Tuesday, March 19, 2024

Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic

Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic


Liam Quinn Jerome Whitfield Michael P. Alpers John Collinge 6 Garrett Hellenthal 6 Simon Mead 6

Open Access Published: March 19, 2024


Summary

Populations of the Eastern Highlands of Papua New Guinea (EHPNG, area 11,157 km2) lived in relative isolation from the rest of the world until the mid-20th century, and the region contains a wealth of linguistic and cultural diversity. Notably, several populations of EHPNG were devastated by an epidemic prion disease, kuru, which at its peak in the mid-twentieth century led to some villages being almost depleted of adult women. Until now, population genetic analyses to learn about genetic diversity, migration, admixture, and the impact of the kuru epidemic have been restricted to a small number of variants or samples. Here, we present a population genetic analysis of the region based on genome-wide genotype data of 943 individuals from 21 linguistic groups and 68 villages in EHPNG, including 34 villages in the South Fore linguistic group, the group most affected by kuru. We find a striking degree of genetic population structure in the relatively small region (average FST between linguistic groups 0.024). The genetic population structure correlates well with linguistic grouping, with some noticeable exceptions that reflect the clan system of community organization that has historically existed in EHPNG. We also detect the presence of migrant individuals within the EHPNG region and observe a significant excess of females among migrants compared to among non-migrants in areas of high kuru exposure (p = 0.0145, chi-squared test). This likely reflects the continued practice of patrilocality despite documented fears and strains placed on communities as a result of kuru and its associated skew in female incidence.

Snip…

Discussion

We have presented an in-depth study of the population structure of a remote highland region of PNG, based on a dataset that includes most of the linguistic groups and extensive sampling by village, affording a level of resolution that has not previously been possible. We show that despite covering an area of only 11,157 km2, roughly the size of the island of Jamaica, the genetic differentiation between linguistic groups in the EHPNG region is strikingly high (maximum FST = 0.066, average FST = 0.024, average distance 45 km). This differentiation is comparable to that previously reported for the entire PNG Highlands region,19 of which EHPNG is only a small sub-region. Furthermore, our analyses reveal the presence of complex population structure even at dialect and village level. While of interest for understanding the origins of modern populations, these findings also provide the background for study of the genetic impact of the large-scale prion disease epidemic, kuru.

A key question is what factors have contributed to such strong population structure in such a small region. One possible factor is that while the Western Highlands had optimal conditions for taro cultivation, which originated there, whereas the conditions were suboptimal in EHPNG.10 Indeed, some groups in EHPNG have been described as having been “proto-agriculturalists” retaining elements of hunter-gatherer subsistence in their lifestyles.10 Analogous to other hunter-gatherer groups, most EHPNG linguistic groups have greatly reduced population densities compared to other highland regions1 and lower historical effective population sizes.19 These reduced population densities have likely led to increased effects of genetic drift between groups.

In addition to geography, overall broad-scale population structure correlates with linguistics. For example, the best estimated linguistic tree for these groups analyzed shows the Pawaian and Anga as outgroups (Figure 1C), echoing the genetic analysis. We even see examples of fine-scale parallels between linguistic and genetic differences in the Fore dialect groups. However, the correlation between linguistic groupings and geographical regions makes it difficult to disentangle the relative role of these two factors. When more linguistic data become available for these populations in the future, approaches that quantitatively explore these relationships will add greatly to our understanding of these dynamics.

The colonial era definition of linguistic groups, which has been used in previous genetic studies, does not always satisfactorily describe population structure in the region. For example, linguistic groups are barely distinguishable from one another genetically in the northwest of EHPNG. This relative homogeneity may be due to more intensely practised agriculture and higher population densities in this sub-region,35 where the geography is different, with wide valleys in contrast to the highly dissected terrain in the southeast. Furthermore, in the village-level analyses of the Fore, we found genetic affinity of some villages to be closer to non-Fore groups. This observation is not completely surprising, as it is well understood that the clan structure of political, economic, and social unions that comprised the pre-colonial landscape in EHPNG often spanned linguistic group boundaries. This observed signature (for example as observed with Ilesa in the South Fore, Figure 3) could also be the result of a village founding event when a whole village is uprooted (e.g., due to conflict) and moves considerable distance to new territory, with members acquiring the language of their new residence. Such founding events in the past have been observed in the anthropological record within EHPNG.12

Several analyses revealed the presence of recent long-distance migration in the region. For instance, we found three potential migrants from the Fore linguistic group into the Pawaian (Figure 1A). One individual moved to the Pawaian linguistic area after marrying into a family there. However, marriages across the Fore/Pawaian divide are believed to be very rare or possibly nonexistent in pre-European-contact times, due to the considerable barriers of endemic warfare and extreme terrain. Consistent with this we found that all three observed migrants were born after European contact (although these individuals may be the descendants of migrants), which resulted in a cessation of warfare and the development of transport infrastructure which may have facilitated these movements. Hence it is possible that such long-distance migration is a recent phenomenon, consistent with the two groups being so genetically distant.

A final example demonstrating that analysis of population structure using linguistic group labels is not fully satisfactory was where we observed a clear resolution of village differences based on South Fore dialect spoken within the linguistic group (Figure 3C). This suggests that pooling all South Fore into a single population may not adequately capture population structure, though in this case the small genetic difference does correlate with a small linguistic one. Certainly, it reveals the dynamic and ongoing processes of cultural and demographic change that has been unfolding in the region. Given the small genetic differences between the fineStructure clusters that represent the two dialect groups, the small geographic differences between different dialect villages, and the fact that marital exchange and migration was known to occur between villages across the dialect divide, it is likely that such a split was recent in origin. This echoes oral origin histories held among the Fore that details the expansion and fragmentation of the Fore people into the three distinct dialect groups.

One of the population structure patterns that very clearly follows the linguistic groupings is that the Anga and Pawaian linguistic groups appear highly genetically distant not only from all other groups, but also from each other. Clusters comprising these groups had highest genetic similarity with groups outside of EHPNG, rather than EHPNG neighbors, in contrast to all other EHPNG clusters except a cluster of northwest individuals (EHPNG cluster 10) who were genetically related to the neighboring Chimbu. In the case of the Pawaian, the inferred closest ancestry source was the southern Kiwai, a coastal population more than 300 km from EHPNG. Interestingly, the Pawaian linguistic group is known to live semi-nomadically in forests at lower elevations and lower population densities than the rest of the region,1 which may in itself explain why they have ended up somewhat genetically distinct from the rest of the EHPNG groups. The oral histories held by the Pawaian speak of originating from coastal regions and undertaking long migrations through uninhabited forest regions.26

Our results do not support significant genetic influence on EHPNG populations other than the Anga and Pawaian from outside of the PNG highlands. In particular, unlike in many other regions of the world that have been colonized by countries with people of European descent,36 we found no clear signs of European ancestry in EHPNG individuals (Figure S5). And while we did in our ADMIXTURE analyses observe some signatures that are consistent with a few individuals having a small amount of admixture with people of East Asian ancestry, this could just as well be caused by other PNG populations not being represented in those analyses.19 Our findings of support previously suggested population histories1,19 with an expansion of groups (“neolithic expansion”) emanating from the Western Highlands as a result of the development of taro agriculture and displacement of previous groups that lived there, possibly ancestral to the Anga who have greatly distinct ancestry profiles in our analyses and who now live in the southern fringes of the region. In fact “Anga-like” artifacts, believed to be ancient, have been found as far north as in the Kamano linguistic group, reflecting a more widely dispersed settlement in the region.1

Our observation of recent migrant individuals in multiple analyses allowed the examination of the impact of kuru on migration dynamics in the region. While we observed a higher proportion of females among migrants relative to non-migrants throughout EHPNG, likely due to the general practice of patrilocality, the largest and only significant skew toward female migrants was observed in areas of high kuru incidence. This observation is consistent with accounts from the region that notes during the epidemic the near absence of adult women in villages with high kuru incidence.24 Men would frequently marry multiple times as a result of their previous wives dying from kuru, and strains were also placed on communities as a result of increased child care burden.23 Thus it seems plausible that the need to replace lost adult women and mitigate the impact of kuru on Fore society could have led to an excessive inflow of recent female migrants into villages with high kuru incidence. However, we note that previously the opposite has been reported: that kuru led to a decrease or even a complete cessation of intermarriages between the Fore and neighboring communities, because those communities linked kuru to sorcery, which made them fearful of the Fore.37 In our data, we observed no evidence either for less overall migration into areas with high kuru incidence or for a stop of patrilocal practices in these areas. On the contrary, we observed a significant bias toward females among migrants into high kuru incidence areas. Moreover, the observed difference in the proportion of females among migrants versus migrants is ∼25% higher in the “high” incidence kuru areas relative to the “zero/low” kuru incidence areas. While this difference was not statistically significant using the data here, it may reflect kuru causing a sex bias beyond that driven by patrilocal practices. We note that our approach considers only genetically distinct individuals to be migrants. This means we are also counting migrants that came from greater distances away than would have typically been the case for marital exchange. Hence, it is possible that bachelors within highly kuru-affected communities have sought wives from further afield than usual due to the lack of availability of potential wives more locally and that this led to the observed sex-bias in migration in the high kuru incidence areas. However, additional data and analyses are necessary to validate this. What our current data and analyses do suggest is that there was sex-biased migration into the high-kuru areas despite documented fears and strains placed on communities as a result of kuru.

In summary, our results suggest that the observed population structure is not driven by admixture from outside the highland PNG region, which is consistent with the historical record of the EHPNG region being isolated until recently. Also, while the population structure does to some extent mimic the linguistic groupings in the area, we observe several patterns of population structure that suggest that the different linguistic groups are not entirely genetically distinct and isolated from each other. This is consistent with previous knowledge of clans playing a key role in the cultural grouping in the area and of the presence of cultural features that aided possible migration between neighboring linguistic groups in the region. Finally, we observed signs that long-distance migration has taken place, likely in more recent times. Importantly this, in combination with the understanding of population structure, has permitted an analysis of sex-biased flows of migration that are likely to have been impacted by kuru. This highlights that it is essential to understand the population structure of a region prior to attempting to investigate hypotheses regarding the impact of epidemics on affected populations.

The population structure of EHPNG reveals a complex multi-layered set of factors that have caused high population differentiation, likely including both geographic and cultural factors. Furthermore, it suggests that the current population structure may still be evolving. Overall our results demonstrate that simplistic descriptions of the population structure in regions like EHPNG based on linguistic groupings presumed to be static are likely to neglect the far richer texture of dynamic forces and history that has shaped communities.



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Tuesday, March 9, 2021

Use of modern population genetic techniques to investigate the effects of the epidemic of kuru, a unique prion disease in the Papua New Guinea highlands

 247. Use of modern population genetic techniques to investigate the effects of the epidemic of kuru, a unique prion disease in the Papua New Guinea highlands 


Liam Quinna, Jerome Whitfielda, Garrett Hellenthalb, Michael Alpersc,d, John Collingea, and Simon Meada

aMRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, UK; bDepartment Genetics, Evolution & Environment, University College London; cCentre for International Health, Curtin University, Perth, Australia; dPapua New Guinea Institute of Medical Research, Goroka, Papua New Guinea

CONTACT Liam Quinn l.quinn@prion.ucl.ac.uk; Jerome Whitfield j.whitfield@prion.ucl.ac.uk

ABSTRACT

Background: Kuru was the first observed and to this day remains the largest human prion disease epidemic. It devastatingly affected the Fore linguistic and nearby groups in the Papua New Guinea (PNG) highlands. The condition was transmitted by consumption of prion infected material at mortuary rituals. Over the first 20 documented years of the epidemic ~2,400 people died from kuru in communities with populations of ~40,000 individuals. The Eastern Highlands of Papua New Guinea where the Fore speaking communities reside is marked for its cultural and linguistic diversity. During the kuru epidemic the region was undergoing a marked transition with European contact and colonial administration. These factors present challenges to further understanding the population response to kuru specifically and approaches to find novel variants that affected disease predisposition.

Materials and Methods: We analysed a unique genome wide array dataset of 1,513 individuals from the affected communities from 22 linguistic groups and 50 across the Eastern Highlands of PNG. We used population genetic techniques including Chromopainter analysis and fineStructure clustering to understand the population structure of the region, analyse patterns of gene flow and migration, tested for evidence of historical admixture events and evidence of genetic signatures of the impact of kuru on the Fore region including the marked sex bias in cases observed during the epidemic.

Results: We find a strong population structure with Principal Component Analysis and fineStructure clustering showing a strong tendency for individuals to cluster with individuals from the same linguistic grouping. Mean FST values observed in the Eastern Highlands were 0.02, far greater than those observed in the United Kingdom (0.0007) reflecting the degree of distinction between groups. Although we find that linguistic group membership explains many aspects of population structure we also find that topographical features and cultural differences also exert strong forces. Gene flow between linguistic groups is evident with the presence of individuals reflecting historical processes of short and long distance migration.

Conclusion: We show that the affected populations have displayed remarkable resilience with no perceptible derivation in population genetic parameters overall despite facing such an existential threat. The marked population structure in the region and processes of gene flow present challenges for ongoing investigations into the genetic response and genetic architecture of kuru disease.

KEYWORDS: Kuru; population genetics; natural selection; genetic epidemiology




TSS

Wednesday, April 15, 2015

KURU Transmissible Spongiform Encephalopthy TSE Prion Disease

KURU Transmissible Spongiform Encephalopthy TSE Prion Disease


*** Kuru Video


Kuru: The Science and The Sorcery




*** Scrapie Video

https://histodb11.usz.ch/Images/videos/video-011/video-011.html


*** Human Mad Cow Video

https://histodb11.usz.ch/Images/videos/video-009/video-009.html


*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video




2014


***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.


***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.


*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].


snip...




Monday, October 10, 2011


EFSA Journal 2011 The European Response to BSE: A Success Story


snip...


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far


*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded.


*** Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


snip...






Thursday, August 12, 2010


Seven main threats for the future linked to prions


First threat


The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.


*** Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.


*** These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.


Second threat


snip...




*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO










Tuesday, December 16, 2014


Evidence for zoonotic potential of ovine scrapie prions


Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics


Abstract


Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.


Subject terms: Biological sciences• Medical research At a glance




why do we not want to do TSE transmission studies on chimpanzees $


5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.


snip...


R. BRADLEY




Suspect symptoms


What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?


28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.


Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.


"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...


2001


Suspect symptoms


What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?


28 Mar 01


Like lambs to the slaughter


31 March 2001


by Debora MacKenzie Magazine issue 2284.


FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.


Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.


Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.


"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.


Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.


Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.


As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.


"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.


But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.


People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.


But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."


There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.


Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.




Thursday, March 20, 2014


CHRONIC WASTING DISEASE CWD TSE PRION OF CERVID AND THE POTENTIAL FOR HUMAN TRANSMISSION THEREFROM 2014




Tuesday, July 01, 2014


*** CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND POTENTIAL RISK FACTORS THERE FROM ***




Thursday, July 03, 2014


*** How Chronic Wasting Disease is affecting deer population and what’s the risk to humans and pets? ***




Thursday


CWD TO HUMANS, AND RISK FACTORS THERE FROM (see latest science)


Tuesday, November 04, 2014


*** Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011




Friday, January 30, 2015


*** Scrapie: a particularly persistent pathogen ***




Sunday, April 12, 2015


*** Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies 2014 Annual Report ***




Saturday, April 11, 2015


*** ISU veterinary researchers study retinal scans as early detection method for mad cow disease




Sunday, November 23, 2014


*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***




Monday, November 3, 2014


USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014


National Prion Disease Pathology Surveillance Center Cases Examined1 (October 7, 2014)


***6 Includes 11 cases in which the diagnosis is pending, and 19 inconclusive cases;


***7 Includes 12 (11 from 2014) cases with type determination pending in which the diagnosis of vCJD has been excluded.


***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob disease (sCJD),


***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)


***and 21 cases of sporadic Fatal Insomnia (sFI).




Thursday, January 15, 2015


41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report




Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type disease


what is CJD ? just ask USDA inc., and the OIE, they are still feeding the public and the media industry fed junk science that is 30 years old.


why doesn’t some of you try reading the facts, instead of rubber stamping everything the USDA inc says.


sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and there is much concern now for CWD and risk factor for humans.


My sincere condolences to the family and friends of the House Speaker Becky Lockhart. I am deeply saddened hear this.


with that said, with great respect, I must ask each and every one of you Politicians that are so deeply saddened to hear of this needless death of the Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am seriously going to ask you all this...I have been diplomatic for about 17 years and it has got no where. people are still dying. so, are you all stupid or what??? how many more need to die ??? how much is global trade of beef and other meat products that are not tested for the TSE prion disease, how much and how many bodies is this market worth?


Saturday, January 17, 2015


*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease




*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report ***




Tuesday, November 04, 2014


Towards an Age-Dependent Transmission Model of Acquired and Sporadic Creutzfeldt-Jakob Disease




Thursday, January 22, 2015


Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?






Sunday, July 06, 2014


Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study


Conclusions—The a priori hypotheses were supported.


*Consumption of various meat products may be one method of transmission of the infectious agent for sCJD.




PLEASE REMEMBER ;


The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.


HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???


if not, why not...


Friday, November 30, 2007


CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION






Friday, January 10, 2014


vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???






Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease


Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014




Singeltary comment ;




Saturday, December 13, 2014


Terry S. Singeltary Sr. Publications TSE prion disease


Diagnosis and Reporting of Creutzfeldt-Jakob Disease


Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA


snip...





TSS

Monday, October 28, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility

 we are (in my opinion), exposed to the TSE prion in so many different ways in every day life, the potential for exposure and then becoming infected via taking care of a loved one with TSE prion disease, in my opinion risk factor there from is minimal, if proper precautions are taken, and even if they were not, the chance of becoming infected from a kiss, or casual contact is low, but I do not think it is zero, actually, far from it. I put this all together for a documentation of the known facts to date, of the potential casual human to human transmission. I did not put it together to scare anyone. with aerosol transmission of the TSE prion a reality now, infectivity in urine and feces and transmission there from being reality now with the TSE prion disease, I don’t see how anyone can rule _out_ the potential for transmission of the TSE prion via a kiss (a vehicle for transmission of the TSE prion via saliva), or even for a cut or open wound (all a cut is and transmission there from, is an crude inoculation of sorts, and inoculation has been proven to be an efficient mode of transmission for the TSE prion disease), even the eye, from either one of the body fluids now that how proven to be infections. I can’t see why we have such safety protocols for laboratory workers working with the TSE prion disease, but yet the same officials will say it’s o.k. for the public, friends, and or family members to do just the opposite with their loved ones when succumbing to the CJD TSE prion disease. don’t get me wrong, I did it too, and would probably do it again as far as kissing my mom. but science is science, and the transmission studies speak for themselves with the bodily fluids. simply put, which is all I was saying, we can’t say never, and or that none of these cases to date, have not been, and or will not be, a potential vehicle for transmission. I believe, and this is my opinion, that more concern for casual transmission with body fluids and materials there from, should be put forth to families with their loved ones, and I think that the safety protocols there from should be revised, to match that of the laboratory settings. again, this is my opinion. your opinion, and or others here, may read the same science and feel different out the findings. ...take care, kind regards, terry

SUBSTANCE DATA SHEET

HUMAN PRION AGENTS


FOR USE IN RESEARCH LABORATORIES


SECTION I - INFECTIOUS AGENT


Name: Creutzfeldt-Jakob agent, Kuru agent


Synonym or Cross Reference:: Subacute spongiform encephalopathy, Creutzfeldt-Jakob disease (CJD), Kuru, Transmissible Spongiform Encephalopathy (TSE).


Characteristics: Filterable, self-replicating agent, slow infectious pathogen, prion protein (PrP)


SECTION II - RECOMMENDED PRECAUTIONS


Containment Requirements: Biosafety level 3 facilities, practices and containment equipment for activities involving these agents; also listed under biosafety level 2 with special precautions; level of containment will depend on the nature of the manipulations and the amount of sera, bio/necropsy materials handled


Protective Clothing: Gown and gloves when handling potentially infectious materials; eye protection may also be indicated


Other Precautions: Extreme care must be taken to avoid accidental autoinoculation or other parenteral inoculations of infectious tissues and fluids


SECTION III - HANDLING INFORMATION


Spills: Allow any potential aerosols to settle; wearing protective clothing, gently cover spill with paper towel and apply 1N sodium hydroxide, starting at perimeter and working towards the center; allow sufficient contact time (1 hour) before clean up


Disposal: Decontaminate before disposal; steam sterilization (132·C for 1 hour), disinfection with 1N sodium hydroxide for 1 hour, incineration


Storage: In sealed containers that are appropriately labeled




The main precaution to be taken by laboratorians working with prion-infected or contaminated material is to avoid accidental puncture of the skin.3 Persons handling contaminated specimens should wear cut-resistant gloves if possible. If accidental contamination of unbroken skin occurs, the area should be washed with detergent and abundant quantities of warm water (avoid scrubbing); brief exposure (1 minute to 1N NaOH or a 1:10 dilution of bleach) can be considered for maximum safety.6 Additional guidance related to occupational injury are provided in the WHO infection control guidelines.6 Unfixed samples of brain, spinal cord, and other tissues containing human prions should be processed with extreme care in a BSL-2 facility utilizing BSL-3 practices.


Bovine Spongiform Encephalopathy Although the eventual total number of variant CJD cases resulting from BSE transmission to humans is unknown, a review of the epidemiological data from the United Kingdom indicates that BSE transmission to humans is not efficient.9 The most prudent approach is to study BSE prions at a minimum in a BSL-2 facility utilizing BSL-3 practices. When performing necropsies on large animals where there is an opportunity that the worker may be accidentally splashed or have contact with high-risk materials (e.g., spinal column, brain) personnel should wear full body coverage personal protective equipment (e.g., gloves, rear closing gown and face shield). Disposable plasticware, which can be discarded as a dry regulated medical waste, is highly recommended. Because the paraformaldehyde vaporization procedure does not diminish prion titers, BSCs must be decontaminated with 1N NaOH and rinsed with water. HEPA filters should be bagged out and incinerated. Although there is no evidence to suggest that aerosol transmission occurs in the natural disease, it is prudent to avoid the generation of aerosols or droplets during the manipulation of tissues or fluids and during the necropsy of experimental animals. It is further strongly recommended that impervious gloves be worn for activities that provide the opportunity for skin contact with infectious tissues and fluids.




The main precaution to be taken when working with prion-infected or contaminated material is to avoid puncture of the skin. If accidental contamination of skin occurs, the area is swabbed with In sodium hydroxide (NaOH) for 5 minutes and then washed with copious amounts of water. Unfixed samples of brain, spinal cord, and other tissues containing human prions should be processed with extreme care at BSL 3.


Prions are characterized by extreme resistance to conventional inactivation procedures including irradiation, boiling, dry heat, and chemicals (formalin, betapropiolactone, alcohols). Sterilization of rodent brain extracts with high titers of prions requires autoclaving at 132C for 4.5 hours. Denaturing organic solvents such as phenol or chaotropic reagents such as guanidine isothiocyanate or alkali such as NaOH can also be used for sterilization. Disposable plasticware, which can be discarded as a dry waste, is highly recommended.


Although there is no evidence to suggest that aerosol transmission occurs in the natural disease, it is prudent to avoid the generation of aerosols or droplets during the manipulation of tissues or fluids and during the necropsy of experimental animals. Formaldehyde-fixed and paraffin-embedded tissues, especially of the brain, remain infectious. Some investigators recommend that formalin-fixed tissues from suspected cases of prion disease be immersed for 30 min in 96% formic acid or phenol before histopathologic processing, but such treatment may severely distort the microscopic neuropathology.




another interesting aspect of the TSE prion disease is KURU ;


Figure 25. All cooking. including that of human flesh from diseased kinsmen. was done in pits with steam made by pouring water over the hot stones, or cooked in bamboo cylinders in the hot ashes. Children participated in both the butchery and the handling of cooked meat, rubbing their soiled hands in their armpits or hair, and elsewhere on their bodies. They rarely or never washed. Infection with the kuru virus was most probably through the cuts and abrasions of the skin. or from nose-picking, rye (eye...tss) rubbing, or mucosal injury.



These detailed descriptions will be published elsewhere but have reaffirmed the oral histories of endocannibalism in the Fore recorded previously12,22–24 and that this practice ceased abruptly at the time of Australian administrative control over the kuru areas. Although isolated events might have occurred for a few years after this prohibition, we are confident that new exposures of individuals to kuru at mortuary feasts would not have occurred after 1960. Not only have no cases of kuru been recorded in people born after 1959 (and only nine were recorded in those born after 1956); but also all the 11 last recorded cases of kuru that we report here were born before 1950. If any source of infection remained, whether from surreptitious cannibalism, possible ground contam-ination with human prions at sites where food was prepared, or other lateral routes, we would expect individuals born after this period to have kuru—especially since children are thought to have had shorter incubation periods than adults. However, no such cases have been observed. Additionally, although a fraction of hamster-adapted scrapie prions have been shown to survive in soil for at least 3 years,25 the mortuary feast practices (during which the entire body would be consumed) were undertaken so that any substantial contamination of soil would not have occurred, and traditional bamboo knives and leaf plates were burned after the feast. Furthermore, no clusters of kuru cases, as seen earlier in the epidemic,26 have been recorded for many years....




Kuru: The Science and the Sorcery


Special Jury Prize Winner, Pacific International Documentary Film Festival 2011.


This is the true story of one of the most incredible and challenging medical detective stories of the 20th Century; a history of human tragedy, adventure and discovery. It is the story of the Fore, a Papuan community immersed in cannibalistic mortuary practices and sorcery in one of the most remote regions on the planet, and the tragic disease that threatened to wipe out their entire population.


In 1961, a young Australian medical researcher, Michael Alpers, puts up his hand to work on a new and strange disease in the Eastern Highlands of Papua New Guinea. There, he teams up with an American outer, Dr Carleton Gajdusek, who has been in the local Fore region since 1957. For Michael it is the beginning of a lifelong obsession.


Together, they are amidst a major epidemic. It is killing over 200 people a year with devastating effects. It mainly targets women and children. The local people, the Fore, call the disease kuru, their word for shivering. They believe it is caused by sorcery.


Michael and Carleton are baffled by the disease. There are no scientific disciplines to guide them as they attempt to unravel its mysteries. By pure chance, a link is made to a strange transmissible animal disease in sheep, Scrapie. The two kuru researchers embark on a 10-year experiment to see if the fatal degenerative brain disease in humans could be transmissible like Scrapie.


The decision is made to perform an autopsy on a kuru victim and inoculate the kuru material into a chimpanzee. Kigea, ayoung girl in the village is identified as being in the early stages of kuru. Kigea’s family, gives Michael permission to perform an autopsy upon her death.


A brain sample taken from Kigea after her death is flown to the USA and injected into a chimpanzee called Daisy. While Michael follows the progress of the transmission experiment, he starts to collate all the recorded data on kuru and begins to suspect cannibalism as the cause of the spreadof the disease.


Within two years, he diagnoses Daisy with kuru. This is a defining moment. It confirms kuru is transmissible and can cross the species barrier. The revelation, together with epidemiological data collated with anthropologist Shirley Lindenbaum, links the Fore’s mortuary feasts (consumption of dead relatives) to the transmission of kuru. Cannibalism is the cause, and its origin is linked to a rare disease called Creutzfeldt Jakob Disease(CJD), but the story of kuru is far from over.


The infecting agent is the first new pathogen – prions – to be discovered in over 100 years. Research results in two Nobel prizes: it’s discoveries turning scientific understanding upside down, causing rifts in the beliefs ofthe science community.


Then Mad Cow Disease (Bovine Spongiform Encephalopathy or BSE) reared its head in the mid 1980s, and 10 years later the human variant CJD. All eyes turned to kuru, the only model of a prion epidemic in human populations. Many unknowns still surround prion diseases: there is no cure for kuru, or any of the prion diseases. The effects are devastating and unprecedented incubation periods can extend beyond 50 years.


Michael is the key and heart to this story, providing unique access to the Fore people, and the world’s other leading authorities on the matter; including Americans Prof. DC Gajdusek (Nobel Prize 1976), Prof. Stan Prusiner (Nobel Prize 1997), Prof Shirley Lindenbaum (Anthropologist) and British Prof. John Collinge (Director, MRC Prion Unit, UK).


Kuru: The Science and the Sorcery combines history, science and anthropology to tell a unique and ongoing ‘history of science’ documentary spanning five decades. It intertwines the thinking of great minds, locally and internationally, to reveal how this rare disease in the remote highlands of PNG exploded to international attention and how Prion research has now revealed we are all descendants of a remote past of cannibal practices.






Kuru: The Science and the Sorcery Australian scientist Michael Alpers dedicated over 50 years to researching Kuru, an obscure and incurable brain disease unique to the Fore people of New Guinea. Kuru was once thought to be a psychosomatic illness, an infection, a genetic disorder, even a sorcerer's curse, but Alpers' findings pointed to cannibalism as the culprit. Yet a recent discovery has proven to be even more disturbing: the malady is linked to mad cow disease and its human equivalent, variant CJD. With a decades-long incubation period, could a larger outbreak be on its way?









human flesh taste very sweet





KURU EPIDEMIOLOGICAL PATROLS





Michael Alpers





First Reports





People of the Kuru region part 1


boy playing with animal bladder, blowing it up like a balloon. ...





People of the Kuru region part 2





Monday, November 19, 2012


Prion in Saliva of Bovine Spongiform Encephalopathy–Infected Cattle




please see full text ;



Sunday, October 27, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility



kind regards,
terry



Wednesday, November 18, 2009

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure


Simon Mead, M.R.C.P., Jerome Whitfield, M.A., Mark Poulter, B.Sc., Paresh Shah, Ph.D., James Uphill, B.Sc., Tracy Campbell, B.Sc., Huda Al-Dujaily, B.Sc., Holger Hummerich, Ph.D., Jon Beck, B.Sc., Charles A. Mein, Ph.D., Claudio Verzilli, Ph.D., John Whittaker, Ph.D., Michael P. Alpers, F.R.S., and John Collinge, F.R.S.


ABSTRACT

Background Kuru is a devastating epidemic prion disease that affected a highly restricted geographic area of the Papua New Guinea highlands; at its peak, it predominantly affected adult women and children of both sexes. Its incidence has steadily declined since the cessation of its route of transmission, endocannibalism.

Methods We performed genetic and selected clinical and genealogic assessments of more than 3000 persons from Eastern Highland populations, including 709 who participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru.

Results Persons who were exposed to kuru and survived the epidemic in Papua New Guinea are predominantly heterozygotes at the known resistance factor at codon 129 of the prion protein gene (PRNP). We now report a novel PRNP variant — G127V — that was found exclusively in people who lived in the region in which kuru was prevalent and that was present in half of the otherwise susceptible women from the region of highest exposure who were homozygous for methionine at PRNP codon 129. Although this allele is common in the area with the highest incidence of kuru, it is not found in patients with kuru and in unexposed population groups worldwide. Genealogic analysis reveals a significantly lower incidence of kuru in pedigrees that harbor the protective allele than in geographically matched control families.

Conclusions The 127V polymorphism is an acquired prion disease resistance factor selected during the kuru epidemic, rather than a pathogenic mutation that could have triggered the kuru epidemic. Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.

Source Information

From the Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology (S.M., J. Whitfield, M.P., P.S., J.U., T.C., H.A.-D., H.H., J.B., M.P.A., J.C.); the Genome Centre, Barts and the London Queen Mary's School of Medicine and Dentistry, John Vane Science Centre (C.A.M.); and the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine (C.V., J. Whittaker) — all in London; Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea (J. Whitfield, M.P.A.); and the Centre for International Health, Curtin University, Perth, WA, Australia (M.P.A.).

Address reprint requests to Dr. Collinge at the Department of Neurodegenerative Disease, Institute of Neurology, Queen Sq., London WC1N 3BG, United Kingdom, or at j.collinge@prion.ucl.ac.uk.


http://content.nejm.org/cgi/content/short/361/21/2056



Brain disease “resistance gene” could offer insights into CJD19 November 2009 A community in Papua New Guinea that suffered a major epidemic of a CJD-like fatal brain disease called kuru has developed strong genetic resistance to the disease, according to new research by Medical Research Council (MRC) scientists.

Kuru is a fatal prion disease, similar to CJD in humans and BSE in animals, and is geographically unique to an area in Papua New Guinea. In the mid 20th Century, an epidemic of kuru devastated a population in the Eastern Highlands of Papua New Guinea. The infection was passed on at mortuary feasts, where mainly women and children consumed their deceased relatives as a mark of respect and mourning. This practice was banned and ceased in the late 1950s.

Scientists from the MRC Prion Unit, a national centre of excellence in prion diseases, assessed over 3000 people from the affected and surrounding Eastern Highland populations, including 709 who had participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru. They discovered a novel and unique variation in the prion protein gene called G127V in people from the Purosa valley region where kuru was most rife.

This gene mutation, which is found nowhere else in the world, seems to offer high or even complete protection against the development of kuru and has become frequent in this area through natural selection over recent history, in direct response to the epidemic. This is thought be perhaps the strongest example yet of recent natural selection in humans.

Lead author Professor John Collinge, Director of the MRC Prion Unit said:

“It’s absolutely fascinating to see Darwinian principles at work here. This community of people has developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable. Kuru comes from the same disease family as CJD so the discovery of this powerful resistance factor opens up new areas for research taking us closer to understanding, treating and hopefully preventing a range of prion diseases.”

The study “A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure”, which began in 1996, will be published in the New England Journal of Medicine on 19 November 2009.

ENDS

Notes to editors 1. Study available on request.

2. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

3. Prion diseases or transmissible spongiform encephalopathies (TSEs) belong to group of progressive conditions that affect the nervous system in humans and animals. In humans, prion diseases impair brain function, causing memory changes, personality changes, a decline in intellectual function (dementia), and problems with movement that worsen over time. They are fatal conditions. Familial prion diseases of humans include classic Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) fatal insomnia (FI) and Kuru.

4. Kuru was restricted to the Fore linguistic groups and their immediate neighbours which whom they intermarried. It was the practice in the Fore society for kinship groups to consume deceased relatives at mortuary feasts, a practice that resulted in human-to-human prion transmission. On the whole, men and children over 8 years of age did not participate in the feast, with the result that kuru at its peak predominantly affected women and children. As recorded in oral history the first cases appeared in the early 20th century and thereafter the number of cases increased in incidence. A peak annual mortality of more than 2% was recorded in some villages. Some villages became largely devoid of young women. More information on the Papua New Guinea Institute of Medical Research is available here www.pngimr.org.pg.

5. The study was lead by the Medical Research Council Prion Unit, and involved scientists from the University College London Institute of Neurology; Papua New Guinea Institute of Medical Research; and Curtin University Australia. Other institutions participating; the Genome Centre, Barts the London Queen Mary’s School of Medicine and Dentistry; London School of Hygiene and Tropical Medicine.

Press contact: 020 7637 6011 press.office@headoffice.mrc.ac.uk


http://www.mrc.ac.uk/Newspublications/News/MRC006502





November 19, 2009

Brain-eating tribe enriches understanding of mad cow disease

Mark Henderson, Science Editor Recommend? A cannibalistic ritual in which the brains of dead tribespeople were eaten by their relatives has triggered one of the most striking examples of rapid human evolution on record, scientists have discovered.

In the middle of the 20th century the Fore tribe of the Eastern Highlands province of Papua New Guinea was devastated by a CJD-like disease called kuru, which was passed on by mortuary feasts in which the brains of the dead were consumed.

Although the practice was banned in the 1950s and kuru has disappeared, it has left an imprint on the tribe’s DNA. Research has now identified a genetic mutation unique to the Fore that protects against the brain disease and which has spread swiftly through the population by natural selection.

As the mutation confers high or almost complete resistance to kuru, carriers have a survival advantage and have had more descendants. About 8 per cent of people from the Purosa Valley region, where kuru hit hardest, now have the gene, which is unknown anywhere else in the world.

Related Links Daniel Gajdusek New wave of mad cow disease feared What the cannibals taught us The findings, from a team led by Simon Mead, of the Medical Research Council Prion Unit at University College London, show how quickly human evolution can respond to new environmental pressures.

They are described today in The New England Journal of Medicine as scientists prepare to celebrate the 150th anniversary of the publication of Charles Darwin’s On the Origin of Species on Tuesday.

Professor John Collinge, the director of the prion unit, said: “It’s absolutely fascinating to see Darwinian principles at work here. This community of people have developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable.”

The research is also significant because it promises to shed light on the rogue prion proteins that cause Creutzfeldt-Jakob disease (vCJD), the human form of mad cow disease.

Dr Mead said: “It isn’t going to lead to a drug tomorrow but it would improve our background understanding of how prion diseases work and how they might be prevented.”

Oral histories provided by elderly members of the Fore tribe suggest that kuru emerged in the early 20th century and developed into a serious epidemic with an annual mortality rate of more than 2 per cent in some villages.

It mainly affected women and children, who would eat the remains of dead relatives. Kuru disappeared when cannibal rituals were stopped in the 1950s under the influence of missionaries.

In the new study scientists analysed the DNA of more than 3,000 people from affected and unaffected parts of the Eastern Highlands, including 709 who had taken part in cannibalistic rituals and 152 who had died of kuru.

The variant in the prion protein gene, called G127V, appears to have emerged about 1800 and then became advantageous with the arrival of kuru.

Dr Mead said that the variant would have spread rapidly for two reasons: “First, if you’re a carrier you’re resistant to the disease. More subtly, it also had benefits in terms of the relatives eaten. If you were in a family protected against kuru and ate auntie’s brain you were less likely to be eating an infected brain.”

In the genes

Sickle-cell anaemia This genetic disease is more common among African and Mediterranean people because the gene responsible also confers resistance to malaria

Blood groups People with blood group O are more vulnerable to cholera but less susceptible to malaria, spread by mosquitoes

HIV There is evidence that a variant of a gene called CCR5-32, which offers resistance against HIV, is increasing in frequency in Africa

Lactose tolerance Common in ethnic groups with a strong pastoral tradition such as North Europeans and East Africans

Skin colour Natural selection favours dark skins at equatorial latitudes for cancer protection, but pale skins at high latitudes, because they allow greater production of vitamin D

Source: Times database


http://www.timesonline.co.uk/tol/news/science/biology_evolution/article6922057.ece




Tuesday, July 28, 2009

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents


http://kuru-tse.blogspot.com/2009/07/kuru-infectious-agent-is-unique.html




Kuru in the 21st century—an acquired human prion disease Thu Jun 22, 2006 19:44 70.110.82.186

The Lancet 2006; 367:2068-2074

DOI:10.1016/S0140-6736(06)68930-7

Kuru in the 21st century—an acquired human prion disease with very long incubation periods John Collinge a , Jerome Whitfield a b, Edward McKintosh a, John Beck a, Simon Mead a, Dafydd J Thomas a and Michael P Alpers a c

Summary Background Kuru provides the principal experience of epidemic human prion disease. Its incidence has steadily fallen after the abrupt cessation of its route of transmission (endocannibalism) in Papua New Guinea in the 1950s. The onset of variant Creutzfeldt-Jakob disease (vCJD), and the unknown prevalence of infection after the extensive dietary exposure to bovine spongiform encephalopathy (BSE) prions in the UK, has led to renewed interest in kuru. We investigated possible incubation periods, pathogenesis, and genetic susceptibility factors in kuru patients in Papua New Guinea.

Methods We strengthened active kuru surveillance in 1996 with an expanded field team to investigate all suspected patients. Detailed histories of residence and exposure to mortuary feasts were obtained together with serial neurological examination, if possible.

Findings We identified 11 patients with kuru from July, 1996, to June, 2004, all living in the South Fore. All patients were born before the cessation of cannibalism in the late 1950s. The minimum estimated incubation periods ranged from 34 to 41 years. However, likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. PRNP analysis showed that most patients with kuru were heterozygous at polymorphic codon 129, a genotype associated with extended incubation periods and resistance to prion disease.

Interpretation Incubation periods of infection with human prions can exceed 50 years. In human infection with BSE prions, species-barrier effects, which are characteristic of cross-species transmission, would be expected to further increase the mean and range of incubation periods, compared with recycling of prions within species. These data should inform attempts to model variant CJD epidemiology.

Affiliations

a. MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK b. Papua New Guinea Institute of Medical Research, Goroka, EHP, Papua New Guinea c. Centre for International Health, Curtin University, Perth, Australia

Correspondence to: Prof John Collinge

http://www.thelancet.com/journals/lancet/article/PIIS0140673606689307/abstract


TSS

Listen to The Lancet This week's audio summary discusses an Article entitled "Kuru in the 21st century - an acquired human prion disease with very long incubation periods". Also covered is a Lecture assessing climate change and its impact on health, and an Editorial about the roll-out of cervical cancer vaccines worldwide. >>

http://www.thelancet.com/webfiles/images/clusters/thelancet/audio/24June2006.mp3


further into this study;

Discussion

The early clinical, epidemiological, and anthropological study of kuru; the recognition of its neuropathological, and then causal parallels to ovine scrapie;20 and then crucially, the experimental transmission of the disease

to primates,21 originated the concept of the human transmissible spongiform encephalopathies, which was followed in turn by the eventual unifying concept of the mammalian prion diseases. However, in addition to the central historical importance of kuru, study of the end-stage of this epidemic offers a unique opportunity to study the variables of a near-complete epidemic of human prion disease. In particular, recognition of the incubation periods possible after natural prion infection in people is important in providing an insight (from actual case histories rather than from mathematical models) into the probable span of the vCJD epidemic in the UK. Although estimation of kuru incubation periods early in the epidemic was difficult, and the timing of the actual infecting event for an individual can rarely be determined, the abrupt and permanent interruption of the source of infection, endocannibalism, in the late 1950s, has progressively allowed recognition of an enormous span of possible incubation periods, at its shortest extreme bracketed by the rare onset of disease in children as young as 5 years and extending up to (and perhaps beyond) the incubations covering more than half a century, as we describe here.In our field studies, we have interviewed many individuals who participated in traditional mortuary feasting or who described the participation of family members from the preceding generation. These detailed descriptions will be published elsewhere but have reaffirmed the oral histories of endocannibalism in the Fore recorded previously12,22–24 and that this practice ceased abruptly at the time of Australian administrative control over the kuru areas. Although isolated events might have occurred for a few years after this prohibition, we are confident that new exposures of individuals to kuru at mortuary feasts would not have occurred after 1960. Not only have no cases of kuru been recorded in people born after 1959 (and only nine were recorded in those born after 1956); but also all the 11 last recorded cases of kuru that we report here were born before 1950. If any source of infection remained, whether from surreptitious cannibalism, possible ground contam-ination with human prions at sites where food was prepared, or other lateral routes, we would expect individuals born after this period to have kuru—especially since children are thought to have had shorter incubation periods than adults. However, no such cases have been observed. Additionally, although a fraction of hamster-adapted scrapie prions have been shown to survive in soil for at least 3 years,25 the mortuary feast practices (during which the entire body would be consumed) were undertaken so that any substantial contamination of soil would not have occurred, and traditional bamboo knives and leaf plates were burned after the feast. Furthermore, no clusters of kuru cases, as seen earlier in the epidemic,26 have been recorded for many years. We have also reviewed the assertion that maternal transmission of kuru did not occur, and saw no evidence for maternal transmission from kuru archives, interviews of colleagues who have practised medicine in the Fore, or local oral history. Again, any possible vertical route of kuru transmission would have resulted in the presence of kuru in children born after 1960, especially since kuru was common in women of childbearing age; no such cases have occurred.With respect to extrapolation of incubation periods of BSE prion infection in people, we should recognise that the kuru epidemic arose from intraspecies recycling of infectious prions. However, transmission of prions between different mammalian species is associated with a species barrier, which is better described as a transmission barrier, because of the importance of within-species prion strain type, in addition to species-specific differences in its determination.27 The biological effects of such a barrier are: extended mean incubation period; increased spread of incubation periods in individual animals; and reduced attack rate (in which only a fraction of inoculated animals will succumb), by comparison with the 100% mortality generally associated with within-species inoculation with high-titre infectivity. Incubation periods approaching the natural lifespan of the inoculated species are often seen in such primary cross-species transmissions of prions. Second and subsequent passage of prions within the new species is always associated with adaptation involving a considerable shortening of the mean and spread of incubation periods and high or total lethality to high-titre inocula. Thus, estimation of the range of possible incubation periods in human BSE infection needs superimposition of the effect of a transmission barrier onto these findings of natural human incubation periods. The mean incubation period for kuru has been estimated to be around 12 years,27 with a similar estimate in iatrogenic CJD associated with the use of human-cadaver-derived pituitary growth hormone.28 As shown here, maximum incubation periods in kuru can exceed 50 years. The transmission barrier of BSE between cattle and human beings is unknown and cannot be directly measured. However, the cattle-to-mouse barrier for BSE has been well characterised experimentally by comparative endpoint titration. BSE prions transmit readily to laboratory mice, including after oral dosing.29 The murine LD50 (lethal dose causing 50% mortality) in C57Bl/6 mice is about 500-fold higher than that in cattle;30 this barrier also results in a three-fold to four-fold increase in mean incubation period.27 Mean incubation periods of human BSE infection of 30 years or more should therefore be regarded as possible, if not probable,27 with the longest incubation periods approaching (and perhaps exceeding) the typical human lifespan. The shortest incubation periods in kuru were estimated from the age of the youngest patients—suggesting that the shortest incubation period was Articles www.thelancet.com Vol 367 June 24, 2006 2073 4–5 years. Similarly in vCJD, although the total clinical caseload so far has been small, the youngest onsets of vCJD have been at age 12 years or above, providing an early estimate of a minimum incubation period. Furthermore, prion disease in mice follows a well-defined course with a highly distinctive and repeatable incubation time for a specific prion strain in a defined inbred mouse line. In addition to the PrP gene, a few additional genetic loci with a major effect on incubation period have been mapped.4,31,32 Human homologues of such loci could be important in human susceptibility to prion disease, both after accidental human prion exposure and after exposure to the BSE agent. By definition, patients identified so far with vCJD are those with the shortest incubation periods for BSE. These patients could have received an especially high dose of BSE prions. However, no unusual history of dietary, occupational, or other exposure to BSE has been reported from case-control studies. Because of the powerful genetic effects on incubation period in laboratory animals, vCJD patients identified could represent a distinct genetic subpopulation with unusually short incubation periods to BSE prions, with vCJD so far occurring predominantly in those individuals with short incubation time alleles at these multiple genetic loci, in addition to having the homozygous PRNP genotype of codon 129 methionine. Therefore, a human BSE epidemic may be multiphasic, and recent estimates of the size of the vCJD epidemic based on uniform genetic susceptibility could be substantial underestimations.33,34 Genes implicated in species-barrier effects, which would further increase both the mean and range of human BSE incubation periods, are also probably relevant. In this context, a human epidemic will be difficult to accurately model until such modifier loci are identified and their gene frequencies in the population can be measured.4Heterozygosity at PRNP codon 129 is a major determinant of susceptibility to and incubation time of human prion diseases.5,7,9,35 As expected, most of these recent kuru cases with extended incubation periods (eight of ten) were heterozygotes. We have reported previously that most elderly survivors of exposure to traditional mortuary feasts are heterozygous.9 Although the study included a small number of patients with kuru with long incubation periods, we saw no evidence of association with PRNP haplotype,10 HLA-DQ7,18 APOE,36 or PRND alleles.13

Contributors

J Whitfield led the field patrol team throughout the study and investigated all suspect cases; E McKintosh provided assistance during this time. J Beck and S Mead undertook the molecular genetic studies. J Collinge, M P Alpers, E McKintosh, and D J Thomas did field neurological examinations. J Collinge and M P Alpers supervised the study and drafted the manuscript. All authors contributed to and approved the final version of the manuscript. .........

snip...end...TSS

Posted by: Terry S. Singeltary Sr. July 25, 2006 07:05 PM


http://blogs.nature.com/news/blog/2006/06/cjdrelated_disease_can_incubat.html



http://kuru-tse.blogspot.com/




TSS