Leprosy reactions: The predictive value of Mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR)

Hungria, Emerith Mayra; Bührer-Sékula, Samira; Oliveira, Reinaldo Cunha de; Aderaldo, Lúcio Cartaxo; Pontes, Araci de Andrade; Cruz, Rossilene Conceição da Silva; Gonçalves, Heitor de Sá; Penna, Maria Lúcia Fernandes; Penna, Gerson Oliveira; Stefani, Mariane Martins de Araújo

doi:10.1371/journal.pntd.0005396

Cited by 31 publications

(32 citation statements)

References 43 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IgG anti-LID-1 (LID-1-lot: November 14, 2011, Dr. Duthie, USA) and IgG and IgM anti-ND-O-LID (ND-O-LID-lot: August 17, 2012, Dr. Duthie, USA) were detected by ELISA as described by Hungria et al [31]. For anti-LID-1 and anti-ND-O-LID serology, the cutoff was determined by the ROC curve analysis using samples of leprosy cases and samples from EC.…”

Section: Methodsmentioning

confidence: 99%

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts

et al. 2019

View full text Add to dashboard Cite

Background Early detection of Mycobacterium leprae is a key strategy for disrupting the transmission chain of leprosy and preventing the potential onset of physical disabilities. Clinical diagnosis is essential, but some of the presented symptoms may go unnoticed, even by specialists. In areas of greater endemicity, serological and molecular tests have been performed and analyzed separately for the follow-up of household contacts, who are at high risk of developing the disease. The accuracy of these tests is still debated, and it is necessary to make them more reliable, especially for the identification of cases of leprosy between contacts. We proposed an integrated analysis of molecular and serological methods using artificial intelligence by the random forest (RF) algorithm to better diagnose and predict new cases of leprosy. Methods The study was developed in Governador Valadares, Brazil, a hyperendemic region for leprosy. A longitudinal study was performed, including new cases diagnosed in 2011 and their respective household contacts, who were followed in 2011, 2012, and 2016. All contacts were diligently evaluated by clinicians from Reference Center for Endemic Diseases (CREDEN-PES) before being classified as asymptomatic. Samples of slit skin smears (SSS) from the earlobe of the patients and household contacts were collected for quantitative polymerase chain reaction (qPCR) of 16S rRNA, and peripheral blood samples were collected for ELISA assays to detect LID-1 and ND-O-LID. Results The statistical analysis of the tests revealed sensitivity for anti-LID-1 (63.2%), anti-ND-O-LID (57.9%), qPCR SSS (36.8%), and smear microscopy (30.2%). However, the use of RF allowed for an expressive increase in sensitivity in the diagnosis of multibacillary leprosy (90.5%) and especially paucibacillary leprosy (70.6%). It is important to report that the specificity was 92.5%. Conclusion The proposed model using RF allows for the diagnosis of leprosy with high sensitivity and specificity and the early identification of new cases among household contacts.

show abstract

Section: Methodsmentioning

confidence: 99%

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Thus anti-LID-1 serology may be used as a predictive marker for the development of ENL, with a sensitivity of 71% and a specificity of 80%. [ 78 ] CCL-11 CCL-11, produced by monocytes, is a known chemoattractant for eosinophils and Th2 lymphocytes. It has been found to be a potential plasma marker for ENL.…”

Section: Risk Factorsmentioning

confidence: 99%

“…Thus anti-LID-1 serology may be used as a predictive marker for the development of ENL, with a sensitivity of 71% and a specificity of 80%. [ 78 ]…”

Section: Risk Factorsmentioning

confidence: 99%

What is new in the pathogenesis and management of erythema nodosum leprosum

Bhat

Vaidya

2020

Indian Dermatol Online J

View full text Add to dashboard Cite

“…Previous studies have investigated the potential use of leprosy serology as a marker of reactional episodes ( 50 – 52 ). Two previous publications from our group using the U-MDT database and sera bank ( 40 , 41 ) have described the impact of baseline serology on the development of leprosy reactions. The baseline ML flow test results showed limited sensitivity and specificity as prognostic markers for the development of leprosy reactions during subsequent follow-up ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…The baseline ML flow test results showed limited sensitivity and specificity as prognostic markers for the development of leprosy reactions during subsequent follow-up ( 40 ). Also, the analyses of anti-PGL-I, anti-LID-1, anti-ND-O-LID antibodies at diagnosis showed low sensitivity and specificity for predicting reversal reaction while anti-LID-1 serology at diagnosis showed prognostic value for the development of ENL in BI positive patients ( 41 ). We acknowledge the importance of the analysis of the impact of reactional episodes on longitudinal serology data, however, these analyses are out of the scope of the current study which focused on the effect of different treatment regimens on leprosy serology to three antigens.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT

et al. 2018

Self Cite

View full text Add to dashboard Cite

Leprosy serology reflects the bacillary load of patients and multidrug therapy (MDT) reduces Mycobacterium leprae-specific antibody titers of multibacillary (MB) patients. The Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil (U-MDT/CT-BR) compared outcomes of regular 12 doses MDT/R-MDT and the uniform 6 doses MDT/U-MDT for MB leprosy, both of regimens including rifampicin, clofazimine, and dapsone. This study investigated the impact of R-MDT and U-MDT and the kinetic of antibody responses to M. leprae-specific antigens in MB patients from the U-MDT/CT-BR. We tested 3,400 serum samples from 263 MB patients (R-MDT:121; U-MDT:142) recruited at two Brazilian reference centers (Dona Libânia, Fortaleza, Ceará; Alfredo da Matta Foundation, Manaus, Amazonas). Enzyme-linked immunosorbent assays with three M. leprae antigens [NT-P-BSA: trisaccharide-phenyl of phenollic glycolipid-I antigen (PGL-I); LID-1: Leprosy Infectious Disease Research Institute Diagnostic 1 di-fusion recombinant protein; and ND-O-LID: fusion complex of disaccharide-octyl of PGL-I and LID-1] were performed using around 13 samples per patient. Samples were collected at baseline/M0, during MDT (R-MDT:M1–M12 months, U-MDT:M1–M6 months) and after MDT discontinuation (first, second year). Statistical significance was assessed by the Mann–Whitney U test for comparison between groups (p values < 0.05). Mixed effect multilevel regression analyses were used to investigate intraindividual serological changes overtime. In R-MDT and U-MDT groups, males predominated, median age was 41 and 40.5 years, most patients were borderline lepromatous and lepromatous leprosy (R-MDT:88%, U-MDT: 90%). The bacilloscopic index at diagnosis was similar (medians: 3.6 in the R-MDT and 3.8 in the U-MDT group). In R-MDT and U-MDT groups, a significant decline in anti-PGL-I positivity was observed from M0 to M5 (p = 0.035, p = 0.04, respectively), from M6 to M12 and at the first and second year posttreatment (p < 0.05). Anti-LID-1 antibodies declined from M0 to M6 (p = 0.024), M7 to M12 in the R-MDT; from M0 to M4 (p = 0.003), M5 to M12 in the U-MDT and posttreatment in both groups (p > 0.0001). Anti-ND-O-LID antibodies decreased during and after treatment in both groups, similarly to anti-PGL-I antibodies. Intraindividual serology results in R-MDT and U-MDT patients showed that the difference in serology decay to all three antigens was dependent upon time only. Our serology findings in MB leprosy show that regardless of the duration of the U-MDT and R-MDT, both of them reduce M. leprae-specific antibodies during and after treatment. In leprosy, antibody levels are considered a surrogate marker of the bacillary load; therefore, our serological results suggest that shorter U-MDT is also effective in reducing the patients’ bacillary burden similarly to R-MDT.Clinical Trial Registration, NCT00669643.

show abstract

Leprosy reactions: The predictive value of Mycobacterium leprae-specific serology evaluated in a Brazilian cohort of leprosy patients (U-MDT/CT-BR)

Cited by 31 publications

References 43 publications

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts

What is new in the pathogenesis and management of erythema nodosum leprosum

Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT

Contact Info

Product

Resources

About