits HL, van der Hoorn MA, Goris MG. Simple latex agglutination assay for rapid serodiagnosis of human leptospirosis. J Clin Microbiol 2000;38(3):1272-1275.

(33.) Sekhar WY, Soo EH, Gopalakrishnan V, Devi S. Leptospirosis in Kuala Lumpur and the comparative evaluation of two rapid commercial diagnostic kits against the MAT test for the detection of antibodies to leptospira interrogans. Singapore Med J 2000;41(8):370-375.

(34.) Levett PN, Branch SL, Whittington CU, Edwards CN, Paxton H. Two methods for rapid serological diagnosis of acute leptospirosis. Clin Diagn Lab Immunol 2001;8(2):349-351.

(35.) Smits HL, Chee HD, Eapen CK, Kuriakose M, Sugathan S, Gasem MH, Yersin C, Sakasi D, Lai-A-Fat RF, Hartskeerl RA, Liesdek B, Abdoel TH, Goris MG, Gussenhoven GC. Latex based, rapid and easy assay for human leptospirosis in a single test format. Trop Med Int Health 2001;6(2):114-118.

(36.) Zochowski WJ, Palmer MF, Coleman TJ. An evaluation of three commercial kits for use as screening methods for the detection of leptospiral antibodies in the UK. J Clin Pathol 2001;54(1):25-30.

(37.) Bharadwaj R, Bal AM, Joshi SA, Kagal A, Pol SS, Garad G, Arjunwadkar V, Katti R. An urban outbreak of leptospirosis in Mumbai, India. Jpn J Infect Dis 2002;55(6):194-196.

(38.) Cespedes Z M, Glenny A M, Felices AV, Balda J L, Suarez MV. Prueba de Elisa indirecta para la deteccion de anticuerpos IgM para el diagnostico de Leptospirosis humana. Revista Peruana de Medicina Experimental y Salud Publica 2002;19(1):1924-1927.

(39.) Effler PV, Bogard AK, Domen HY, Katz AR, Higa HY, Sasaki DM. Evaluation of eight rapid screening tests for acute leptospirosis in Hawaii. J Clin Microbiol 2002;40(4):1464-1469.

(40.) Levett PN, Branch SL. Evaluation of two enzyme-linked immunosorbent assay methods for detection of immunoglobulin M antibodies in acute leptospirosis. Am J Trop Med Hyg 2002;66(6):745-748.

(41.) Bajani MD, Ashford DA, Bragg SL, Woods CW, Aye T, Spiegel RA, Plikaytis BD, Perkins BA, Phelan M, Levett PN, Weyant RS. Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis. J Clin Microbiol 2003;41(2):803-809.

(42.) Sehgal SC, Vijayachari P, Sugunan AP, Umapathi T. Field application of Lepto lateral flow for rapid diagnosis of leptospirosis. J Med Microbiol 2003;52(Pt 10):897-901.

(43.) Nakarin J, Pradutkanchana S. Evaluation of enzyme-linked immunosorbent assay and indirect hemagglutination assay for detection of leptospiral antibody by using three different antigens. J Med Assoc Thai 2004;87(10):1218-1224.

(44.) Obregon AM, Martinez G, Martinez R, Llop A, Rodriguez I, Rodriguez J, Fernandez C. Serological response by ELISA and MAT in Cuban volunteers vaccinated with vax SPIRAL. Rev Cubana Med Trop 2004;56(2):148-1451.

(45.) Vitale G, La Russa C, Galioto A, Chifari N, Mocciaro C, Caruso R, Micalizzi A, Mansueto P, Di Rosa S, Mansueto S.Evaluation of an IgM-ELISA test for the diagnosis of human leptospirosis. New Microbiol 2004;27(2):149-154.

(46.) Tansuphasiri U, Deepradit S, Phulsuksombati D, Tangkanakul W. Two simple immunoassays using endemic leptospiral antigens for serodiagnosis of human leptospirosis. Southeast Asian J Trop Med Public Healt. 2005;36(2):302-311.

(47.) Blacksell SD, Smythe L, Phetsouvanh R, Dohnt M, Hartskeerl R, Symonds M, Slack A, Vongsouvath M, Davong V, Lattana O, Phongmany S, Keolouangkot V, White NJ, Day NP, Newton PN. Limited diagnostic capacities of two commercial assays for the detection of Leptospira immunoglobulin M antibodies in Laos. Clin Vaccine Immunol 2006;13(10):1166-1169.

(48.) de Abreu Fonseca C, Teixeira de Freitas VL, Calo Romero E, Spinosa C, Arroyo Sanches MC, da Silva MV, Shikanai-Yasuda MA. Polymerase chain reaction incomparison with serological tests for early diagnosis of human leptospirosis. Trop Med Int Health 2006;11(11):1699-1707.

(49.) Ooteman MC, Vago AR, Koury MC. Evaluation of MAT, IgM ELISA and PCR methodsfor the diagnosis of human leptospirosis. J Microbiol Methods 2006;65(2):247-257.

(50.) McBride AJ, Santos BL, Queiroz A, Santos AC, Hartskeerl RA, Reis MG, Ko AI. Evaluation of four whole-cell Leptospira-based serological tests for diagnosis of urban leptospirosis. Clin Vaccine Immunol 2007;14(9):1245-1248.

(51.) McBride AJ, Pereira FA, da Silva ED, Ferreira AG, Reis MG, Ko AI. Evaluation of the EIE-IgM-Leptospirose assay for the serodiagnosis of leptospirosis. Acta Trop 2007;102(3):206-211.

(52.) Velineni S, Asuthkar S, Umabala P, Lakshmi V, Sritharan M. Serological evaluation of leptospirosis in Hyderabad Andhra Pradesh: a retrospective hospital-based study. Indian J Med Microbiol 2007;25(1):24-27.

(53.) Dey S, Mohan CM, Ramadass P, Nachimuthu K. Diagnosis of leptospirosis by recombinant antigen based single serum dilution ELISA. Indian J Med Res 2008;128(2):172-177.

(54.) Honarmand HR, Nezafat TM, Heydarzadeh A, Soltani B, Mirzajani E, Asmar M. Evaluation an in-house IgM-ELISA for the diagnosis of human leptospirosis. Journal of Semnan University of Medical Sciences 2008;9(4):309-313.

(55.) Srimanote P, Wongdeethai N, Jieanampunkul P, Samonkiert S, Leepiyasakulchai C, Kalambaheti T, Prachayasittikul V.Recombinant ligA for leptospirosis diagnosis and ligA among the Leptospira spp. clinical isolates. J Microbiol Methods 2008;72(1):73-78.

(56.) Blanco RM, Takei K, Romero EC. Leptospiral glycolipoprotein as a candidate antigen for serodiagnosis of human leptospirosis. Lett Appl Microbiol 2009;49(2):267-273.

(57.) Pol S, Bharadwaj R. Evaluation of high performance liquid chromatography purified leptospiral antigen for the diagnosis of leptospirosis. Jpn J Infect Dis 2009;62(6):428-431.

(58.) Aviat F, Rochereau-Roulet S, Branger C, Estavoyer JM, Chatrenet B, Orsonneau JL, Thorin C, Andre-Fontaine G. Synthetic peptide issued from Hap1/LipL32 for new early serodiagnosis of human leptospirosis. Comp Immunol Microbiol Infect Dis 2010;33(5):375-387.

(59.) Shekatkar SB, Harish BN, Menezes GA, Parija SC. Clinical and serological evaluation of Leptospirosis in Puducherry, India. J Infect Dev Ctries 2010a 29;4(3):139-143.

(60.) Shekatkar S, Acharya NS, Harish BN, Parija SC. Comparison of an in-house latex agglutination test with IgM ELISA and MAT in the diagnosis of leptospirosis. Indian J Med Microbiol 2010;28(3):238-240.

(61.) Trombert-Paolantoni S, Thomas P, Hermet F, Clairet V, Litou N, Maury L..Leptospirosis screening: performance of the Serion Elisa Classic Leptospira IgM KIT. Pathol Biol (Paris) 2010;58(1):95-99.

(62.) Kucerova P, Cermakova Z, Pliskova L, Valenta Z, Pavlis O, Kubickova P Comparison of results of two serological methods for diagnosing leptospirosis--microagglutination test and ELISA. Klin Mikrobiol Infekc Lek 2011;17(5):173-178.

(63.) Silpasakorn S, Waywa D, Hoontrakul S, Suttinont C, Losuwanaluk K, Suputtamongkol Y. Performance of Leptospira immunoglobulin M ELISA and rapid immunoglobulin G immunochromatographic assays for the diagnosis of leptospirosis. J Med Assoc Thai 2011;94(Suppl.1):203-206.

(64.) Desakorn V, Wuthiekanun V, Thanachartwet V, Sahassananda D, Chierakul W, Apiwattanaporn A, Day NP, Limmathurotsakul D, Peacock SJ.Accuracy of a commercial IgM ELISA for the diagnosis of human leptospirosis in Thailand. Am J Trop Med Hyg 2012;86(3):524-527.

(65.) Kumar A, Rajasekar V, Selvakumar G, Dhanalakshmi DP. Comparison study between in-house IgM DOT-ELISA and the microscopic agglutination test (MAT) for the diagnosis of human leptospirosis. Int Research J of Pharmacy 2012;3(4):314-317.

(66.) Tanganuchitcharnchai A, Smythe L, Dohnt M, Hartskeerl R, Vongsouvath M, Davong V, Lattana O, Newton PN, Blacksell SD. Evaluation of the Standard DiagnosticsLeptospira IgM ELISA for diagnosis of acute leptospirosis in Lao PDR. Trans R Soc Trop Med Hyg 2012;106(9-2):563-566.

(67.) Bourhy P, Vray M, Picardeau M. Evaluation of an in-house ELISA using the intermediate species Leptospira fainei for diagnosis of leptospirosis. J Med Microbiol 2013;62(Pt 6):822-857.

(68.) Premlatha MM, Kaur IR, Avasthi R, Dey AB, Chaudhry R. A newer approach for the serodiagnosis of leptospirosis using outer membrane proteins of leptospira interrogans serovar tarassovi. Asian Journal of Medical Sciences 2013;4(2):41-46.

(69.) Vedhagiri K, Velineni S, Timoney JF, Shanmughapriya S, 1 Vijayachari P, Narayanan R, Natarajaseenivasan K. Detection of LipL32-specific IgM by ELISA in sera of patients with a clinical diagnosis of leptospirosis. Pathog Glob Health 2013;107(3):130-135.

(70.) Banoo S, Bell D, Bossuyt P, Herring A, Mabey D, Poole F, Smith PG, Sriram N, Wongsrichanalai C, Linke R, O'Brien R, Perkins M, Cunningham J, Matsoso P, Nathanson CM, Olliaro P, Peeling RW, Ramsay A.Evaluation of diagnostic tests for infectious diseases: general principles. Nat Rev Microbiol 2010;8(Suppl.):S17-29.

(71.) Agampodi SB, Matthias MA, Moreno AC, Vinetz JM. Utility of quantitative polymerase chain reaction in leptospirosis diagnosis: association of level of leptospiremia and clinical manifestations in Sri Lanka. Clin Infect Dis 2012;54(9):1249-1255.

(72.) Signorini ML, Lottersberger J, Tarabla HD, Vanasco NB. Enzyme-linked immunosorbent assay to diagnose human leptospirosis: a meta-analysis of the published literature. Epidemiol Infect. 2013;141(1):22-32

(73.) Levett PN. Leptospirosis. Clinical Microbiology Reviews 2001; 14(2):296-326.

(74.) Ahmed A, Anthony RM, Hartskeerl RA. A simple and rapid molecular method for Leptospira species identification. Infect Genet Evol 2010;10(7):955-962.

(75.) Ahmed A, Klaassen HLMB, Van der Veen M, van der Linden H, Goris MGA, Hartskeerl RA. Evaluation of real-time PCR and culturing for the detection of leptospires in canine samples. Advances in Microbiology 2012;2(2):162-170.

(76.) Goris MGA, Leeflang MMG, Boer KR, Goeijenbier M, van Gorp ECM4, Wagenaar JFP, Hartskeerl RA. Establishment of valid laboratory case definition for human leptospirosis. J Bacteriol Parasitol [periodico na Internet]. 2012 [acessado 2017 Ago 25];3. Disponivel em: doi: 10.4172/2155-9597.1000132

Artigo apresentado em 25/05/2016

Aprovado em 23/08/2016

Versao final apresentada em 25/08/2016

Maria Ines Rosa [1]

Maria Fernandes dos Reis [2]

Carla Simon [3]

Eduardo Dondossola [3]

Maria Cecilia Alexandre [3]

Tamy Colonetti [2]

Fernanda Oliveira Meller [1]

[1] Programa de Pos-Graduacao em Saude Coletiva, Universidade do Extremo Sul Catarinense (UNESC). Av. Universitaria 1105, Bairro Universitario. 88806-000 Criciuma SC Brasil.

[2] Programa de Pos-Graduacao em Ciencias da Saude, UNESC. Criciuma SC Brasil.

[3] Laboratorio de Epidemiologia, UNESC. Criciuma SC Brasil.

Caption: Figure 1. Flow diagram of the study selection process.

Caption: Figure 2. Results of the evaluation of each study according to QUADAS 2.

Caption: Figure 4. Summary receiver operating characteristic curves. A: all studies and B: acute phase.
Table 1. Characteristics of the primary diagnostic studies.

Author/year                Country           N (samples)   Mean Age

Aviat et al. 2009          France            48            NR
Bajani et al. 2003         EUA               775           NR
Bharadwaj et al. 2002      India             169           NR
Blacksell et al. 2006      Laos              70            NR
Blanco et al. 2008         Brazil            138           NR
Bourhy et al. 2013         France            197           45,05
Brandao et al. 1998        Brazil            353           32(6-67)
Cespedes et al. 2002       Peru              120           NR
Cinco et al. 1992          Italy             260           NR
Cumberland et al. 1999     United Kingdon    638           45.9(14-85)
Da Silva et al. 1988       Brazil            142           NR
Da Silva et al. 1990       Brazil            71            NR
Da Silva et al. 1992       Brazil            57            30.9
Da Silva et al. 1997       Brazil            114           30.5(12-52)
Desakorn et al. 2012       Thailand          214           NR
Dey et al. 2008            India             136           NR
Effler et al. 2002         Hawaii            217           NR
Fonseca et al. 2006        Brazil            124           34.4
Honarmand et al. 2008      Iran              152           NR
Kucerova et al. 2011       Czech Republic    45            44.24(19-82)
Kumar et al. 2012          India             319           NR
Levett et al. 2002         Barbados          48            NR
Levett et al. 2001         Barbados          51            NR
Mc Bride et al. 2007       Brazil            204           NR
Mc Bride et al. 2007b      Brazil            72            NR
Nakarin et al. 2004        Thailand          282           NR
Obregon et al. 2004        Cuba              71            NR
Ooteman et al. 2006        Brazil            158           NR
Pappas et al. 1985         EUA               172           NR
Pol and Bharadwaj 2009     India             50            NR
Polanco et al. 1997        Venezuela         181           NR
PremLtha et al. 2013       India             328           (3-75)
Ribeiro et al. 1995        Brazil            89            NR
Ribeiro et al. 1996        Brazil            89            NR
Sehgal et al. 2003         India             117           NR
Sekhar et al. 2000         Malaysia          70            NR
Shekathar et al. 2010a     India             110           NR
Shekatkar et al. 2010b     India             150           40.5(15-84)
Silpasakorn et al. 2011    Thailand          161           NR
Smits et al. 2000          Hawaii            686           NR
Smits et al. 2001          Hawaii            420           NR
Srimanote et al. 2007      Thailand          75            NR
Tanganuchitcharnchai       Laos              70            30(12-50)
  et al. 2012
Tansuphasiri et al. 2005   Thailand          343           NR
Terpstra et al. 1980       The Netherlands   313           NR
Trombert-Paolantoni        France            79            NR
  et al. 2010
Vedhagiri et al. 2013      India             1289          NR
Velineni et al. 2006       India             32            NR
Vitale et al. 2003         Italy             71            NR
Winslow et al. 1997        Australia         274           NR
Yersin et al. 1999         The Netherlands   161           NR
Zochowski et al. 2001      UK                200           NR
TOTAL                                        10775

Author/year                Cut-off   Stage        TP     FP    FN

Aviat et al. 2009          0.5       Acute        12     3     26
Bajani et al. 2003         NR        Unspecific   115    38    18
Bharadwaj et al. 2002      NR        Acute        67     11    7
Blacksell et al. 2006      NR        Acute        7      18    3
Blanco et al. 2008         NR        Acute        27     0.5   3
Bourhy et al. 2013         0,4       Unspecific   141    0.5   8
Brandao et al. 1998        NR        Acute        107    1     1
Cespedes et al. 2002       0.6       Acute        39     1     1
Cinco et al. 1992          0.245     Acute        110    08    25
Cumberland et al. 1999     NR        Acute        167    19    154
Da Silva et al. 1988       0.589     Acute        41     21    9
Da Silva et al. 1990       0.382     Acute        21     0.5   9
Da Silva et al. 1992       0.630     Acute        26     0.5   0.5
Da Silva et al. 1997       NR        Acute        65     0.5   1
Desakorn et al. 2012       NR        Acute        56     36    51
Dey et al. 2008            0.8       Unspecific   77     0.5   3
Effler et al. 2002         NR        Acute        16     18    17
Fonseca et al. 2006        NR        Acute        47     07    13
Honarmand et al. 2008      NR        Unspecific   88     1     10
Kucerova et al. 2011       NR        Acute        10     4     0.5
Kumar et al. 2012          NR        Acute        130    2     2
Levett et al. 2002         NR        Unspecific   24     9     4
Levett et al. 2001         NR        Acute        25     9     3
Mc Bride et al. 2007       NR        Acute        41     36    0.5
Mc Bride et al. 2007b      NR        Acute        25     0.5   4
Nakarin et al. 2004        0.9       Acute        79     0.5   6
Obregon et al. 2004        NR        Unspecific   37     2     1
Ooteman et al. 2006        NR        Unspecific   44     12    3
Pappas et al. 1985         NR        Unspecific   93     14    4
Pol and Bharadwaj 2009     0.41      Unspecific   17     2     3
Polanco et al. 1997        NR        Unspecific   44     63    5
PremLtha et al. 2013       NR        Unspecific   32     50    31
Ribeiro et al. 1995        NR        Acute        23     24    3
Ribeiro et al. 1996        NR        Unspecific   23     28    1
Sehgal et al. 2003         NR        Acute        35     10    35
Sekhar et al. 2000         0.5       Acute        26     01    12
Shekathar et al. 2010a     0.5       Acute        15     26    25
Shekatkar et al. 2010b     NR        Acute        29     0.9   9
Silpasakorn et al. 2011    NR        Acute        54     0.5   35
Smits et al. 2000          0.4       Acute        286    7     48
Smits et al. 2001          0.1       Acute        120    17    15
Srimanote et al. 2007      0,75      Acute        32     04    14
Tanganuchitcharnchai       NR        Acute        09     17    01
  et al. 2012
Tansuphasiri et al. 2005   NR        Acute        95     15    01
Terpstra et al. 1980       0,45      Unspecific   91     01    05
Trombert-Paolantoni        NR        Acute        27     09    03
  et al. 2010
Vedhagiri et al. 2013      NR        Acute        1137   10    43
Velineni et al. 2006       0,45      Unspecific   26     04    02
Vitale et al. 2003         0,45      Acute        19     02    0,5
Winslow et al. 1997        NR        Acute        41     16    0,5
Yersin et al. 1999         NR        Acute        36     03    01
Zochowski et al. 2001      0,40      Unspecific   96     07    04
TOTAL                                             4050   605   682

Author/year                TN

Aviat et al. 2009          7
Bajani et al. 2003         604
Bharadwaj et al. 2002      84
Blacksell et al. 2006      42
Blanco et al. 2008         108
Bourhy et al. 2013         48
Brandao et al. 1998        244
Cespedes et al. 2002       79
Cinco et al. 1992          117
Cumberland et al. 1999     298
Da Silva et al. 1988       71
Da Silva et al. 1990       41
Da Silva et al. 1992       31
Da Silva et al. 1997       48
Desakorn et al. 2012       71
Dey et al. 2008            51
Effler et al. 2002         166
Fonseca et al. 2006        57
Honarmand et al. 2008      53
Kucerova et al. 2011       31
Kumar et al. 2012          185
Levett et al. 2002         11
Levett et al. 2001         14
Mc Bride et al. 2007       127
Mc Bride et al. 2007b      38
Nakarin et al. 2004        197
Obregon et al. 2004        31
Ooteman et al. 2006        99
Pappas et al. 1985         61
Pol and Bharadwaj 2009     28
Polanco et al. 1997        69
PremLtha et al. 2013       215
Ribeiro et al. 1995        39
Ribeiro et al. 1996        37
Sehgal et al. 2003         37
Sekhar et al. 2000         31
Shekathar et al. 2010a     44
Shekatkar et al. 2010b     103
Silpasakorn et al. 2011    72
Smits et al. 2000          345
Smits et al. 2001          268
Srimanote et al. 2007      25
Tanganuchitcharnchai       43
  et al. 2012
Tansuphasiri et al. 2005   232
Terpstra et al. 1980       216
Trombert-Paolantoni        40
  et al. 2010
Vedhagiri et al. 2013      99
Velineni et al. 2006       0,5
Vitale et al. 2003         50
Winslow et al. 1997        217
Yersin et al. 1999         121
Zochowski et al. 2001      93
TOTAL                      5438

NR, not reported; TP, true-positive; FP, false-positive,
FN, false-negative, TN, true-negative.

Figure 3. Forest plot of sensitivity (A) and
specificity (B) of the all studies included in this review.

Study                                 Sensitivity
                                   (95% Conf Interval)

Aviat et al. 2009                   0,32 (0,18-0,49)
Bajani et al. 2003                  0,86 (0,79-0,92)
Bharadwaj et al. 2002               0,91 (0,81-0.96)
Blacksell et al. 2006               0,70 (0,35-0,93)
Blanco et al. 2008                  0,90 (0,73-0,98)
Bourhy et al. 2013                  0,99 (0,91-1,00)
Brandao et al. 1998                 0,99 (0,95-1,00)
Cespedes et al. 2002                0,98 (0,87-1,00)
Cinco et al. 1992                   0,81 (0,74-0,88)
Cumberland et al. 1999              0,52 (0,46-0,58)
Da Silva et al. 1988                0,82 (0,69-0,91)
Da Silva et al. 1990                0,70 (0,51-0,85)
Da Silva et al. 1992                0,98 (0,84-1,00)
Da Silva et al. 1994                0,98 (0,79-1,00)
Da Silva et al. 1997                0,98 (0,92-1,00)
Desakorn et al. 2012                0,52 (0,42-0,62)
Dey et al. 2008                     0,96 (0,89-0,99)
Effler et al. 2002                  0,48 (0,31-0,66)
Fonseca et al. 2006                 0,78 (0,66-0,88)
Honarmand et al. 2008               0,90 (0,82-0,95)
Kucerova et al. 2011                0,95 (0,63-1,00)
Kumar et al. 2012                   0,98 (0,95-1,00)
Levett et al. 2002                  0,86 (0,67-0,96)
Levett et al. 2001                  0,89 (0,72-0,98)
Mc Bride et al. 2007                0,99 (0,72-0,98)
Mc Bride et al . 2007b              0,86 (0,68-0,96)
Nakarin et al. 2004                 0,93 (0,85-0,97)
Obregon et al. 2004                 0,97 (0,86-1,00)
Ooteman et al. 2006                 0,94 (0,82-0,99)
Pappas et al. 1985                  0,96 (0,90-0,99)
Pol and Bharadwaj 2009              0,85 (0,62-0,97)
Polanco et al. 1997                 0,90 (0,78-0,97)
Ribeiro et al. 1996                 0,88 (0,70-0,98)
Ribeiro et al. 1995                 0,96 (0,79-1,00)
Sehgal et al. 2003                  0,50 (0,38-0,62)
Sekhar et al. 2000                  0,68 (0,51-0,82)
Shekathar et al. 2010b              0,38 (0,23-0,54)
Shekatkar et al. 2010a              0,76 (0,60-0,89)
Silpasakorn et al. 2011             0,61 (0,50-0,71)
Smits et al. 2000                   0,86 (0,81-0,89)
Smits et al. 2001                   0,89 (0,82-0,94)
Srimanote et al. 2007               0,70 (0,54-0,82)
Tanganuchitcharnchai et al. 2012    0,90 (0,55-1,00)
Tansuphasiri et al. 2005            0,99 (0,94-1,00)
Terpstra et al. 1980                0,95 (0,88-0,98)
Trombert-Paolantoni et al. 2010     0,90 (0,73-0,98)
Vedhagiri et al. 2013               0,96 (0,95-0, 97)
Velineni et al. 2006                0,93 (0,76-0,99)
Vitale et al. 2003                  0,97 (0,78-1,00)
Winslow et al. 1997                 0,99 (0,89-1,00)
Yersin et al. 1999                  0,97 (0,86-1,00)
Zochowski et al. 2001               0,96 (0,90-0,99)

Pooled Sensitivity = 0,86 (0,85 to ,87)

Heterogeneity chi-squared = 873,87 (d.f.= 51) p = 0,0000
Inconsistency (I-square) = 94,2%

Aviat et al. 2009                   0,70 (0,35-0,93)
Bajani et al. 2003                  0,94 (0,92-0,96)
Bharadwaj et al. 2002               0,88 (0,80-0,94)
Blacksell et al. 2006               0,70 (0,57-0,81)
Blanco et al. 2008                  1,00 (0,96-1,00)
Bourhy et al .2013                  0,95 (0,90-0,98)
Brandao et al. 1998                 1,00 (0,98-1,00)
Cespedes et al. 2002                0,99 (0,93-1,00)
Cinco et al. 1992                   0,94 (0,88-0,97)
Cumberland et al. 1999              0,94 (0,91-0,96)
Da Silva et al. 1988                0,77 (0,94-0,85)
Da Silva et al. 1990                0,99 (0,89-1,00)
Da Silva et al. 1992                0,98 (0,86-1,00)
Da Silva et al. 1994                0,97 (0,74-1,00)
Da Silva et al. 1997                0,99 (0,91-1,00)
Desakorn et al. 2012                0,66 (0,57-0,75)
Dey et al. 2008                     0,91 (0,80-0,97)
Efflr et al. 2002                   0,90 (0,85-0,94)
Fonseca et al. 2006                 0,89 (0,79-0,95)
Honarmand et al. 2008               0,98 (0,90-1,00)
Kucerova et al. 2011                0,89 (0,73-0,97)
Kumar et al. 2012                   0,99 (0,96-1,00)
Levett et al. 2002                  0,55 (0,32-0,77)
Levett et al. 2001                  0,61 (0,39-0,80)
Mc Bride et al. 2007                0,78 (0,71-0,84)
Mc Bride et al. 2007b               0,88 (0,75-0,96)
Nakarin et al. 2004                 1,00 (0,98-1,00)
Obregon et al. 2004                 0,94 (0,80-0,99)
Ooteman et al. 2006                  0,89 (0,82-0,94)
Pappas et al. 1985                  0,81 (0,71-0,89)
Pol and Bharadwaj 2009              0,93 (0,78-0,99)
Polanco et al. 1997                 0,52 (0,43-0,61)
Ribeiro et al. 1996                 0,62 (0,49-0,74)
Ribeiro et al. 1995                 0,57 (0,44-0,69)
Sehgal et al. 2003                   0,79 (0,64-0,89)
Sekhar et al. 2000                  0,97 (0,84-1,00)
Shekathar et al. 2010b              0,63 (0,50-0,74)
Shekatkar et al. 2010a              0,92 (0,85-0,96)
Silpasakorn et al. 2011             0,99 (0,94-1,00)
Smits et al. 2000                   0,98 (0,96-0,99)
Smits et al. 2001                   0,94 (0,91-0,96)
Srimanote et al. 2007               0,86 (0,68-0,96)
Tanganuchitcharnchai et al. 2012     0,72 (0,59-0,83)
Tansuphasiri et al. 2005            0,94 (0,90-0,97)
Terpstra et al. 1980                1,00 (0,97-1,00)
Trombert-Paolantoni et al. 2010     0,82 (0,68-0,91)
Vedhagiri et al. 2013               0,91 (0,84-0,96)
Velineni et al. 2006                0,11 (0,00-0,67)
Vitale et al. 2003                  0,96 (0,87-1,00)
Winslow et al. 1997                 0,93 (0,89-0,96)
Yersin et al. 1999                  0,98 (0,93-0,99)
Zochowski et al. 2001               0,93 (0,86-0,97)

Pooled Specificity = 0,90 (0,90 to 0,91)

Heterogeneity chi-squared = 716,96 (d.f.= 51) p = 0,0000
Inconsistency (I-square) = 92,9%
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Author:Rosa, Maria Ines; Reis, Maria Fernandes dos; Simon, Carla; Dondossola, Eduardo; Alexandre, Maria Cec
Publication:Ciencia & Saude Coletiva
Date:Dec 1, 2017
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