[Study of names and folklore associated with Mycobacterium ulcerans infection in various endemic countries in Africa]. / Etude des appellations et des représentations attachées à l'infection à Mycobacterium ulcerans dans différents pays endémiques d'Afrique.

The purpose of this article is to present names used for Mycobacterium ulcerans infection (Buruli ulcer) and explain their meanings in various African languages. Representations associated with the disease were also studied. The study approach involved qualitative analysis of information from interviews and literature. Interviews were conducted with the directors of various programs and management centers. Findings from 9 African countries where Buruli ulcer is known to be endemic, i.e., Benin, Cameroon, Congo-Brazzaville, Côte d'Ivoire, Ghana, Uganda, Democratic Republic of Congo, Southern Sudan and Togo, showed that the names used for the disease could be classified into three categories based on the geographical origin of infection, the features of the observed lesions, and aspects of ost often associated with belief in witch-craft, i.e., bad luck, fetishes, and curses. Representation of the disease in different African languages were similar and appear to demonstrate a good understanding of the disease in the countries where Buruli ulcer is prevalent. The impact of the representations of the disease on therapeutic choices and itineraries is also discussed.

Etude des appellations et des representations attachees a l'infection a Mycobacterium ulcerans dans differents pays endemiques d'Afrique

L'objectif de ce travail est de presenter les appellations de l'infection a Mycobacterium ulcerans (ulcere de Buruli) dans les langues africaines et leurs significations. Il vise egalement a explorer les representations attachees a la maladie dans differents pays endemiques d'Afrique. La methodologie utilisee implique l'analyse d' entretiens indivi- duels et de publications scientifiques. Les entretiens individuels ont ete menes aupres de differents chefs de programme et responsables de structures de prise en charge de cette maladie. Les resultats de notre analyse montrent que dans les pays d'Afrique ou l'ulcere de Buruli est endemique (Benin; Cameroun; Congo-Brazzaville; Cote d'Ivoire; Ghana; Ouganda; Republique Democratique du Congo; Sud Soudan et Togo); les appellations de cette maladie peuvent etre classees en trois categories; suivant qu'elles evoquent les origines geographiques de la maladie; les caracteristiques des lesions observees; ou les aspects d'incurabilite et de mystere; en lien avec la sorcellerie. Les representations de cette maladie dans les langues africaines apparaissent identiques et semblent traduire une connaissance relativement bonne de la maladie dans les pays ou l'ulcere de Buruli sevit. L'impact de ces representations influence egalement les types de recours aux soins

Etude des appellations et des representations attachees a l'infection a mycobacterium ulcerans dans differents pays endemiques d'Afrique

L'objectif de ce travail est de presenter les appellations de l'infection a Mycobacterium ulcerans (ulcere de Buruli) dans les langues africaines et leurs significations. Il vise egalement a explorer les representations attachees a la maladie dans differents pays endemiques d'Afrique. La methodologie utilisee implique l'analyse d'entretiens individuels et de publications scientifiques. Les entretiens individuels ont ete menes aupres de differents chefs de programme et responsables de structures de prise en charge de cette maladie. Les resultats de notre analyse montrent que dans les pays d'Afrique ou l'ulcere de Buruli est endemique (Benin; Cameroun; Congo-Brazzaville; Cote d'Ivoire; Ghana; Ouganda; Republique Democratique du Congo; Sud Soudan et Togo); les appellations de cette maladie peuvent etre classees en trois categories; suivant qu'elles evoquent les origines geographiques de la maladie; les caracteristiques des lesions observees; ou les aspects d'incurabilite et de mystere; en lien avec la sorcellerie. Les representations de cette maladie dans les langues africaines apparaissent identiques et semblent traduire une connaissance relativement bonne de la maladie dans les pays ou l'ulcere de Buruli sevit. L'impact de ces representations influence egalement les types de recours aux soins

Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity.

During the 5-year period, 1997-2001, 1700 patients with a clinical diagnosis of Mycobacterium ulcerans disease [Buruli ulcer (BU)] were treated at the Centre Sanitaire et Nutritionnel Gbemoten, Zagnanado, Benin. The patients lived in the four regions of southern Benin: Atlantique, Mono, Oueme and Zou, with the largest number coming from the Zou Region where the centre is located. The median age of BU patients was 15 years (q1=7, q3=30). Lower limbs are involved 3.2 times more frequently than upper limbs in older patients and younger patients have the highest prevalence of multiple lesions. The latter are frequently associated with bone lesions. Specific detection rates for age and gender showed a distribution with maximum peaks in the 10-14 years group and among adults between 75 and 79 years. Over 59 years, males are more at risk of developing M. ulcerans disease than females. Children under 15 years represent the largest part of the BU disease burden and of the general population. The highest detection rates (per 100,000 population) were in the 75-79-year-old patients. The most likely explanation of this was reactivation of disease from a latent infection of M. ulcerans. Educational programmes should target especially these two groups of population at risk.

Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease.

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.

Prophylactic effect of mycobacterium bovis BCG vaccination against osteomyelitis in children with Mycobacterium ulcerans disease (Buruli Ulcer).

Mycobacterium ulcerans disease, or Buruli ulcer (BU), causes significant morbidity in West Africa. In 233 consecutive, laboratory-confirmed samples from BU patients in Benin whose Mycobacterium bovis BCG scar status was known, 130 children (<15 years old) and 75 adults had a neonatal BCG vaccination scar. Of 130 children with BCG scars, 10 (7.7%) had osteomyelitis, while 3 of 9 children without BCG scars (33.3%) had osteomyelitis. Our observations support the conclusion that having a BCG vaccination scar provides significant protection against M. ulcerans osteomyelitis in children with BU disease.

Anti-leprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: lepromin skin test results.

Groups of rhesus monkeys (RM) were vaccinated and boosted with living Mycobacterium bovis Bacillus Calmette-Guerin (BCG) or BCG + low dose (LD) heat-killed Mycobacterium leprae (HKML) or high dose (HD) HKML or were unvaccinated. Animals vaccinated with BCG + LD and HD HKML were lepromin skin tested 2 weeks after boosting. All groups were lepromin tested 37 and 46 months after challenge with live M. leprae. Fernandez (72 h) and Mitsuda (28 day) responses were recorded. Ten of 10 rhesus monkeys in each of the two BCG + HKML-vaccinated groups significantly converted to strong positive Fernandez status within 2 weeks of boosting, compared to one of six positives in the unvaccinated unchallenged normal control group. Both BCG + HKML groups were significantly protected from clinical leprosy. Six of 10 in each of the two BCG + HKML groups significantly converted to Mitsuda positivity within 2 weeks of boosting compared to zero of six in the normal control group. The sizes of the Mitsuda responses were larger in the LD group than the HD HKML vaccinated/boosted group, suggesting suppression by vaccination with higher doses of HKML in combination with BCG. Fernandez responses were negative in normal RM as well as in the unvaccinated, ML-challenged group and the BCG-vaccinated, ML-challenged group at 37 or 46 months after ML inoculation, although the BCG-vaccinated group was significantly protected from leprosy and the unvaccinated group was not. In contrast, at 37 months the Fernandez reaction was positive in the BCG plus LD and the BCG plus HD HKML-vaccinated groups, both of which were significantly protected from clinical leprosy. By 46 months, the Fernandez responses were below significance in all groups. Thus, Fernandez reactivity is not a reliable correlate to protection from experimental leprosy in RM. Mitsuda responses became strongly positive in all four ML-challenged groups by 37 months and remained strongly positive at 46 months after ML inoculation, suggesting that strong Mitsuda reactivity reflects responses to living ML. BCG or BCG + LD or HD HKML vaccination/boosting of RM produced significant clinical protection from leprosy and there was a good correlation between protection from LL forms of leprosy and positive Mitsuda skin test responses after challenge with live ML. Positive Mitsuda responses were generated in essentially all individuals after challenge with live ML, and this response was primed by prior vaccination/boosting with BCG + HKML as shown by conversion to positivity 2 weeks after boosting. The data show that resistance to clinical leprosy is reflected by Mitsuda responses in ML-exposed RM, similar to results from human studies, and confirm the suitability of RM as a model for leprosy vaccine studies.

Characterization of an unusual Mycobacterium: a possible missing link between Mycobacterium marinum and Mycobacterium ulcerans.

In an attempt to characterize an unusual mycobacterial isolate from a 44-year-old patient living in France, we applied phenotypic characterizations and various previously described molecular methods for the taxonomic classification of mycobacteria. The results of the investigations were compared to those obtained in a previous study with a set of temporally and geographically diverse Mycobacterium ulcerans (n = 29) and Mycobacterium marinum (n = 29) isolates (K. Chemlal, G. Huys, P.-A. Fonteyne, V. Vincent, A. G. Lopez, L. Rigouts, J. Swings, W. M. Meyers, and F. Portaels, J. Clin. Microbiol. 39:3272-3278, 2001). The isolate, designated ITM 00-1026 (IPP 2000-372), is closely related to M. marinum according to its phenotypic properties, lipid pattern, and partial 16S rRNA sequence. Moreover, fingerprinting by amplified fragment length polymorphism (AFLP) analysis unequivocally classified this strain as a member of the species M. marinum, although it lacked two species-specific AFLP marker bands. However, PCR and restriction fragment length polymorphism analysis based on M. ulcerans-specific insertion sequence IS2404 showed the presence of this element in a low copy number in isolate ITM 00-1026. In conclusion, the designation of this isolate as a transitional species further supports the recent claim by Stinear et al. (T. Stinear, G. Jenkin, P. D. Johnson, and J. K. Davies, J. Bacteriol. 182:6322-6330, 2000) that M. ulcerans represents a relatively recent phylogenetic derivative of M. marinum resulting from the systematic acquisition of foreign DNA fragments.

Evaluation of PCR-restriction profile analysis and IS2404 restriction fragment length polymorphism and amplified fragment length polymorphism fingerprinting for identification and typing of Mycobacterium ulcerans and M. marinum.

Mycobacterium ulcerans and M. marinum are emerging necrotizing mycobacterial pathogens that reside in common reservoirs of infection and exhibit striking pathophysiological similarities. Furthermore, the interspecific taxonomic relationship between the two species is not clear as a result of the very high phylogenetic relatedness (i.e., >99.8% 16S rRNA sequence similarity), in contrast to only 25 to 47% DNA relatedness. To help understand the genotypic affiliation between these two closely related species, we performed a comparative analysis including PCR restriction profile analysis (PRPA), IS2404 restriction fragment length polymorphism (RFLP), and amplified fragment length polymorphism (AFLP) on a set of M. ulcerans (n = 29) and M. marinum (n = 28) strains recovered from different geographic origins. PRPA was based on a triple restriction of the 3' end region of 16S rRNA, which differentiated M. ulcerans into three types; however, the technique could not distinguish M. marinum from M. ulcerans isolates originating from South America and Southeast Asia. RFLP based on IS2404 produced six M. ulcerans types related to six geographic regions and did not produce any band with M. marinum, confirming the previous findings of Chemlal et al. (K. Chemlal, K. DeRidder, P. A. Fonteyne, W. M. Meyers, J. Swings, and F. Portaels, Am. J. Trop. Med. Hyg. 64:270-273, 2001). AFLP analysis resulted in profiles which grouped M. ulcerans and M. marinum into two separate clusters. The numerical analysis also revealed subgroups among the M. marinum and M. ulcerans isolates. In conclusion, PRPA appears to provide a rapid method for differentiating the African M. ulcerans type from other geographical types but is unsuitable for interspecific differentiation of M. marinum and M. ulcerans. In comparison, whole- genome techniques such as IS 2404-RFLP and AFLP appear to be far more useful in discriminating between M. marinum and M. ulcerans, and may thus be promising molecular tools for the differential diagnosis of infections caused by these two species.

The use of IS2404 restriction fragment length polymorphisms suggests the diversity of Mycobacterium ulcerans from different geographical areas.

Buruli ulcer, caused by Mycobacterium ulcerans, has been reported in five continents: Africa, Asia, Australia, and North and South America. In the present study, restriction fragment length polymorphism with the recently described M. ulcerans specific insertion sequence IS2404 as a probe, was applied to Mycobacterium shinshuense, Mycobacterium marinum, and 14 clinical M. ulcerans isolates originating from six geographic areas: Africa (n = 6), Australia (n = 2), Mexico (n = 1), south Asia (n = 2), Asia (n = 1), and South America (n = 2). Using this probe, six subtypes of M. ulcerans, related to the six geographic origins of the isolates were distinguished, confirming that M. ulcerans can be divided into subgroups corresponding to different geographic variants of the same species.

Mycobacterium ulcerans in wild animals.

Mycobacterium ulcerans infection, or Buruli ulcer, is the third most frequent mycobacterial disease in humans, often causing serious deformities and disability. The disease is most closely associated with tropical wetlands, especially in west and central Africa. Most investigators believe that the aetiological agent proliferates in mud beneath stagnant waters. Modes of transmission may involve direct contact with the contaminated environment, aerosols from water surfaces, and water-dwelling fauna (e.g. insects). Person-to-person transmission is rare. Trauma at the site of skin contamination by M. ulcerans appears to play an important role in initiating disease. Once introduced into the skin or subcutaneous tissue, M. ulcerans multiplies and produces a toxin that causes necrosis. However, the type of disease induced varies from a localised nodule or ulcer, to widespread ulcerative or non-ulcerative disease and osteomyelitis. Although culture of M. ulcerans from a patient was first reported in 1948, attempts to culture the mycobacterium from many specimens of flora and fauna have been unsuccessful. Failure to cultivate this organism from nature may be attributable to inadequate sampling, conditions of transport, decontamination and culture of this fastidious heat-sensitive organism, and to a long generation time relative to that of other environmental mycobacteria. Nevertheless, recent molecular studies using specific primers have revealed M. ulcerans in water, mud, fish and insects. Although no natural reservoir has been found, the possibility that M. ulcerans may colonise microfauna such as free-living amoebae has not been investigated. The host range of experimental infection by M. ulcerans includes lizards, amphibians, chick embryos, possums, armadillos, rats, mice and cattle. Natural infections have been observed only in Australia, in koalas, ringtail possums and a captive alpaca. The lesions were clinically identical to those observed in humans. Mycobacterium ulcerans infection is a rapidly re-emerging disease in some developing tropical countries. The re-emergence may be related to environmental and socioeconomic factors, for example, deforestation leading to increased flooding, and population expansion without improved agricultural techniques, thus putting more people at risk. Eradication of diseases related to these factors is difficult. Whether wild animals have a role in transmission is an important question that, to date, has been virtually unexplored. To address this question, surveys of wild animals are urgently required in those areas in which Buruli ulcer is endemic.

Detection of phospholipase C in nontuberculous mycobacteria and its possible role in hemolytic activity.

Phospholipase C plays a key role in the pathogenesis of several bacterial infections, for example, those caused by Clostridium perfringens and Listeria monocytogenes. Previous studies have reported multiple copies of plc genes homologous to Pseudomonas aeruginosa plcH and plcN genes encoding the hemolytic and nonhemolytic phospholipase C enzymes in the genomes of Mycobacterium tuberculosis, M. marinum, M. bovis, and M. ulcerans. In this study we analyzed the possible relationship between phospholipase C and hemolytic activity in 21 strains of nontuberculous mycobacteria representing nine different species. Detection of phospholipase C enzymatic activity was carried out using thin-layer chromatography to detect diglycerides in the hydrolysates of radiolabeled phosphatidylcholine. DNA sequences of M. kansasii and M. marinum homologous to the genes encoding phospholipase C from M. tuberculosis and M. ulcerans were identified by DNA-DNA hybridization and sequencing. Finally, we developed a direct and simple assay to detect mycobacterial hemolytic activity. This assay is based on a modified blood agar medium that allows the growth and expression of hemolysis of slow-growing mycobacteria. Hemolytic activity was detected in M. avium, M. intracellulare, M. ulcerans, M. marinum, M. tuberculosis, and M. kansasii mycobacteria with phospholipase C activity, but not in M. fortuitum. No hemolytic activity was detected in M. smegmatis, M. gordonae, and M. vaccae. Whether or not phospholipase C enzyme plays a role in the pathogenesis of nontuberculous mycobacterial diseases needs further investigation.

Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of rhesus monkeys were vaccinated and boosted with Mycobacterium bovis bacillus Calmette Guerin (BCG) or BCG plus low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. Vaccination with BCG plus HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to lepromin, which returned to baseline post-boosting and post-live-ML-challenge, minimally reappearing significantly 2 years post-ML-challenge. Vaccination with BCG failed to stimulated positive blastogenic responses to lepromin before ML-challenge but small, marginally positive, intermittent responses were seen post-ML-challenge. Compared to the unvaccinated ML-challenged group, significant increases in the numbers of blood CD4+ and CD8+ T-cell subsets and an increased CD4+:CD8+ ratio were observed in both BCG plus HKML-vaccinated, ML-challenged groups, but not in the BCG-only-vaccinated, ML-challenged group. CD4+CD29+ and CD4+CD45RA+ subset numbers increased significantly over time in only the BCG plus LD HKML-vaccinated, ML-challenged group. Compared to unvaccinated, ML-challenged groups, vaccination with BCG or BCG plus HKML followed by ML-challenge produced lower IgM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody ratios and protected rhesus monkeys from clinical leprosy, consistent with prior observations that low IgM:IgG anti-PGL-I responses correlated with resistance to and protection from leprosy.

Biochemical and genetic evidence for phospholipase C activity in Mycobacterium ulcerans.

This study reports the existence of phospholipase C and D enzymatic activities in Mycobacterium ulcerans cultures as determined by use of thin-layer chromatography to detect diglycerides in hydrolysates of radiolabeled phosphatidylcholine. M. ulcerans DNA sequences homologous to the genes encoding phospholipase C in Mycobacterium tuberculosis and Pseudomonas aeruginosa were identified by sequence analysis and DNA-DNA hybridization. Whether or not the phospholipase C and D enzymes of M. ulcerans plays a role in the pathogenesis of the disease needs further investigation.

Mycobacterium ulcerans infection (Buruli ulcer): a case report of the disseminated nonulcerative form.

The World Health Organization recognizes Mycobacterium ulcerans infection (Buruli ulcer) as a reemerging disease. Classically, lesions are indolent, undermined ulcers of the skin. The characteristic histopathologic changes are provoked by a soluble toxin of M ulcerans that is necrotizing and immunosuppressive. After tuberculosis and leprosy, Buruli ulcer is the third most common mycobacterial disease in humans. We report Buruli ulcer in a patient in Benin, West Africa, with widespread edema and diffuse induration of approximately one half of the skin of the trunk. There was no ulceration. The tissue studied was a 16-cm portion excised from the center of the large surgical specimen. Histopathologic analysis showed massive contiguous necrosis of the dermis and subcutis in sections of biopsy specimens from the center, at 2-cm intervals in two radii from the center to the periphery, and at 5-cm intervals around the margin. Acid-fast bacilli infiltrated all specimens except at one peripheral site. Samples of the entire surgical specimen taken from seven sites before fixation were polymerase chain reaction and culture positive for M ulcerans. The disseminated nonulcerative form of M ulcerans infection is well known, but is now increasingly frequent in some highly endemic areas, especially in West Africa. This patient died within 48 hours postsurgery, but cause of death was not established. The only regularly effective treatment for advanced lesions is surgical excision of all infected tissue. Estimation of the lateral limits of invasion by M ulcerans may help the surgeon establish the optimal extent of excision. Refinement of the basic concept we used and adaptation to preoperative assessment of the limit of bacterial invasion are urgently needed, especially for massive lesions.

[Buruli ulcer: risk of bone involvement! Apropos of 33 cases observed in Benin]. / L'ulcère de Buruli: attention aux atteintes osseuses! A propos de 33 cas observés au Bénin.

Skin lesions are the best known manifestations of Mycobacterium ulcerans infection. However osteomyelitis is not uncommon with incidences as high as 14 p. 100 having been reported. The literature contains little specific data on bone lesions. This report describes a series of 33 patients presenting bacteriologically and/or histologically confirmed osteomyelitis induced by Mycobacterium ulcerans. In 64 p. 100 of cases, bone involvement occurred within the first year of the disease. In 70 p. 100 of cases, the site of involvement was on extremities. The median number of sites per patient was two (range, 1 to 5) and the number of bones was not correlated with the duration of disease. Overall, 41 p. 100 of bone sites occurred locally beneath skin lesions and 59 p. 100 were distant metastases. Osteomyelitis was associated with other germs in only 16 p. 100 of cases and superinfection was not a prerequisite for development of bone involvement. Clinical manifestations were usually low-grade with non-inflammatory, slightly painful local mass. The patient's general health status was unaffected in 79 p. 100. Histological examination allowed identification of the type of bone lesions induced by Mycobacterium ulcerans. For the first time, bone biopsy specimens were cultured. Based on bacteriological and histological findings, several postulations can be made about underlying pathophysiological mechanisms. The role of Buruli toxin is dealt with in the discussion.

Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of sooty mangabey monkeys (SMM) were vaccinated and boosted with Mycobacterium bovis bacillus Calmette-Guerin (BCG), or BCG + low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were immunologically observed longitudinally for approximately 3 years. SMM [multibacillary (MB) leprosy-prone as a species] were not protected clinically by BCG or BCG + HKML, although the disease progress was slowed by vaccination with BCG alone. The longitudinal immune response profiles to BCG or BCG + HKML in SMM showed that: 1) vaccination with BCG or BCG + HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to ML antigens, which returned to baseline post-boosting and post-live ML challenge; 2) BCG + LD HKML-vaccinated groups gave the largest blastongenic response (SI = 23) followed by the BCG + HD HKML group (SI = 14.5) and by the BCG-only vaccinated group (SI = 3.6); 3) significantly diminished numbers of blood CD4+ (helper) and CD4+CD29+ (helper-inducer) T-cell subsets were observed longitudinally in all ML-challenged groups compared to controls regardless of whether they had been vaccinated or not; 4) CD8+ (suppressor) T-cell numbers remained longitudinally constant, on average, in all ML-challenged groups (vaccinated or not) compared to controls; 5) there was a significant decrease in the CD4+:CD8+ ratio over time in all ML-challenged groups (vaccinated or not); 6) vaccination with BCG or BCG + LD or HD HKML resulted in significantly increased numbers of CD4+CD45RA+ (suppressor-inducer) T cells longitudinally compared to the unvaccinated, ML-challenged control group; and 7) over time, vaccination with BCG + HKML followed by live ML-challenge produced higher IGM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody response ratios than BCG-only vaccinated, ML-challenged monkeys or unvaccinated, ML-challenged SMM, consistent with prior observations that IgG anti-PGL-I responses correlate with resistance to and protection from clinical leprosy and IgM anti-PGL-I responses correlate with increased susceptibility.

Transmission of Mycobacterium ulcerans to the nine-banded armadillo.

Animal models for Mycobacterium ulcerans infections (Buruli ulcer) include guinea pigs, rats, and mice, but each has limitations in replicating the spectrum of human disease. Here, 19 adult nine-banded armadillos were inoculated intradermally with M. ulcerans. Injection sites were examined and skin samples obtained for histologic and microbiology studies. Necropsies were conducted to assess systemic involvement. In group 1 (n = 4), 2 animals developed progressive skin ulcers with undermined borders at the injection sites within 6-10 weeks. Biopsies showed features similar to human disease including extensive necrosis in the deep dermis and subcutaneous fat, mixed cellular infiltrates, and acid-fast bacilli (AFB). In group 2 (n = 15), 5 animals developed progressive skin ulcers, 3 had evanescent papulo-nodules, 3 died shortly after inoculation of unknown causes, and 4 showed no signs of infection. Lesion samples from 3 animals with progressive ulcers were culture positive for AFB. Our findings indicate that nine-banded armadillos are susceptible to M. ulcerans and may develop cutaneous lesions that closely mimic Buruli ulcer.

Unusual cutaneous infectious and parasitic diseases.

The cutaneous manifestations of thirteen unusual infections and parasitic diseases are described. Their geographic distribution, morphologic features of the causative organism, histopathologic changes, criteria for diagnosis, and treatment are included.