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Biomedical subjects

W M Meyers

Publications and source records attributed to W M Meyers.

At least 19 recordsLinked to original sources
PubMed1992

Nonhuman sources of leprosy.

Our findings establish that there are known extrahuman reservoirs of M. leprae in three animal species. There is considerable evidence that the armadillo plays a role in the epidemiology of leprosy in humans in Texas and Louisiana. The elimination of leprosy as a public health problem (defined by the World Health Organization as one active patient per 10,000 population) may be attainable by the wide application of current control measures; however, the ultimate eradication of leprosy must take into account extrahuman reservoirs of M. leprae. The impact that attempts to control or to eliminate leprosy in such reservoirs (e.g., the armadillo in Louisiana and Texas) would have on environmental and wild-life considerations would be profound. Whether or not similar situations prevail in other leprosy-endemic geographic areas is not known. Based on the armadillo experience, there seems to be ample justification for undertaking, forthwith, carefully designed surveys for enzootic leprosy in some of the major endemic areas of leprosy. At the current state of our knowledge of the subject, such surveys should be initiated in the natural habitats of the mangabey monkey and chimpanzees--in West Africa.

Animals↗
PubMed1992

Leprosy.

Growing out of the successful transmission of leprosy to armadillos, making available large quantities of M. leprae, there have been remarkable recent advances in the knowledge of the leprosy bacillus. These bacilli and their isolated chemical constituents provide organisms for in vitro testing of new drugs, reagents for the study of the immunologic dysfunction in leprosy patients, development of early diagnostic methods, and the preparation of candidate vaccines. Leprosy is usually transmitted by the nasorespiratory route, but occasionally, there is transplacental infection. There are reports suggesting that patients have acquired leprosy by contact with wild M. leprae-infected armadillos in Louisiana and Texas. Perturbations in lymphocyte-macrophage interaction appear to be most closely related to the defective CMI in leprosy. The helper T/suppressor T cell populations vary markedly in lesions of the various forms of leprosy, with enhanced suppression of T-cell activity in lepromatous disease. Infiltration of IL-2 and gamma-interferon seems to stimulate CMI in situ in lesions of lepromatous leprosy. Vaccination of lepromatous patients with a killed M. leprae-plus-BCG preparation stimulates CMI and clears tissues of leprosy bacilli, providing an immunotherapeutic approach to the management of leprosy. Immunoprophylactic vaccine trials are in progress, and initial results should be available in 1991. Because of drug resistance, dapsone monotherapy of leprosy is no longer recommended. Multidrug regimens, composed of dapsone, rifampin, and clofazimine or a thioamide, are now required and appear to reduce the incidence of leprosy when applied assiduously. Newer experimental drugs that may eventually be included in these regimens include the fluoroquinolones, minocycline, and clarithromycin. There is no clear evidence that the early serologic diagnosis of leprosy is generally applicable. Favorable response to therapy in multibacillary patients, however, may be assessed by noting drops in levels of M. leprae-specific antigens in blood and urine and, to a lesser extent, levels of specific antibodies in serum. There are conflicting reports on the influence of AIDS on leprosy. There are no convincing data showing that AIDS and leprosy affect each other. Although chemotherapy offers the best current hope for the control of leprosy, effective immunoprophylaxis and improved socioeconomic conditions in endemic areas are thought to be essential in programs for the eradication of leprosy.

Animals↗
PubMed1991

Current concepts in the pathogenesis of leprosy. Clinical, pathological, immunological and chemotherapeutic aspects.

In recent years there have been notable advances in the laboratory investigation and field management of leprosy. Progress, however, continues to be hindered by the lack of efficient methods for early diagnosis and implementation of control and treatment measures. Diagnosis is still made on the same principles as a century ago (clinical and histopathological findings), and only 1 in 3 known patients worldwide receives optimal chemotherapy. In 1988, nearly 1 in 10 newly diagnosed patients already had debilitating deformities. Contributing factors are operational, administrative and financial difficulties in implementing multidrug therapeutic regimens, inadequately trained personnel, and lack of priority and political commitment to leprosy control. The formulation and implementation of multidrug therapy is the most important development in leprosy in the past 10 years. Dapsone monotherapy was the mainstay for treatment and control for approximately 40 years, but secondary dapsone-resistant strains, first noted in 1964, now infect as many as 50% of all new patients. Multidrug regimens recommended by the WHO consist of various combinations of therapy using dapsone, rifampicin, clofazimine and a thionamide. Duration of therapy is limited to 6 months for paucibacillary and 2 years or more for multibacillary patients; relapse rates thus far are low. The average cost of treatment worldwide, including the cost of drugs, is estimated at $US150 per patient. The recent annual drop of nearly 8% in newly registered patients may be due to the implementation of these therapeutic regimens. Newer drugs that may be introduced into these regimens include fluoroquinolones, minocycline and clarithromycin. While knowledge of the microbiology of the leprosy bacillus and host response has advanced remarkably, there is little improvement in the understanding or amelioration of social aspects of leprosy. Better treatment and control reduces the stigma, but improvements in the attitudes of patients and society towards leprosy are as important as advances in medical science in achieving ultimate eradication of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Naturally acquired and experimental leprosy in nonhuman primates.

Naturally-acquired leprosy has been observed in chimpanzees and sooty mangabey monkeys. Experimental multibacillary leprosy was established in 24 of 36 mangabey monkeys, 7 of 34 rhesus monkeys, and 15 of 19 African green monkeys following intravenous and intradermal inoculation of Mycobacterium leprae. The experimental disease strongly resembles leprosy in humans clinically, histopathologically, and immunologically. Thus, in addition to nine-banded armadillos in Louisiana and Texas, chimpanzees and sooty mangabeys in Africa, in the wild or in captivity, may serve as a zoonotic source of M. leprae. Investigators using chimpanzees and monkeys should be alerted to the possibility of naturally-acquired leprosy.

Animals↗
PubMed1991

Experimental borderline lepromatous leprosy with intraneural erythema nodosum leprosum in a mangabey monkey (Cercocebus atys).

A sooty mangabey monkey (Cercocebus atys) was inoculated with Mycobacterium leprae and developed borderline lepromatous leprosy and intraneural erythema nodosum leprosum. Previously studied mangabeys have developed only disseminated lepromatous leprosy without reactions. This case broadens the spectrum of leprosy seen in experimentally inoculated animals and further characterizes the nonhuman primate model of leprosy.

Animals↗
PubMed1991

A serologic study of naturally acquired leprosy in chimpanzees.

Data from longitudinally obtained serum samples spanning several years has permitted us to identify two chimpanzees with leprosy and to estimate the time of Mycobacterium leprae exposure/infection. The results confirm high levels of specific anti-M. leprae phenolic glycolipid-I (PGL-I) as well as anti-lipo-arabinomannan (anti-LAM) antibodies in both chimpanzees, and identify additional chimpanzees with possible M. leprae exposure. The observations are consistent with the hypothesis that leprosy exists in chimpanzees in the U.S.A. and suggest the possibility that M. leprae may be transmitted among chimpanzees. The data suggest that monitoring anti-PGL-I and anti-LAM IgG and IgM levels longitudinally in leprosy contacts may be useful in the recognition of preclinical leprosy.

Animals↗
PubMed1991

Ocular lesions in leprosy.

Leprosy is the world's third leading cause of blindness. Mechanisms of ocular infection include direct or hematogenous invasion of the globe, or involvement of branches of the facial or corneal nerves, contributing to exposure keratitis. Lesions of ocular leprosy can be classified as potentially sight threatening or academic. A review of the world's literature showed no geographic or climactic trends in disease course. Leprosy in humans is contrasted with experimental disease in animal models; early experimental disease may be primarily neurally mediated rather than hematogenously mediated as previously thought.

Animals↗
PubMed1990

Pathology of dual Mycobacterium leprae and simian immunodeficiency virus infection in rhesus monkeys.

Three rhesus monkeys were experimentally inoculated with sooty-mangabey-derived Mycobacterium leprae and were inadvertently infected with the simian immunodeficiency virus (SIV) as well. They died of an immunodeficiency syndrome, and at autopsy all had lesions caused by M. leprae. One monkey was inoculated twice with M. leprae, initially with an inoculum from a sooty mangabey that was not infected with SIV and, subsequently, with an inoculum from a mangabey that was SIV infected. The monkey did not develop clinical lesions and became strongly lepromin skin test (LST) positive after the first inoculation, but became infected with both agents and LST negative following the second inoculation. These observations suggest that SIV-infected rhesus monkeys have an increased susceptibility to M. leprae infection and, by analogy, imply that HIV-infected human beings may have an increased susceptibility as well.

Animals↗
PubMed1990

Antibodies to lipoarabinomannan antigen in sooty mangabey monkeys experimentally inoculated with Mycobacterium leprae.

IgG and IgM antibody levels to mycobacterial lipoarabinomannan (LAM) antigen were determined by ELISA in eight sooty mangabey monkeys (Cercocebus atys) prior to and at intervals after experimental inoculation with Mycobacterium leprae. High levels of anti-LAM IgG were present before inoculation and increased thereafter in the five mangabeys that developed lepromatous (LL) forms of leprosy; lower levels of anti-LAM IgG were observed in two mangabeys that developed indeterminate leprosy and tuberculoid/neuritic leprosy, respectively, and in a mangabey that was leprosy resistant. IgM anti-LAM levels were near zero before M. leprae inoculation in all eight animals, rose significantly in only three LL-leprosy-susceptible animals after inoculation, and returned to near zero in all animals within 3 years. Anti-LAM antibody levels appear to be potentially valuable as an indicator of leprosy susceptibility, and when measured longitudinally together with antibody levels to M. leprae-specific phenolic glycolipid-I antigen, as a means to detect preclinical M. leprae infections in high-risk individuals.

Animals↗
PubMed1989

Interactions between simian immunodeficiency virus and Mycobacterium leprae in experimentally inoculated rhesus monkeys.

Thirty-four rhesus monkeys were inoculated with Mycobacterium leprae inoculum isolated from sooty mangabey monkeys with leprosy. Later it was learned that one of the M. leprae-donor mangabeys was asymptomatically infected with simian immunodeficiency virus (SIV). Thus, five of the rhesus monkey were coinoculated with M. leprae and SIV. Three of the five became SIV-positive and developed signs of leprosy and an AIDS-like illness. Two animals remained healthy. The coinoculated leprosy-positive rhesus monkeys developed leprosy despite serologic response patterns to M. leprae antigens that usually indicate leprosy resistance. Three (60%) of the five SIV-positive rhesus monkeys developed leprosy compared with 21% of the animals who received SIV-free M. leprae inocula. Diminished lepromin skin test responses and decreasing T-helper cell percentages were observed in SIV-coinoculated rhesus monkeys with leprosy. These observations suggest that SIV increases the susceptibility of rhesus monkeys to leprosy, possibly related to loss of T-helper cell function.

Animals↗
PubMed1989

An electron microscopic study of lymphatics in the dermal lesions of human leprosy.

The dermal lymphatic vessels in lepromatous and tuberculoid leprosy lesions were studied by light- and electron-microscopy. In the lepromatous patient, lymphatic vessels were seen in both intra- and peri-granulomatous areas. The lymphatic lining cells contained lipid droplets, lysosomes, and numerous pinocytotic vesicles. Cells bearing bacilli were only occasionally seen. In the tuberculoid cases, lymphatic vessels were seen only along the edges of the granulomas and the lining cells were less prominent. Inflammatory cells, both lymphocytes and histiocytes, were found traversing the walls of lymphatic vessels in both groups of patients. The results of the study confirm the continued and increased functioning of the lymphatic drainage system in dermal leprosy lesions, and indicates that it may be a major route for the clearance of lipids from the lipid-rich bacilliferous lesions in the lepromatous patient. The lymphatic pathway appears to be a minor pathway for the dissemination of Mycobacterium leprae in comparison with the blood vascular system.

Humans↗
PubMed1988

Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-I antigen in sooty mangabey monkeys with experimental leprosy.

Four pairs of sooty mangabey monkeys (Cercocebus atys) were inoculated with serial, 10-fold dilutions of Mycobacterium leprae. The highest-dose pair received 4.8 X 10(10) M. leprae. Serum samples were obtained and clinical signs of leprosy were recorded at intervals of 35 months. Longitudinal serum samples were assayed by an ELISA method for the presence of IgG and IgM antibodies to the M. Leprae-specific phenolic glycolipid-I (PGL-I) antigen. In general, the onset of disease symptoms paralleled the number of M. leprae inoculated, but the ultimate course of disease depended upon individual animal susceptibility. Both IgG and IgM anti-PGL-I isotypes were observed in variable levels and patterns, related to the disease stage, among the eight mangabeys. The data suggest that high IgG and low IgM anti-PGL-I levels correlated with less severe disease; whereas initial high IgM titers and/or rising or sustained high IgM titers, especially together with low IgG anti-PGL-I titers, preceded or corresponded to periods of progressive leprosy. The results show that IgG and IgM anti-PGL-I antibodies can be present in significant titers among mangabeys early after infection with M. leprae. It appears likely that the relative levels of these anti-PGL-I isotypes may be correlated with the susceptibility of individual animals to the development of lepromatous leprosy.

Animals↗
PubMed1988

Histologic responses in sixty multibacillary leprosy patients inoculated with autoclaved Mycobacterium leprae and live BCG.

Sixty lepromatous or borderline lepromatous patients were submitted to immunotherapy with a mixture of autoclaved Mycobacterium leprae and BCG. The histopathologic findings in skin biopsy specimens taken before and after immunotherapy were evaluated independently by six histopathologists in a workshop setting. Their pooled observations on diagnosis and classification were analyzed to assess the histopathologic changes following various periods of immunotherapy. Expressing the results as the average value of five to six independent observations, there were changes in classification of reversal or upgrading toward the tuberculoid end of the leprosy spectrum in 90.5% of the patients initially classified as lepromatous (LL), and in 83.3% of those initially classified as borderline lepromatous (BL). The histopathologic findings amply support the clinical, bacteriologic and immunological changes following immunotherapy from LL or BL, to BL, mid-borderline (BB) or even borderline tuberculoid (BT) leprosy.

BCG Vaccine↗