Prophylactic Effect of Mycobacterium bovis BCG Vaccination against Osteomyelitis in Children with Mycobacterium ulcerans Disease (Buruli Ulcer) (original) (raw)
Related papers
Infection and Immunity, 2004
Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. Clinically, the disease presents in the skin as either nonulcerative or ulcerative forms and often invades bones either subjacent to the skin lesion (contiguous osteomyelitis) or remote from the skin lesion (metastatic osteomyelitis). Osteomyelitis represents a severe form of the disease that often requires numerous surgical interventions, even amputations. Surgery is accepted as the present definitive treatment for BU. In the absence of an effective drug treatment, the need for the development of preventive and control strategies becomes paramount. No specific vaccine, however, is presently available for BU. Of 372 consecutive patients in Benin presenting with BU (confirmed by microbiological and histopathological analyses) whose Mycobacterium bovis BCG scar statuses were known, 196 children (<15 years old) and 108 adults had neonatal BCG vaccination scars. Of 196 children with BCG scars, 17 (8.7%) had osteomyelitis, while 7 of 28 children without BCG scars (25.0%) had osteomyelitis. Of 108 adults with BCG scars, 17 (15.7%) had osteomyelitis, while 14 of 40 adults without BCG scars (35.0%) had osteomyelitis. Our results show that effective BCG vaccination at birth provides significant protection against the development of M. ulcerans osteomyelitis in children and adults. Therefore, health authorities should give attention to the enhancement of neonatal BCG vaccination coverage in all countries of Africa where BU is endemic. Protection against severe forms of BU and childhood tuberculosis would likewise be improved by this intervention.
Buruli Ulcer (Mycobacterium ulcerans Infection): a Re-emerging Disease
Clinical Microbiology Newsletter, 2009
Mycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Approximately 10% of patients develop reactive osteitis or osteomyelitis beneath skin lesions or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. Pathogenesis is mediated by a necrotizing, immunosuppressive toxin produced by M. ulcerans called mycolactone. The incidence of BU is highest in children up to 15 years old and is a public health problem in countries of endemicity due to disabling scarring and bone destruction. Today, most BU occurs in West Africa, but the disease has been reported in over 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against BU and prevents osteomyelitis. HIV seropositivity may increase the risk for BU and render BU osteomyeletis highly aggressive.
Clinical and Immune Impact of Mycobacterium bovis BCG Vaccination Scarring
Infection and Immunity, 2002
The World Health Organization recommends Mycobacterium bovis BCG vaccination in areas of high tuberculosis prevalence. BCG's clinical and immune effects, not necessarily Mycobacterium tuberculosis specific, are unclear. BCG vaccine scarring often is used as a surrogate marker of vaccination or of effective vaccination. We evaluated BCG scarring status in relation to clinical findings and outcome in 700 hospitalized Malawians, of whom 32 had M. tuberculosis bloodstream infections (BSI) (10 of whom had cellular immune studies done) and of whom 48 were infants <6 months old and therefore recently vaccinated (19 of whom had immune studies). In the patients ≥6 months old, scarring was not related to the presence of pulmonary symptoms (35 versus 30%), chronic cough or fever, mortality, or M. tuberculosis BSI. In M. tuberculosis BSI patients, scarring was unrelated to mortality, vital signs, or clinical symptoms but those with scarring had higher proportions of memory and activated ...
The American journal of tropical medicine and hygiene, 2006
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.
American Journal of Tropical Medicine and Hygiene, 2009
Mycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU) and occasional contiguous or metastatic bone lesions. Buruli ulcer is named after Buruli County in Uganda (east Africa), where an epidemic occurred in the 1960s. Today, BU is most common in central and west Africa. We describe clinical and molecular evidence for a case of BU in Kenya.
Clinical Infectious Diseases, 2005
infection is postulated to be environmentally acquired, the natural reservoir and precise mode(s) of M. ulcerans transmission are unclear. Diagnostic methods to confirm M. ulcerans infection are expensive and ill-suited to low-resource areas. The effectiveness of antimycobacterial drug therapy has not been proven [6, 7]; consequently, surgery is the recommended treatment option. Unique among mycobacteria, M. ulcerans produces a macrolide toxin, mycolactone, that promotes coagulation necrosis of subcutaneous adipose tissue surrounding sites of bacterial colonization [2, 8-10]. BUD involves 3 clinical stages: preulcerative, ulcerative, and
2006
Buruli ulcer caused by Mycobacterium ulcerans is of important public health problem especially in West-Africa. It is the third most common mycobacterial disease, after tuberculosis and leprosy. The World Health Organisation currently recommends the use of a combination of streptomycin and rifampicin for eight weeks before surgical excision. Stepwise implementation of this recommendation has started in some of the worst affected West African countries, including Ghana. Therefore this study was initiated to assess the susceptibility of M. ulcerans isolates from Ghana to isoniazid, rifampicin, ethambutol and streptomycin, using a microplate Alamar blue assay. Out of the 28 isolates tested, one was resistant to all four drugs analysed. All isolates with the exception of two (7.1%) and three (10.7%) were resistant to isoniazid and ethambutol respectively. On the contrary all isolates, except two (7.1%) and three (10.7%), were susceptible to rifampicin and streptomycin, respectively. This first report of rifampicin resistance in clinical M. ulcerans isolates raises major concern about antibiotic treatment modalities for Buruli ulcer.
Vaccine, 2012
Background: Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. Methods: Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferongamma (IFN-␥), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders. Results: Both specific and non-specific IFN-␥, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p < 0.001). Scarred infants had higher IFN-␥ and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p = 0.025). Mortality differences were not significant. Conclusions: Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-␥ and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime-boost sequences, or as a vector for other vaccine antigens.
Mycobacterium ulcerans infection: control, diagnosis, and treatment
The Lancet Infectious Diseases, 2006
The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy and mainly aff ects remote rural African communities. Although the disease is known to be linked to contaminated water, the mode of transmission is not yet understood, which makes it diffi cult to propose control interventions. The disease is usually detected in its later stages, when it has caused substantial damage and disability. Surgery remains the treatment of choice. Although easy and eff ective in the early stages of the disease, treatment requires extended excisions and long hospitalisation for the advanced forms of the disease. Currently, no antibiotic treatment has proven eff ective for all forms of M ulcerans infection and research into a new vaccine is urgently needed. While the scientifi c community works on developing non-invasive and rapid diagnostic tools, the governments of endemic countries should implement active case fi nding and health education strategies in their aff ected communities to detect the disease in its early stages. We review the diagnosis, treatment, and control of Buruli ulcer and list priorities for research and development. Lancet Infect Dis 2006; 6: 288-96 Médecins Sans Frontières,