Vaccine against MAC?

Posted by Armando @bolso1, Nov 19, 2020

Does anybody know about a vaccine against MAC? I found the paper ["Protection against Mycobacterium avium by DNA Vaccines Expressing Mycobacterial Antigens as Fusion Proteins with Green Fluorescent Protein" (INFECTION AND IMMUNITY, Aug. 1999, Vol. 67, No. 8 p. 4243–4250)] that claimed to be "...first report of successful DNA vaccination against M. avium", but nothing else.

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@sueinmn

There has been some recent research about a vaccine for MAC that sounds promising. I cannot post the links from my phone, but Google mycobabterium avium complex vaccine and look for articles from 2019.
Probably the biggest issue is that ours is something of an "orphan" only affecting about .1% of the population and not contagious, so not a very high priority.
Let us know of you learn anything new from your doc @irene5 .
Sue

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@sueinmn Good morning Sue. I had quite a lengthy discussion with my pulmonologist at UMASS on Friday. I brought the research article with me that @bolso1 had referenced. What I gleaned from our conversation is that while it is good research, it is missing a next step which would be to see if humans would develop the same antibodies as the mice. Unfortunately, a vaccine would not help those of us who are already diagnosed/struggling with MAC infection. irene5

REPLY

I want to share an interesting and recent paper (attached) that concludes that BCG-vaccination induces non-tuberculous mycobacterial (NTM) cross-reactive immunity, and has the potential for use as a vaccine or immunotherapy to prevent and/or treat pulmonary NTM disease.
Also, in the Introduction, the authors stated: "In North America, the incidence of pulmonary nontuberculous mycobacteria (NTM) is higher than the incidence of tuberculosis (TB) (1). In addition, the prevalence of multiple NTM infections and the mortality rates associated with NTM infections are increasing (2–5). A study of Medicare part B beneficiaries showed that the prevalence of NTM increased from 20 to 47 per 100,000 persons between 1997 and 2007, an increase of 8.2% per year (2). A more recent report estimated that the number of pulmonary NTM cases in the US increased by at least another two-fold between 2010 and 2014 (5). The causes for these increases in prevalence of pulmonary NTM are not known."

Shared files

fimmu-10-00234 (fimmu-10-00234.pdf)

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@bolso1

I want to share an interesting and recent paper (attached) that concludes that BCG-vaccination induces non-tuberculous mycobacterial (NTM) cross-reactive immunity, and has the potential for use as a vaccine or immunotherapy to prevent and/or treat pulmonary NTM disease.
Also, in the Introduction, the authors stated: "In North America, the incidence of pulmonary nontuberculous mycobacteria (NTM) is higher than the incidence of tuberculosis (TB) (1). In addition, the prevalence of multiple NTM infections and the mortality rates associated with NTM infections are increasing (2–5). A study of Medicare part B beneficiaries showed that the prevalence of NTM increased from 20 to 47 per 100,000 persons between 1997 and 2007, an increase of 8.2% per year (2). A more recent report estimated that the number of pulmonary NTM cases in the US increased by at least another two-fold between 2010 and 2014 (5). The causes for these increases in prevalence of pulmonary NTM are not known."

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Very interesting study, thanks for sharing. I am always interested in treatments for NTM or MAC infections other than the standard course of antibiotic therapy. Can anyone answer the question about what is causing the increase in cases of pulmonary NTM?

REPLY

@poodledoc There are probably multiple reasons for the increase of NTM. “The number of people at risk is increasing because the population is aging and more people are living with chronic lung diseases. Increasing environmental exposure is also likely a factor, as is greater awareness of NTM disease among physicians.” With the many women who get NTM, I read that it is because we live longer and are more likely to seek medical care. There may be unidentified biological and genetic factors that contribute to the greater incidence and prevalence among women. Personally, I believe there is a genetic and/or biological connection. With that said, I am wondering about the increase in environmental exposure. As I typed this I started thinking about autism. When I was a child in the 1950’s, nobody ever mentioned autism. Before I retired in 2014, there was an entire program at my school, at the middle school, and at the high school for these children. One of my fourteen grandbabies has autism, and I worked with a sweet woman who had three children with autism. Three of my grown children teach children with autism. All this, in my opinion, also begs the question “why”? None of what I read about NTM @poodledoc answers “why” sufficiently for me. When I was first diagnosed doctors asked me if I lived on a farm or worked with animals ( especially birds). That might be food for thought for some of us but certainly only a small percentage. I too would like answers to the question. irene5

REPLY
@poodledoc

Very interesting study, thanks for sharing. I am always interested in treatments for NTM or MAC infections other than the standard course of antibiotic therapy. Can anyone answer the question about what is causing the increase in cases of pulmonary NTM?

Jump to this post

Here are a few references on the ecology of NTM that, while they do not address specifically the increase in rates of pulmonary NTM, provide information about conditions that favor such increases.
1. Health impacts of environmental mycobacteria. Todd P Primm, Christie A Lucero, Joseph O Falkinham 3rd. Clin Microbiol Rev. 2004 Jan;17(1):98-106. doi: 10.1128/cmr.17.1.98-106.2004. Abstract: Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
2. Ecology of nontuberculous mycobacteria--where do human infections come from?Joseph O Falkinham 3rd. Semin Respir Crit Care Med. 2013 Feb;34(1):95-102. doi: 10.1055/s-0033-1333568. Epub 2013 Mar 4. Abstract: Nontuberculous mycobacteria (NTM) are environmental, opportunistic human pathogens whose reservoirs include peat-rich potting soil and drinking water in buildings and households. In fact, humans are likely surrounded by NTM. NTM are ideally adapted for residence in drinking water distribution systems and household and building plumbing as they are disinfectant-resistant, surface adherent, and able to grow on low concentrations of organic matter. For individuals at risk for NTM infection, measures can be taken to reduce NTM exposure. These include avoiding inhalation of dusts from peat-rich potting soil and aerosols from showers, hot tubs, and humidifiers. A risk analysis of the presence of NTM in drinking water has not been initiated because the virulence of independent isolates of even single NTM species (e.g., Mycobacterium avium) is quite broad, and virulence determinants have not been identified.
3. Environmental sources of nontuberculous mycobacteria. Joseph O Falkinham 3rd. Clin Chest Med. 2015 Mar;36(1):35-41. doi: 10.1016/j.ccm.2014.10.003. Abstract: Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
4. Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM). Joseph O Falkinham 3rd. Curr Environ Health Rep. 2016 Jun;3(2):161-7. doi: 10.1007/s40572-016-0086-z. Abstract: The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

REPLY
@irene5

@poodledoc There are probably multiple reasons for the increase of NTM. “The number of people at risk is increasing because the population is aging and more people are living with chronic lung diseases. Increasing environmental exposure is also likely a factor, as is greater awareness of NTM disease among physicians.” With the many women who get NTM, I read that it is because we live longer and are more likely to seek medical care. There may be unidentified biological and genetic factors that contribute to the greater incidence and prevalence among women. Personally, I believe there is a genetic and/or biological connection. With that said, I am wondering about the increase in environmental exposure. As I typed this I started thinking about autism. When I was a child in the 1950’s, nobody ever mentioned autism. Before I retired in 2014, there was an entire program at my school, at the middle school, and at the high school for these children. One of my fourteen grandbabies has autism, and I worked with a sweet woman who had three children with autism. Three of my grown children teach children with autism. All this, in my opinion, also begs the question “why”? None of what I read about NTM @poodledoc answers “why” sufficiently for me. When I was first diagnosed doctors asked me if I lived on a farm or worked with animals ( especially birds). That might be food for thought for some of us but certainly only a small percentage. I too would like answers to the question. irene5

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Thanks for info.

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@poodledoc

Very interesting study, thanks for sharing. I am always interested in treatments for NTM or MAC infections other than the standard course of antibiotic therapy. Can anyone answer the question about what is causing the increase in cases of pulmonary NTM?

Jump to this post

Poodledoc - In addition to the causes cited in your post, I can think of a number of reasons for the increasing prevalence.

I believe one cause yet to be addressed is the replacement of copper pipe in plumbing with plastics. The copper was naturally resistant to bacterial colonization, the plastics seem to attract the biofilm in which the mycobacteria can colonize. At some point I expect this will be more thoroughly studied.

Another is better and more thorough testing. I was treated for over 2 years, in 2 different states, for pneumonia, bronchitis & asthma (all of which I definitely had.) My sputum was frequently rapid-tested, but never cultured. Medication would occasionally ease the symptoms for a few weeks, then I was sick again. This describes how my mother lived for many years, until she ultimately died of CHF in her 80's. MAC was never diagnosed, but I am now quite certain she had it.

A sharp-eyed radiologist finally recognized signs of bronchiectasis in an x-ray and called my primary, who promptly ordered a CT scan and sent me to a pulmonologist for sputum culturing and the rest is history.

Finally, the "globalization" of soil-containing products - such as peat and potted plants, which we used to acquire locally, but are now shipped cross country may be exposing us to new variants of mycobacteria. Plants purchased from big box stores all over the country are largely raised, potted and shipped from Mississippi, Georgia and other places in the Southeast. So maybe we possess some tolerance for or immunity to the organism in the local soil, to which we have long been exposed, but not to a different strain shipped from another part of the country. For example, I gardened for over 40 years in Minnesota without issue, but when I began gardening in Texas, I acquired MAC.

Sue

REPLY
@bolso1

Here are a few references on the ecology of NTM that, while they do not address specifically the increase in rates of pulmonary NTM, provide information about conditions that favor such increases.
1. Health impacts of environmental mycobacteria. Todd P Primm, Christie A Lucero, Joseph O Falkinham 3rd. Clin Microbiol Rev. 2004 Jan;17(1):98-106. doi: 10.1128/cmr.17.1.98-106.2004. Abstract: Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
2. Ecology of nontuberculous mycobacteria--where do human infections come from?Joseph O Falkinham 3rd. Semin Respir Crit Care Med. 2013 Feb;34(1):95-102. doi: 10.1055/s-0033-1333568. Epub 2013 Mar 4. Abstract: Nontuberculous mycobacteria (NTM) are environmental, opportunistic human pathogens whose reservoirs include peat-rich potting soil and drinking water in buildings and households. In fact, humans are likely surrounded by NTM. NTM are ideally adapted for residence in drinking water distribution systems and household and building plumbing as they are disinfectant-resistant, surface adherent, and able to grow on low concentrations of organic matter. For individuals at risk for NTM infection, measures can be taken to reduce NTM exposure. These include avoiding inhalation of dusts from peat-rich potting soil and aerosols from showers, hot tubs, and humidifiers. A risk analysis of the presence of NTM in drinking water has not been initiated because the virulence of independent isolates of even single NTM species (e.g., Mycobacterium avium) is quite broad, and virulence determinants have not been identified.
3. Environmental sources of nontuberculous mycobacteria. Joseph O Falkinham 3rd. Clin Chest Med. 2015 Mar;36(1):35-41. doi: 10.1016/j.ccm.2014.10.003. Abstract: Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
4. Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM). Joseph O Falkinham 3rd. Curr Environ Health Rep. 2016 Jun;3(2):161-7. doi: 10.1007/s40572-016-0086-z. Abstract: The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

Jump to this post

Bolso1 and @irene5 If most of us in this group did not also suffer from bronchiectasis (most likely incurred by acid reflux); a mac vaccine sounds nice. But, because of the bronchiectasis, we are prone to a number of bacterial infections, not just a. mycobacterium (mac). It would have to be a wide spectrum vaccine that also covers, pseudomonas, m. fortuitum, chimaera, m. gordonae, serratia marcescens, chelonae, m. boletti, etc. See where I am going with this? A vaccine for one thing will not stop opportunistic pathogens from infecting damaged lungs..........Although we seem like a small orphan group, we really aren't. Like you stated, mac infections are climbing. Not only that, but we share the same lung infections that Cystic Fibrosis patients get on a regular basis. My dr told me once that we with bronchiectasis were very similar in idiology to CF patients only we lack the CF gene.

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@sueinmn

Poodledoc - In addition to the causes cited in your post, I can think of a number of reasons for the increasing prevalence.

I believe one cause yet to be addressed is the replacement of copper pipe in plumbing with plastics. The copper was naturally resistant to bacterial colonization, the plastics seem to attract the biofilm in which the mycobacteria can colonize. At some point I expect this will be more thoroughly studied.

Another is better and more thorough testing. I was treated for over 2 years, in 2 different states, for pneumonia, bronchitis & asthma (all of which I definitely had.) My sputum was frequently rapid-tested, but never cultured. Medication would occasionally ease the symptoms for a few weeks, then I was sick again. This describes how my mother lived for many years, until she ultimately died of CHF in her 80's. MAC was never diagnosed, but I am now quite certain she had it.

A sharp-eyed radiologist finally recognized signs of bronchiectasis in an x-ray and called my primary, who promptly ordered a CT scan and sent me to a pulmonologist for sputum culturing and the rest is history.

Finally, the "globalization" of soil-containing products - such as peat and potted plants, which we used to acquire locally, but are now shipped cross country may be exposing us to new variants of mycobacteria. Plants purchased from big box stores all over the country are largely raised, potted and shipped from Mississippi, Georgia and other places in the Southeast. So maybe we possess some tolerance for or immunity to the organism in the local soil, to which we have long been exposed, but not to a different strain shipped from another part of the country. For example, I gardened for over 40 years in Minnesota without issue, but when I began gardening in Texas, I acquired MAC.

Sue

Jump to this post

That makes a lot of sense Sue. I never thought about the import of soil and plants bringing in germs that we don't have a regional immunity to. My lung damage started when I was 30 yrs old when I moved to Arizona and caught 'Valley Fever' from cactus spores. That illness put holes and nodules in my lungs and made me deathly ill for two months. My lungs went downhill ever since that.

REPLY
@bolso1

Here are a few references on the ecology of NTM that, while they do not address specifically the increase in rates of pulmonary NTM, provide information about conditions that favor such increases.
1. Health impacts of environmental mycobacteria. Todd P Primm, Christie A Lucero, Joseph O Falkinham 3rd. Clin Microbiol Rev. 2004 Jan;17(1):98-106. doi: 10.1128/cmr.17.1.98-106.2004. Abstract: Environmental mycobacteria are emerging pathogens causing opportunistic infections in humans and animals. The health impacts of human-mycobacterial interactions are complex and likely much broader than currently recognized. Environmental mycobacteria preferentially survive chlorination in municipal water, using it as a vector to infect humans. Widespread chlorination of water has likely selected more resistant environmental mycobacteria species and potentially explains the shift from M. scrofulaceum to M. avium as a cause of cervical lymphadenitis in children. Thus, human activities have affected mycobacterial ecology. While the slow growth and hydrophobicity of environmental mycobacteria appear to be disadvantages, the unique cell wall architecture also grants high biocide and antibiotic resistance, while hydrophobicity facilitates nutrient acquisition, biofilm formation, and spread by aerosolization. The remarkable stress tolerance of environmental mycobacteria is the major reason they are human pathogens. Environmental mycobacteria invade protozoans, exhibiting parasitic and symbiotic relationships. The molecular mechanisms of mycobacterial intracellular pathogenesis in animals likely evolved from similar mechanisms facilitating survival in protozoans. In addition to outright infection, environmental mycobacteria may also play a role in chronic bowl diseases, allergies, immunity to other pulmonary infections, and the efficacy of bacillus Calmette-Guerin vaccination.
2. Ecology of nontuberculous mycobacteria--where do human infections come from?Joseph O Falkinham 3rd. Semin Respir Crit Care Med. 2013 Feb;34(1):95-102. doi: 10.1055/s-0033-1333568. Epub 2013 Mar 4. Abstract: Nontuberculous mycobacteria (NTM) are environmental, opportunistic human pathogens whose reservoirs include peat-rich potting soil and drinking water in buildings and households. In fact, humans are likely surrounded by NTM. NTM are ideally adapted for residence in drinking water distribution systems and household and building plumbing as they are disinfectant-resistant, surface adherent, and able to grow on low concentrations of organic matter. For individuals at risk for NTM infection, measures can be taken to reduce NTM exposure. These include avoiding inhalation of dusts from peat-rich potting soil and aerosols from showers, hot tubs, and humidifiers. A risk analysis of the presence of NTM in drinking water has not been initiated because the virulence of independent isolates of even single NTM species (e.g., Mycobacterium avium) is quite broad, and virulence determinants have not been identified.
3. Environmental sources of nontuberculous mycobacteria. Joseph O Falkinham 3rd. Clin Chest Med. 2015 Mar;36(1):35-41. doi: 10.1016/j.ccm.2014.10.003. Abstract: Nontuberculous mycobacteria (NTM) include over 150 species. The source for human infection is the environment. NTM are normal inhabitants of soil and drinking water. NTM grow and persist in many buildings. They are not contaminants of drinking water, but members of the natural drinking water microbial population. Infection occurs because humans share the same habitats. Because the ecology, antibiotic susceptibility, and virulence of individual species differs, identifying NTM isolates to species is important. Treatment requires multiple antibiotics. NTM patients are innately sensitive to NTM infection, resulting in reinfection. Knowledge of the sources of NTM can reduce exposure to environmental NTM.
4. Current Epidemiologic Trends of the Nontuberculous Mycobacteria (NTM). Joseph O Falkinham 3rd. Curr Environ Health Rep. 2016 Jun;3(2):161-7. doi: 10.1007/s40572-016-0086-z. Abstract: The nontuberculous mycobacteria (NTM) are waterborne opportunistic pathogens of humans. They are normal inhabitants of premise plumbing, found, for example, in household and hospital shower heads, water taps, aerators, and hot tubs. The hydrophobic NTM are readily aerosolized, and pulmonary infections and hypersensitivity pneumonitis have been traced to the presence of NTM in shower heads. Hypersensitivity pneumonitis in automotive workers was traced to the presence of NTM in metal recovery fluid used in grinding operations. Recently, NTM bacteremia in heart transplant patients has been traced to the presence of NTM in water reservoirs of instruments employed in operating rooms to heat and cool patient blood during periods of mechanical circulation. Although NTM are difficult to eradicate from premise plumbing as a consequence of their disinfectant-resistance and formation of biofilms, measures such as reduction of turbidity and reduction in carbon and nitrogen for growth and the installation of microbiological filters can reduce exposure of NTM to susceptible individuals.

Jump to this post

Bolso1 and @irene5 If most of us in this group did not also suffer from bronchiectasis (most likely incurreesd by acid reflux); a mac vaccine sounds nice. But, because of the bronchiectasis, we are prone to a number of bacterial infections, not just a. mycobacterium (mac). It would have to be a wide spectrum vaccine that also covers, pseudomonas, m. fortuitum, chimaera, m. gordonae, serratia marcescens, chelonae, m. boletti, etc. See where I am going with this? A vaccine for one thing will not stop opportunistic pathogens from infecting damaged lungs.

REPLY
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