scholarly journals Skin-specific antibodies neutralizing mycolactone toxin during the spontaneous healing of Mycobacterium ulcerans infection

2020 ◽  
Vol 6 (9) ◽  
pp. eaax7781 ◽  
Author(s):  
Mélanie Foulon ◽  
Amélie Pouchin ◽  
Jérémy Manry ◽  
Fida Khater ◽  
Marie Robbe-Saule ◽  
...  
Keyword(s):  
Healing Process ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Immunomodulatory Activity ◽  
Spontaneous Healing ◽  
Specific Antibodies ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Health Organization

Buruli ulcer, a neglected tropical infectious disease, is caused by Mycobacterium ulcerans. Without treatment, its lesions can progress to chronic skin ulcers, but spontaneous healing is observed in 5% of cases, suggesting the possible establishment of a host strategy counteracting the effects of M. ulcerans. We reveal here a skin-specific local humoral signature of the spontaneous healing process, associated with a rise in antibody-producing cells and specific recognition of mycolactone by the mouse IgG2a immunoglobulin subclass. We demonstrate the production of skin-specific antibodies neutralizing the immunomodulatory activity of the mycolactone toxin, and confirm the role of human host machinery in triggering effective local immune responses by the detection of anti-mycolactone antibodies in patients with Buruli ulcer. Our findings pave the way for substantial advances in both the diagnosis and treatment of Buruli ulcer in accordance with the most recent challenges issued by the World Health Organization.

scholarly journals Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease

2017 ◽  
Vol 56 (4) ◽  
Author(s):  
Jeannette Guarner
Keyword(s):  
Clinical Presentation ◽  
Oral Treatment ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Tissue Necrosis ◽  
Content Type ◽  
Skin Nodule ◽  
The World ◽  
Health Organization

ABSTRACTBuruli ulcer is caused byMycobacterium ulcerans. This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performingM. ulceransPCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.

scholarly journals Aquatic Snails, Passive Hosts of Mycobacterium ulcerans

2004 ◽  
Vol 70 (10) ◽  
pp. 6296-6298 ◽  
Author(s):  
Laurent Marsollier ◽  
Tchibozo Sévérin ◽  
Jacques Aubry ◽  
Richard W. Merritt ◽  
Jean-Paul Saint André ◽  
...  
Keyword(s):  
Buruli Ulcer ◽  
Indirect Evidence ◽  
Mycobacterium Ulcerans ◽  
Aquatic Environments ◽  
Potential Vector ◽  
Ulcer Disease ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Favorable Conditions ◽  
Water Bugs

ABSTRACT Accumulative indirect evidence of the epidemiology of Mycobacterium ulcerans infections causing chronic skin ulcers (i.e., Buruli ulcer disease) suggests that the development of this pathogen and its transmission to humans are related predominantly to aquatic environments. We report that snails could transitorily harbor M. ulcerans without offering favorable conditions for its growth and replication. A novel intermediate link in the transmission chain of M. ulcerans becomes likely with predator aquatic insects in addition to phytophage insects. Water bugs, such as Naucoris cimicoides, a potential vector of M. ulcerans, were shown to be infected specifically by this bacterium after feeding on snails experimentally exposed to M. ulcerans.

scholarly journals Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection

2018 ◽  
Author(s):  
Alexandra G. Fraga ◽  
Gabriela Trigo ◽  
Juan Dominguez ◽  
Rita Silva-Gomes ◽  
Carine M. Gonçalves ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Soft Tissues ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Lipolytic Enzyme ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Advanced Stages ◽  
Health Organization

Buruli Ulcer (BU) is a cutaneous disease caused by Mycobacterium ulcerans. The pathogenesis of BU is closely related to the secretion of the toxin mycolactone that induces extensive destruction of the skin and soft tissues. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages often requires extensive surgical resection of the infected tissue. Therefore, it is important to develop alternative strategies for the treatment of BU. Endolysins (lysins) are phage encoded enzymes that degrade peptidoglycan of bacterial cell walls. Over the past years, lysins have been emerging as alternative antimicrobial agents against Gram-positive bacteria. Amongst Gram-positive bacteria, mycobacteria have an unusual outer membrane that is covalently attached to the mycolyl arabinogalactan-peptidoglycan complex. To overcome this additional barrier to phage-mediated lysis, some mycobacteriophages encode a lipolytic enzyme, Lysin B (Lys B). In this study, we demonstrated for the first time that recombinant Lys B displays lytic activity against M. ulcerans isolates. Moreover, using a mouse model of M. ulcerans footpad infection, we show that subcutaneous treatment with Lys B leads to a reduction in bacterial burdens, associated with IFN-γ and TNF production in the draining lymph node. These findings highlight the potential use of lysins as a novel therapeutic approach against this neglected tropical disease.

scholarly journals Aquatic Insects as a Vector for Mycobacterium ulcerans

2002 ◽  
Vol 68 (9) ◽  
pp. 4623-4628 ◽  
Author(s):  
Laurent Marsollier ◽  
Raymond Robert ◽  
Jacques Aubry ◽  
Jean-Paul Saint André ◽  
Henri Kouakou ◽  
...  
Keyword(s):  
Aquatic Insects ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Laboratory Mice ◽  
Healthy Humans ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Set Up ◽  
Aquatic Bugs

ABSTRACT Mycobacterium ulcerans is an emerging environmental pathogen which causes chronic skin ulcers (i.e., Buruli ulcer) in otherwise healthy humans living in tropical countries, particularly those in Africa. In spite of epidemiological and PCR data linking M. ulcerans to water, the mode of transmission of this organism remains elusive. To determine the role of aquatic insects in the transmission of M. ulcerans, we have set up an experimental model with aquariums that mimic aquatic microenvironments. We report that M. ulcerans may be transmitted to laboratory mice by the bite of aquatic bugs (Naucoridae) that are infected with this organism. In addition, M. ulcerans appears to be localized exclusively within salivary glands of these insects, where it can both survive and multiply without causing any observable damage in the insect tissues. Subsequently, we isolated M. ulcerans from wild aquatic insects collected from a zone in the Daloa region of Ivory Coast where Buruli ulcer is endemic. Taken together, these results point to aquatic insects as a possible vector of M. ulcerans.

scholarly journals Bactericidal Activity of Rifampin-Amikacin against Mycobacterium ulcerans in Mice

2002 ◽  
Vol 46 (10) ◽  
pp. 3193-3196 ◽  
Author(s):  
Herve Dega ◽  
Abdelhalim Bentoucha ◽  
Jerome Robert ◽  
Vincent Jarlier ◽  
Jacques Grosset
Keyword(s):  
Clinical Trial ◽  
Bactericidal Activity ◽  
Buruli Ulcer ◽  
Acid Fast Bacillus ◽  
Drug Dosage ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Health Organization ◽  
The Impact ◽  
Lesion Index

ABSTRACT To identify the most active curative treatment of Buruli ulcer, two regimens incorporating the use of rifampin (RIF) were compared with the use of RIF alone in a mouse footpad model of Mycobacterium ulcerans infection. Treatments began after footpad swelling from infection and continued for 12 weeks with five doses weekly of one of the following regimens: (i) 10 mg of RIF/kg alone; (ii) 10 mg of RIF/kg and 100 mg of amikacin (AMK)/kg; and (iii) 10 mg of RIF/kg, 100 mg of clarithromycin (CLR)/kg, and 50 mg of sparfloxacin (SPX)/kg. The activity of each regimen was assessed in terms of the reduction of the average lesion index and acid-fast bacillus (AFB) and CFU counts. All three regimens displayed various degrees of bactericidal activity against M. ulcerans. The ranking of bactericidal activity was found to be as follows: RIF-AMK > RIF-CLR-SPX > RIF. RIF-AMK was able to cure M. ulcerans-infected mice and prevent relapse 26 weeks after completion of treatment. To determine the impact of different rhythms of administration of RIF-AMK on the suppression of M.ulcerans growth, mice were given the RIF-AMK combination for 4 weeks but doses were administered either 5 days a week or twice or once weekly. After completion of treatment, the mice were kept under supervision for 30 additional weeks. M. ulcerans was considered to have grown in the footpad if swelling was visually observed and harvests contained more than 5 × 105 AFB per footpad. The proportion of mice in which growth of M. ulcerans occurred, irrespective of drug dosage, was compared with the control mice to determine the proportion of M. ulcerans killed. Each dosage of RIF-AMK was bactericidal for M. ulcerans (P < 0.001), but the effect was significantly stronger in mice treated 5 days per week. The promising results of RIF-AMK treatment in M. ulcerans-infected mice support the clinical trial that is currently in progress under World Health Organization auspices in Ghana.

scholarly journals The changing epidemiology worldwide ofMycobacterium ulcerans

2018 ◽  
Vol 147 ◽  
Author(s):  
D. P. O'Brien ◽  
I. Jeanne ◽  
K. Blasdell ◽  
M. Avumegah ◽  
E. Athan
Keyword(s):  
Mycobacterial Infection ◽  
Mycobacterium Ulcerans ◽  
Health Interventions ◽  
World Health ◽  
Transmission Mechanisms ◽  
Current State ◽  
The World ◽  
Environmental Reservoir ◽  
Endemic Areas ◽  
Health Organization

AbstractMycobacterium ulceransis recognised as the third most common mycobacterial infection worldwide. It causes necrotising infections of skin and soft tissue and is classified as a neglected tropical disease by the World Health Organization (WHO). However, despite extensive research, the environmental reservoir of the organism and mode of transmission of the infection to humans remain unknown. This limits the ability to design and implement public health interventions to effectively and consistently prevent the spread and reduce the incidence of this disease. In recent years, the epidemiology of the disease has changed. In most endemic regions of the world, the number of cases reported to the WHO are reducing, with a 64% reduction in cases reported worldwide in the last 9 years. Conversely, in a smaller number of countries including Australia and Nigeria, reported cases are increasing at a rapid rate, new endemic areas continue to appear, and in Australia cases are becoming more severe. The reasons for this changing epidemiology are unknown. We review the epidemiology ofM. ulceransdisease worldwide, and document recent changes. We also outline and discuss the current state of knowledge on the ecology ofM. ulcerans, possible transmission mechanisms to humans and what may be enabling the spread ofM. ulceransinto new endemic areas.

scholarly journals Mycolactone Is Responsible for the Painlessness of Mycobacterium ulcerans Infection (Buruli Ulcer) in a Murine Study

2008 ◽  
Vol 76 (5) ◽  
pp. 2002-2007 ◽  
Author(s):  
Junichiro En ◽  
Masamichi Goto ◽  
Kazue Nakanaga ◽  
Michiyo Higashi ◽  
Norihisa Ishii ◽  
...  
Keyword(s):  
Buruli Ulcer ◽  
Pulmonary Hemorrhage ◽  
Nerve Damage ◽  
Mycobacterium Ulcerans ◽  
Nerve Degeneration ◽  
Limb Amputation ◽  
Cell Nuclei ◽  
Neutrophilic Infiltration ◽  
Sensory Recovery ◽  
Chronic Skin

ABSTRACT Buruli ulcer is a chronic skin disease caused by Mycobacterium ulcerans, which produces a toxic lipid mycolactone. Despite the extensive necrosis and tissue damage, the lesions are painless. This absence of pain prevents patients from seeking early treatment and, as a result, many patients experience severe sequelae, including limb amputation. We have reported that mice inoculated with M. ulcerans show loss of pain sensation and nerve degeneration. However, the molecules responsible for the nerve damage have not been identified. In order to clarify whether mycolactone alone can induce nerve damage, mycolactone A/B was injected to footpads of BALB/c mice. A total of 100 μg of mycolactone induced footpad swelling, redness, and erosion. The von Frey sensory test showed hyperesthesia on day 7, recovery on day 21, and hypoesthesia on day 28. Histologically, the footpads showed epidermal erosion, moderate stromal edema, and moderate neutrophilic infiltration up to day 14, which gradually resolved. Nerve bundles showed intraneural hemorrhage, neutrophilic infiltration, and loss of Schwann cell nuclei on days 7 and 14. Ultrastructurally, vacuolar change of myelin started on day 14 and gradually subsided by day 42, but the density of myelinated fibers remained low. This study demonstrated that initial hyperesthesia is followed by sensory recovery and final hypoesthesia. Our present study suggests that mycolactone directly damages nerves and is responsible for the absence of pain characteristic of Buruli ulcer. Furthermore, mice injected with 200 μg of mycolactone showed pulmonary hemorrhage. This is the first study to demonstrate the systemic effects of mycolactone.

scholarly journals The Role of Micronutrients to Support Immunity for COVID-19 Prevention

2021 ◽  
Author(s):  
Mukhtar H. Ahmed ◽  
Arez Hassan ◽  
Judit Molnár
Keyword(s):  
Immune System ◽  
Healing Process ◽  
Strong Relationship ◽  
The Body ◽  
World Health ◽  
Disease Spread ◽  
Food Sources ◽  
Novel Coronavirus ◽  
Health Organization ◽  
The Impact

AbstractThe World Health Organization declared the novel coronavirus, named as SARS-CoV-2, as a global pandemic in early 2020 after the disease spread to more than 180 countries leading to tens of thousands of cases and many deaths within a couple of months. Consequently, this paper aims to summarize the evidence for the relationships between nutrition and the boosting of the immune system in the fight against the disease caused by SARS-CoV-2. This review, in particular, assesses the impact of vitamin and mineral supplements on the body’s defence mechanisms against SARS-CoV-2. The results revealed that there is a strong relationship between the ingestion of biological ingredients like vitamins C–E, and minerals such as zinc, and a reduction in the effects of coronavirus infection. These can be received from either nutrition rich food sources or from vitamin supplements. Furthermore, these macromolecules might have roles to play in boosting the immune response, in the healing process and the recovery time. Hence, we recommend that eating healthy foods rich in vitamins C–E with zinc and flavonoids could boost the immune system and consequently protect the body from serious infections. Graphical Abstract

scholarly journals Mekanisme probiotik lactobacillus plantarum dalam sistem imun pada penderita diare

2020 ◽  
Vol 2 (1) ◽  
pp. 79-82
Author(s):  
Nadia Afifah
Keyword(s):  
Lactobacillus Plantarum ◽  
Intestinal Epithelium ◽  
Pathogenic Bacteria ◽  
Healing Process ◽  
Immunoglobulin A ◽  
Food Poisoning ◽  
Intestinal Wall ◽  
World Health ◽  
Bowel Movements ◽  
Health Organization

Probiotics are defined as living microorganisms which, when consumed in sufficient quantities, can provide health benefits. Lactobacillus Plantarum and Lactobacillus acidophilus include probiotics. Probiotics can protect the digestive tract from adhesion to pathogenic bacteria. Diarrhea is a disease characterized by increasing the frequency of bowel movements more than 3-4 days. The cause of diarrhea can be in the form of infections (bacteria, viruses, parasites), food poisoning, drug use, and others. Diarrhea can also occur due to physiological changes such as: (1) increased intraluminal osmolarity, (2) increased fluid and electrolyte secretion, (3) presence of infectious agents in the intestinal wall. The management of the World Health Organization (WHO) is rehydration (ORS fluids), diet, zinc, selective antibiotics, and education to parents of patients. But lately, probiotics have been proven to accelerate the healing process of diarrhea patients. There are emat mechanisms in the immune system process for patients with first diarrhea, preventing adhesion of pathogenic bacteria to the intestinal epithelium, both improving the function of the intestinal epithelium, the therapeutic effect of L. Plantarum will prevent bacteria from passing through the parasellular and transepithelial (transcellular) pathways to tissues outside the intestine, third inhibits pro-inflammatory cytokines, fourth induces immunoglobulin A (IgA)

scholarly journals Co-Management of Active Tuberculosis and Diabetes Mellitus Under Supervised DOTS Strategy—A Saudi Perspective

Reports ◽  
2018 ◽  
Vol 1 (3) ◽  
pp. 25
Author(s):  
Sarvath Ali ◽  
Marepalli Rao ◽  
Ahmed Sahly ◽  
Abdulazeez Alfageeh ◽  
Abdulrahman Bakari
Keyword(s):  
Diabetes Mellitus ◽  
Classification Tree ◽  
Healing Process ◽  
World Health ◽  
Health Concern ◽  
Global Public Health ◽  
Tb Treatment ◽  
Short Course ◽  
Directly Observed Treatment ◽  
Health Organization

Tuberculosis (TB) is a global public health concern, specifically in countries which have high prevalence of HIV/AIDS, malnutrition, unhygienic conditions, etc. Some evidence has been presented that diabetes mellitus (DM) is a risk factor for TB. On the other hand, among those who have DM, TB infection enhances glucose intolerance and worsens glycemic control. The combination of TB and DM, due to immuno-compromised status of DM, can delay the healing process of TB. The focus of this paper is the World Health Organization directly observed treatment, short course (DOTS) program implemented in Gazan province, Saudi Arabia, to treat TB. The data included some patients with both TB and DM. The data has been analyzed to assess how effective the DOTS program was in managing TB. It was found that DM was not a significant factor in the outcome of TB treatment. We used the same data and observed that the non-significance of DM is due to heterogeneity of patient population, Saudis and Non-Saudis. The prevalence of DM was very high among Saudis. This is understandable in view of different lifestyles. Non-Saudis are predominantly Yemenis. For Saudis, DM was indeed found to play a role in the treatment outcome of TB, after an application of a classification tree methodology on the data. This is the main focus of the paper.

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