Long-term ulcerations caused by Mycobacterium lepromatosis.

Patients with leprosy rarely present ulcerated lesions that can appear during reactional states like Lucio's phenomenon (LP), as in our case. LP is a rare complication of multibacillary leprosy due to massive bacilli invasion of endothelial cells causing a thrombotic syndrome. The initial macular lesion is purpuric followed by multiple infiltrated papules and nodules, some of them ulcerated, associated to loss of sensation on lower limbs. The importance of recognizing ulcers as a specific cutaneous manifestation of leprosy allows early diagnosis and treatment, and therefore avoiding the development of disabilities and persistence of illness. Infection by Mycobacterium lepromatosis is associated with LP and it should be especially sought in patients from endemic areas.

Role for mycobacterial infection in pathogenesis of primary biliary cirrhosis?

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterized by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterized by circulating antimitochondrial antibodies (AMAs) as well as disease-specific antinuclear antibodies, cholestatic liver function tests, and characteristic histological features, including granulomas. A variety of organisms are involved in granuloma formation, of which mycobacteria are the most commonly associated. This has led to the hypothesis that mycobacteria may be involved in the pathogenesis of PBC, along with other infectious agents. Additionally, AMAs are found in a subgroup of patients with mycobacterial infections, such as leprosy and pulmonary tuberculosis. Antibodies against species-specific mycobacterial proteins have been reported in patients with PBC, but it is not clear whether these antibodies are specific for the disease. In addition, data in support of the involvement of the role of molecular mimicry between mycobacterial and human mitochondrial antigens as triggers of cross-reactive immune responses leading to the loss of immunological tolerance, and the induction of pathological features have been published. Thus, antibodies against mycobacterial heat shock protein appear to cross-recognize AMA-specific autoantigens, but it is not clear whether these autoantibodies are mycobacterium-species-specific, and whether they are pathogenic or incidental. The view that mycobacteria are infectious triggers of PBC is intriguing, but the data provided so far are not conclusive.

Mycobacteria in Crohn's disease: a persistent hypothesis.

Efforts to explore a mycobacterial origin for Crohn's disease typically have involved an epidemiological approach, searching for Mycobacterium avium subsp. paratuberculosis in patient tissue. An alternative approach involves consideration of genetic and experimental data regarding host resistance to mycobacteria. From human and mycobacterial genetics, it is known that mycobacterial diseases depend on both pathogen and host factors and that tuberculosis and leprosy are effectively genetic diseases. The discovery of a number of Crohn's susceptibility genes, including NOD2/CARD15, demonstrates that Crohn's also is a complex genetic disease. Mutations in NOD2/CARD15 do not necessarily lead to Crohn's disease, so other mitigating factors, genetic and/or environmental, probably are required to produce illness. Recent work has shown that NOD2/CARD15 serves a role in bacterial sensing and activation of innate immune responses, providing a link between Crohn's genetics and an environmental factor, potentially a bacterial trigger. In this review, we discuss the current understanding of mycobacterial and Crohn's genetic susceptibility and review the evidence that NOD2/CARD15 may mediate host resistance to mycobacterial infection.

Palsy of the rear limbs in Mycobacterium lepraemurium-infected mice results from bone damage and not from nerve involvement.

A small but relatively constant proportion (3-5%) of mice chronically infected with Mycobacterium lepraemurium (MLM) develops bilateral paralysis of the rear limbs. The aim of the study was to investigate whether or not the bilateral leg palsy results from nerve involvement. Direct bacterial nerve infection or acute/delayed inflammation might possibly affect the nerves. Therefore, palsied animals were investigated for the presence of: (a) histopathological changes in the leg tissues including nerves, bones and annexes, and (b) serum antibodies to M. lepraemurium and M. leprae lipids, including phenolic glycolipid I from M. leprae. Histopathological study of the palsied legs revealed that the paralysis was not the result of direct involvement of the limb nerves, as neither bacilli nor inflammatory cells were observed in the nerve branches studied. Antibodies to brain lipids and cardiolipin were not detected in the serum of the palsied animals, thus ruling out an immune response to self-lipids as the basis for the paralysis. Although high levels of antibodies to MLM lipids were detected in the serum of palsied animals they were not related to limb paralysis, as the nerves of the palsied legs showed no evidence of inflammatory damage. In fact, nerves showed no evidence of damage. Paralysis resulted from severe damage of the leg bones. Within the bones the bone marrow became replaced by extended bacilli-laden granulomas that frequently eroded the bone wall, altering the normal architecture of the bone and its annexes, namely muscle, tendons and connective tissue. Although this study rules out definitively the infectious or inflammatory damage of nerves in murine leprosy, it opens a new avenue of research into the factors that participate in the involvement or the sparing of nerves in human and murine leprosy, respectively.

Use of liposome preparation to treat mycobacterial infections.

Infections caused by organisms of the genus mycobacteria, such as tuberculosis M. avium disseminated infection in AIDS patients and leprosy, are extremely common around the world. Mycobacteria are intracellular organisms that invade and multiply chiefly within phagocytic cells. Antibiotic resistance among mycobacteria is a growing concern. M. tuberculosis resistant to INH and rifampin are increasing in major urban centers of the developed and in the developing world. M. avium is characteristically resistant to most anti-tuberculosis antibiotics. Furthermore, therapy of mycobacterial infections takes a long time and most of the drugs have potential side effects and toxicity. In addition, mycobacteria is found within cells and antimicrobials need to be able to achieve adequate concentration within the compartment where mycobacteria is located. Liposome preparations, containing antibiotics, have a theoretical advantage in being able to deliver high concentrations of antimicrobials into the infected cell. Studies done thus far, in vitro and in vivo, have confirmed this premise, when comparing drug entrapped in liposomes with free drug. This paper summarizes the results obtained using liposome preparations to treat mycobacterial infections.

Slow bacterial infections or autoimmunity?

In this article, Graham Rook and John Stanford propose that a group of idiopathic diseases that are often associated with a degree of autoimmunity and arthritis, including rheumatoid arthritis, inflammatory bowel disease, sarcoidosis and psoriasis, are caused by extremely slow-growing bacteria. They suggest that these diseases are one end of a continuous spectrum caused by related slow-growing genera, which ranges from rheumatoid arthritis, through Takayasu's arteritis and Whipple's disease, to reach the conventional mycobacterioses such as tuberculosis and leprosy.

Mycobacteria and AIDS.

Mycobacteria are acid-fast, slow-growing microorganisms which have gained attention due to increasing prevalence in AIDS patients. Until the advent of AIDS, the only true pathogens of this group were Mycobacterium tuberculosis and M. leprae and the remaining mycobacteria were considered to be saprophytes or opportunistic pathogens. Infection with the MOTT (mycobacteria other than tuberculosis) bacilli was only seen in elderly or immunocompromised patients and was generally limited to caseating pulmonary granulomas, with rare extrapulmonary involvement. In AIDS patients, however, the incidence of mycobacterial infections ranges from 10 to 60% of HIV-positive persons, depending on location, method of identification, and patient population. Furthermore the pathogenesis of these mycobacterioses is distinct from that seen in non-AIDS patients because disseminated disease is the rule rather than the exception. Finally treatment of mycobacterial infections is increasingly difficult due to multiple drug resistances as well as the length of antimicrobial therapy required to cure the disease. Because of the prevalence and importance of these microorganisms, much research has been performed with the mycobacteria to develop new therapies and to understand their modes of pathogenesis.

Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population.

Mycobacterial infections and AIDS.

PIP: In the West, 1 of the most common opportunistic bacterial infections in AIDS patients is Mycobacterium avium-intracellulare (MAI). Physicians have diagnosed it in 15-20% of AIDS patients before they died, and it was identified in 50% of dead AIDS patients. Only 2 cases have been diagnosed in Africa. Before AIDS began afflicting the human population, dissemination of MAI was rare, but in AIDS patients the degree of dissemination is widespread and has been found, at least, in the spleen, lymph nodes, lung, liver, and gastrointestinal (GI) tract. The portal of entry in MAI infections has not been clearly identified, but some evidence suggests that in AIDS patients the disseminated infection enters through the GI tract. Response to antibiotic treatment for MAI in AIDS patients is poor. Other nontuberculous mycobacteria, such as M. kansasii and 1 case of M. leprae, have also been found in association with AIDS. In the United States, tuberculosis is often associated with AIDS, especially if the cases are black, of foreign origin (particularly from Haiti), or had a history of intravenous drug abuse. Tuberculosis in AIDS patients is more likely to be lymphatic and disseminated than pulmonary. 1 study revealed that 30% of AIDS cases with tuberculosis had pulmonary tuberculosis compared with 80% of those with only tuberculosis. Further, pericardial disease commonly accompanies tuberculosis in AIDS patients. The treatment for tuberculosis in AIDS patients is standard antituberculous drugs. It appears that, at least in the case of tuberculosis, HIV infection causes reactivation of latent infections 1st acquired in childhood. Further research on the association of mycobacterial infection and AIDS will lead to a greater understanding of the immune defense system in all types of patients.^ieng

Chest infection due to M. fortuitum in a case of lepromatous leprosy--a case report.

Lepromatous leprosy cases may be immunocompromised due to the extensive disease and also because of steroid therapy for repeated reactions. Such patients are likely to be at higher risk for getting opportunistic infection due to various environmental microbes. This paper reports a case of lepromatous leprosy with repeated lepra reaction who was found to have chest infection due to M. fortuitum. It is suggested that mycobacterial culture and sensitivity should be recommended in cases who are immunocompromised and whose pathological specimens contain acid fast bacilli. Species identification and sensitivity can be very helpful in proper management of such cases who will otherwise pass off as tuberculosis.

Mycobacterium fortuitum: an unsuspected cause of synovitis and osteomyelitis

Two men with progressive synovitis and osteomyelitis of the wrist were found to have infection with Mycobacterium fortuitum. Immunological defects were demonstrated in both cases in association with renal failure and renal transplantation respectively. Failure of appropriate antibiotic therapy to eradicate infection necessitated amputation in one case. M. fortuitum is frequently sensitive to only amikacin or kanamycin. Treatment with amikacin alone was unsuccessful. This organism is widespread in the environment and may need to be considered in undiagnosed chronic infection in the immunologically suspectible host, as it poses unusual problems in diagnosis and therapy.