Saturday, November 25, 2017
Saturday, November 18, 2017
The Woodrow Wilson Center may still have changed the history of African Swine Fever
When a blog by Alex Long on the Woodrow Wilson
Center website appeared on November 14, it described African Swine Fever as
being zoonotic.The sentence originally on the
site was this one: "Organizations, like the previously mentioned One
Health, are looking at specific zoonotic diseases like Rift Valley Fever,
African Swine Fever, or Zika." One Health seems to be one of those
fuzzy-wuzzy fronts organizations for the CDC that pretends to be separated. One Health
describes itself this way:
We contacted the Woodrow Wilson center to make sure Alex Long had not made a mistake, because all hell would break loose if he indeed had been informed by any organization like One Health that they consider African Swine Fever to be zoonotic and capable of infecting human beings. We also contacted the CDC.
The CDC media office sent this response:
Not aware of any evidence to suggest African Swine Fever (ASF) infects humans. Here is some additional info that maybe helpful.
Thanks,
Tom Skinner
CDC
As usual, the CDC either doesn't know the ASFV literature or is covering up an epidemic the same way they have covered up the Chronic Fatigue Syndrome epidemic for over three decades. (See Truth to Power for a full description of that cover-up.)
Interestingly, the Woodrow Wilson Center did not fully retract their original reference to African Swine Fever as being zoonotic. They took African Swine Fever out of the original sentence and added this at the end of Alex Long's blog:
Update: A previous version of this blog post suggested that African swine fever (ASFV) is zoonotic. In fact, the zoonotic nature of ASFV is open to debate. See additional references [A] and [B] for two contrasting viewpoints.
References:
A) Loh, J., et al. 2009. Detection of novel sequences related to african Swine Fever virus in human serum and sewage. J Virol, 83 (24), 13019-25.
B) The Center for Food Security and Public Health. 2015. African Swine Fever. Accessed November 16, 2017. http://www.cfsph.iastate.edu/Factsheets/pdfs/african_swine_fever.pdf
The folks at Woodrow Wilson Center are probably not aware that even suggesting "the zoonotic nature of ASFV is open to debate" is big news. It's so big they should send a press release out about it. The scientific establishment and the media has generally turned a blind eye to the zoonotic possibilities of African Swine Fever. Unfortunately, when it comes to diseases that affect pigs, the USDA is the 600-pound gorilla in the room. The last thing the USDA wants is for there to be a Woodrow-Wilson-Center-inspired discussion of "the zoonotic nature of ASFV." The pork industry basically is in bed with the USDA and the pork industry would not like there to be a Woodrow-Wilson-Center-inspired discussion of "the zoonotic nature of ASFV."As usual, the CDC either doesn't know the ASFV literature or is covering up an epidemic the same way they have covered up the Chronic Fatigue Syndrome epidemic for over three decades. (See Truth to Power for a full description of that cover-up.)
Interestingly, the Woodrow Wilson Center did not fully retract their original reference to African Swine Fever as being zoonotic. They took African Swine Fever out of the original sentence and added this at the end of Alex Long's blog:
Update: A previous version of this blog post suggested that African swine fever (ASFV) is zoonotic. In fact, the zoonotic nature of ASFV is open to debate. See additional references [A] and [B] for two contrasting viewpoints.
References:
A) Loh, J., et al. 2009. Detection of novel sequences related to african Swine Fever virus in human serum and sewage. J Virol, 83 (24), 13019-25.
B) The Center for Food Security and Public Health. 2015. African Swine Fever. Accessed November 16, 2017. http://www.cfsph.iastate.edu/Factsheets/pdfs/african_swine_fever.pdf
Alex Long has written an e-mail saying he made a mistake:
"Just to explain, but not excuse, my mistake: On the CEEZAD website (Center for Excellence for Emerging and Zoonotic Animal Disease) They discuss the work they do on the page and they mention putting R&D into funding African Swine Fever epidemiological research and prevent it from coming to the US, along with Rift Valley Fever (Source: http://ceezad.org/research/epidemiology/ You can find this excerpt under the subheading Kansas Biosciences Authority Funded Projects). When I was on that page I saw African Swine Fever and thought they were referring to African Hemorrhagic Fever, a known zoonotic disease, so my mind just made the illogical jump and just read ASF as AHF. By making this jump, I did not think to double check with if it was the disease I blindly thought it was."
You could say that this was a fortuitous mistake, because the admission by a major think tank like Woodrow Wilson Center that "the zoonotic nature of ASFV is open to debate," has helped bring the issue of potential human infections with ASFV out of the closet. That is a very good outcome.
If Alex Long is ever concerned about emerging new human diseases coming from pigs he will have to deal with the USDA. Good luck with that. The USDA usually goes into emergency mode when anyone dares to suggest that ASFV is zoonotic. Anyone curious about how the USDA rolls these days should read this fascinating piece in Vanity Fair.
We applaud the Woodrow Wilson Center for not just retracting what Alex Long wrote and saying that he made a mistake and the matter is closed. They didn't close the debate about the zoonotic nature of African Swine Fever by pretending that it is settled science. It is refreshing that they have been so honest about the matter.
We hope that the Woodrow Wilson Center will keep an eye on this issue. The whole point of Alex Long's piece seems to be that as the environment changes, new diseases can emerge. Anyone who says that ASFV can never infect humans is not being truthful.
We provide the information below for anyone who takes what the CDC says about African Swine Fever (or anything, for that matter) with a grain of salt. We hope this information will inspire Alex Long and the Woodrow Wilson Center to look hard and long at the potential of African Swine Fever to be one of the next big threats to public health.
Information gathered by the joint efforts of HHV-6 University and African Swine Fever University.
Russian Scientist: ASF could become a human health risk
"The African swine fever (ASF) virus, may in the future become
dangerous for humans, according to the head of the Russian Epidemiology
Service, Chief State Sanitary Doctor Gennady Onishchenko, at the
press-conference in St. Petersburg. According to him almost all viruses
from time to time go through mutation processes which can give them some
additional functions."
http://www.pigprogress.net/Health-Diseases/Outbreaks/2013/7/ASF-could-become-a-human-health-risk-1308047W/
Background on African Swine Fever Virus as a human pathogen:
"African Swine fever is an endemic disease in sub-Saharan Africa and
many other parts of the developing world. It is caused by the African
Swine virus that primarily replicates in macrophages and monocytes
leading to the impairment of the structure and function of the immune
system of the infected organisms. Until now the African Swine epidemic
continues to spread despite all efforts to contain it. Thus, there is
an objective need for effective, safe and affordable preventive and
therapeutic approaches, in particular for effective vaccines, to
control and eventually eradicate this disease. Since the characteristic
feature of the African Swine virus is to impair the immune system and
to cause immune deficiencies in its hosts the development of vaccines
and other therapeutic approaches against the African Swine virus has
implications for other immune deficiencies or diseases. Several other
viruses are also known to cause immunodeficiency-like syndromes in
humans, including cytomegalovirus, Epstein Barr Virus
and others. Moreover, a series of cases of so-called "idiopathic"
immunodeficiencies have been documented that display
CD4+T-lymphocytopenia with opportunistic infections, but show no
evidence of HIV infection. Since antibodies for the African Swine virus
have been detected in humans, the possibility of human infection with
the African Swine virus exists and may thus far have escaped any systematic screening. Thus, any preventive and therapeutic approach to African Swine fever can have far-reaching implications to control immune deficiency conditions in humans."http://www.faqs.org/patents/app/20080207875
Detection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
http://www.ncbi.nlm.nih.gov/pubmed/19812170?dopt=AbstractDetection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
African Swine Fever Virus (Asfarviridae) sequences found in people with febrile illnesses
Abstract
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
Dengue virus is an emerging infectious agent that infects an estimated
50–100 million people annually worldwide, yet current diagnostic
practices cannot detect an etiologic pathogen in ∼40% of dengue-like
illnesses. Metagenomic approaches to pathogen detection, such as viral
microarrays and deep sequencing, are promising tools to address
emerging and non-diagnosable disease challenges. In this study, we
used the Virochip microarray and deep sequencing to characterize the
spectrum of viruses present in human sera from 123 Nicaraguan patients
presenting with dengue-like symptoms but testing negative for dengue
virus. We utilized a barcoding strategy to simultaneously deep
sequence multiple serum specimens, generating on average over 1
million reads per sample. We then implemented a stepwise bioinformatic
filtering pipeline to remove the majority of human and low-quality
sequences to improve the speed and accuracy of subsequent unbiased
database searches. By deep sequencing, we were able to detect virus
sequence in 37% (45/123) of previously negative cases. These included
13 cases with Human Herpesvirus 6 sequences. Other samples contained
sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae
families. In some cases, the putative viral sequences were virtually
identical to known viruses, and in others they diverged, suggesting
that they may derive from novel viruses. These results demonstrate the
utility of unbiased metagenomic approaches in the detection of known
and divergent viruses in the study of tropical febrile illness.
Detection of African swine fever virus-like sequences in ponds in the Mississippi Delta through metagenomic sequencing
http://link.springer.com/article/10.1007%2Fs11262-013-0878-2
ASF virus, adapted to grow in VERO cells, produces a strong cytopathic effect in human macrophages leading to cell destruction.
More evidence that African Swine Fever is a human infection and connected to HHV-6?
"The 19R Protein of HHV-6 has significant amino acid sequence homology . . . to a protein encoded by African Swine Fever Virus."
--Glenda L. Lawrence, John Nicholas and Bart G. Barrell
Journal of General virology (1995), 76, 147-152
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
John Beldekas
(Photo by Jane Teas)
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
http://www.keephopealive.org/report10.html
Is African Swine Fever Virus causing K.S. in Italy?
High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia
http://www.ncbi.nlm.nih.gov/pubmed/9607855
Infection with human herpesvirus type 8 and Kaposi's sarcoma in Sardinia.
http://www.ncbi.nlm.nih.gov/pubmed/16501902
Epidemiology of HHV8 in Sardinian emigrants
http://www.dsnm.univr.it/?ent=progetto&id=565
Both ASFV and HHV-8 Interfere with apoptosis.
Are ASFV-infected Pigs the viral source of HHV-8 related Kaposi's Sarcoma in Sardinia? Is a ASFV-related Kaposi's Sarcoma epidemic possible in Russia where ASFV is spreading?
https://hhv6.jottit.com/35._pigs_and_kaposi%27s_sarcoma_in_sardinia
The world's highest incidence of Kaposi's sarcoma occurs in Sardinia (Reference) Is it possible that it is due to the fact that African Swine Fever Virus is endemic on the island? (Reference) One study suggests that the incidence of K.S. in northern Sardinia is highest in a countryside area where people have contact with animals. (Reference) Given the high prevalence of HHV-8,--the so-called K.S. herpes virus--in Sardinia (Reference) is it at all possible that HHV-8 may have been misclassified and actually is a human-adapted form of African Swine Fever Virus? (ASFV has been at least visually mistaken for another herpes virus, CMV, in the past.)
A number of experiments could be conducted to explore this hypothesis. In addition to a direct comparison of ASFV and HHV-8, pigs with African Swine Fever Virus could be tested for sequences of HHV-8. People with Kaposi's sarcoma could be tested for sequences of African Swine Fever, including new Asfaviridae sequences recently discovered. (Reference)
A comparison of the K.S. lesions in humans and ASFV lesions in pigs might be in order.Given that African Swine Fever is currently spreading in Russia and is now threatening Europe and China, (Reference) it would be useful to know whether people who are exposed to pigs with ASFV are at increased risk for HHV-8, Kaposi's sarcoma and the other pathologies associated with HHV-8. A study in sub-Saharan Africa where ASFV is endemic and HHV-8 is also endemic (Reference) might be useful. And areas of Russia where ASFV is spreading could be monitored closely for any signs of an increase of K.S. or HHV-8 infection and HHV-8 related pathologies.HHV-8 is an emerging health problem. HHV-8-associated K.S. is a significant problem in AIDS patients. It may also be the key to Chronic Fatigue Syndrome. HHV-8 has been found in the cerebrospinal fluid of 50% of Chronic Fatigue Syndrome patients. (Reference) HHV-8 has been linked to type 2 diabetes. (Reference) HHV-8 has been detected in B-cells in Castleman's disease and primary effusion lymphoma. (Reference).
If HHV-8 is a form of ASFV, it is possible that pigs might constitute a useful animal model for the study of possible treatments for K.S. and other pathologies associated with HHV-8. And if there is any relationship between ASFV and HHV-8, people may have to be warned to take special precautions around pigs in areas where there are ASFV outbreaks. And countries where undercooked pork is consumed (like Ukraine where salo is a staple) may need to alert the public to cook all pork products thoroughly during ASFV epidemics.
A number of years ago, Neenyah Ostrom reported in the New
York Native on the lesions in CFS patients which seem
to resemble Kaposi's Sarcoma (KS). The current
thinking is that a virus called HHV-8 is the cause of
KS. (Although HHV-6 has recently also been implicatedonce again.) If KS is a problem in CFS (and we
suspect it is) then one should be able to find HHV-8 and
HHV-6 in CFS patients. Apparently, in this small
study, one can. Below is a rather explosive abstract:
York Native on the lesions in CFS patients which seem
to resemble Kaposi's Sarcoma (KS). The current
thinking is that a virus called HHV-8 is the cause of
KS. (Although HHV-6 has recently also been implicatedonce again.) If KS is a problem in CFS (and we
suspect it is) then one should be able to find HHV-8 and
HHV-6 in CFS patients. Apparently, in this small
study, one can. Below is a rather explosive abstract:
Prevalence in the cerebrospinal fluid of the following
infectious agents in a cohort of 12 CFS subjects:
human herpes virus-6 and 8; chlamydia species;
mycoplasma species; EBV; CMV; and Coxsackievirus.
Levine, S.
Journal of Chronic Fatigue Syndrome, 2001, 9, 1/2,
41-51.
infectious agents in a cohort of 12 CFS subjects:
human herpes virus-6 and 8; chlamydia species;
mycoplasma species; EBV; CMV; and Coxsackievirus.
Levine, S.
Journal of Chronic Fatigue Syndrome, 2001, 9, 1/2,
41-51.
Abstract:
Over the last decade a wide variety of infectious
agents have been associated with the CFS as potential
etiologies for this disorder. Many of these agents are
neurotrophic and have been linked previously to other
diseases involving the central nervous system (CNS).
Human herpes virus-6 (HHV-6), especially the B
variant, has been found in autopsy specimens of
patients who suffered from MS. Because patients with
CFS manifest a wide range of symptoms involving the
CNS as shown by abnormalities on brain MRIs, SPECT
scans of the brain and results of tilt table testing
we sought to determine the prevalence of HHV-6, HHV-8,
Epstein-Barr Virus (EBV), cytomegalovirus (CMV),
mycoplasma species, chlamydia species, and Coxsackie
virus in the spinal fluid of a group of 12 patients
with CFS (CDC criteria '94).
Over the last decade a wide variety of infectious
agents have been associated with the CFS as potential
etiologies for this disorder. Many of these agents are
neurotrophic and have been linked previously to other
diseases involving the central nervous system (CNS).
Human herpes virus-6 (HHV-6), especially the B
variant, has been found in autopsy specimens of
patients who suffered from MS. Because patients with
CFS manifest a wide range of symptoms involving the
CNS as shown by abnormalities on brain MRIs, SPECT
scans of the brain and results of tilt table testing
we sought to determine the prevalence of HHV-6, HHV-8,
Epstein-Barr Virus (EBV), cytomegalovirus (CMV),
mycoplasma species, chlamydia species, and Coxsackie
virus in the spinal fluid of a group of 12 patients
with CFS (CDC criteria '94).
We found evidence of HHV-6, HHV-8, chlamydia species,
CMV and Coxsackie virus in 6/12 samples. Plasma tests
were negative. It was surprising to obtain such a
relatively high yield of infectious agents in cell
free specimens of spinal fluid that had not been
centrifuged. Future research in spinal fluid analysis,
in addition to testing tissue samples by polymerase
chain reaction (PCR) and other direct viral isolation
techniques will be important in characterizing
subpopulations of CFS patients, especially those with
involvement of the CNS.
CMV and Coxsackie virus in 6/12 samples. Plasma tests
were negative. It was surprising to obtain such a
relatively high yield of infectious agents in cell
free specimens of spinal fluid that had not been
centrifuged. Future research in spinal fluid analysis,
in addition to testing tissue samples by polymerase
chain reaction (PCR) and other direct viral isolation
techniques will be important in characterizing
subpopulations of CFS patients, especially those with
involvement of the CNS.
The low rate of isolation of HHV-6 may be related to
the lack of gross neurological findings in the
patients at the time of testing.
the lack of gross neurological findings in the
patients at the time of testing.
An overview of KS:http://www.thebody.com/nmai/ks.html
Except for those who have made a lifelong commitment
to denial, finding the so-called "KS virus" (HHV-8)
and the "supporting KS virus" (HHV-6) in CFIDS patients
should help settle the question of the overlapping
nature of the AIDS and CFIDS epidemics.
to denial, finding the so-called "KS virus" (HHV-8)
and the "supporting KS virus" (HHV-6) in CFIDS patients
should help settle the question of the overlapping
nature of the AIDS and CFIDS epidemics.
Thursday, November 16, 2017
Are pigs the source of the Black Plague in Madagascar?????
Abstract
Pig production in Madagascar is not sufficient for domestic consumption. Unfortunately, African swine fever (ASF), which is a severe disease, is endemic in Madagascar and constitutes a constant threat for farmers. Therefore, ASF must be eradicated in order to guarantee the development of pig production. One of the main strategies in controlling ASF is stamping out which requires the farmers’ collaboration in reporting cases or suspected cases. The objective of this study was to estimate the proportion of farmers who knowingly sell ASF-infected meat without reporting. Since selling ASF-infected meat is prohibited by the government, we used the item count technique (ICT), an indirect questioning technique appropriate for measuring the proportion of people engaged in sensitive behavior, for one subsample, while another subsample was asked directly whether they sell ASF-infected meat. Based on the ICT, approximately 73.2% of farmers who have experienced ASF sell the ASF-infected meat. This estimate was not statistically different from that obtained by direct questioning. In the 28% of interviewed farmers who believe ASF can affect humans, the ICT yielded a higher estimate than did direct questioning, indicating that pig farmers who sell ASF-infected meat hide that fact because of their belief that infected meat might harm human consumers, not because of the law. The ICT was thus a suitable technique to address the problem of sensitive behavior. In the case of ASF outbreaks, the Malagasy government should enforce the law more strictly and provide compensation as incentive for reporting cases.
http://www.sciencedirect.com/science/article/pii/S0167587714004437
Is this the source of the plague in Madagascar?
Almost three-quarters of farmers questioned in Madagascar said they have sold meat from pigs infected with African swine fever (ASF) despite the fact that the government has outlawed this practice.
Is Black Plague connected to pigs sick with African Swine Fever in Madagascar?
Abstract
"This article aims to discuss the social factors associated with brucellosis and African swine fever (ASF) in Sri Lanka and Madagascar, respectively. In 2016, cross-sectional surveys were conducted in both countries. On the basis of the results of these surveys, we describe how brucellosis is more prevalent in certain ethnicities than others in Sri Lanka. Furthermore, in Madagascar, fihavanana, a social norm, encourages farmers to buy ASF-contaminated meat, resulting in ASF spread during outbreaks."
https://juniperpublishers.com/jdvs/pdf/JDVS.MS.ID.555555.pdf
"African Swine Fever Virus has devastated more than the half of the domestic pig population in Madagascar since its introduction, probably in 1997-1998. One of the hypotheses to explain its persistence on the island is its establishment in local Ornithodoros soft ticks, whose presence has been reported in the past from the north-western coast to the Central Highlands. The aim of the present study was to verify such hypothesis by conducting tick examinations in three distinct zones of pig production in Madagascar where African Swine Fever outbreaks have been regularly reported over the past decade and then to improve our knowledge on the tick distribution and taxonomy."
African swine fever is endemic in most of sub-Saharan Africa including the island of Madagascar. Outbreaks have been reported periodically outside Africa. The virus was eventually eradicated in most cases, although it remains endemic on the island of Sardinia (Italy) in the Mediterranean. In 2007, ASFV was introduced into the Caucasus region of Eurasia, via the Republic of Georgia, and it has spread to domesticated pigs and/or wild boars in a number of countries in this region. As of 2015, infections had been reported as far west as Lithuania, Latvia and Poland. Viruses that apparently originated from this outbreak have also been found in wild boar in the Middle East (Iran).
http://www.cfsph.iastate.edu/Factsheets/pdfs/african_swine_fever.pdf
Black Death plague escalates as DOCTORS struck down by lethal disease sweeping Madagascar
https://www.dailystar.co.uk/news/latest-news/660252/black-death-plague-doctors-madagascar-latest-news-update-disease
"This article aims to discuss the social factors associated with brucellosis and African swine fever (ASF) in Sri Lanka and Madagascar, respectively. In 2016, cross-sectional surveys were conducted in both countries. On the basis of the results of these surveys, we describe how brucellosis is more prevalent in certain ethnicities than others in Sri Lanka. Furthermore, in Madagascar, fihavanana, a social norm, encourages farmers to buy ASF-contaminated meat, resulting in ASF spread during outbreaks."
https://juniperpublishers.com/jdvs/pdf/JDVS.MS.ID.555555.pdf
"African Swine Fever Virus has devastated more than the half of the domestic pig population in Madagascar since its introduction, probably in 1997-1998. One of the hypotheses to explain its persistence on the island is its establishment in local Ornithodoros soft ticks, whose presence has been reported in the past from the north-western coast to the Central Highlands. The aim of the present study was to verify such hypothesis by conducting tick examinations in three distinct zones of pig production in Madagascar where African Swine Fever outbreaks have been regularly reported over the past decade and then to improve our knowledge on the tick distribution and taxonomy."
African swine fever is endemic in most of sub-Saharan Africa including the island of Madagascar. Outbreaks have been reported periodically outside Africa. The virus was eventually eradicated in most cases, although it remains endemic on the island of Sardinia (Italy) in the Mediterranean. In 2007, ASFV was introduced into the Caucasus region of Eurasia, via the Republic of Georgia, and it has spread to domesticated pigs and/or wild boars in a number of countries in this region. As of 2015, infections had been reported as far west as Lithuania, Latvia and Poland. Viruses that apparently originated from this outbreak have also been found in wild boar in the Middle East (Iran).
http://www.cfsph.iastate.edu/Factsheets/pdfs/african_swine_fever.pdf
Black Death plague escalates as DOCTORS struck down by lethal disease sweeping Madagascar
https://www.dailystar.co.uk/news/latest-news/660252/black-death-plague-doctors-madagascar-latest-news-update-disease
CDC disputes Woodrow Wilson Center blog by Alex Long that says ASFV can in infect humans
We received this e-mail from the CDC:
"Climate change as well as human overpopulation and industry have drastically altered environments and changed the population dynamics. These changes are important to understanding new ecosystem interactions but are largely ignored by the organizations tasked with zoonosis research. Organizations, like the previously mentioned One Health, are looking at specific zoonotic diseases like Rift Valley Fever, African Swine Fever, or Zika. But what they are not always doing is monitoring the general environment around the disease vectors. Without sufficient evidence that a species or area is under the threat of a disease, these organizations redirect their resources to locations of high risk."
https://www.wilsoncenter.org/blog-post/zoonotic-diseases-and-the-possibilities-ebv-monitoring
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
" . .. further study is needed to characterize their potential risks to both public health and agricultural development."
http://link.springer.com/article/10.1007%2Fs11262-013-0878-2
http://vir.sgmjournals.org/content/34/3/455.short
More evidence that African Swine Fever is a human infection and connected to HHV-6?
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
Not aware of any evidence to suggest African Swine Fever (ASF) infects humans. Here is some additional info that maybe helpful.
Thanks,
Tom Skinner
CDC
The Woodrow Wilson Center blog:
The Woodrow Wilson Center blog:
"Climate change as well as human overpopulation and industry have drastically altered environments and changed the population dynamics. These changes are important to understanding new ecosystem interactions but are largely ignored by the organizations tasked with zoonosis research. Organizations, like the previously mentioned One Health, are looking at specific zoonotic diseases like Rift Valley Fever, African Swine Fever, or Zika. But what they are not always doing is monitoring the general environment around the disease vectors. Without sufficient evidence that a species or area is under the threat of a disease, these organizations redirect their resources to locations of high risk."
https://www.wilsoncenter.org/blog-post/zoonotic-diseases-and-the-possibilities-ebv-monitoring
John Beldekas
(Photo by Jane Teas)
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
http://www.keephopealive.org/report10.html
Russian Scientist: ASF could become a human health risk
"The African swine fever (ASF) virus, may in the future become
dangerous for humans, according to the head of the Russian Epidemiology
Service, Chief State Sanitary Doctor Gennady Onishchenko, at the
press-conference in St. Petersburg. According to him almost all viruses
from time to time go through mutation processes which can give them some
additional functions."
http://www.pigprogress.net/Health-Diseases/Outbreaks/2013/7/ASF-could-become-a-human-health-risk-1308047W/
Background on African Swine Fever Virus as a human pathogen:
"African Swine fever is an endemic disease in sub-Saharan Africa and
many other parts of the developing world. It is caused by the African
Swine virus that primarily replicates in macrophages and monocytes
leading to the impairment of the structure and function of the immune
system of the infected organisms. Until now the African Swine epidemic
continues to spread despite all efforts to contain it. Thus, there is
an objective need for effective, safe and affordable preventive and
therapeutic approaches, in particular for effective vaccines, to
control and eventually eradicate this disease. Since the characteristic
feature of the African Swine virus is to impair the immune system and
to cause immune deficiencies in its hosts the development of vaccines
and other therapeutic approaches against the African Swine virus has
implications for other immune deficiencies or diseases. Several other
viruses are also known to cause immunodeficiency-like syndromes in
humans, including cytomegalovirus, Epstein Barr Virus
and others. Moreover, a series of cases of so-called "idiopathic"
immunodeficiencies have been documented that display
CD4+T-lymphocytopenia with opportunistic infections, but show no
evidence of HIV infection. Since antibodies for the African Swine virus
have been detected in humans, the possibility of human infection with
the African Swine virus exists and may thus far have escaped any systematic screening. Thus, any preventive and therapeutic approach to African Swine fever can have far-reaching implications to control immune deficiency conditions in humans."http://www.faqs.org/patents/app/20080207875
Detection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
http://www.ncbi.nlm.nih.gov/pubmed/19812170?dopt=AbstractDetection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
African Swine Fever Virus (Asfarviridae) sequences found in people with febrile illnesses
Abstract
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
Dengue virus is an emerging infectious agent that infects an estimated
50–100 million people annually worldwide, yet current diagnostic
practices cannot detect an etiologic pathogen in ∼40% of dengue-like
illnesses. Metagenomic approaches to pathogen detection, such as viral
microarrays and deep sequencing, are promising tools to address
emerging and non-diagnosable disease challenges. In this study, we
used the Virochip microarray and deep sequencing to characterize the
spectrum of viruses present in human sera from 123 Nicaraguan patients
presenting with dengue-like symptoms but testing negative for dengue
virus. We utilized a barcoding strategy to simultaneously deep
sequence multiple serum specimens, generating on average over 1
million reads per sample. We then implemented a stepwise bioinformatic
filtering pipeline to remove the majority of human and low-quality
sequences to improve the speed and accuracy of subsequent unbiased
database searches. By deep sequencing, we were able to detect virus
sequence in 37% (45/123) of previously negative cases. These included
13 cases with Human Herpesvirus 6 sequences. Other samples contained
sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae
families. In some cases, the putative viral sequences were virtually
identical to known viruses, and in others they diverged, suggesting
that they may derive from novel viruses. These results demonstrate the
utility of unbiased metagenomic approaches in the detection of known
and divergent viruses in the study of tropical febrile illness.
Detection of African swine fever virus-like sequences in ponds in the Mississippi Delta through metagenomic sequencing
http://link.springer.com/article/10.1007%2Fs11262-013-0878-2
ASF virus, adapted to grow in VERO cells, produces a strong cytopathic effect in human macrophages leading to cell destruction.
More evidence that African Swine Fever is a human infection and connected to HHV-6?
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
Wednesday, November 15, 2017
Breaking News: The Woodrow Wilson International Center for Scholars calls ASFV a zoonotic disease.
"Climate change as well as human overpopulation and industry have drastically altered environments and changed the population dynamics. These changes are important to understanding new ecosystem interactions but are largely ignored by the organizations tasked with zoonosis research. Organizations, like the previously mentioned One Health, are looking at specific zoonotic diseases like Rift Valley Fever, African Swine Fever, or Zika. But what they are not always doing is monitoring the general environment around the disease vectors. Without sufficient evidence that a species or area is under the threat of a disease, these organizations redirect their resources to locations of high risk."
https://www.wilsoncenter.org/blog-post/zoonotic-diseases-and-the-possibilities-ebv-monitoring
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
https://www.wilsoncenter.org/blog-post/zoonotic-diseases-and-the-possibilities-ebv-monitoring
John Beldekas
(Photo by Jane Teas)
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
http://www.keephopealive.org/report10.html
Tuesday, November 14, 2017
"Organizations, like the previously mentioned One Health, are looking at specific zoonotic diseases like Rift Valley Fever, African Swine Fever, or Zika."
https://www.wilsoncenter.org/blog-post/zoonotic-diseases-and-the-possibilities-ebv-monitoring
Is African Swine Fever now considered a zoonotic disease?
Were these scientists right about African Swine Fever 31 years ago?
http://www.nytimes.com/1986/09/23/science/no-swine-fever-link-to-aids-seen.html
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
Is African Swine Fever now considered a zoonotic disease?
Were these scientists right about African Swine Fever 31 years ago?
http://www.nytimes.com/1986/09/23/science/no-swine-fever-link-to-aids-seen.html
John Beldekas
(Photo by Jane Teas)
"In August, 1986, John Beldekas was invited to go to the NCI and present his findings on the link between ASFV [African Swine Fever virus] and AIDS, which he did. Beldekas gave samples of all his lab work to Gallo. Later, the government asked Beldekas to turn over all his reagents and lab work to the government, which he did. Beldekas had found ASFV presence in nine of 21 AIDS patients using two standard procedures. At the meeting, Gallo was reported saying: “we know it is not ASFV.” How could Gallo know this as he hadn’t done any of his own tests to look for ASFV?
Two months later, Gallo published an article in Science (Oct 31, 1986) that he discovered a new possible co-factor in AIDS, a virus he called Human B Cell Lymphotropic Virus which he named HBLV. Like ASFV, HBLV infected B cells and also lived in macrophages. Did Gallo steal Beldekas’s ASF virus he found in AIDS patients and rename it HBLV? Later on, when Gallo found that HBLV could also infect other immune cells, he changed the name of HBLV to HHV-6. Eventually, Gallo identified his HBLV as the variant A strain of HHV-6 and called it a human herpesvirus."
--Mark Konlee
http://www.keephopealive.org/report10.html
Friday, November 10, 2017
Thursday, November 9, 2017
Friday, November 3, 2017
Risk of African Swine Fever increases in England
http://www.smallholder.co.uk/news/15630203.Risk_of_African_Swine_Fever_raised/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
" . .. further study is needed to characterize their potential risks to both public health and agricultural development."
http://link.springer.com/article/10.1007%2Fs11262-013-0878-2
http://vir.sgmjournals.org/content/34/3/455.short
More evidence that African Swine Fever is a human infection and connected to HHV-6?
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
Russian Scientist: ASF could become a human health risk
"The African swine fever (ASF) virus, may in the future become
dangerous for humans, according to the head of the Russian Epidemiology
Service, Chief State Sanitary Doctor Gennady Onishchenko, at the
press-conference in St. Petersburg. According to him almost all viruses
from time to time go through mutation processes which can give them some
additional functions."
http://www.pigprogress.net/Health-Diseases/Outbreaks/2013/7/ASF-could-become-a-human-health-risk-1308047W/
Background on African Swine Fever Virus as a human pathogen:
"African Swine fever is an endemic disease in sub-Saharan Africa and
many other parts of the developing world. It is caused by the African
Swine virus that primarily replicates in macrophages and monocytes
leading to the impairment of the structure and function of the immune
system of the infected organisms. Until now the African Swine epidemic
continues to spread despite all efforts to contain it. Thus, there is
an objective need for effective, safe and affordable preventive and
therapeutic approaches, in particular for effective vaccines, to
control and eventually eradicate this disease. Since the characteristic
feature of the African Swine virus is to impair the immune system and
to cause immune deficiencies in its hosts the development of vaccines
and other therapeutic approaches against the African Swine virus has
implications for other immune deficiencies or diseases. Several other
viruses are also known to cause immunodeficiency-like syndromes in
humans, including cytomegalovirus, Epstein Barr Virus
and others. Moreover, a series of cases of so-called "idiopathic"
immunodeficiencies have been documented that display
CD4+T-lymphocytopenia with opportunistic infections, but show no
evidence of HIV infection. Since antibodies for the African Swine virus
have been detected in humans, the possibility of human infection with
the African Swine virus exists and may thus far have escaped any systematic screening. Thus, any preventive and therapeutic approach to African Swine fever can have far-reaching implications to control immune deficiency conditions in humans."http://www.faqs.org/patents/app/20080207875
Detection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
http://www.ncbi.nlm.nih.gov/pubmed/19812170?dopt=AbstractDetection of Novel Sequences Related to African Swine Fever Virus in Human Serum and Sewage.
Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, Girones R, Wang D, Virgin HW.
Departments of Pathology & Immunology and Molecular Microbiology, Department of Medicine and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
"The family Asfarviridae contains only a single virus species, African swine fever virus (ASFV). ASFV is a viral agent with significant economic impact due to its devastating effects on populations of domesticated pigs during outbreaks, but has not been reported to infect humans. We report here the discovery of novel viral sequences in human serum and sewage which are clearly related to the Asfarvirus family, but highly divergent from ASFV. Detection of these sequences suggests that greater genetic diversity may exist among Asfarviruses than previously thought, and raises the possibility that human infection by Asfarviruses may occur."
African Swine Fever Virus (Asfarviridae) sequences found in people with febrile illnesses
Abstract
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
Dengue virus is an emerging infectious agent that infects an estimated
50–100 million people annually worldwide, yet current diagnostic
practices cannot detect an etiologic pathogen in ∼40% of dengue-like
illnesses. Metagenomic approaches to pathogen detection, such as viral
microarrays and deep sequencing, are promising tools to address
emerging and non-diagnosable disease challenges. In this study, we
used the Virochip microarray and deep sequencing to characterize the
spectrum of viruses present in human sera from 123 Nicaraguan patients
presenting with dengue-like symptoms but testing negative for dengue
virus. We utilized a barcoding strategy to simultaneously deep
sequence multiple serum specimens, generating on average over 1
million reads per sample. We then implemented a stepwise bioinformatic
filtering pipeline to remove the majority of human and low-quality
sequences to improve the speed and accuracy of subsequent unbiased
database searches. By deep sequencing, we were able to detect virus
sequence in 37% (45/123) of previously negative cases. These included
13 cases with Human Herpesvirus 6 sequences. Other samples contained
sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae
families. In some cases, the putative viral sequences were virtually
identical to known viruses, and in others they diverged, suggesting
that they may derive from novel viruses. These results demonstrate the
utility of unbiased metagenomic approaches in the detection of known
and divergent viruses in the study of tropical febrile illness.
Detection of African swine fever virus-like sequences in ponds in the Mississippi Delta through metagenomic sequencing
http://link.springer.com/article/10.1007%2Fs11262-013-0878-2
ASF virus, adapted to grow in VERO cells, produces a strong cytopathic effect in human macrophages leading to cell destruction.
More evidence that African Swine Fever is a human infection and connected to HHV-6?
Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3274504/
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