Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application.

Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette-Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development.

Leprosy-like illness in a patient with Mycobacterium lepromatosis from Ontario, Canada.

Here we present the first case of a patient from Ottawa Canada, presenting with leprosy-like illness associated with Mycobacterium lepromatosis. The patient had no history of travel to leprosy-endemic areas or any obvious risk factors. Clinically, the patient presented with an anesthetic maculopapular rash on the trunk, back, and extremities. A skin biopsy of a lesion revealed a dermal lymphohistiocytic infiltration involving the vessels with an inflammatory process extending to the nerves. A neurological exam also identified a severe sensorimotor polyneuropathy. Concurrently, the patient was diagnosed with non-resectable, non small cell carcinoma of the lung, further complicating his clinical presentation. A Kinyoun stain of nasal blows and a Fite stain of the skin biopsy revealed few to moderate acid fast bacilli respectively. Cultures of the skin biopsy and multiple nasal blows were negative. Molecular studies of a skin biopsy sample including sequence analysis of a 765 bp region of the 16s rRNA gene eventually identified the organism with 100% homology to M. lepromatosis. The patient was treated for leprosy and appeared to improve slightly on therapy but died as a result of his malignancy approximately five months after the initiation of therapy. This represents the first case of a patient with M. lepromatosis like illness outside of Mexico and Singapore.

VNTR typing of Mycobacterium leprae in South Indian leprosy patients.

OBJECTIVES: To study the suitability, stability and diversity of short tandem repeat (STR) genomic markers to elicit strain variation in the Mycobacterium leprae isolates within leprosy patients from Andhra Pradesh and Tamil Nadu states in South India. MATERIALS AND METHODS: Slit skin smear (SSS) samples were collected from lesions and various body sites of newly diagnosed leprosy patients. The SSSs from each patient were pooled, except in the case of five patients. Total DNA was extracted from SSS samples. M. leprae STRs were amplified from the DNA either by multiplex PCR (MP) or single PCR methods. The number of repeats for each STR locus (the STR allele) was obtained either by fragment length analysis (FLA) or by DNA sequencing of the PCR amplicons. RESULTS AND CONCLUSION: Multiplex PCR minimised the use of DNA and reagents, and together with FLA, was time and cost effective for STR strain typing. After examination of the isolates of South Indian origin at 13 STR loci, it was determined that the alleles for (AC)8b, (GGT)5, 6-3a (rpoT), 21-3, 27-5, and 23-3 were conserved in two study populations. In a family from Andhra Pradesh, the M. leprae STR patterns in two patients were identical in 16 of 18 loci which indicate a common source of infection. Fourteen of 15 STR loci showed no intra-patient variation in the five patients tested in Tamil Nadu. Altogether, these studies indicate the suitability of STR strain typing for assessing short-range transmission chains.

Informe del primer encuentro de la asociación ideal (iniciativa para las pruebas diagnósticas celebrado en el instituto de investigación Armauer Hansen, Alert, Addis Abada, Etiopía del 24-27 de octubre de 2004 / No disponible

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