Abstract
Leprosy is an infectious disease caused by Mycobacterium leprae with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of M. leprae infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load. Therefore, serosurveillance utilizing field-friendly tests detecting anti-PGL-I antibodies, can be applied to identify those who may transmit bacteria and to study (reduction of) M. leprae transmission. However, serology based on antibody detection cannot discriminate between past and present M. leprae infection in humans, nor can it detect individuals carrying low bacillary loads. In humans, anti-PGL-I IgM levels are long-lasting and usually detected in more individuals than anti-PGL-I IgG levels. Inherent to the characteristically long incubation time of leprosy, IgM/IgG relations (antibody kinetics) in leprosy patients and infected individuals are not completely clear. To investigate the antibody response directly after infection, we have measured antibody levels by ELISA, in longitudinal samples of experimentally M. leprae infected, susceptible nine-banded armadillos (Dasypus novemcinctus). In addition, we assessed the user- and field-friendly, low-cost lateral flow assay (LFA) utilizing upconverting reporter particles (UCP), developed for quantitative detection of human anti-PGL-I IgM (UCP-LFA), to detect treatment- or vaccination-induced changes in viable bacterial load. Our results show that serum levels of anti-PGL-I IgM, and to a lesser extent IgG, significantly increase soon after experimental M. leprae infection in armadillos. In view of leprosy phenotypes in armadillos, this animal model can provide useful insight into antibody kinetics in early infection in the various spectral forms of human leprosy. The UCP-LFA for quantitative detection of anti-PGL-I IgM allows monitoring the efficacy of vaccination and rifampin-treatment in the armadillo leprosy model, thereby providing a convenient tool to evaluate the effects of drugs and vaccines and new diagnostics.
Highlights
Leprosy is a severe, communicable disease characterized by skin lesions and peripheral nerve alterations associated with a wide-ranging spectrum of clinical symptoms
To assess the kinetics of humoral antiM. leprae responses in armadillos, we first assessed the levels of anti-PGL-I antibodies by ELISA in serum obtained from 17 armadillos that were experimentally infected with M. leprae [1 × 109 bacilli; National Hansen’s Disease Program (NHDP) 63 (n = 9), NHDP 98 (n = 4), or Brazil 4923 (n = 4)]
Armadillos were sampled at multiple time points and divided into three categories according to the time of dissemination of M. leprae infection (Pena et al, 2016; Supplementary Table 2)
Summary
Communicable disease characterized by skin lesions and peripheral nerve alterations associated with a wide-ranging spectrum of clinical symptoms. Leprosy elimination is still hampered by intense transmission of Mycobacterium leprae, which is not restricted to patients’ households (Ortuno-Gutierrez et al, 2019; Tió-Coma et al, 2020). Detection of M. leprae infection in persons without symptoms is essential to detect patients at early, still well-treatable stages of leprosy. On the other hand, detection of M. leprae infection bears relevance to monitoring transmission in an area on the way to elimination of this disease, and can help to assess the effects of prophylactic community interventions. Interruption of M. leprae transmission is crucial and concomitantly are tests to detect asymptomatically infected individuals who can still perpetuate transmission
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