Pancytopenia due to lepromatous involvement of the bone marrow: successful treatment with multidrug therapy.

Leprosy is a chronic infectious disease with a wide spectrum of signs and symptoms depending on the ability of the host's immune system to resist the infection. The disease is frequently associated with sensory loss in skin lesions and damage in peripheral nerve trunks leading to nerve function impairment. In lepromatous leprosy, the immune system offers no protection against the multiplying bacilli and this results in heavy infiltration of the internal organs. We report a case of florid lepromatous leprosy with bone marrow suppression due to the disease, presenting with anemia, leukocytopenia and thrombocytopenia. The hematological abnormalities were fully reversed by mutidrug therapy for leprosy. We suggest that infiltration of the bone marrow by Mycobacterium leprae can cause pancytopenia, which can be cured by treatment of the leprosy alone.

Incidence of leprosy in school-children and their family members in Berhampur.

A school survey, followed by a contact survey, was carried out in Berhampur, a city in southern Orissa. In a study of 8,870 school-children, leprosy was detected in 15, giving a prevalence rate of 16.91 per 10,000 with a male:female ratio of 8:7. Of these, 14 (93.99%) had paucibacillary leprosy. More cases [11 (73.33%)] were seen in the age-group of 10-15 years. Exposed parts, such as lower limbs, upper limbs and head and neck in that order, were the sites of predilection, accounting for 85.71% of total lesions. Nerve involvement was found in 2 (13.33%) girls with deformity (ulnar claw) in one of them (6.66%). BCG scar was present in 11 (73.33%) cases. Among the vaccinated cases, tuberculoid type was the most common, followed by indeterminate, pure neuritic and borderline, in that order. A contact survey detected 2 multibacillary cases in two families (13.33%). In each case, the father was the index source. The study revealed that a maximum number of students, 8 (53.3%), belonged to the middle socioeconomic class. Of the 15 affected, 60% were undernourished and the rest well nourished. No other systemic disease was found clinically associated with leprosy.

Experimental Mycobacterium leprae infection in BALB/c mice: effect of BCG administration on TNF-alpha production and granuloma development.

In the present study, the experimental model of Mycobacterium leprae infection in the foot pads of BALB/c mice was used to investigate the effects of BCG administration on tumor necrosis factor-alpha (TNF-alpha) production and granuloma development. It was observed that mice intravenously infected with BCG 7 months after M. leprae inoculation into the foot pads presented a more effective mycobacteria clearance, revealed by a significant reduction of BCG-colony forming units in the spleen and by the reduction of acid-fast bacilli (AFB) in the foot pads. BCG infection at the peak of M. leprae infection also modulated the granulomatous response to M. leprae by converting mononuclear granulomas into an epithelioid-cell granuloma. Furthermore, lower TNF-alpha serum levels were detected in M. leprae-infected mice when compared to mice infected with M. leprae + BCG. An analysis of the TNF-alpha gene expression in the spleen by semiquantitative reverse transcription-polymerase chain reactions (RT-PCR) demonstrated that co-infection with BCG induced an earlier expression of TNF-alpha mRNA than in M. leprae-infected mice. The numbers of TNF-alpha-positive cells and apoptotic cells were also enhanced in epithelioid versus non-epithelioid granulomas. As a whole, the data suggest that co-infection of M. leprae-infected mice with BCG modulates TNF-alpha synthesis which, in turn, leads to induction of protective epithelioid granuloma formation in the foot pads and subsequent mycobacterial clearance. Macrophage differentiation into epithelioid cells, in association with the enhancement of TNF-alpha production at the granuloma site, may represent a triggering signal that induced apoptosis in these cells, leading to mycobacterial elimination. Moreover, the rate of apoptosis in epithelioid granulomas may well be related to the extent of immunopathologically mediated tissue damage.

Infection of SCID mice with Mycobacterium leprae and control with antigen-activated "immune" human peripheral blood mononuclear cells.

The SCID (severe combined immunodeficient) mouse lacks both B and T cells and tolerates injected mononuclear cells from humans, the principal hosts of Mycobacterium leprae. A SCID mouse model of leprosy could be useful to investigate potential vaccine strategies using human cells in a context in which the growth of the organism is monitored. Initial experiments determined that SCID mice are more susceptible than normal mice to infection and dissemination of M. leprae. Cells from humans, either BCG vaccinated or from countries where leprosy is endemic, were stimulated in vitro with a number of mycobacterial antigens--whole M. leprae, M. leprae cell walls, purified protein derivative of M. tuberculosis, and Mycobacterium bovis BCG--and tested for proliferation and production of interleukin-6, tumor necrosis factor alpha, and gamma interferon. Cell walls were the most efficient and consistent in inducing all of these activities. In vitro-activated human cells retain function better after injection into SCID mice than nonactivated cells. To test the ability of cells to affect the growth of M. leprae in the footpads of SCID mice, cells from a known responder to mycobacterial antigens and from a nonresponder were activated by M. leprae cell wall antigens. The cells were harvested and coinjected with fresh M. leprae into the right hind footpads of SCID mice. After 3 months, there was no growth of M. leprae in the footpads of mice coinjected with cells from the mycobacterial antigen responder, while growth was uninhibited in mice receiving cells from the nonresponder. Future experiments will determine requirements for antigen specificity in inhibiting M. leprae multiplication.

Evoluçäo das lesöes induzidas por micobactérias BCG e por H37RV em hamster (Mesocricetus auratus) / Evoution of the injuries induced by BCG mycobacterium and by H37RV in hamster (Mesocricetus auratus)

Foram investigados experimentalmente alguns aspectos da patogenia da tuberculose através da inoculaçao de uma cepa de micobactéria de virulência atenuada - BCG e outra cepa altamente virulenta - M. tuberculosis H37 Rv no tecido sub-epitelial do coxim plantar e no tecido sub-epitelial do terço distal da bolsa cervical de hamster, um sítio desprovido de drenagem linfática. A inoculaçao desses agentes determinou diferentes perfis de evoluçao das lesoes, sendo que as lesoes produzidas pelo BCG na pata apresentaram uma tendência de declínio do tamanho após 21 dias e as lesoes produzidas pelo H37 Rv mostraram uma evoluçao progressiva. O mesmo perfil foi observado nas lesoes induzidas na bolsa cervical por ambos os agentes. Contudo, diferentemente do BCG, o H37 Rv disseminou-se para os órgaos internos, causando extensas lesoes. A inoculaçao de BCG ou H37 Rv na pata provocou um aumento de 21 e 68 vezes, respectivamente, o peso do linfonodo satélite em relaçao ao controle, evidenciado a disseminaçao do bacilo por via linfática. Todavia, quando essas amostras foram inoculadas na bolsa, nao determinaram significativas mudanças de peso do linfonodo cervical, mas evidenciou-se a disseminaçao do bacilo virulento por via sangüínea, pelas lesoes produzidas no baço e pulmao.