Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts

Abstract

BackgroundHousehold contacts constitute the highest risk group for leprosy development, and despite significant progress in the disease control, early diagnosis remains the primary goals for leprosy management programs.MethodsWe have recruited 175 seropositive and 35 seronegative household contacts from 2014 to 2016, who were subjected to an extensive protocol that included clinical, molecular (peripheral blood qPCR, slit-skin smear qPCR, skin biopsy qPCR) and electroneuromyographic evaluations.Results/Principal findingsThe positivity of peripheral blood qPCR of seropositive contacts was 40.6% (71/175) whereas only 8.6% (3/35) were qPCR positive in seronegative contacts (p = 0.0003). For the slit-skin smear, only 4% (7/175) of seropositive contacts presented positive bacilloscopy, whereas the qPCR detected 47.4% (83/175) positivity in this group compared with only 17.1% (6/35) in seronegative contacts (p = 0.0009). In the ENMG evaluation of contacts, 31.4% (55/175) of seropositives presented some neural impairment, and 13.3% (4/35) in seronegatives (p = 0.0163). The presence of neural thickening conferred a 2.94-fold higher chance of ENMG abnormality (p = 0.0031). Seropositive contacts presented a 4.04-fold higher chance of neural impairment (p = 0.0206). The peripheral blood qPCR positivity presented odds 2.08-fold higher towards neural impairment (OR, 2.08; p = 0.028). Contrarily, the presence of at least one BCG vaccine scar demonstrated 2.44-fold greater protection against neural impairment (OR = 0.41; p = 0.044).Conclusions/SignificanceELISA anti-PGL-I is the most important test in determining the increased chance of neural impairment in asymptomatic leprosy household contacts. The combination of the two assays (ELISA anti-PGL-I and peripheral blood qPCR) and the presence of BCG scar may identify individuals with higher chances of developing leprosy neuropathy, corroborating with the early diagnosis and treatment.

Genomic Characterization of Mycobacterium leprae to Explore Transmission Patterns Identifies New Subtype in Bangladesh

“…higher positivity (21.0%) in SSS of HHC was reported (Turankar et al, 2014) whereas in two Brazilian studies from Uberlandia, up to 42.4% positivity in SSS (Santos et al, 2018) and 49.0% in NS (Araujo et al, 2016) were observed. Three factors may limit the translation of these high positive results from India and Brazil to our study: (i) the sample sizes of the Indian (Turankar et al, 2014) and one of the Brazilian studies (Araujo et al, 2016) were smaller (n = 28 and n = 104, respectively vs. n = 250 HHC in this study); (ii) we conducted a more stringent approach by testing the samples in three independent PCRs; and (iii) the epidemiology and incidence of MB cases in India and Brazil differ from the studied area in Bangladesh where MB leprosy cases occur less frequently than PB and also usually display a low BI (Richardus et al, 2017;van Hooij et al, 2019).…”

“…PCR and quantitative PCR (qPCR) are reliable techniques to detect M. leprae DNA and have been proposed as tools for early diagnosis of leprosy, particularly among household contacts of newly diagnosed patients (Gama et al, 2018(Gama et al, , 2019. In Brazil, M. leprae DNA has been detected in 15.9-42.4% of healthy household contacts (HHC) in SSS, 9.7-35.2% in blood (Gama et al, 2018;Santos et al, 2018) and 8.9-49.0% in NS (Brito e Cabral et al, 2013;Araujo et al, 2016;Carvalho et al, 2018). Other studies from India, Indonesia and Colombia reported 21% of M. leprae positivity in SSS of HHC (Turankar et al, 2014), 7.8% (van Beers et al, 1994 and 16.0-31.0% in NS (Cardona-Castro et al, 2008;Romero-Montoya et al, 2017).…”

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011–2018

“…More recently, PCR screening in the blood of PGL-I positive contacts increased the rate of PCR positivity, having found 40% of qPCR positivity in this group. Nevertheless, authors fail to provide a follow-up to evaluate those who progressed towards leprosy 28 . Our data clearly demonstrate that qPCR alone is not a good estimate to infer the risk for a contact to develop leprosy.…”

Blood RNA signature RISK4LEP predicts leprosy years before clinical onset

“…In the past years, several studies have searched for biomarkers to (early) detect leprosy either based on the host immune response [26] , [27] , [28] , [29] , [30] , [31] , the pathogen [32] , [33] , [34] , [35] , [36] , [37] , or a combination of both [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] . Molecular detection by identification of the repetitive element RLEP by (quantitative) PCR [ 33 , 46 , 47 ] as well as detection of anti- M. leprae phenolic glycolipid I (PGL-I) IgM in blood [ 28 , 29 ] are methods employed to assist leprosy diagnosis.…”