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News Article | March 1, 2017
Site: www.eurekalert.org

A new long-term study uses social media data to learn why people use e-cigarettes and why they started in the first place A new study harnesses social media data to explore--in their own words--the reasons people use e-cigarettes and why they started vaping in the first place. Nearly half of people say they began vaping in an effort to quit smoking cigarettes, while other reasons included their taste, the ability to use them indoors and their "cool factor." The work, led by San Diego State University researcher and public health surveillance expert John W. Ayers and published today in the journal PLOS ONE, gets around the inherent limitations and inaccuracies of survey responses by sourcing data directly from people's own comments on social media. "Just look to surveys from the recent presidential election or Brexit as examples of surveys' weakening ability to gauge public sentiment, attitudes or behaviors," Ayers said. "But what if we could listen in to what people are naturally saying about e-cigarettes to their friends rather than a surveyor?" To do just that, Ayers and colleagues mined Twitter data from more than 3 million public tweets about e-cigarettes between 2012 and 2015 to understand vaping's surge in popularity over that time. All English-language public tweets that included several e-cigarette terms (such as "e-cigarette" and "vape," among dozens of others) were captured from the Twitter data stream over that time period. After excluding spam, advertisements, and retweets, posts from real Twitter users indicating their rationale for vaping were retained and classified. During 2012, quitting "combustibles"--cigarettes and other smoking tobacco products--was the most commonly cited reason for using e-cigarettes, mentioned in nearly half (43 percent) of all rationale-related tweets. Coming in second place was social image (21 percent), followed by ability to use indoors (14 percent), available flavors (14 percent), perceived safety (9 percent), cost (3 percent) and agreeable odor (2 percent). By 2015, though, the Tweeted reasons for using e-cigarettes had shifted. Both "quitting combustibles" and "ability to use indoors" significantly decreased in mentions. At the same time, social image became the most mentioned rationale in 2015, cited in 37 percent of the collected tweets. "The reasons people vape shifted away from cessation and toward social image during the time that e-cigarettes evolved from a cessation device to a freestanding tobacco product attracting smokers and nonsmokers alike," said Jon-Patrick Allem, one of the study's coauthor and fellow at the University of Southern California's Tobacco Center of Regulatory Science. "By utilizing Twitter, we can make public health more data-driven and understand vapers or those thinking of vaping," he added. Misinformation appears to drive some vapers' rationales for using e-cigarettes, the authors noted. "Some of the reasons people vape appear to be dubious," said Eric Leas, another coauthor and a graduate student in the SDSU-UCSD Public Health Joint Doctoral Program. "For example, vaping may be no less expensive than smoking combustibles, despite their naming that as a reason for vaping. Understanding how the public is potentially misinformed, rather than guessing, is a tremendous benefit for public health surveillance and practice." Monitoring social media data is a strategy that should be a standard practice in public health, the researchers argue. "Given the current prevalence of vaping, it would require more than 50,000 screening interviews and cost millions of dollars to have a single snapshot comparable to our study," said Mark Dredze, study coauthor and computer scientist at Johns Hopkins University. Ayers added that by thinking of Twitter and other social media streams as "a massive, passive focus group" allows for public health researchers to be better connected to the people they serve. "Without any priming or direct costs associated with data collection, public health can use social media surveillance to understand why people vape, yielding actionable intelligence for decision making on how to discourage vaping," he said. "Given that reasons for vaping can and do change, as we saw in our study, staying on top of these changes can potentially improve public health advocacy." The study was funded in collaboration with the University of Southern California's Tobacco Center of Regulatory Science by the National Cancer Institute and U.S. Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not represent the official views of the funders. The funders had no role in the design, conduct, or interpretation of the study nor the preparation, review, or approval of the manuscript. Additional collaborators on this study included Tess Cruz and Jennifer Unger of the University of Southern California; Benjamin Althouse of the Institute for Disease Modeling and Santa Fe Institute; and Adrian Benton of Johns Hopkins University.


News Article | November 23, 2016
Site: www.eurekalert.org

Malaria elimination in historically high transmission areas like southern Africa is possible with tools that are already available, provided those tools are deployed aggressively - according to new research published in PLOS Computational Biology. While the past century has seen many countries eliminate malaria, and many regions have dramatically reduced malaria burden in the last fifteen years, no sub-Saharan African country has yet eliminated malaria. In the Lake Kariba region of Southern Province, Zambia, villages with high and low malaria burden are interconnected through human travel, making elimination potentially very challenging. Milen Nikolov and colleagues at the Institute for Disease Modeling (Bellevue, WA), the Zambia National Malaria Control Centre (Lusaka, Zambia), and PATH Malaria Control and Elimination Partnership in Africa (Lusaka, Zambia), combine a mathematical model of malaria transmission with field data from Zambia to computationally test a variety of strategies for eliminating malaria in a southern African setting. The authors used detailed spatial surveillance data from field studies in southern Zambia to construct a model of interconnected villages, then tested a variety of intervention scenarios to see which ones could lead to elimination. The study shows that elimination requires high, yet realistic, levels of vector control, and mass drug campaigns deployed to kill parasites within the human population can boost the chances of achieving elimination as long as vector control is well-implemented. The results of their work suggest that elimination programs in sub-Saharan Africa should focus on how to achieve and maintain excellent coverage of vector control measures rather than spending resources on mass drug campaigns that are predicted to have little effect without well-implemented vector control already in place. Human movement within the region should be targeted to achieve elimination as well as the importation of infections from outside the region. This is because both impact the likelihood of achieving elimination and understanding regional movement patterns can help guide strategies on targeting specific groups of at-risk people. While no sub-Saharan African country has yet eliminated malaria, the authors predict that regional malaria elimination is nevertheless within reach with current tools, provided the efficacy and operational efficiency attained in southern Zambia can be extended and targeted to other key areas. In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: http://journals. Citation: Nikolov M, Bever CA, Upfill-Brown A, Hamainza B, Miller JM, Eckhoff PA, et al. (2016) Malaria Elimination Campaigns in the Lake Kariba Region of Zambia: A Spatial Dynamical Model. PLoS Comput Biol 12(11): e1005192. doi:10.1371/journal.pcbi.1005192 Funding: JMM: Bill and Melinda Gates Foundation (OPP 1089412 to PATH MACEPA). MN, CAB, AUB, PAE, EAW, JG: Bill and Melinda Gates through the Global Good Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.


News Article | November 16, 2016
Site: www.eurekalert.org

CAMBRIDGE, MA -- Researchers at MIT and Brigham and Women's Hospital have developed a new drug capsule that remains in the stomach for up to two weeks after being swallowed, gradually releasing its drug payload. This type of drug delivery could replace inconvenient regimens that require repeated doses, which would help to overcome one of the major obstacles to treating and potentially eliminating diseases such as malaria. In a study described in the Nov. 16 issue of Science Translational Medicine, the researchers used this approach to deliver a drug called ivermectin, which they believe could aid in malaria elimination efforts. However, this approach could be applicable to many other diseases, says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT's Koch Institute for Integrative Cancer Research. "Until now, oral drugs would almost never last for more than a day," Langer says. "This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer's or mental health disorders. There are a lot of exciting things this could someday enable." Langer and Giovanni Traverso, a research affiliate at the Koch Institute and a gastroenterologist and biomedical engineer at Brigham and Women's Hospital, are the senior authors of the paper. The paper's lead authors are former MIT postdoc Andrew Bellinger, MIT postdoc Mousa Jafari, and former MIT postdocs Tyler Grant and Shiyi Zhang. The team also includes researchers from Harvard University, Imperial College London, and the Institute for Disease Modeling in Bellevue, Washington. The research has led to the launching of Lyndra, a Cambridge-based company that is developing the technology with a focus on diseases for which patients would benefit the most from sustained drug delivery, including neuropsychiatric disorders, HIV, diabetes, and epilepsy. Drugs taken orally tend to work for a limited time because they pass rapidly through the body and are exposed to harsh environments in the stomach and intestines. Langer's lab has been working for several years to overcome this challenge, with an initial focus on malaria and ivermectin, which kills any mosquito that bites a person who is taking the drug. This can greatly reduce the transmission of malaria and other mosquito-borne illnesses. The team envisions that long-term delivery of ivermectin could help with malaria elimination campaigns based on mass drug administration -- the treatment of an entire population, whether infected or not, in an area where a disease is common. In this scenario, ivermectin would be paired with the antimalaria drug artemisinin. "Getting patients to take medicine day after day after day is really challenging," says Bellinger, now a cardiologist at Brigham and Women's Hospital and chief scientific officer at Lyndra. "If the medicine could be effective for a long period of time, you could radically improve the efficacy of your mass drug administration campaigns." To achieve ultra-long-term delivery, drugs need to be packaged in a capsule that is stable enough to survive the harsh environment of the stomach and can release its contents over time. Once the drug is released, the capsule must break down and pass safely through the digestive tract. Working with those criteria in mind, the team designed a star-shaped structure with six arms that can be folded inward and encased in a smooth capsule. Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down. After the capsule is swallowed, acid in the stomach dissolves the outer layer of the capsule, allowing the six arms to unfold. Once the star expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract. "When the star opens up inside the stomach, it stays inside the stomach for the duration that you need," says Grant, now a product development engineer at Lyndra. In tests in pigs, the researchers confirmed that the drug is gradually released over two weeks. The linkers that join the arms to the core then dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract. "This is a platform into which you can incorporate any drug," Jafari says. "This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration." This type of delivery could also help doctors to run better clinical trials by making it easier for patients to take the drugs, Zhang says. "It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs, because currently a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies," he says. The new study includes mathematical modeling done by researchers at Imperial College London and the Institute for Disease Modeling to predict the potential impact of this approach. The models suggest that if this technology were used to deliver ivermectin along with antimalaria treatments to 70 percent of a population in a mass drug administration campaign, disease transmission could be reduced the same amount as if 90 percent were treated with antimalaria treatments alone. "What we showed is that we stand to significantly amplify the effect of those campaigns," Traverso says. "The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication." Researchers led by Traverso are working on developing similar capsules to deliver drugs against other tropical diseases, as well as HIV and tuberculosis. The research was funded by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Max Planck Research Award.


News Article | November 17, 2016
Site: www.biosciencetechnology.com

Researchers at MIT and Brigham and Women’s Hospital have developed a new drug capsule that remains in the stomach for up to two weeks after being swallowed, gradually releasing its drug payload. This type of drug delivery could replace inconvenient regimens that require repeated doses, which would help to overcome one of the major obstacles to treating and potentially eliminating diseases such as malaria. In a study described in the Nov. 16 issue of Science Translational Medicine, the researchers used this approach to deliver a drug called ivermectin, which they believe could aid in malaria elimination efforts. However, this approach could be applicable to many other diseases, said Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research. “Until now, oral drugs would almost never last for more than a day,” Langer said. “This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders. There are a lot of exciting things this could someday enable.” Langer and Giovanni Traverso, a research affiliate at the Koch Institute and a gastroenterologist and biomedical engineer at Brigham and Women’s Hospital, are the senior authors of the paper. The paper’s lead authors are former MIT postdoc Andrew Bellinger, MIT postdoc Mousa Jafari, and former MIT postdocs Tyler Grant and Shiyi Zhang. The team also includes researchers from Harvard University, Imperial College London, and the Institute for Disease Modeling in Bellevue, Washington. The research has led to the launching of Lyndra, a Cambridge-based company that is developing the technology with a focus on diseases for which patients would benefit the most from sustained drug delivery, including neuropsychiatric disorders, HIV, diabetes, and epilepsy. Drugs taken orally tend to work for a limited time because they pass rapidly through the body and are exposed to harsh environments in the stomach and intestines. Langer’s lab has been working for several years to overcome this challenge, with an initial focus on malaria and ivermectin, which kills any mosquito that bites a person who is taking the drug. This can greatly reduce the transmission of malaria and other mosquito-borne illnesses. The team envisions that long-term delivery of ivermectin could help with malaria elimination campaigns based on mass drug administration — the treatment of an entire population, whether infected or not, in an area where a disease is common. In this scenario, ivermectin would be paired with the antimalaria drug artemisinin. “Getting patients to take medicine day after day after day is really challenging,” said Bellinger, now a cardiologist at Brigham and Women’s Hospital and chief scientific officer at Lyndra. “If the medicine could be effective for a long period of time, you could radically improve the efficacy of your mass drug administration campaigns.” To achieve ultra-long-term delivery, drugs need to be packaged in a capsule that is stable enough to survive the harsh environment of the stomach and can release its contents over time. Once the drug is released, the capsule must break down and pass safely through the digestive tract. Working with those criteria in mind, the team designed a star-shaped structure with six arms that can be folded inward and encased in a smooth capsule. Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down. After the capsule is swallowed, acid in the stomach dissolves the outer layer of the capsule, allowing the six arms to unfold. Once the star expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract. “When the star opens up inside the stomach, it stays inside the stomach for the duration that you need,” said Grant, now a product development engineer at Lyndra. In tests in pigs, the researchers confirmed that the drug is gradually released over two weeks. The linkers that join the arms to the core then dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract. “This is a platform into which you can incorporate any drug,” Jafari said. “This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration.” This type of delivery could also help doctors to run better clinical trials by making it easier for patients to take the drugs, Zhang said. “It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs, because currently a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies,” he said. The new study includes mathematical modeling done by researchers at Imperial College London and the Institute for Disease Modeling to predict the potential impact of this approach. The models suggest that if this technology were used to deliver ivermectin along with antimalaria treatments to 70 percent of a population in a mass drug administration campaign, disease transmission could be reduced the same amount as if 90 percent were treated with antimalaria treatments alone. “What we showed is that we stand to significantly amplify the effect of those campaigns,” Traverso said. “The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication.” Peter Agre, director of the Johns Hopkins Malaria Research Institute, who was not involved in the research, described the new approach as a “remarkable” advance that could improve treatment of malaria and any other disease that requires long-term treatment. “If you could reduce the frequency of dosing, and one treatment would continue to release medicine until the course is completed, that would be very beneficial,” Agre said. Researchers led by Traverso are working on developing similar capsules to deliver drugs against other tropical diseases, as well as HIV and tuberculosis. The research was funded by the Bill and Melinda Gates Foundation, the National Institutes of Health, and the Max Planck Research Award.


News Article | November 17, 2016
Site: phys.org

In a study described in the Nov. 16 issue of Science Translational Medicine, the researchers used this approach to deliver a drug called ivermectin, which they believe could aid in malaria elimination efforts. However, this approach could be applicable to many other diseases, says Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT's Koch Institute for Integrative Cancer Research. "Until now, oral drugs would almost never last for more than a day," Langer says. "This really opens the door to ultra-long-lasting oral systems, which could have an effect on all kinds of diseases, such as Alzheimer's or mental health disorders. There are a lot of exciting things this could someday enable." Langer and Giovanni Traverso, a research affiliate at the Koch Institute and a gastroenterologist and biomedical engineer at Brigham and Women's Hospital, are the senior authors of the paper. The paper's lead authors are former MIT postdoc Andrew Bellinger, MIT postdoc Mousa Jafari, and former MIT postdocs Tyler Grant and Shiyi Zhang. The team also includes researchers from Harvard University, Imperial College London, and the Institute for Disease Modeling in Bellevue, Washington. The research has led to the launching of Lyndra, a Cambridge-based company that is developing the technology with a focus on diseases for which patients would benefit the most from sustained drug delivery, including neuropsychiatric disorders, HIV, diabetes, and epilepsy. Drugs taken orally tend to work for a limited time because they pass rapidly through the body and are exposed to harsh environments in the stomach and intestines. Langer's lab has been working for several years to overcome this challenge, with an initial focus on malaria and ivermectin, which kills any mosquito that bites a person who is taking the drug. This can greatly reduce the transmission of malaria and other mosquito-borne illnesses. The team envisions that long-term delivery of ivermectin could help with malaria elimination campaigns based on mass drug administration—the treatment of an entire population, whether infected or not, in an area where a disease is common. In this scenario, ivermectin would be paired with the antimalaria drug artemisinin. "Getting patients to take medicine day after day after day is really challenging," says Bellinger, now a cardiologist at Brigham and Women's Hospital and chief scientific officer at Lyndra. "If the medicine could be effective for a long period of time, you could radically improve the efficacy of your mass drug administration campaigns." To achieve ultra-long-term delivery, drugs need to be packaged in a capsule that is stable enough to survive the harsh environment of the stomach and can release its contents over time. Once the drug is released, the capsule must break down and pass safely through the digestive tract. Working with those criteria in mind, the team designed a star-shaped structure with six arms that can be folded inward and encased in a smooth capsule. Drug molecules are loaded into the arms, which are made of a rigid polymer called polycaprolactone. Each arm is attached to a rubber-like core by a linker that is designed to eventually break down. After the capsule is swallowed, acid in the stomach dissolves the outer layer of the capsule, allowing the six arms to unfold. Once the star expands, it is large enough to stay in the stomach and resist the forces that would normally push an object further down the digestive tract. However, it is not large enough to cause any harmful blockage of the digestive tract. "When the star opens up inside the stomach, it stays inside the stomach for the duration that you need," says Grant, now a product development engineer at Lyndra. In tests in pigs, the researchers confirmed that the drug is gradually released over two weeks. The linkers that join the arms to the core then dissolve, allowing the arms to break off. The pieces are small enough that they can pass harmlessly through the digestive tract. "This is a platform into which you can incorporate any drug," Jafari says. "This can be used with any drug that requires frequent dosing. We can replace that dosing with a single administration." This type of delivery could also help doctors to run better clinical trials by making it easier for patients to take the drugs, Zhang says. "It may help doctors and the pharma industry to better evaluate the efficacy of certain drugs, because currently a lot of patients in clinical trials have serious medication adherence problems that will mislead the clinical studies," he says. The new study includes mathematical modeling done by researchers at Imperial College London and the Institute for Disease Modeling to predict the potential impact of this approach. The models suggest that if this technology were used to deliver ivermectin along with antimalaria treatments to 70 percent of a population in a mass drug administration campaign, disease transmission could be reduced the same amount as if 90 percent were treated with antimalaria treatments alone. "What we showed is that we stand to significantly amplify the effect of those campaigns," Traverso says. "The introduction of this kind of system could have a substantial impact on the fight against malaria and transform clinical care in general by ensuring patients receive their medication." Peter Agre, director of the Johns Hopkins Malaria Research Institute, who was not involved in the research, described the new approach as a "remarkable" advance that could improve treatment of malaria and any other disease that requires long-term treatment. "If you could reduce the frequency of dosing, and one treatment would continue to release medicine until the course is completed, that would be very beneficial," Agre says. Researchers led by Traverso are working on developing similar capsules to deliver drugs against other tropical diseases, as well as HIV and tuberculosis. Explore further: Ultra-long acting pill offers new hope in eliminating malaria More information: Bellinger AM et al. "Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals." Science Translational Medicine DOI: 10.1126/scitranslmed.aag2374


News Article | November 16, 2016
Site: www.eurekalert.org

Cambridge, MA - Lyndra, a healthcare company developing ultra long-acting oral drug delivery technologies, announced the publication of a scientific paper describing its novel technology in one of its earliest applications. Lyndra's revolutionary platform was initially developed at the Massachusetts Institute of Technology in the laboratory of Dr. Robert Langer. Lyndra has begun its own development work on internal and partner candidates. Lyndra's technology, which redefines ultra-long acting oral therapeutic delivery, has the potential to transform care by improving effectiveness, reducing side effects, and creating substantial savings for patients, the healthcare system, and governments. Data on the early use of this technology for the treatment of malaria was published today in Science Translational Medicine. The publication entitled "Oral Ultra Long-Acting Drug Delivery: Single Encounter Ivermectin for Malaria Elimination," describes an ingested capsule that, upon entering the stomach, assumes a geometry that prevents passage through the GI tract, enabling prolonged gastric residence. The Lyndra technology can deliver small molecule therapies for seven days and potentially longer, and, upon the predetermined breakdown of its structure, can safely pass through the gastrointestinal tract. The study demonstrated the long-acting controlled release of invermectin, a treatment to interrupt the vector transmission of malaria, for up to 14 days. "This technology promises to rewrite the definition of ultra-long acting oral therapies," said Dr. Robert Langer, Lyndra co-founder, MIT Institute Professor, and corresponding author on the paper. "Current extended and sustained release technologies achieve therapeutic serum levels for up to 12-24 hours. Lyndra's technology stands alone by pushing this timeline out to more than a week. The implications for patients are tremendous." "People around the world depend on medications that require taking a pill every single day or even multiple times a day," said Amy Schulman, a co-founder of Lyndra and its CEO. "That approximately 50% of patients in the developed world do not take their medicines as prescribed, a statistic that is even more challenging in the developing world, has a demonstrable effect on healthcare outcomes and a cost estimates to the US healthcare system alone of over $100 billion annually. Lyndra's long acting technology should make a real dent in this protracted problem and help change the lives of millions of patients who feel tethered to the daily pill." Schulman noted that Lyndra's system offers a number of clinically meaningful benefits including convenient, once weekly (or less frequent) oral dosing, improvements in patient adherence, near constant therapeutic serum levels with more predictable pharmacodynamics, and potential of side effect reductions due to decreased variability of drug concentration. Safety mechanisms to prevent obstruction of food, perforation, mucosal injury and other adverse events are built into the design of Lyndra's polymer based system. Lyndra's next applications extend beyond infectious disease, including chronic diseases such as psychiatric disease, renal disease and addiction. Lyndra will initiate clinical trials for its primary internal product in mid 2017. Lyndra is also partnering with a select number of leading pharmaceutical and biopharmaceutical companies to develop ultra-long acting oral products of their proprietary small molecule therapies. Each product will undergo pre-clinical and clinical testing to satisfy regulatory requirements before being made available to the public. The study was published today in Science Translational Magazine. (print, online) Authors include: Andrew Bellinger, MIT, Harvard Medical School, Lyndra; Mousa Jafari, MIT; Tyler Grant, MIT, Lyndra; Shiyi Zhang, MIT; Hannah Slater, Imperial College London; Edward Wenger, Institute for Disease Modeling; Stacy Mo, MIT; Young-Ah Lucy Lee, MIT; Hormoz Mazdiyasni, MIT; Lawrence Kogan, MIT; Ross Barman, MIT; Cody Cleveland, MIT and Harvard Medical School; Lucas Booth MIT; Taylor Bensel, MIT; Daniel Minahan, MIT; Haley Hurowitz, MIT; Tammy Tai, MIT; Johanna Daily, Einstein Medical College; Boris Nikolic, Biomatics Capital; Lowell Wood and Philip Eckhoff, Institute for Disease Modeling; Robert Langer, MIT; Giovanni Traverso, MIT and Harvard Medical School.


Bershteyn A.,Institute for Disease Modeling
Journal of the Royal Society, Interface / the Royal Society | Year: 2013

Efficient planning and evaluation of human immunodeficiency virus (HIV) prevention programmes requires an understanding of what sustains the epidemic, including the mechanism by which HIV transmission keeps pace with the ageing of the infected population. Recently, more detailed population models have been developed which represent the epidemic with sufficient detail to characterize the dynamics of ongoing transmission. Here, we describe the structure and parameters of such a model, called EMOD-HIV v. 0.7. We analyse the chains of transmission that allow the HIV epidemic to propagate across age groups in this model. In order to prevent the epidemic from dying out, the virus must find younger victims faster than its extant victims age and die. The individuals who enable such transmission events in EMOD-HIV v. 0.7 are higher concurrency, co-infected males aged 26-29 and females aged 23-24. Prevention programmes that target these populations could efficiently interrupt the mechanisms that allow HIV to transmit at a pace that is faster than the progress of time.


Famulare M.,Institute for Disease Modeling | Hu H.,Institute for Disease Modeling
International Health | Year: 2015

Background: Phylogeography improves our understanding of spatial epidemiology. However, application to practical problems requires choices among computational tools to balance statistical rigor, computational complexity, sensitivity to sampling strategy and interpretability. Methods: We introduce a fast, heuristic algorithm to reconstruct partially-observed transmission networks (POTN) that combines features of phylogenetic and transmission tree approaches. We compare the transmission network generated by POTN with existing algorithms (BEAST and SeqTrack), and discuss the benefits and challenges of phylogeographic analysis on examples of epidemic and endemic diseases: Ebola virus, H1N1 pandemic influenza and polio. Results: For the 2014 Sierra Leone Ebola virus outbreak and the 2009 H1N1 outbreak, all three methods provide similarly plausible transmission histories but differ in detail. For polio in northern Nigeria, we discuss performance trade-offs between the POTN and discrete phylogeography in BEASTand conclude that spatial history reconstruction is limited by under-sampling. Conclusions: POTN is complementary to available tools on densely-sampled data, fails gracefully on undersampled data and is scalable to accommodate larger datasets. We provide further evidence for the utility of phylogeography for understanding transmission networks of rapidly evolving epidemics. We propose simple heuristic criteria to identify how sampling rates and disease dynamics interact to determine fundamental limitations of phylogeographic inference. © The Author 2015.


Famulare M.,Institute for Disease Modeling
PLoS ONE | Year: 2015

Wild poliovirus type 3 (WPV3) has not been seen anywhere since the last case of WPV3-associated paralysis in Nigeria in November 2012. At the time of writing, the most recent case of wild poliovirus type 1 (WPV1) in Nigeria occurred in July 2014, and WPV1 has not been seen in Africa since a case in Somalia in August 2014. No cases associated with circulating vaccine-derived type 2 poliovirus (cVDPV2) have been detected in Nigeria since November 2014. Has WPV1 been eliminated from Africa? Has WPV3 been eradicated globally? Has Nigeria interrupted cVDPV2 transmission? These questions are difficult because polio surveillance is based on paralysis and paralysis only occurs in a small fraction of infections. This report provides estimates for the probabilities of poliovirus elimination in Nigeria given available data as of March 31,2015. It is based on a model of disease transmission that is built from historical polio incidence rates and is designed to represent the uncertainties in transmission dynamics and poliovirus detection that are fundamental to interpreting long time periods without cases. The model estimates that, as of March 31, 2015, the probability of WPV1 elimination in Nigeria is 84%, and that if WPV1 has not been eliminated, a new case will be detected with 99% probability by the end of 2015. The probability of WPV3 elimination (and thus global eradication) is > 99%. However, it is unlikely that the ongoing transmission of cVDPV2 has been interrupted; the probability of cVDPV2 elimination rises to 83% if no new cases are detected by April 2016. Copyright: © 2015 Michael Famulare.


Bayati B.S.,Institute for Disease Modeling
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2016

We couple a stochastic collocation method with an analytical expansion of the canonical epidemiological master equation to analyze the effects of both extrinsic and intrinsic noise. It is shown that depending on the distribution of the extrinsic noise, the master equation yields quantitatively different results compared to using the expectation of the distribution for the stochastic parameter. This difference is incident to the nonlinear terms in the master equation, and we show that the deviation away from the expectation of the extrinsic noise scales nonlinearly with the variance of the distribution. The method presented here converges linearly with respect to the number of particles in the system and exponentially with respect to the order of the polynomials used in the stochastic collocation calculation. This makes the method presented here more accurate than standard Monte Carlo methods, which suffer from slow, nonmonotonic convergence. In epidemiological terms, the results show that extrinsic fluctuations should be taken into account since they effect the speed of disease breakouts and that the gamma distribution should be used to model the basic reproductive number. © 2016 American Physical Society.

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