Insights from animal models on the immunogenetics of leprosy: a review

Adams, Linda B.; Peña, María; Sharma, Rahul; Hagge, Deanna A.; Schurr, Erwin; Truman, Richard W.

doi:10.1590/s0074-02762012000900028

Cited by 43 publications

(39 citation statements)

References 67 publications

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“…A total of 6% of animals screened (all resistant to the disease) showed that homozygous G/G allele is associated with resistance to the disease (28).…”

Section: Resultsmentioning

confidence: 99%

Red squirrels in the British Isles are infected with leprosy bacilli

Avanzi

Del-Pozo

Benjak

et al. 2016

Science

144

180

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British squirrels infected with leprosy With the exception of armadillos in the Americas, leprosy infections are considered almost exclusively restricted to humans. Avanzi et al. examined warty growths on the faces and extremities of red squirrels in the British Isles and found that two species of leprosy-causing organisms were to blame (see the Perspective by Stinear and Brosch). Mycobacterium leprae in the southern population of Brownsea Island squirrels originated from a medieval human strain. M. lepromatosis was found in red squirrels from elsewhere in the United Kingdom and Ireland. Human leprosy is proving hard to eradicate, despite available drugs. Perhaps other wildlife species are also reservoirs for this stubborn disease. Science , this issue p. 744 ; see also p. 702

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“…A total of 6% of animals screened (all resistant to the disease) showed that homozygous G/G allele is associated with resistance to the disease (28).…”

Section: Resultsmentioning

confidence: 99%

Red squirrels in the British Isles are infected with leprosy bacilli

Avanzi

Del-Pozo

Benjak

et al. 2016

Science

144

180

View full text Add to dashboard Cite

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“…Freshly harvested bacilli are stored at 4°C and used within 24 hours of harvest [9]. In this study, BALB/c and athymic nu/nu mice (Harlin Sprague-Dawley, Inc., Indianapolis, IN) were infected by inoculating each hind FP with 3×10 7 M. leprae in 0.03 ml PBS (Irvine Scientific, Santa Ana, CA) [33], [34]. FPs were harvested on Day 1 post infection and at 4, 8, 12 and 17 weeks.…”

Section: Methodsmentioning

confidence: 99%

Molecular Assays for Determining Mycobacterium leprae Viability in Tissues of Experimentally Infected Mice

et al. 2013

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BackgroundThe inability of Mycobacterium leprae to grow on axenic media has necessitated specialized techniques in order to determine viability of this organism. The purpose of this study was to develop a simple and sensitive molecular assay for determining M. leprae viability directly from infected tissues.Methodology/Principle FindingsTwo M. leprae-specific quantitative reverse transcription PCR (qRT-PCR) assays based on the expression levels of esxA, encoding the ESAT-6 protein, and hsp18, encoding the heat shock 18 kDa protein, were developed and tested using infected footpad (FP) tissues of both immunocompetent and immunocompromised (athymic nu/nu) mice. In addition, the ability of these assays to detect the effects of anti-leprosy drug treatment on M. leprae viability was determined using rifampin and rifapentine, each at 10 mg/kg for 1, 5, or 20 daily doses, in the athymic nu/nu FP model. Molecular enumeration (RLEP PCR) and viability determinations (qRT-PCR) were performed via Taqman methodology on DNA and RNA, respectively, purified from ethanol-fixed FP tissue and compared with conventional enumeration (microscopic counting of acid fast bacilli) and viability assays (radiorespirometry, viability staining) which utilized bacilli freshly harvested from the contralateral FP. Both molecular and conventional assays demonstrated growth and high viability of M. leprae in nu/nu FPs over a 4 month infection period. In contrast, viability was markedly decreased by 8 weeks in immunocompetent mice. Rifapentine significantly reduced bacterial viability after 5 treatments, whereas rifampin required up to 20 treatments for the same efficacy. Neither drug was effective after a single treatment. In addition, host gene expression was monitored with the same RNA preparations.Conclusions hsp18 and esxA qRT-PCR are sensitive molecular indicators, reliably detecting viability of M. leprae in tissues without the need for bacterial isolation or immediate processing, making these assays applicable for in vivo drug screening and promising for clinical and field applications.

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“…This technique has been applied not only to skin biopsy samples, but also to several different types of specimens such as skin smears, nerves, urine, oral or nasal swabs, blood, and ocular lesions [11], [35]–[41]. Different sequences were used as targets for PCR, such as genes encoding the 36-kDa antigen [42], 18-kDa antigen [43], 65-kDa antigen [44], complex 85 [37], 16S rDNA [45], and the repetitive sequences [46] among other M. leprae genes. More recently, real-time PCR technology has improved detection, increasing sensitivity and specificity as it appears to be a robust tool for mycobacteria recognition in selected clinical situations, as well as for quantitation in experimental settings [37], [45], [47]–[50].…”

Section: Pcr As a Detection Toolmentioning

confidence: 99%

PCR-Based Techniques for Leprosy Diagnosis: From the Laboratory to the Clinic

Talhari²,

et al. 2014

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In leprosy, classic diagnostic tools based on bacillary counts and histopathology have been facing hurdles, especially in distinguishing latent infection from active disease and diagnosing paucibacillary clinical forms. Serological tests and IFN-gamma releasing assays (IGRA) that employ humoral and cellular immune parameters, respectively, are also being used, but recent results indicate that quantitative PCR (qPCR) is a key technique due to its higher sensitivity and specificity. In fact, advances concerning the structure and function of the Mycobacterium leprae genome led to the development of specific PCR-based gene amplification assays for leprosy diagnosis and monitoring of household contacts. Also, based on the validation of point-of-care technologies for M. tuberculosis DNA detection, it is clear that the same advantages of rapid DNA detection could be observed in respect to leprosy. So far, PCR has proven useful in the determination of transmission routes, M. leprae viability, and drug resistance in leprosy. However, PCR has been ascertained to be especially valuable in diagnosing difficult cases like pure neural leprosy (PNL), paucibacillary (PB), and patients with atypical clinical presentation and histopathological features compatible with leprosy. Also, the detection of M. leprae DNA in different samples of the household contacts of leprosy patients is very promising. Although a positive PCR result is not sufficient to establish a causal relationship with disease outcome, quantitation provided by qPCR is clearly capable of indicating increased risk of developing the disease and could alert clinicians to follow these contacts more closely or even define rules for chemoprophylaxis.

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Insights from animal models on the immunogenetics of leprosy: a review

Cited by 43 publications

References 67 publications

Red squirrels in the British Isles are infected with leprosy bacilli

Red squirrels in the British Isles are infected with leprosy bacilli

Molecular Assays for Determining Mycobacterium leprae Viability in Tissues of Experimentally Infected Mice

PCR-Based Techniques for Leprosy Diagnosis: From the Laboratory to the Clinic

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