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Biomedical subjects

Wayne M Meyers

Publications and source records attributed to Wayne M Meyers.

16 recordsLinked to original sources
PubMed2006

Evidence for an intramacrophage growth phase of Mycobacterium ulcerans.

Mycobacterium ulcerans is the etiologic agent of Buruli ulcer (BU), an emerging tropical skin disease. Virulent M. ulcerans secretes mycolactone, a cytotoxic exotoxin with a key pathogenic role. M. ulcerans in biopsy specimens has been described as an extracellular bacillus. In vitro assays have suggested a mycolactone-induced inhibition of M. ulcerans uptake by macrophages in which its proliferation has not been demonstrated. Therefore, and uniquely for a mycobacterium, M. ulcerans has been classified as an extracellular pathogen. In specimens from patients and in mouse footpad lesions, extracellular bacilli were concentrated in central necrotic acellular areas; however, we found bacilli within macrophages in surrounding inflammatory infiltrates. We demonstrated that mycolactone-producing M. ulcerans isolates are efficiently phagocytosed by murine macrophages, indicating that the extracellular location of M. ulcerans is not a result of inhibition of phagocytosis. Additionally, we found that M. ulcerans multiplies inside cultured mouse macrophages when low multiplicities of infection are used to prevent early mycolactone-associated cytotoxicity. Following the proliferation phase within macrophages, M. ulcerans induces the lysis of the infected host cells, becoming extracellular. Our data show that M. ulcerans, like M. tuberculosis, is an intracellular parasite with phases of intramacrophage and extracellular multiplication. The occurrence of an intramacrophage phase is in accordance with the development of cell-mediated and delayed-type hypersensitivity responses in BU patients.

Animals↗
PubMed2006

Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure.

In the southern and southeastern United States, the 9-banded armadillo is an important reservoir for Mycobacterium leprae, the causative agent of leprosy (Hansen's disease). Here, we describe a woman living in Georgia with borderline tuberculoid leprosy who worked for many years in a garden where armadillos burrowed or were buried. There was no history of foreign travel or known exposure to a person with leprosy. Treatment with 6 once-monthly combined doses of rifampin, ofloxacin, and minocycline was successful.

Animals↗
PubMed2006

Heterogeneity among Mycobacterium ulcerans isolates from Africa.

Mycobacterium ulcerans causes Buruli ulcer, an ulcerative skin disease in tropical and subtropical areas. Despite restricted genetic diversity, mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis on M. ulcerans revealed 3 genotypes from different African countries. It is the first time this typing method succeeded directly on patient samples.

Africa↗
PubMed2006

Mycobacterium ulcerans disease (Buruli ulcer) in a rural hospital in Bas-Congo, Democratic Republic of Congo, 2002-2004.

Buruli ulcer (BU), which is caused by Mycobacterium ulcerans, is an important disabling skin disease. Its prevalence is highest in west and central Africa. We report an apparent resurgence of BU in the Bas-Congo Province, Democratic Republic of Congo. During a 28-month period in 2002-2004, the rural hospital of the Institut Médical Evangélique at Kimpese admitted 51 patients suspected of having BU. Bacteriologic, molecular biologic, and histopathologic studies confirmed BU in 36 of these patients. Extensive clinical data, treatment outcomes, and socioeconomic correlations are summarized. Osteomyelitis was an important complication. A multidisciplinary approach to BU control in the Bas-Congo is proposed, aimed primarily at active case detection.

Adolescent↗
PubMed2005

Infection with Mycobacterium ulcerans induces persistent inflammatory responses in mice.

Buruli ulcer (BU) is a devastating, necrotizing, tropical skin disease caused by infections with Mycobacterium ulcerans. In contrast to other mycobacterioses, BU has been associated with minimal or absent inflammation. However, here we show that in the mouse M. ulcerans induces persistent inflammatory responses with virulence-dependent patterns. Mycolactone-positive, cytotoxic strains are virulent for mice and multiply progressively, inducing both early and persistent acute inflammatory responses. The cytotoxicity of these strains leads to progressive destruction of the inflammatory infiltrates by postapoptotic secondary necrosis, generating necrotic acellular areas with extracellular bacilli released by the lysis of infected phagocytes. The necrotic areas, always surrounded by acute inflammatory infiltrates, expand through the progressive invasion of healthy tissues around the initial necrotic lesions by bacteria and by newly recruited acute inflammatory cells. Our observations show that the lack of inflammatory infiltrates in the extensive areas of necrosis seen in advanced infections results from the destruction of continuously produced inflammatory infiltrates and not from M. ulcerans-induced local or systemic immunosuppression. Whether this is the mechanism behind the predominance of minimal or absent inflammatory responses in BU biopsies remains to be elucidated.

Animals↗
PubMed2005

Genotyping Mycobacterium ulcerans and Mycobacterium marinum by using mycobacterial interspersed repetitive units.

A novel category of variable tandem repeats (VNTR) called mycobacterial interspersed repetitive units (MIRUs) has been identified for Mycobacterium ulcerans (n = 39), M. marinum (n = 27), and one related organism. Fifteen MIRU loci were identified in the genome of M. marinum and were used to genotype M. ulcerans, M. marinum, and an M. marinum-like organism that is considered a possible missing link between M. marinum and M. ulcerans. Seven MIRU loci were polymorphic, and locus-specific PCRs for four of these loci differentiated seven M. ulcerans genotypes, four M. marinum genotypes, and a unique genotype for the missing link organism. The seven M. ulcerans genotypes were related to six different geographic origins of isolates. All isolates from West and Central Africa, including old and recent isolates, belonged to the same genotype, emphasizing the great spatiotemporal homogeneity among African isolates. Unlike the M. ulcerans genotypes, the four M. marinum genotypes could not be clearly related to the geographic origins of the isolates. According to MIRU-VNTR typing, all M. ulcerans and M. marinum isolates of American origin were closely related, suggesting a common American ancestor for these two pathogenic species on the American continents. MIRU typing has significant potential value for discriminating between reoccurrence and reinfection for M. ulcerans disease.

Bacterial Typing Techniques↗
PubMed2005

Buruli ulcer recurrence, Benin.

Buruli ulcer is a recognized public health problem in West Africa. In Benin, from 1989 to 2001, the Centre Sanitaire et Nutritionnel Gbemoten (CSNG) treated >2,500 Buruli ulcer patients. From March 2000 to February 2001, field trips were conducted in the Zou and Atlantique regions. The choice of the 2 regions was based on the distance from CSNG and on villages with the highest number of patients treated at CSNG. A total of 66 (44.0%) of 150 former patients treated at CSNG were located in the visited villages. The recurrence rate of CSNG-treated patients after a follow-up period of up to 7 years was low (6.1%, 95% confidence interval [CI] 2.0-15.6). We attribute this low rate to the high quality of Buruli ulcer treatment at an accessible regional center (CSNG). The World Health Organization definition of a Buruli ulcer recurrent case should be revised to include a follow-up period >1 year.

Anti-Bacterial Agents↗
PubMed2005

High rates of apoptosis in human Mycobacterium ulcerans culture-positive buruli ulcer skin lesions.

Buruli ulcer, a disease caused by Mycobacterium ulcerans, causes ulcerative skin disease likely generated by a toxin that mediates apoptosis. We analyzed paraffin-embedded sections of surgically excised Buruli ulcer lesions (two ulcers and one edematous plaque) and adjacent non-lesional skin samples (n = 9) for apoptosis by an indirect immunofluorescent terminal deoxynucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. All samples were stained for acid-fast bacilli (AFB) and cultured for mycobacteria, and most were analyzed with an M. ulcerans-specific diagnostic polymerase chain reaction (PCR). TUNEL (+) bodies were numerous in both ulcers and the plaque, and sparse or absent in adjacent non-lesional skin. The AFB tissue stains and cultures for M. ulcerans were positive only in the three lesions. The result of the PCR for M. ulcerans was positive in all three lesions and in four of six non-lesional tissue samples; three contained sparse TUNEL (+) bodies. An abundance of TUNEL (+) bodies in the three AFB stain (+), culture (+), and PCR (+) Buruli ulcer lesional samples, but not in nearby AFB stain (-), culture (-), and PCR (+) non-lesional skin samples, strengthen the evidence that apoptosis is an important tissue destruction mechanism in human lesions closely associated with viable M. ulcerans.

Adolescent↗
PubMed2004

Potential role for fish in transmission of Mycobacterium ulcerans disease (Buruli ulcer): an environmental study.

This study reports a potential role that fish may play in the transmission of Mycobacterium ulcerans disease (Buruli ulcer). Fish found positive for M. ulcerans DNA all appear to feed on insects or plankton and are believed to concentrate M. ulcerans from this usual food source. These observations provide additional data supporting our previous hypothesis on sources of M. ulcerans and modes of transmission.

Animals↗
PubMed2004

Mycobacterium ulcerans disease (Buruli ulcer) in rural hospital, Southern Benin, 1997-2001.

Data from 1,700 patients living in southern Benin were collected at the Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin, from 1997 through 2001. In the Zou region in 1999, Buruli ulcer (BU) had a higher detection rate (21.5/100,000) than leprosy (13.4/100,000) and tuberculosis (20.0/100,000). More than 13% of the patients had osteomyelitis. Delay in seeking treatment declined from 4 months in 1989 to 1 month in 2001, and median hospitalization time decreased from 9 months in 1989 to 1 month in 2001. This reduction is attributed, in part, to implementing an international cooperation program, creating a national BU program, and making advances in patient care.

Benin↗
PubMed2003

Buruli ulcer: a systemic disease.

We studied a 4-year-old boy from Angola who presented with 2 cutaneous ulcerations of the right hip and osteomyelitis of the left knee and right ankle. Mycobacterium ulcerans disease was confirmed by direct smear examination and by polymerase chain reaction. The patient was treated with antimycobacterial drugs, repeated surgical debridement, skin grafting, and daily hyperbaric oxygenation. Despite significant improvement of the local lesions in response to hyperbaric oxygenation, swelling of the right knee, without associated skin lesions, was noted. Radiological evaluation and open biopsy revealed extensive metaphyseal osteomyelitis of the right distal femur. A 99technetium bone scan revealed an additional focus in the diaphysis of the left humerus, without soft-tissue involvement. This case documents, for the first time (to our knowledge), the systemic spread of M. ulcerans, with subsequent multifocal osteomyelitis and secondary involvement of soft tissues and supports the hypothesis that low tissue oxygen levels promote hematogenous spread of M. ulcerans. Sickle cell anemia, with associated microthrombosis and microinfarction, may have contributed to tissue hypoxia.

Antitubercular Agents↗
PubMed2003

First case of Mycobacterium ulcerans disease (Buruli ulcer) following a human bite.

Mycobacterium ulcerans disease (MUD) is rapidly reemerging in many countries, especially in West African countries. Antecedent trauma has often been related to the lesions that characterize this frequently crippling disease. We report here the first case of MUD that followed a human bite at the site where the lesion later occurred.

Adolescent↗
PubMed2003

Under-explored experimental topics related to integral mycobacterial vaccines for leprosy.

Many leprosy vaccine studies have utilized live or killed whole mycobacteria, such as Bacille Calmette-Guérin, Indian Cancer Research Center (ICRC) bacilli and Mycobacterium w either alone or in combination with killed Mycobacterium leprae. For Bacille Calmette-Guérin, the vaccine dose is generally that which gives the largest delayed-type hypersensitivity response with minimal side effects. The doses of other integral mycobacterial vaccines appear to be arbitrarily chosen. Hypotheses governing immunologic responses to complex antigens predict that the doses used may be too high, resulting in protection of some individuals and increasing the susceptibility of other individuals to leprosy. The natural history of an individual's prior exposure to environmental mycobacteria will affect the outcome of protective vaccination using a given dose of mycobacterial vaccine in the individual.

Animals↗
PubMed2002

A pilot study of treatment of Buruli ulcer with rifampin and dapsone.

OBJECTIVE: Buruli ulcer disease (BU), caused by Mycobacterium ulcerans, is endemic in many regions of Africa and causes substantial physical disability. Surgical resection, currently the mainstay of clinical management of BU, is impractical in many endemic areas. Therefore, the study was undertaken to evaluate an antibiotic regimen for medical management of BU. METHODS: A randomized, placebo-controlled pilot study of dapsone plus rifampin versus placebo was conducted. RESULTS: Forty-one participants were recruited in a BU-endemic zone of Côte d'Ivoire. Thirty persons completed the 2-month trial: 15 were treated with placebo and 15 with dapsone and rifampin. On blinded evaluation of photographs of the ulcers, clinicians with experience examining BU judged that 82% of ulcers in the treatment group improved compared with 75% in the placebo group (P=0.51). The median change in ulcer size was a decrease of 14.0 cm2 in the treatment group and a decrease of 2.5 cm2 in the placebo group (P=0.02), but initial ulcer sizes were larger in the treatment group (median 26.2 cm2) compared with the placebo group (median 4.8 cm2) (P=0.04). CONCLUSIONS: Results of this study indicate that larger studies of antimycobacterial therapy of BU are warranted and can be successfully undertaken.

Adolescent↗