Abstract
Although curable, leprosy requires better diagnostic and prognostic tools to accompany therapeutic strategies. We evaluated the serum samples of leprosy patients from Venezuela and Brazil for reactivity against the specific recombinant proteins, ML0405 and ML2331, and the LID-1 fusion protein that incorporates both of these antigens. Antigen-specific IgG was highest in lepromatous leprosy patients (LL) and decreased across the disease spectrum, such that only a small subset of true tuberculoid patients (TT) tested positive. The impact of multidrug therapy (MDT) on these antibody responses was also examined. Several years after treatment, the vast majority of Venezuelan patients did not possess circulating anti-LID-1, anti-ML0405, and anti-ML2331 IgG, and the seropositivity of the remaining cases could be attributed to irregular treatment. At discharge, the magnitude and proportion of positive responses of Brazilian patients against the proteins and phenolic glycolipid (PGL)-I were lower for most of the clinical forms. The monthly examination of IgG levels in LL patient sera after MDT initiation indicated that these responses are significantly reduced during treatment. Thus, responses against these antigens positively correlate with bacillary load, clinical forms, and operational classification at diagnosis. Our data indicate that these responses could be employed as an auxiliary tool for the assessment of treatment efficacy and disease relapse.




Abbreviations
- BB:
-
Borderline borderline
- BI:
-
Bacterial index
- BL:
-
Borderline lepromatous
- BT:
-
Borderline tuberculoid
- C:
-
Control
- EC:
-
Endemic control
- HHC:
-
Healthy household contact
- LI:
-
Leprosy indeterminate
- LID:
-
Leprosy Infectious Disease Research Institute (IDRI) diagnostic
- LL:
-
Lepromatous leprosy
- MB:
-
Multibacillary
- MDT:
-
Multidrug therapy
- NEC:
-
Non-endemic control
- PB:
-
Paucibacillary
- PGL:
-
Phenolic glycolipid
- TT:
-
True tuberculoid
References
Scollard DM (2004) Classification of leprosy: a full color spectrum, or black and white? Int J Lepr Other Mycobact Dis 72:166–168
Ridley DS, Jopling WH (1966) Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 34:255–273
World Health Organization (WHO) (2007) Global leprosy situation, 2007. Wkly Epidemiol Rec 82:225–232
Meima A, Richardus JH, Habbema JD (2004) Trends in leprosy case detection worldwide since 1985. Lepr Rev 75:19–33
Ji B, Jamet P, Sow S, Perani EG, Traore I, Grosset JH (1997) High relapse rate among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks. Antimicrob Agents Chemother 41:1953–1956
Cambau E, Bonnafous P, Perani E, Sougakoff W, Ji B, Jarlier V (2002) Molecular detection of rifampin and ofloxacin resistance for patients who experience relapse of multibacillary leprosy. Clin Infect Dis 34:39–45
Maeda S, Matsuoka M, Nakata N, Kai M, Maeda Y, Hashimoto K et al (2001) Multidrug resistant Mycobacterium leprae from patients with leprosy. Antimicrob Agents Chemother 45:3635–3639
Matsuoka M, Kashiwabara Y, Liangfen Z, Goto M, Kitajima S (2003) A second case of multidrug-resistant Mycobacterium leprae isolated from a Japanese patient with relapsed lepromatous leprosy. Int J Lepr Other Mycobact Dis 71:240–243
Matsuoka M, Kashiwabara Y, Namisato M (2000) A Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Int J Lepr Other Mycobact Dis 68:452–455
Reece ST, Ireton G, Mohamath R, Guderian J, Goto W, Gelber R et al (2006) ML0405 and ML2331 are antigens of Mycobacterium leprae with potential for diagnosis of leprosy. Clin Vaccine Immunol 13:333–340
Duthie MS, Goto W, Ireton GC, Reece ST, Cardoso LP, Martelli CM et al (2007) Use of protein antigens for early serological diagnosis of leprosy. Clin Vaccine Immunol 14:1400–1408
Duthie MS, Ireton GC, Kanaujia GV, Goto W, Liang H, Bhatia A et al (2008) Selection of antigens and development of prototype tests for point-of-care leprosy diagnosis. Clin Vaccine Immunol 15:1590–1597
Duthie MS, Hay MN, Morales CZ, Carter L, Mohamath R, Ito L et al (2010) Rational design and evaluation of a multiepitope chimeric fusion protein with the potential for leprosy diagnosis. Clin Vaccine Immunol 17:298–303
Rudeeaneksin J, Srisungngam S, Sawanpanyalert P, Sittiwakin T, Likanonsakul S, Pasadorn S et al (2008) LightCycler real-time PCR for rapid detection and quantitation of Mycobacterium leprae in skin specimens. FEMS Immunol Med Microbiol 54:263–270
Lobato J, Silva DA, Mineo TW, Amaral JD, Segundo GR, Costa-Cruz JM et al (2006) Detection of immunoglobulin G antibodies to Neospora caninum in humans: high seropositivity rates in patients who are infected by human immunodeficiency virus or have neurological disorders. Clin Vaccine Immunol 13:84–89
Rada E, Ulrich M, Aranzazu N, Rodriguez V, Centeno M, Gonzalez I et al (1997) A follow-up study of multibacillary Hansen’s disease patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT). Int J Lepr Other Mycobact Dis 65:320–327
Cho SN, Cellona RV, Villahermosa LG, Fajardo TT Jr, Balagon MV, Abalos RM et al (2001) Detection of phenolic glycolipid I of Mycobacterium leprae in sera from leprosy patients before and after start of multidrug therapy. Clin Diagn Lab Immunol 8:138–142
Silva EA, Iyer A, Ura S, Lauris JR, Naafs B, Das PK et al (2007) Utility of measuring serum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoring leprosy patients during multi-drug treatment and reactions. Trop Med Int Health 12:1450–1458
Lockwood DN, Reid AJ (2001) The diagnosis of leprosy is delayed in the United Kingdom. QJM 94:207–212
Flower C, Gaskin D, Marquez S (2007) A case of recurrent rash and leg numbness mimicking systemic rheumatic disease: the occurrence of leprosy in a nonendemic area. J Clin Rheumatol 13:143–145
Anderson H, Stryjewska B, Boyanton BL, Schwartz MR (2007) Hansen disease in the United States in the 21st century: a review of the literature. Arch Pathol Lab Med 131:982–986
Ellard GA, Pannikar VK, Jesudasan K, Christian M (1988) Clofazimine and dapsone compliance in leprosy. Lepr Rev 59:205–213
Honrado ER, Tallo V, Balis AC, Chan GP, Cho SN (2008) Noncompliance with the World Health Organization—multidrug therapy among leprosy patients in Cebu, Philippines: its causes and implications on the leprosy control program. Dermatol Clin 26:221–229
Miller RA, Gorder D, Harnisch JP (1987) Antibodies to phenolic glycolipid-I during long-term therapy: serial measurements in individual patients. Int J Lepr Other Mycobact Dis 55:633–636
Roche PW, Britton WJ, Failbus SS, Neupane KD, Theuvenet WJ (1993) Serological monitoring of the response to chemotherapy in leprosy patients. Int J Lepr Other Mycobact Dis 61:35–43
Chanteau S, Cartel JL, Celerier P, Plichart R, Desforges S, Roux J (1989) PGL-I antigen and antibody detection in leprosy patients: evolution under chemotherapy. Int J Lepr Other Mycobact Dis 57:735–743
Ebenezer GJ, Norman G, Joseph GA, Daniel S, Job CK (2002) Drug resistant-Mycobacterium leprae—results of mouse footpad studies from a laboratory in south India. Indian J Lepr 74:301–312
Williams DL, Gillis TP (2004) Molecular detection of drug resistance in Mycobacterium leprae. Lepr Rev 75:118–130
Matsuoka M, Budiawan T, Aye KS, Kyaw K, Tan EV, Cruz ED et al (2007) The frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines. Lepr Rev 78:343–352
Roche PW, Neupane KD, Failbus SS, Butlin CR (2000) Dapsone drug resistance in the MDT era. Int J Lepr Other Mycobact Dis 68:323–325
Grosset JH, Guelpa-Lauras CC, Bobin P, Brucker G, Cartel JL, Constant-Desportes M et al (1989) Study of 39 documented relapses of multibacillary leprosy after treatment with rifampin. Int J Lepr Other Mycobact Dis 57:607–614
Gelber RH, Murray LP, Siu P, Tsang M, Rea TH (1994) Efficacy of minocycline in single dose and at 100 mg twice daily for lepromatous leprosy. Int J Lepr Other Mycobact Dis 62:568–573
Ji B, Grosset J (2000) Combination of rifapentine–moxifloxacin–minocycline (PMM) for the treatment of leprosy. Lepr Rev 71(Suppl):S81–S87
Ji B, Perani EG, Petinom C, N’Deli L, Grosset JH (1994) Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy. Antimicrob Agents Chemother 38:662–667
Balagon MF, Cellona RV, Abalos RM, Gelber RH, Saunderson PR (2010) The efficacy of a four-week, ofloxacin-containing regimen compared with standard WHO-MDT in PB leprosy. Lepr Rev 81:27–33
Acknowledgments
This work was conducted with support from the American Leprosy Missions and the National Institutes of Health (1R43AI066613-01A1 and 2R44AI066613-02). The National Reference Center of Leprosy, Uberlândia, Brazil, was also supported by the Brazilian Ministry of Health, DECIT/MS, CNPq/MCT, CAPES/MEC, and FAPEMIG. The Infectious Disease Research Institute (IDRI) is a member of the IDEAL (Initiative for Diagnostic and Epidemiological Assays for Leprosy) Consortium.
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Duthie, M.S., Hay, M.N., Rada, E.M. et al. Specific IgG antibody responses may be used to monitor leprosy treatment efficacy and as recurrence prognostic markers. Eur J Clin Microbiol Infect Dis 30, 1257–1265 (2011). https://doi.org/10.1007/s10096-011-1221-2
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DOI: https://doi.org/10.1007/s10096-011-1221-2