Table 4 Characteristics of studies selected in the systematic review of studies evaluating the diagnostic accuracy of MAT, PCR, and IgM ELISA, published global and between 1950 – 2022 for MAT, PCR and IgM accuracy evaluation
A. MAT endemic studies | ||||||||||||||||
Study first author (ref) | Title | Journal | Year of recruitment | Country | Endemicity | Study setting | Type of study | Participants included | Mean age / Children | Case definition | MAT panel | Comparator test | DPO of fever at recruitment | Sample type for PCR test | Acute sample data/Convalescent samples data | Interval between acute and convalescent samples |
Woods K [25] | A comparison of two molecular methods for diagnosing leptospirosis from three different sample types in patients presenting with fever in Laos | Clin Microbiol Infect | 2014 | Vietiane, Laos | Yes | Mahosot Hospital | Prospective | Suspected leptospirosis | 39 years (0.5–97) / Yes | Titers of ≥ 1:400 or a fourfold rise in titre | 22 serovars. Performed at the WHO/FAO/OIE Collaborating Centre for Leptospirosis Reference and Research, Queensland, Australia | Blood culture and PCR | 1–30 days | Serum or buffy coat | Yes/Yes | 10–14 days |
Blanco R [26] | Evaluation of nested polymerase chain reaction for the early detection of Leptospira spp. DNA in serum samples from patients with leptospirosis | Diagn Microbiol Infect Dis | 2010 | Brazil, Sao Paulo | Yes | Not stated | Prospective | Suspected leptospirosis | Not stated | Threshold: ≥ 1:800 or a fourfold rise | 21 serovars most frequently found in São Paulo, Brazil | PCR | Not stated | Serum | Yes/Yes | Not stated |
Merien F [27] | A rapid and quantitative method for the detection of Leptospira species in human leptospirosis | FEMS Microbiol Lett | 2004–2005 | Pacific Island Countries and Territories | Yes | Not stated | Prospective | Suspected leptospirosis | 30 years / Yes | Threshold: ≥ 1:400 or a fourfold rise | Not described | PCR | 1–30 days | Serum | Yes/Yes | Not stated |
Dittrich S [28] | A Prospective Hospital Study to Evaluate the Diagnostic Accuracy of Rapid Diagnostic Tests for the Early Detection of Leptospirosis in Laos | Am J Trop Med Hyg | 2014–2015 | Laos | Yes | Mahosot Hospital | Prospective | Suspected leptospirosis or typhus | 39 years (0.5–92) / Yes | Threshold: ≥ 1:400 or fourfold rise | MAT was performed and interpreted by the WHO Collaborating Center for Reference and Research on Leptospirosis, Australia | Blood culture and PCR | Interquartile range: 3–7 days | Serum | Yes/Yes | Not stated |
Albuquerque A [29] | Validation of a case definition for leptospirosis diagnosis in patients with acute severe febrile disease admitted in reference hospitals at the State of Pernambuco, Brazil | Rev Soc Bras Med Trop | 2009 | Pernambuco, Brazil | Yes | Hospital Barão de Lucena and Hospital Universitário Oswaldo Cruz | Prospective | Suspected leptospirosis | 32.9 (Standard deviation 13.2) / No | Threshold: > 1:800 or a fourfold rise | 22 serovars | Blood culture | 6.1 ± 2.6 DPO days | Not applicable | Yes/Yes | ≥ 14 days |
Philip N [30] | Combined PCR and MAT improves the early diagnosis of the biphasic illness leptospirosis | PLoS One | 2016–2017 | Malasya | Yes | Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan | Prospective | Suspected leptospirosis | Not stated | Threshold: > 1:400 or a fourfold rise | 20 serovars local and internationals | PCR | Not stated | Serum and Whole blood | Yes/Yes | Not stated |
Dinhuzen J [31] | A prospective study to evaluate the accuracy of rapid diagnostic tests for diagnosis of human leptospirosis | PLoS Negl Trop Dis | 2015–2016 | Thailand | Yes | 15 hospitals in the Srisaket province | Prospective | Suspected leptospirosis | 46 (Standard deviation 17) / No | Threshold: > 1:400 or a fourfold rise | Not described | Blood culture and PCR | Interquartile range 2–6 days | Whole blood | Yes/Yes | 7 days |
Mullan S [32] | An Important Tool for Early Diagnosis of Leptospirosis Cases | J Clin Diagn Res | 2008 | India | Yes | New Civil Hospital and peripheral health centre of South Gujarat | Prospective | Suspected leptospirosis | Unclear / No | No | 11 serogroups | Blood culture | Not stated | Not applicable | No/Yes | 15 days |
Vijayachari P [33] | Evaluation of Lepto Dri Dot as a rapid test for the diagnosis of leptospirosis | Epidemiol Infect | 2000–2001 | India | Yes | 3 primary health centres in South Andaman | Prospective | Suspected leptospirosis | Not stated | No | 10 serovars commonly encountered in India | Blood culture | Not stated | Not applicable | No/Yes | Not stated |
Kakita T [34] | Laboratory diagnostic, epidemiological, and clinical characteristics of human leptospirosis in Okinawa Prefecture, Japan, 2003–2020 | PLoS Negl Trop Dis | 2003–2020 | Japan, Okinawa Prefecture | Yes | Clinics and hospitals in Okinawa Prefecture | Prospective | Suspected leptospirosis | Not stated | No | 13 serovar strains of 12 serogroups | Blood culture and PCR | 0–14 days | Whole blood | No/Yes | Not stated |
Alia S [35] | Diagnostic accuracy of rapid diagnostic tests for the early detection of leptospirosis | J Infect Public Health | 2016–2017 | Malasya | Yes | Hospital Serdang | Prospective | Suspected leptospirosis | Not stated | Threshold: ≥ 1:400 or a fourfold rise | 20 serovars | PCR | Not stated | Whole blood | Yes/No | 21–30 days |
Sukmark T [36] | Diagnostic accuracy of rapid diagnostic tests for the early detection of leptospirosis | PLoS Negl Trop Dis | 2012–2014 | Thailand | Yes | 11 centers in 8 provinces around Thailand | Prospective | Suspected leptospirosis | Not stated | Threshold: ≥ 1:400 or a fourfold rise | Not described | Blood culture | Interquartile range 2–5 days | Not applicable | Yes/No | Not stated |
B. MAT non-endemic studies | ||||||||||||||||
Study first author (ref) | Title | Journal | Year of recruitment | Country | Endemicity | Study setting | Type of study | Participants included | Mean age / Children included | Case definition | MAT panel | Comparator test | DPO of fever at recruitment | Sample type for PCR test | Acute sample data/Convalescent sample data | Days between acute and convalescent sample |
Podgoršek D [37] | Evaluation of real-time PCR targeting the lipL32 gene for diagnosis of Leptospira infection | BMC Microbiology | Not stated | Slovenia | No | Different hospitals in Slovenia | Prospective | Febrile Patients | Not stated | Titers of ≥ 1:100 | 15 serovars from the geographic area | Blood culture | Not stated | Not stated | Yes/No | Not stated |
Podgoršek D [38] | Evaluation of the immunochromatographic (Leptocheck) test for detection of specific antibodies against leptospires | Wien Klin Wochenschr | Not stated | Slovenia | No | Different hospitals in Slovenia | Prospective | Suspected leptospirosis | Not stated | Titers of ≥ 1:100 | 13 serovars from the geographic area | Blood culture and PCR | No stated | Whole blood | Yes/Yes | 14–30 days |
Earl L [39] | An evaluation of diagnostic tests in a case series of suspected leptospirosis patients seen in primary care | N Z Med J | Not stated | New Zealand | No | General practices in Waikato and 3 medical centers in Wairoa | Prospective | Suspected for Leptospirosis | 39 years (11–73) /Yes | Threshold: > 1:400 andourfold rise | 8 serovars | Blood culture and PCR | Not stated | Whole Blood | No/Yes | Not stated |
C. PCR studies | ||||||||||||||||
Study first author (ref) | Title | Journal | Year of recruitment | Country | Endemicity | Study setting | Type of study | Participants included | Mean age / Children included | DPO of fever at recruitment | Sample type for PCR test | Comparator test | MAT Case definition for a positive acute sample | MAT case definition for a positive convalescent sample | MAT Paired samples | MAT panel |
Merien F [27] | A rapid and quantitative method for the detection of Leptospira species in human leptospirosis | FEMS Microbiology Letters | 2004–2005 | Pacific Island Countries and Territories | High | Not stated | Prospective | Suspected leptospirosis | 30 years / Yes | 1–30 days | Serum | MAT | ≥ 1:400 titer | Seroconversion or two fold-rise between titers | 10/41 | Unclear |
Esteves L [40] | Diagnosis of Human Leptospirosis in a Clinical Setting: Real-Time PCR High Resolution Melting Analysis for Detection of Leptospira at the Onset of Disease | Scientific Reports | 2015–2016 | Azores | High | Hospital | Prospective | Suspected leptospirosis | 48,2 years (Standard deviation 16,4) / Not stated | Unclear | Serum | PCR rrs | Not applicable | Not applicable | Not applicable | Not applicable |
D. IgM ELISA studies | ||||||||||||||||
Study first author (ref) | Title | Journal | Year of recruitment | Country | Endemicity | Study setting | Type of study | Participants included | Median age / Children included | DPO of fever at recruitment | Sample type for IgM ELISA | Comparator test | MAT Case definition for a positive acute sample | MAT case definition for a positive convalescent sample | MAT Paired samples | MAT panel |
Bourhy P [41] | Evaluation of an in-house ELISA using the intermediate species Leptospira fainei for diagnosis of leptospirosis | Journal of clinical microbiology | Not applicable | Mainland France and French overseas territories | High and low | Hospital | Case–control, with mixed population | Suspected leptospirosis, other diseases, healthy donors | 44 years / Yes | Not stated | Serum | MAT | ≥ 1:400 titer | Seroconversion | Unclear | 22 serogroups |