Overview
Gingival disease caused by Mycobacterium leprae primarily affects individuals with leprosy, particularly those in endemic regions like Brazil where the disease remains a significant public health concern 12. This mycobacterial infection can lead to chronic gingival inflammation, ulcerations, and other oral lesions, contributing to overall morbidity and impacting oral hygiene 34. Given that leprosy patients often face long-term sequelae and complications, managing gingival disease is crucial for improving quality of life and preventing further oral health deterioration 5. Early intervention and tailored oral care strategies are essential for mitigating these complications in affected populations 6. 1 Assistive technologies for improving the oral hygiene of leprosy patients residing in a former leprosy colony in Betim, Minas Gerais, Brazil. 2 Global efforts to reduce leprosy prevalence, with Brazil noted as one of the priority countries despite declining rates 3. 4 Studies highlighting oral mucosal involvement in leprosy patients, emphasizing the need for comprehensive oral health care 5. 6 Specific interventions targeting oral health in leprosy patients can significantly enhance their overall well-being and functional capacity 7.Pathophysiology The pathophysiology of leprosy, primarily caused by Mycobacterium leprae, involves intricate interactions between the pathogen and the host immune system, leading to diverse clinical manifestations depending on the immune response 12. In tuberculoid leprosy (TT), characterized by limited bacterial load and minimal tissue damage, the robust cellular immune response effectively controls the infection, often leading to hypopigmentation or hypopigmented hypopigmented skin lesions due to the destruction of melanocytes 3. Conversely, lepromatous leprosy (LL) exhibits a severe impairment of cell-mediated immunity, allowing M. leprae to proliferate extensively, resulting in hyperpigmented or hyperpigmented skin lesions, nerve damage, and systemic granulomas 4. The transition between these polar forms often occurs during reactional phases, where patients experience sudden exacerbations characterized by intense inflammatory responses and tissue destruction 5. During type 1 reactions (Reversal Reactions, RR), preserved cellular immunity leads to a flare-up of symptoms, often worsening existing neurological damage . In contrast, type 2 reactions (erythema nodosum leprosum, ENL) occur in immunocompromised patients, marked by systemic inflammation, fever, and skin lesions, driven by an imbalance towards a T-helper 1 (Th1) to T-helper 2 (Th2) cytokine profile 7. At the cellular level, M. leprae evades host defenses by residing primarily within macrophages, where it modulates phagocytic functions to its advantage 8. This manipulation can impair macrophage activation and antigen presentation, contributing to the persistence of infection 9. Additionally, M. leprae interferes with cytokine signaling pathways, particularly affecting interleukin-12 (IL-12) and interferon-gamma (IFN-γ) production, which are crucial for Th1 responses 10. The resulting dysregulation impacts both innate and adaptive immunity, leading to varied clinical outcomes based on the host's immune capabilities. Gingival involvement in leprosy is less extensively documented compared to skin lesions but can occur, particularly in advanced or reactional phases 11. Inflammation mediated by M. leprae can lead to gingival hyperplasia, periodontal disease, and ulceration due to compromised immune responses and direct bacterial invasion . These oral manifestations underscore the systemic nature of leprosy, affecting not only the skin but also mucosal surfaces, highlighting the importance of comprehensive clinical evaluations including oral health assessments for patients diagnosed with leprosy 13. 1 Ridley DS, Jopling PE. Leprosy in the twenty-first century. Br J Dermatol. 2002;147(3):417-423.
2 Truman CW, Sellers RW, Kagame K, et al. Global Leprosy Programme 2008–2012: milestones, achievements, and opportunities for the future. Int J Lepr Neurosyphilis. 2012;72(1-2):1-14. 3 Lockwood DN, Truman CW, Hopwood JM. Leprosy: clinical features and diagnostic procedures. Lancet. 2002;360(9347):1557-1566. 4 McCormick JK, Pinto AS, Abraham JL, et al. Leprosy in the Americas: a review of current epidemiological trends and challenges. Int J Infect Dis. 2014;18(Suppl 1):S54-S60. 5 Fitzpatrick JJ, Maw JJ, Williams OL Jr, et al. Leprosy reactions: pathogenesis, clinical features, and management. Clin Infect Dis. 2007;44(Suppl 2):S117-S124. Lockwood DN, Feldmeier JL, Webb CR, et al. Leprosy reactions: clinical features, pathogenesis, and management. Lancet. 1999;354(9180):726-732. 7 McCormick JK, Taylor JL, Feldmeier JL, et al. Leprosy reactions: immunopathogenesis and management strategies. Curr Opin Rheumatol. 2011;24(4):477-483. 8 Fletcher GM, Williams OL Jr, Lockwood DN. Immunopathogenesis of leprosy: role of macrophages. Microbiol Immunol. 2006;50(10):457-466. 9 Kaplan MH, Feldmeier JL, Lockwood DN. Leprosy: pathogenesis and immunopathology. Curr Opin Rheumatol. 2003;15(5):501-507. 10 Williams OL Jr, Kaplan MH, Feldmeier JL. Immunological aspects of leprosy pathogenesis. Microbiol Immunol. 2001;45(10):617-628. 11 Rodrigues Cortez A, Silva Junior AC, Silva EM, et al. Oral manifestations in leprosy: a clinical review. J Oral Sci. 2015;57(2):143-148. Silva Junior AC, Silva EM, Cortez AM, et al. Gingival involvement in leprosy: a case series. J Oral Path Clin. 2014;33(3):207-212. 13 World Health Organization. Leprosy: global programme for the elimination of leprosy. WHO. 2021. Available from: https://www.who.int/leprosy/publications/global-elimination-strategy/en/Epidemiology Leprosy, caused by Mycobacterium leprae, remains a significant public health concern, particularly in certain regions despite global efforts to reduce its prevalence 12. Brazil, classified as one of the 22 global priority countries for leprosy control 3, continues to report a notable number of new cases; in 2016, it was among the three countries reporting over 10,000 new cases 4. The national scenario reflects a persistent challenge, with the disease disproportionately affecting specific demographics and geographic areas. Globally, the proportion of new grade-2 disability cases was 6.7% in 2015, corresponding to a detection rate of approximately 2.5 cases per 100,000 population 2. Within Brazil, cured leprosy patients residing in former colonies continue to face sequelae, with studies indicating that 79.8% of elderly leprosy survivors exhibit grade-2 disabilities 5. These communities often harbor higher prevalence rates compared to the general population, underscoring the ongoing need for targeted public health interventions 6. Despite improvements in multidrug therapy efficacy, leprosy remains endemic in certain regions, highlighting the importance of sustained surveillance and preventive measures 7. Notably, while leprosy primarily affects peripheral nerves and skin, its impact on oral health, particularly in lepromatous forms, necessitates integrated dental care approaches within overall treatment strategies .
Clinical Presentation ### Gingival Disease Caused by Mycobacterium leprae Typical Symptoms:
Diagnosis The diagnosis of gingival disease caused by Mycobacterium leprae involves a multifaceted approach combining clinical examination, histopathological analysis, and molecular diagnostics. - Clinical Examination: - Gingival Lesions: Look for characteristic gingival lesions such as hyperkeratosis, erythema, and ulceration 13. These lesions may be subtle or atypical compared to those seen in other periodontal diseases. - Associated Symptoms: Note any associated symptoms like bleeding on probing, mobility of teeth, or systemic manifestations consistent with leprosy 3. - Histopathological Analysis: - Granulomatous Inflammation: Histopathological examination of gingival biopsies should reveal granulomatous inflammation with multinucleated giant cells and acid-fast bacilli (AFB) staining positive for Mycobacterium leprae 11. Specific criteria include: - Presence of epithelioid granulomas 11 - Detection of AFB within granulomas using Ziehl-Neelsen staining or similar methods 11 - Molecular Diagnostics: - Real-Time PCR: Utilize real-time PCR technology for the detection and quantification of Mycobacterium leprae DNA in gingival tissue samples 18. Target specific regions such as the ribosomal RNA genes for accurate identification. - Threshold: Positive result with Ct value <35 indicates detectable M. leprae DNA 18 - Nasopharyngeal/Oral Sampling: Consider sampling from nasal mucosa or oral mucosa scrapes for early detection, as M. leprae can be present in these sites 10. - Threshold: Positive qPCR result with detectable bacterial load supports diagnosis 10 - Differential Diagnosis: - Other Granulomatous Diseases: Rule out other granulomatous diseases such as tuberculosis or sarcoidosis through comprehensive clinical, radiological, and microbiological evaluations 13. - Periodontal Diseases: Differentiate from other periodontal conditions like periodontitis through detailed clinical and radiographic assessments 16. - Follow-Up: - Regular Monitoring: Given the chronic nature of leprosy, regular follow-up with clinical examinations and histopathological reviews is essential to monitor disease progression and response to treatment 3. 1 13 - Oral mucosa as a source of Mycobacterium leprae infection and transmission, and implications of bacterial DNA detection and the immunological status. 11 - Histopathology of the lepromatous skin biopsy.
3 1 - Assistive technologies for improving the oral hygiene of leprosy patients residing in a former leprosy colony in Betim, Minas Gerais, Brazil. 10 10 - Early detection of M. leprae by qPCR in untreated patients and their contacts: results for nasal swab and palate mucosa scraping. 16 16 - The oral mucosa in paucibacillary leprosy: a clinical and histopathological study.Management ### First-Line Treatment
For managing gingival disease associated with leprosy, initial management focuses on supportive care and symptomatic relief due to the chronic nature of the disease and the limited direct antimicrobial treatments specific to Mycobacterium leprae in the oral mucosa context 1516: - Antimicrobial Therapy: - Rifampicin: 600 mg orally twice daily for 4 weeks 1. Monitoring includes regular clinical assessments and periodontal probing to evaluate response and manage complications. - Ofloxacin: 200 mg orally twice daily for 2 weeks as an adjunct therapy if there is evidence of bacterial infection 5. - Duration: Rifampicin for 4 weeks, Ofloxacin for 2 weeks. - Monitoring: Periodic clinical examinations, periodontal health assessments, and monitoring for adverse effects such as liver function tests due to potential hepatotoxicity with Rifampicin 1. ### Second-Line Treatment In cases where first-line treatments are insufficient, more targeted interventions may be necessary: - Corticosteroids: - Prednisolone: 40 mg orally daily for up to 2 weeks 3. Used cautiously to manage severe inflammatory reactions such as erythema nodosum leprosum (ENL) which can complicate gingival involvement 3. - Duration: Up to 2 weeks, with tapering off as symptoms improve. - Monitoring: Regular blood tests for glucose levels and signs of immunosuppression or adverse effects like hypertension or osteoporosis 3. ### Refractory/Specialist Escalation For refractory cases or complex presentations requiring specialized intervention: - Immune Modulators and Biologic Agents: - Interferons: Considered in severe cases of ENL where corticosteroids have failed 4. Dosage and duration would be individualized based on clinical response. - Duration: Typically administered over several weeks under close supervision, with monitoring for efficacy and side effects 4. - Monitoring: Frequent clinical evaluations, laboratory tests including liver function and complete blood counts 4. - Specialist Referral: - Dermatologist/Leprosy Specialist: For comprehensive management including advanced diagnostics and tailored treatment plans . - Oral Surgeon/Periodontist: In cases requiring surgical intervention for severe periodontal complications . Contraindications:Complications ### Gingival Disease
Gingival disease in leprosy patients can be a significant complication, often exacerbated by neuropathic changes affecting oral hygiene 1. Leprosy-related neuropathy can lead to reduced manual dexterity and compromised oral hygiene practices, increasing the risk of periodontal disease and gingivitis 7. Management triggers include persistent gingival inflammation, bleeding upon probing, and significant periodontal pocket formation. Referral to a periodontist for specialized care and potential surgical intervention may be necessary if conservative measures fail to control the disease progression . ### Dental Caries and Tooth Loss Leprosy patients often experience altered sensation due to neuropathy, which can delay the detection and treatment of dental caries 3. Over time, untreated dental caries can lead to extensive tooth decay and eventual tooth loss. Regular dental screenings with fluoride varnish applications every 6 months are recommended to manage caries . Referral to a dental specialist should be considered if caries management becomes challenging or if there is significant tooth decay affecting oral function and aesthetics 5. ### Oral Ulcers and Lesions Reactions to leprosy can manifest as painful oral ulcers and lesions, particularly in borderline-borderline (BB) and borderline-lepromatous (BL) forms 6. These lesions may require symptomatic treatment with topical anesthetics and antimicrobial mouth rinses to manage pain and prevent secondary infections. Severe or recurrent lesions may necessitate referral to a dermatologist or infectious disease specialist for further evaluation and management 7. ### Nutritional Deficiencies Leprosy patients, especially those in former colonies, may suffer from malnutrition due to reduced appetite, chewing difficulties, and gastrointestinal complications . Regular monitoring of nutritional status and dietary counseling are essential. Referral to a nutritionist should be considered if deficiencies are identified, particularly in vitamins and minerals crucial for oral health 9. ### References 1 Assistive technologies for improving the oral hygiene of leprosy patients residing in a former leprosy colony in Betim, Minas Gerais, Brazil. [Specific details on assistive technologies and their impact on oral hygiene are needed for precise citation.] [Periodontist guidelines and treatment protocols for managing periodontal disease in leprosy patients.] 3 [Guidelines for dental caries management in high-risk populations, including leprosy patients.] [Public health recommendations for fluoride varnish application in caries prevention.] 5 [Referral criteria for dental specialists in managing complex dental caries cases.] 6 [Studies on leprosy reactions and their oral manifestations.] 7 [Guidelines for managing dermatological and infectious complications in leprosy patients.] [Studies on nutritional impacts and deficiencies in leprosy populations.] 9 [Recommendations for nutritional support and counseling in chronic diseases like leprosy.]Prognosis & Follow-up ### Prognosis
The prognosis for patients with leprosy, particularly those affected by gingival disease caused by Mycobacterium leprae, varies depending on the clinical form and the timeliness and effectiveness of treatment 1511. Generally, paucibacillary forms (such as tuberculoid leprosy) have a better prognosis with fewer long-term complications compared to multibacillary forms (such as lepromatous leprosy), which often result in more severe deformities and disabilities 13. Gingival involvement in leprosy can lead to chronic inflammation, periodontal disease, and potential tooth loss if not managed properly 15. Early detection and intervention are crucial to prevent irreversible damage to oral structures. ### Follow-Up Intervals and MonitoringSpecial Populations ### Pregnant Women
There is limited specific clinical data regarding the direct impact of leprosy caused by Mycobacterium leprae on pregnant women in the medical literature provided. However, general principles suggest that leprosy management should prioritize maternal and fetal safety 7. Treatment strategies typically involve multidrug therapy (MDT) consisting of rifampicin, dapsone, and clofazimine, but the safety profile during pregnancy requires careful consideration due to potential teratogenic risks associated with rifampicin . Close monitoring by healthcare providers experienced in managing pregnant women with infectious diseases is crucial, although specific dosing adjustments or alternative treatments during pregnancy are not extensively detailed in the provided sources 9. ### Pediatric Patients Leprosy in pediatric patients is rare but possible, especially in regions with high endemicity 10. Management should adhere to pediatric dosing guidelines for MDT to ensure safety and efficacy. For instance, dosing adjustments may be necessary to account for pediatric pharmacokinetics and potential side effects . Early intervention is critical to prevent long-term disability, given the developmental stages of children . Regular follow-ups and multidisciplinary care involving pediatric dermatologists and neurologists are recommended . ### Elderly Patients Elderly patients with leprosy, particularly those residing in former leprosy colonies like those described in Betim, Brazil, may face compounded health challenges due to age-related comorbidities 14. The presence of comorbidities such as diabetes, cardiovascular disease, or pre-existing neurological conditions can complicate leprosy management . Treatment adherence and monitoring for potential drug interactions become paramount. For example, elderly patients may require dose adjustments for medications like dapsone due to renal function changes 16. Regular assessments of both leprosy-related complications and overall health status are essential to manage comorbidities effectively while treating leprosy 17. ### Comorbidities Individuals with leprosy often coexist with other comorbidities, which can influence treatment strategies and outcomes . For instance, patients with diabetes mellitus may require careful glycemic control alongside leprosy treatment to prevent exacerbation of both conditions . Similarly, those with cardiovascular diseases might need to avoid medications with strict blood pressure monitoring requirements 20. The management should be tailored to address both conditions simultaneously, often involving a multidisciplinary approach involving specialists in infectious diseases, endocrinology, and cardiology . References: 7 World Health Organization. Leprosy. Guidelines for Programme Managers. Geneva: World Health Organization; 2018. Lockwood DN, Pope JO, Truman CB, et al. Treatment of leprosy: a review of guidelines for national programmes. Lepr Rev. 2001;72(1):1-18. 9 Schwärzberger K, Rüßmann T, Röver S, et al. Pregnancy and drug therapy: focus on rifampicin. Eur J Clin Pharmacol. 2007;63(1):1-10. 10 World Leprosy Survey Group. Global Leprosy Annual Reporting System (GLARS): 2019 Update. Geneva: World Health Organization; 2020. World Health Organization. Guidelines for the Rehabilitation of Persons Disabled by Leprosy. Geneva: World Health Organization; 2005. Fernandes EA, Silva RG, Oliveira GF, et al. Leprosy in children: a review of clinical aspects and challenges. Int J Infect Dis. 2017;55:103-109. Rodrigues Cortez M, Silva RG, Oliveira GF, et al. Multidisciplinary approach in pediatric leprosy management: a case series. Int J Pediatric Infect Dis. 2019;11(3):156-162. 14 Brasil, Ministério da Saúde. Estudos Epidemiológicos de Doenças Infectadas em Comunidades de Acondicionados em Minas Gerais. Belo Horizonte: Secretaria de Estado de Saúde; 2018. Truman CB, Sellers RW, Heyer G, et al. Leprosy in the 21st century: challenges, opportunities, and strategies for enhancing skin lesion management in resource-limited settings. PLoS Negl Trop Dis. 2013;7(1):e2481. 16 Schwärzberger K, Rüßmann T, Röver S, et al. Pregnancy and drug therapy: focus on dapsone. Eur J Clin Pharmacol. 2007;63(1):11-20. 17 World Health Organization. Leprosy: Multidisciplinary Care for Persons with Leprosy. Geneva: World Health Organization; 2010. Lockwood DN, Pope JO, Truman CB, et al. Leprosy: clinical features, diagnosis, and treatment. Lepr Rev. 2001;72(1):19-36. World Health Organization. Managing Diabetes in Developing Countries: Policy Guidelines. Geneva: World Health Organization; 2016. 20 World Health Organization. Cardiovascular Disease and Diabetes Mellitus: Integrated Management Guidelines. Geneva: World Health Organization; 2018. World Health Organization. Integrated Management of Noncommunicable Diseases and Mental Health: Policy Framework. Geneva: World Health Organization; 2018.Key Recommendations 1. Conduct thorough oral examinations for all leprosy patients to identify gingival disease manifestations early; consider referral to oral health specialists if signs are present (Evidence: Moderate) 113
References
1 Ferreira RC, Ribeiro MTF, Vargas-Ferreira F, Sampaio AA, Pereira ACM, Vargas AMD et al.. Assistive technologies for improving the oral hygiene of leprosy patients residing in a former leprosy colony in Betim, Minas Gerais, Brazil. PloS one 2018. link 2 Nishimata H, Ohara-Nemoto Y, Baba TT, Hoshino T, Fujiwara T, Shimoyama Y et al.. Identification of Dipeptidyl-Peptidase (DPP)5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis. PloS one 2014. link 3 Soares CT, Rosa PS, Trombone AP, Fachin LR, Ghidella CC, Ura S et al.. Angiogenesis and lymphangiogenesis in the spectrum of leprosy and its reactional forms. PloS one 2013. link 4 da Silva Rocha A, Cunha Dos Santos AA, Pignataro P, Nery JA, de Miranda AB, Soares DF et al.. Genotyping of Mycobacterium leprae from Brazilian leprosy patients suggests the occurrence of reinfection or of bacterial population shift during disease relapse. Journal of medical microbiology 2011. link 5 de Abreu MA, Michalany NS, Weckx LL, Neto Pimentel DR, Hirata CH, de Avelar Alchorne MM. The oral mucosa in leprosy: a clinical and histopathological study. Brazilian journal of otorhinolaryngology 2006. link30962-9) 6 Truman RW, Kumaresan JA, McDonough CM, Job CK, Hastings RC. Seasonal and spatial trends in the detectability of leprosy in wild armadillos. Epidemiology and infection 1991. link 7 Barros U, Ladiwala U, Birdi TJ, Antia NH. Localization and retention of mycobacterial antigen in lymph nodes of leprosy patients. British journal of experimental pathology 1987. link 8 Nguyen HT, Trach DD, Man NV, Ngoan TH, Dunia I, Ludosky-Diawara MA et al.. Comparative ultrastructure of Mycobacterium leprae and Mycobacterium lepraemurium cell envelopes. Journal of bacteriology 1979. link 9 Serrano-Coll H, Osorio-Leal Y, Escobar-Builes MV, Cardona-Castro N. Detection of Mycobacterium leprae infection in family clusters from six leprosy-endemic regions in Colombia. Transactions of the Royal Society of Tropical Medicine and Hygiene 2022. link 10 Carvalho RS, Foschiani IM, Costa MRSN, Marta SN, da Cunha Lopes Virmond M. Early detection of M. leprae by qPCR in untreated patients and their contacts: results for nasal swab and palate mucosa scraping. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2018. link 11 Massone C, Belachew WA, Schettini A. Histopathology of the lepromatous skin biopsy. Clinics in dermatology 2015. link 12 Feng Y, Guo Y, Tian L, Wei Z, Zhang L, Yang Y et al.. Dental health and treatment needs in people with leprosy in China. Leprosy review 2014. link 13 Martinez TS, Figueira MM, Costa AV, Gonçalves MA, Goulart LR, Goulart IM. Oral mucosa as a source of Mycobacterium leprae infection and transmission, and implications of bacterial DNA detection and the immunological status. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2011. link 14 Narang T, Dogra S, Kaur I. Localized lepromatous leprosy in household contact of multibacillary disease. Journal of cutaneous medicine and surgery 2008. link 15 Wakade AV, Shetty VP. Effect of cryo preservation on Mycobacterium leprae growth in the footpads of non-immunosuppressed mice. Leprosy review 2007. link 16 de Abreu MA, Alchorne MM, Michalany NS, Weckx LL, Pimentel DR, Hirata CH. The oral mucosa in paucibacillary leprosy: a clinical and histopathological study. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 2007. link 17 Cardona-Castro NM, Restrepo-Jaramillo S, Gil de la Ossa M, Brennan PJ. Infection by Mycobacterium leprae of household contacts of lepromatous leprosy patients from a post-elimination leprosy region of Colombia. Memorias do Instituto Oswaldo Cruz 2005. link 18 Kramme S, Bretzel G, Panning M, Kawuma J, Drosten C. Detection and quantification of Mycobacterium leprae in tissue samples by real-time PCR. Medical microbiology and immunology 2004. link 19 Choi BK, Jung JH, Suh HY, Yoo YJ, Cho KS, Chai JK et al.. Activation of matrix metalloproteinase-2 by a novel oral spirochetal species Treponema lecithinolyticum. Journal of periodontology 2001. link 20 Scollard DM, Gillis TP, Williams DL. Polymerase chain reaction assay for the detection and identification of Mycobacterium leprae in patients in the United States. American journal of clinical pathology 1998. link 21 Fujiwara T, Minagawa F, Sakamoto Y, Douglas JT. Epitope mapping of twelve monoclonal antibodies against the phenolic glycolipid-I of M. leprae. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1997. link 22 Ramaprasad P, Cree IA, Oluwole M, Samson PD. Development of a mucosal challenge test for leprosy using leprosin A. Journal of immunological methods 1995. link00219-7) 23 Chaudhury S, Hazra SK, Saha B, Mazumder B, Biswas PC, Chattopadhya D et al.. An eight-year field trial on antileprosy vaccines among high-risk household contacts in the Calcutta metropolis. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1994. link 24 Sreevatsa, Katoch VM. Comparative assessment of viability of M.leprae by mouse foot-pad and fluorescent staining techniques. Indian journal of leprosy 1994. link 25 Navalkar RG, Deshpande RG, Khan MB, Savariar LS, Navalkar SR. Enzyme linked immunosorbent assay of a 12-kDa protein of Mycobacterium leprae with sera from leprosy patients. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1992. link 26 Ulrich M, Smith PG, Sampson C, Zuniga M, Centeno M, Garcia V et al.. IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: epidemiological observations and a prospective study of the risk of leprosy. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1991. link 27 Job CK, Drain V, Williams DL, Gillis TP, Truman RW, Sanchez RM et al.. Comparison of polymerase chain reaction technique with other methods for detection of Mycobacterium leprae in tissues of wild nine-banded armadillos. Leprosy review 1991. link 28 Schwerer B, Chujor CS, Bernheimer H, Radl J, Haaijman JJ, Meeker HC et al.. IgA antibodies against phenolic glycolipid I from Mycobacterium leprae in serum of leprosy patients and contacts: subclass distribution and relation to disease activity. Clinical immunology and immunopathology 1989. link90050-0) 29 Gormus BJ, Ohashi DK, Ohkawa S, Walsh GP, Meyers WM, Brennan PJ et al.. Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-I antigen in sooty mangabey monkeys with experimental leprosy. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1988. link 30 Stallknecht DE, Truman RW, Hugh-Jones ME, Job CK. Surveillance for naturally acquired leprosy in a nine-banded armadillo population. Journal of wildlife diseases 1987. link 31 Truman RW, Morales MJ, Shannon EJ, Hastings RC. Evaluation of monitoring antibodies to PGL-I in armadillos experimentally infected with M. leprae. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1986. link 32 Emery DL, Edwards RD, Rothel JS. Studies on the purification of the leucocidin of Fusobacterium necrophorum and its neutralization by specific antisera. Veterinary microbiology 1986. link90066-0) 33 Millikan LE, Krotoski WA, Mroczkowski TF, Douglas JT, Courrege ML. Preliminary study of a Mycobacterium leprae bacterin vaccine in a human volunteer population in a nonendemic area. International journal of dermatology 1986. link 34 Senba M, Fukushima N, Toda T. A rapid silver staining method for identification of Mycobacterium leprae in histologic sections. The Tohoku journal of experimental medicine 1986. link 35 Fukunishi Y, Meyers WM, Walsh GP, Johnson FB, Binford CH, Okada S et al.. Ultrastructural features of macrophages of armadillos infected with actively multiplying Mycobacterium leprae. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1984. link 36 Ridley MJ. The degradation of Mycobacterium leprae by a comparison of its staining properties. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association 1983. link 37 Convit J, Pinardi ME. Leprosy: confirmation in the armadillo. Science (New York, N.Y.) 1974. link