Insight toward Early Diagnosis of Leprosy through Analysis of the Developing Antibody Responses of Mycobacterium leprae -Infected Armadillos

Abstract

Leprosy is a debilitating chronic disease caused by infection with Mycobacterium leprae. A World HealthOrganization-directed control strategy based upon the identification and treatment of patients has resulted in a marked reduction in the number of registered worldwide leprosy cases over the last 20 years. Despite these efforts, the number of new leprosy cases detected each year now remains relatively stable, and M. leprae infection continues to pose a health problem. It is suggested that earlier diagnosis is required to strengthen control programs. In this study, we have examined the development of antigen-specific immunoglobulin responses within armadillos experimentally infected with M. leprae to identify those responses that develop most rapidly and robustly following infection. Antibody responses to the M. leprae-specific phenolic glycolipid I and several protein antigens previously demonstrated to have diagnostic potential were assessed. Our results identify several antigens that can provide early diagnosis of M. leprae infection but also indicate considerable variability in the development of antigen-specific antibodies. Our data suggest that a combination of antigens is likely required to provide accurate and early leprosy diagnosis. (22,24). The World Health Organization (WHO) has suggested diagnosis of leprosy be made by the observation of one or more of the following: hypopigmented or reddish skin patches with definite loss of sensation; thickened peripheral nerves; and acid-fast bacilli on skin smears/biopsy specimens. In the classification based on skin smears, patients showing negative smears at all sites are grouped as paucibacillary (PB) leprosy, while those showing positive smears at any site are grouped as multibacillary (MB) leprosy. In practice, most programs use the clinical criteria for classifying and selecting the treatment regimen for individual patients. The clinical system includes counting the number of skin lesions and nerves involved as the basis for grouping leprosy patients into the PB (less than 5 lesions) and MB (typically 5 or more lesions) categories. It would be highly beneficial to identify M. leprae infection before such signs appear. Leprosy is caused by infection with the bacteriumIt is believed that a significant number of individuals contain infection such that it remains subclinical or self-cures with minimal sign of disease (2, 11). If left untreated, however, leprosy can progress to a state of high significance and result in irreversible nerve damage with profound sensory and motor nerve loss, deformity, and blindness. It is well established that the earlier a leprosy patient is diagnosed and treated, the better their outcome (12,19). It stands to reason that identifying leprosy patients on the basis of antigen-specific responses, preferably before the onset of symptoms, could have a dramatic effect on clinical outcome.A major obstacle in research to develop new diagnostic tests for leprosy has been the inability to cultivate M. leprae in vitro, rendering it diffic...

A lineage-specific rapid diagnostic test (Chagas Sero K-SeT) identifies Brazilian Trypanosoma cruzi II/V/VI reservoir hosts among diverse mammalian orders

“…Armadillos, especially D. novemcinctus, have been reported as natural hosts of TcIII throughout South America [11,40,41], thus the absence of TcII/V/VI infections from all 49 armadillos was not surprising. Although Chagas Sero K-SeT was shown to be able to detect infection in armadillo [20], positive test line intensity was weak; Protein A may be more appropriate than Protein G for binding of armadillo IgG, as others have reported [42], and which we observed here. No armadillo-specific conjugate was available for ELISA; this also encourages further deployment of Protein A for these important reservoirs hosts.…”

Antigen-specific assessment of the immunological status of various groups in a leprosy endemic region

“…We speculate that agreement in the antigen-specific antibody responses is observed in MB patients because they present with a high bacterial load and a more developed and defined humoral response. Of note, antibody responses to M. leprae appear to develop heterogeneously even in the controlled setting of experimental infection of armadillos [ 17 ], and thus, antigen-specific responses may develop at differing rates and be variable in infected individuals who have not yet exhibited signs of disease.…”

Zoonotic Leprosy in the Southeastern United States

“…Serologic and molecular assays were used to identify armadillos infected with M. leprae. Serum samples were tested for IgM against phenolic glycolipid-1 (PGL1) antigen of M. leprae (BEI Resources, Manassas, VA, USA) and for leprosy IDRI diagnostic-1 (LID1) antigen (Infectious Disease Research Institute, Seattle, WA, USA) by using an ELISA as described ( 19 ). Positive results were determined according to optical density and by using limits described for the PGL1 assay ( 13 , 19 ).…”