Mycobacterium leprae genomes from naturally infected nonhuman primates.

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.

In Vitro Activity of Selected West African Medicinal Plants against Mycobacterium ulcerans Disease.

Buruli ulcer (BU) is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. The currently recommended combination of rifampicin-streptomycin suffers from side effects and poor compliance, which leads to reliance on local herbal remedies. The objective of this study was to investigate the antimycobacterial properties and toxicity of selected medicinal plants. Sixty-five extracts from 27 plant species were screened against Mycobacterium ulcerans and Mycobacterium smegmatis, using the Resazurin Microtiter Assay (REMA). The cytotoxicity of promising extracts was assayed on normal Chang liver cells by an MTT assay. Twenty five extracts showed activity with minimal inhibitory concentration (MIC) values ranging from 16 µg/mL to 250 µg/mL against M. smegmatis, while 17 showed activity against M. ulcerans with MIC values ranging from 125 µg/mL to 250 µg/mL. In most of the cases, plant extracts with antimycobacterial activity showed no cytotoxicity on normal human liver cells. Exception were Carica papaya, Cleistopholis patens, and Polyalthia suaveolens with 50% cell cytotoxic concentrations (CC50) ranging from 3.8 to 223 µg/mL. These preliminary results support the use of some West African plants in the treatment of Buruli ulcer. Meanwhile, further studies are required to isolate and characterize the active ingredients in the extracts.

Ethnopharmacological reports on anti-Buruli ulcer medicinal plants in three West African countries.

ETHNOPHARMACOLOGICAL RELEVANCE: Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control. MATERIAL AND METHODS: A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014. RESULTS: The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius), Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans. CONCLUSIONS: This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control.

[Leprosy in a chimpanzee].

Leprosy is suspected to develop after a long period of latency following infection with Mycobacterium leprae (M. leprae) during infancy, but definitive proof has been lacking. We found a rare case of leprosy in a chimpanzee (Pan troglodytes) born in West Africa (Sierra Leone) and brought to Japan around 2 years of age. At 31, the ape started exhibiting pathognomic signs of leprosy. Pathological diagnosis, skin smear, serum anti-phenolic glycolipid-I (PGL-I) antibody, and by PCR analysis demonstrated lepromatous leprosy. Single-nucleotide polymorphism (SNP) analysis verified the West African origin of the bacilli. This occurrence suggests the possibility of leprosy being endemic among wild chimpanzees in West Africa, potentially posing a zoonotic risk.

[Cutaneous and soft skin infections due to non-tuberculous mycobacteria]. / Infecciones cutáneas y de partes blandas por micobacterias no tuberculosas.

The frequency of isolation as well as the number of species of non-tuberculous mycobacteria (NTM) has increased in the last years. Nearly every pathogenic species of NTM may cause skin and soft tissue infections, but rapidly growing mycobacteria (Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus), Mycobacterium marinum and Mycobacterium ulcerans are the most commonly involved. Many of these cutaneous mycobacteriosis, such as rapidly growing mycobacteria, M. marinum, Mycobacterium avium complex, Mycobacterium kansasii or Mycobacterium xenopi are world-wide distributed. In contrast, some others have a specific geographical distribution. This is the case of M. ulcerans, which causes a cutaneous diseases endemic of Central and West Africa (Buruli ulcer) and Australia (Bairnsdale ulcer), being the third mycobacterial infection after tuberculosis and leprosy. Cutaneous mycobacteriosis usually appear either after contact of traumatic or surgical wounds with water or other contaminated products, or, secondarily, as a consequence of a disseminated mycobacterial disease, especially among immunosuppressed patients. For an early diagnosis, it is necessary to maintain a high degree of suspicion in patients with chronic cutaneous diseases and a history of trauma, risk exposure and negative results of conventional microbiological studies. In general, individualized susceptibility testing is not recommended for most NTM infections, except for some species, and in case of therapeutic failure. Treatment includes a combination of different antimicrobial agents, but it must be taken into account that NTM are resistant to conventional antituberculous drugs. Severe cases or those with deep tissues involvement could also be tributary of surgical resection.

Buruli ulcer disease: prospects for a vaccine.

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD is a mutilating disease leading to severe disability; it is the third most common mycobacterial infection in immunocompetent people after tuberculosis and leprosy. It is most endemic in West Africa, but cases have been reported from more than 30 countries. Treatment with antibiotics is possible, long-lasting and requires injections; there are cases of treatment failures, and the disease is prone to resistance. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas, and could be used as a therapeutic vaccine to shorten the duration of treatment and prevent relapses. There is considerable evidence supporting the notion that generation of a vaccine is feasible. This article reviews the present state of the art with special emphasis on the immunology of the infection and the prospects for development of a vaccine.

Diffuse cutaneous leishmaniasis in an HIV-positive patient in western Africa.

A 36-year-old HIV1-positive woman presented with a 6-month history of a progressive papular and nodular eruption of the face and subsequent extensive spread to the rest of the skin. The diagnosis of diffuse cutaneous leishmaniasis was established by direct examination and skin biopsy. This atypical form had a dramatic improvement after a 21-day treatment with meglumine antimoniate. This clinical form may be confused with other endemic diseases in western Africa, especially leprosy.

Occurrence and diversity of yeasts involved in fermentation of West African cocoa beans.

Samples of cocoa beans were taken on two separate occasions during heap and tray fermentations in Ghana, West Africa. In total 496 yeast isolates were identified by conventional microbiological analyses and by amplification of their ITS1-5.8S rDNA-ITS2 regions. For important species the identifications were confirmed by sequencing of the D1/D2 domain of the 5' end of the large subunit (26S) rDNA. Assimilations of organic acids and other carbon compounds were conducted. For dominant yeasts intraspecies variations were examined by determination of chromosome length polymorphism (CLP) using pulsed-field gel electrophoresis. For the heap fermentations maximum yeast cell counts of 9.1 x 10(7) were reached, whereas maximum yeast counts of 6.0 x 10(6) were reached for the tray fermentations. Candida krusei was found to be the dominant species during heap fermentation, followed by P. membranifaciens, P. kluyveri, Hanseniaspora guilliermondii and Trichosporon asahii, whereas Saccharomyces cerevisiae and P. membranifaciens were found to be the dominant species during tray fermentation followed by low numbers of C. krusei, P. kluyveri, H. guilliermondii and some yeast species of minor importance. For isolates within all dominant species CLP was evident, indicating that several different strains are involved in the fermentations. Isolates of C. krusei, P. membranifaciens, H. guilliermondii, T. asahii and Rhodotorula glutinis could be found on the surface of the cocoa pods and in some cases on the production equipment, whereas the origin of e.g. S. cerevisiae was not indicated by the results obtained. In conclusion, the results obtained show that fermentation of cocoa beans is a very inhomogeneous process with great variations in both yeast counts and species composition. The variations seem to depend especially on the processing procedure, but also the season and the post-harvest storage are likely to influence the yeast counts and the species composition.

[Buruli ulcer--Africa's latest mycobacterial scourge]. / Burulisåret--Afrikas senaste mykobakteriella gissel.

Buruliulcer is an extensive ulceration usually on the extremities. The ulcer can spread to subcutaneous fat, muscle and even bone causing osteomyelitis and death. It is the the third most common mycobacterial disease in humans after tuberculosis and leprosy. The bacterium grows in still standing water and infects children through small ulcerations in their skin. Mycobacterium ulcerans may also be transmitted by the bite of aquatic bugs (Naucordiae), which harbor the bacterium in their salivary glands. The disease affects poor people in rural, tropical areas where deforestation has led to flooding rivers, stagnant bodies of water and marsh. Benin, Cote d'Ivoire and Ghana in West Africa are seriously hit. Skin transplantation is the treatment of choice. Treatment with antibiotics has been disappointing.

Mycobacterium ulcerans infection.

After tuberculosis and leprosy, Buruli-ulcer disease (caused by infection with Mycobacterium ulcerans) is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been identified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, undermined ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M. ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

PIP: This paper focuses on Buruli-ulcer disease, the third most common mycobacterial disease among immunocompetent people. Buruli-ulcer disease is caused by an infection with Mycobacterium ulcerans, which belongs to the large group of environmental mycobacteria. It is endemic in many countries, usually in areas of tropical rain forest. Transmission of infection is through abraded skin or mild traumatic injuries after contact with contaminated water, soil, or vegetation. This disease mostly affects children which manifest from painless nodules to large, undermined ulcerative lesions that heals spontaneously but slowly. Buruli-ulcer disease is accompanied by few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. However, extensive scarring can lead to contractures of the limbs, blindness, and other adverse complications. Management of the disease is still primarily surgical, and includes excision, skin grafting, or both. Although Bacillus Calmette-Guerin vaccine has mild but a significant protective effect, vaccine developments directed at the toxin produced by M. ulcerans are needed.

[Buruli ulcer (Mycobacterium ulcerans infection); report from the International Congress in Yamoussoukro, Ivory Coast]. / Buruli-ulcus (infectie met Mycobacterium ulcerans); verslag van een internationaal congres in Yamoussoukro, Ivoorkust.

Mycobacterium ulcerans infection (Buruli ulcer) is the third important mycobacterial disease world-wide in immunocompetent humans, after tuberculosis and leprosy. M. ulcerans is an environmental mycobacterium which has now been recovered from water and soil in swampy areas, and transmission to man occurs presumably through minor skin traumas. Endemic foci are known throughout the world, predominantly in tropical rain forest areas. The clinical presentation varies between a papule, a nodule or an ulceration with typically undermined edges. Surgery is the only effective treatment. BCG vaccination has a moderate protective effect. An association with HIV infection has not been demonstrated so far. Poor communities, with limited access to health care, and especially children are affected. The medical and socioeconomic burden imposed by the disease is tremendous. During the last decade the incidence of the disease has increased dramatically, particularly in West Africa. Possibly this is connected with changes in the natural ecosystem. The Yamoussoukro declaration on Buruli ulcer, adopted July 6, 1998, is the basis of improvement of awareness, health education, treatment, and research on M. ulcerans infection. Support by the international community is urgently needed.

[Antileprosy polychemotherapy in the member states of the OCCGE: a decade of implementation (1983-19930). The National Coordinators of the Leprosy Program of the 8 states of the OCCGE]. / La polychimiothérapie antilépreuse dans les Etats membres de l'OCCGE: une décennie de mise en oeuvre (1983-1993). Coordonnateurs Nationaux de Programme Lèpre des 8 Etats de l'OCCGE.

MDT for leprosy recommended by WHO in 1981 has been introduced and implemented in 8 Member States of OCCGE (an organization for leprosy control in francophone West Africa). This implementation from 1983 to 1993 can be divided in two phases: 1983-1987: introduction phase by pilot projects; 1988-1993: extension phase by national leprosy control programmes. During the ten years, MDT coverage rose to 68%, leprosy prevalence rate widely decreased (40.71 to 6.56 per 10,000), while annual detection rate weakly varied (1.89 to 1.26 per 10,000). Factors influencing this evolution of leprosy are brought out and recommendations are made about strategies to be developed for leprosy control up to year 2000.

Leprosy: an urgent need to step up use of MDT in Africa.

PIP: 10-12 million people in the world have leprosy. India claims about 4 million of these cases. Overall at least 20% of the cases are children. In the 1940s, dapsone was the only drug used to treat leprosy. By the early 1970s, dapsone did not perform as expected and Mycobacterium leprae were beginning to exhibit resistance to dapsone. In 1982, WHO published results of its study which recommended fixed and relatively short duration regimens of multiple drug therapy (MDT) for all people with leprosy. It also listed recommendations on diagnosis, classification, and distribution of patients to either pauci or multibacillary groups. MDT depends on what type of leprosy patients have. For example, patients with multibacillary leprosy receive rifampicin, clofazimine, and dapsone whereas those with paucibacillary leprosy receive only rifampicin. In many African countries, however, MDT is not used. Yet cases of leprosy exist in 94% of Africa's countries. Moreover 37% have highly prevalent leprosy and the lowest percentage of patients on MDT (18% vs. world average of 56%). In fact, Nigeria is included in the group of 5 countries with 84% of all cases. Until the various countries in Africa can satisfy the ideal requirements for establishing a MDT program, they should begin MDT at least on a small scale. They do need, however, an adequate supply of the drugs. The other requirements include a good plan of action, laboratory facilities, transport, and referral centers. If the period of time needed to meet these requirements is long, then physicians should conduct pre MDT screenings to diagnose cases and determine who needs chemotherapy. The best way to diagnose cases is from clinical experience and paying particular attention to dermatological and neurological findings. Early identification is needed since leprosy cases are stigmatized. This article includes MDT dosages in adults and children.^ieng

[Intensification of the fight against leprosy using early and systematic polychemotherapy]. / Renforcement de la lutte contre la lèpre par une polychimiothérapie précoce et systématique.

The latest epidemiologic enquiries realized in West Africa and Central Africa have shown that real prevalence of leprosy is far greater, at least twice the number of patients than are actually listed in the medical records. This data proves that the fight against leprosy is highly inefficient and stresses the partial failure of the anti-hansenian strategy that has been adopted for over 10 years in this area, in spite of the use of rifampicin in multidrug therapy which would normally cure leprosy. Therefore we suggest that the fight against leprosy should be re-organised and reinforced in high endemic areas. The anti-hansenian programmes should be carried out by specific services composed of mobile and specialised teams whose task would be to aim for the early detection and continual testing for new cases. Only with this kind of organisation can chemotherapy be administered at the beginning, therefore arresting the disease before it reaches the multi-neuritis stage. This strategy offers great epidemiologic and economic advantages and would also give hope and dignity to the patients assured of a permanent cure. Leprosy would then be classed as a disease "just like any other".

AIDS in Africa--an update.

PIP: At least 1 million people in Central and East Africa are infected with HIV-1, and there are 10,000 new cases of AIDS per year. HIV-1 is spreading into the Ivory Coast, Ghana, Mozambique, Angola and southern Africa. HIV-2 is prevalent in West Africa, particularly Senegal and Guinea-Bissau. Groups at greatest risk for HIV-1 are prostitutes, their customers, and patients with a history of sexually-transmitted diseases, which cause breaches in mucosal epithelium. 24% of pregnant women in Uganda are infected, and the risk of transplacental infection is estimated to be between 17% and 79%. Blood transfusion is the 3rd most frequent mode of infection, largely due to need for blood by anemic women. Repeated pregnancy is a cofactor in the progression of AIDS, and infected infants suffer intrauterine growth retardation, premature birth, low birth weight, and high mortality in the 1st week of life. AIDS in adults is often accompanied by tuberculosis, herpes zoster, hepatitis B, herpes type 2, and leprosy. Clinical diagnosis of AIDS is made by enzyme-linked immunosorbent assay, but African patients have a high frequency of anti-p24 antibody which masks the p24 antigenemia. Some African countries have AIDS education programs, condom distribution and blood screening, but AIDS control programs need to be integrated with primary health care.^ieng

[Guinea: detection of leprosy and treatment by polychemotherapy]. / Guinée: dépistage de la lèpre et traitement par polychimiothérapie.

Since a year, the implementation of multidrug therapy on leprosy control in Guinea has been needing a good cooperation between Department of Leprosy Control and local nurses. The known prevalence, in the area of Pita is 1.23%. 246 patients has been detected: 36 multibacillary and 210 paucibacillary. The sex-ratio of the patients has changed, during one year, toward the men. With the sensitivity of the local population, number of detected cases is increasing and the rate of regular attendance at treatment is correct in 87.6% of cases.

Guinée: dépistage de la lèpre et traitement par polychimiothérapie / Guinea: detection of leprosy and treatment by polychemotherapy

Since a year, the implementation of multidrug therapy on leprosy control in Guinea has been needing a good cooperation between Department of Leprosy Control and local nurses. The known prevalence, in the area of Pita is 1.23%. 246 patients has been detected: 36 multibacillary and 210 paucibacillary. The sex-ratio of the patients has changed, during one year, toward the men. With the sensitivity of the local population, number of detected cases is increasing and the rate of regular attendance at treatment is correct in 87.6% of cases.

[Principle findings connected with the problems of implementing the multi-drug therapy for leprosy in West Africa]. / Principales données sur les problèmes de la mise en pratique de la polychimiothérapie de la lèpre en Afrique de l'Ouest.

The Implementation of Multidrug Therapy (MDT) in the states of West Africa oblige to analyse new restraints, in order to modify the existing health structures. The planning of Hansen's programs based on MDT needs to consider the technical and logistic parameters. Solutions are proposed for health workers training course, flow chart, drug supply system and supervision system. The advocated method uses at the existing resources, and aims at the integration into general health services, reinforced by specialized teams.