Leprosy surveillance study in a highly endemic Brazilian area using leprosy specific serologic tests and IFNγ whole blood assay

Gonçalves, Aline do Carmo; Hungria, Emerith Mayra; Freitas, Aline Araújo; Sékula-Bührer, Samira; Gomes, Cassia Maria; Coelho, A. C. O; Nascimento, Laura Branquinho do; Stefani, Mariane Martins de Araújo

doi:10.1007/s10096-020-03979-5

Cited by 3 publications

(5 citation statements)

References 56 publications

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“…Mimetic peptides MPML12 and MPML14 demonstrated very similar results, with low reactivity in paucibacillary patients a gradual increase in the percentage of positives as they approach the lepromatous pole. This characteristic is very similar to that found for the PGL-1 antigen (Fabri et al 2015 ; Do et al 2018 ; Van Hooij et al 2018 ; Leturiondo et al 2019 ; do Carmo Gonçalves et al 2020 ); and its synthetic derivatives ND-O-HSA (Lobato et al 2011 ; van Hooij et al 2018 ; Rumondor et al 2019 ), NT-P-BSA and NT-P-HSA ML Flow (Bührer-Sékula et al 2003 , 2007 ; Moura et al 2014 ; Ule Belotti et al 2021 ). MPML12 and MPML14 detected, respectively, 100.0% and 92.85% of the LL group, while LID-1 (Duthie et al 2011 ) and ML0405 (Duthie et al 2007 ), detected 97.7% and 67.0%, respectively, in multibacillary patients.…”

Section: Discussionsupporting

confidence: 84%

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy

Lima,

Corrêa,

Moraes

et al. 2023

AMB Expr

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The early diagnosis of leprosy serves as an important tool to reduce the incidence of this disease in the world. Phage display (PD) technology can be used for mapping new antigens to the development of immunodiagnostic platforms. Our objective was to identify peptides that mimic Mycobacterium leprae proteins as serological markers using phage display technology. The phages were obtained in the biopanning using negative and positive serum from household contacts and leprosy patients, respectively. Then, the peptides were synthesized and validated in silico and in vitro for detection of IgG from patients and contacts. To characterize the native protein of M. leprae, scFv antibodies were selected against the synthetic peptides by PD. The scFv binding protein was obtained by immunocapture and confirmed using mass spectrometry. We selected two phase-fused peptides, MPML12 and MPML14, which mimic the HSP60 protein from M. leprae. The peptides MPML12 and MPML14 obtained 100% and 92.85% positivity in lepromatous patients. MPML12 and MPM14 detect IgG, especially in the multibacillary forms. The MPML12 and MPML14 peptides had positivity of 11.1% and 16.6% in household contacts, respectively. There was no cross-reaction in patient’s samples with visceral leishmaniasis, tuberculosis and other mycobacteriosis for both peptides. Given these results and the easy obtainment of mimetic antigens, our peptides are promising markers for application in the diagnosis of leprosy, especially in endemic and hyperendemic regions.

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Section: Discussionsupporting

confidence: 84%

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy

Lima,

Corrêa,

Moraes

et al. 2023

AMB Expr

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“…Results showed higher seropositivity to LID-1, including among the incident leprosy cases. 53 In MB or PB leprosy patients from Yunnan, China, higher sensitivity was obtained by the use of ELISA NDO-LID compared to LID-1 and NDO-BSA. 55 A review and meta-analysis that compared the accuracy of leprosy ELISA tests with native PGL-I, NDO-BSA, and LID-1 showed that NDO-BSA serology was better regarding sensitivity, specificity, positive and negative predictive value, and diagnostic value especially among MB patients, while the use of LID-1 gave similar sensitivity (Table 1).…”

Section: The Postgenomic Era: the Characterization Of New M Leprae Re...mentioning

confidence: 95%

Section: Serological Diagnosis Of Leprosy: the State Of The Artmentioning

confidence: 95%

“…Following the PGL-I, the LID-1 chimeric fusion protein antigen represents the second most widely evaluated antigen for leprosy serology in endemic countries. [53][54][55] Instead of searching for new antigens to replace the PGL-I, the current understanding has been to add new promising antigens to PGL-I aiming to improve its specificity, and especially its sensitivity. In this sense, the LID-1 antigen has been tested simultaneously or conjugated with PGL-I regarding its potential to improve leprosy serology.…”

Section: The Postgenomic Era: the Characterization Of New M Leprae Re...mentioning

confidence: 99%

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Challenges and advances in serological and molecular tests to aid leprosy diagnosis

Lopes-Luz,

Saavedra,

Fogaça

et al. 2023

Exp Biol Med (Maywood)

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Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, Mycobacterium leprae and Mycobacterium lepromatosis. Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed M. leprae–specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect M. leprae DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt M. leprae transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect M. leprae DNA.

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“…Currently, very few studies have examined the utility of ELISPOT assays in M. leprae -infected individuals. Some of these studies explored the immune response in M. leprae -stimulated whole-blood assay (WBA) and examined the supernatant levels of IFN-γ stimulated with M. leprae from infected patients ( Hungria et al., 2017 ; Chen et al., 2019b ; Do Carmo Goncalves et al., 2020 ). Others focused on a panel of multiple M. leprae antigen-induced host markers by WBA ( Chen et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis

Jiang

Shi

Chokkakula

et al. 2022

Front. Cell. Infect. Microbiol.

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The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.

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Leprosy surveillance study in a highly endemic Brazilian area using leprosy specific serologic tests and IFNγ whole blood assay

Cited by 3 publications

References 56 publications

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy

HSP60 mimetic peptides from Mycobacterium leprae as new antigens for immunodiagnosis of Leprosy

Challenges and advances in serological and molecular tests to aid leprosy diagnosis

Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis

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