Department of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/1807/16928

Dating back to 1843, the Department of Medicine at the University of Toronto is among the oldest and largest in North America. Coming through with its rich history of medical research breakthroughs, the department currently houses over 400 full-time faculty members and 400 post-graduate trainees and fellows that conduct cutting-edge research in its 19 divisions (cardiology, clinical pharmacology, dermatology, and many others). The department also plays a substantial role in the undergraduate M.D. program, as well as a proud supporter of an extensive program of continuing education as seen with its members engaged in the supervision of over 130 graduate students through the Institute of Medical Science, Program in Clinical Epidemiology and Health Care Research, and basic science departments.

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Non-invasive transcranial ultrasound stimulation for neuromodulation
(2022-03) Darmani, G; Bergmann, T O; Butts Pauly, K; Caskey, C F; de Lecea, L; Fomenko, A; Fouragnan, E; Legon, W; Murphy, K R; Nandi, T; Phipps, M A; Pinton, G; Ramezanpour, H; Sallet, J; Yaakub, S N; Yoo, S S; Chen, R
Transcranial ultrasound stimulation (TUS) holds great potential as a tool to alter neural circuits non-invasively in both animals and humans. In contrast to established non-invasive brain stimulation methods, ultrasonic waves can be focused on both cortical and deep brain targets with the unprecedented spatial resolution as small as a few cubic millimeters. This focusing allows exclusive targeting of small subcortical structures, previously accessible only by invasive deep brain stimulation devices. The neuromodulatory effects of TUS are likely derived from the kinetic interaction of the ultrasound waves with neuronal membranes and their constitutive mechanosensitive ion channels, to produce short term and long-lasting changes in neuronal excitability and spontaneous firing rate. After decades of mechanistic and safety investigation, the technique has finally come of age, and an increasing number of human TUS studies are expected. Given its excellent compatibility with non-invasive brain mapping techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), as well as neuromodulatory techniques, such as transcranial magnetic stimulation (TMS), systemic TUS effects can readily be assessed in both basic and clinical research. In this review, we present the fundamentals of TUS for a broader audience. We provide up-to-date information on the physical and neurophysiological mechanisms of TUS, available readouts for its neural and behavioral effects, insights gained from animal models and human studies, potential clinical applications, and safety considerations. Moreover, we discuss the indirect effects of TUS on the nervous system through peripheral co-stimulation and how these confounding factors can be mitigated by proper control conditions.
Induction of Human Motor Cortex Plasticity by Theta Burst Transcranial Ultrasound Stimulation
(2022-01) Zeng, Ke; Darmani, Ghazaleh; Fomenko, Anton; Xia, Xue; Tran, Stephanie; Nankoo, Jean-François; Shamli Oghli, Yazan; Wang, Yanqiu; Lozano, Andres M; Chen, Robert
Transcranial ultrasound stimulation (TUS) is a promising noninvasive brain stimulation technique with advantages of high spatial precision and ability to target deep brain regions. This study aimed to develop a TUS protocol to effectively induce brain plasticity in human subjects.
Toward a county-level map of tuberculosis rates in the U.S
(Elsevier, 2014-05) Scales, David; Brownstein, John S; Khan, Kamran; Cetron, Martin S
Zika virus in the Americas: Early epidemiological and genetic findings
(American Association for the Advancement of Science, 2016-04-15) Faria, Nuno Rodrigues; Azevedo, Raimunda do Socorro da Silva; Kraemer, Moritz U G; Souza, Renato; Cunha, Mariana Sequetin; Hill, Sarah C; Thézé, Julien; Bonsall, Michael B; Bowden, Thomas A; Rissanen, Ilona; Rocco, Iray Maria; Nogueira, Juliana Silva; Maeda, Adriana Yurika; Vasami, Fernanda Giseli da Silva; Macedo, Fernando Luiz de Lima; Suzuki, Akemi; Rodrigues, Sueli Guerreiro; Cruz, Ana Cecilia Ribeiro; Nunes, Bruno Tardeli; Medeiros, Daniele Barbosa de Almeida; Rodrigues, Daniela Sueli Guerreiro; Nunes Queiroz, Alice Louize; da Silva, Eliana Vieira Pinto; Henriques, Daniele Freitas; Travassos da Rosa, Elisabeth Salbe; de Oliveira, Consuelo Silva; Martins, Livia Caricio; Vasconcelos, Helena Baldez; Casseb, Livia Medeiros Neves; Simith, Darlene de Brito; Messina, Jane P; Abade, Leandro; Lourenço, José; Carlos Junior Alcantara, Luiz; de Lima, Maricélia Maia; Giovanetti, Marta; Hay, Simon I; de Oliveira, Rodrigo Santos; Lemos, Poliana da Silva; de Oliveira, Layanna Freitas; de Lima, Clayton Pereira Silva; da Silva, Sandro Patroca; de Vasconcelos, Janaina Mota; Franco, Luciano; Cardoso, Jedson Ferreira; Vianez-Júnior, João Lídio da Silva Gonçalves; Mir, Daiana; Bello, Gonzalo; Delatorre, Edson; Khan, Kamran; Creatore, Marisa; Coelho, Giovanini Evelim; de Oliveira, Wanderson Kleber; Tesh, Robert; Pybus, Oliver G; Nunes, Marcio R T; Vasconcelos, Pedro F C
Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.
Digital surveillance for enhanced detection and response to outbreaks
(Elsevier, 2014-11) Anema, Aranka; Kluberg, Sheryl; Wilson, Kumanan; Hogg, Robert S; Khan, Kamran; Hay, Simon I; Tatem, Andrew J; Brownstein, John S
Anticipating the international spread of Zika virus from Brazil
(Elsevier, 2016-01-23) Bogoch, Isaac I; Brady, Oliver J; Kraemer, Moritz U G; German, Matthew; Creatore, Marisa I; Kulkarni, Manisha A; Brownstein, John S; Mekaru, Sumiko R; Hay, Simon I; Groot, Emily; Watts, Alexander; Khan, Kamran
Entry and exit screening of airline travellers during the A(H1N1) 2009 pandemic: a retrospective evaluation
(World Health Organization, 2013) Khan, Kamran; Eckhardt, Rose; Brownstein, John S.; Naqvi, Raza; Hu, Wei; Kossowsky, David; Scales, David; Arino, Julien; MacDonald, Michael; Wang, Jun; Searsb, Jennifer; Cetronh, Martin S.
Objective: To evaluate the screening measures that would have been required to assess all travellers at risk of transporting A(H1N1)pdm09 out of Mexico by air at the start of the 2009 pandemic. Methods: Data from flight itineraries for travellers who flew from Mexico were used to estimate the number of international airports where health screening measures would have been needed, and the number of travellers who would have had to be screened, to assess all air travellers who could have transported the H1N1 influenza virus out of Mexico during the initial stages of the 2009 A(H1N1) pandemic. Findings: Exit screening at 36 airports in Mexico, or entry screening of travellers arriving on direct flights from Mexico at 82 airports in 26 other countries, would have resulted in the assessment of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico at the start of the pandemic. Entry screening of 116 travellers arriving from Mexico by direct or connecting flights would have been necessary for every one traveller at risk of transporting A(H1N1)pdm09. Screening at just eight airports would have resulted in the assessment of 90% of all air travellers at risk of transporting A(H1N1)pdm09 out of Mexico in the early stages of the pandemic. Conclusion: During the earliest stages of the A(H1N1) pandemic, most public health benefits potentially attainable through the screening of air travellers could have been achieved by screening travellers at only eight airports.
Active Tuberculosis among Homeless Persons, Toronto, Ontario, Canada, 1998–2007
(Centers for Disease Control and Prevention, 2011) Khan, Kamran; Rea, Elizabeth; McDermaid, Cameron; Stuart, Rebecca; Chambers, Catharine; Wang, Jun; Chan, Angie; Gardam, Michael; Jamieson, Frances; Yang, Jae; Hwang, Stephen W.
While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998–2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The proportion of homeless persons who were foreign-born increased from 24% in 1998–2002 to 39% in 2003–2007. Among foreign-born homeless persons with TB, 56% of infections were caused by strains not known to circulate among homeless persons in Toronto. Only 2% of infections were resistant to first-line TB medications. The rise in foreign-born homeless persons with TB strains likely acquired overseas suggests that the risk for drug-resistant strains entering the homeless shelter system may be escalating.
The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study
(Public Library of Science, 2012) Kwong, Jeffrey C.; Ratnasingham, Sujitha; Campitelli, Michael A.; Daneman, Nick; Deeks, Shelley L.; Manuel, Douglas G.; Allen, Vanessa G.; Bayoumi, Ahmed M.; Fazil, Aamir; Fisman, David N.; Gershon, Andrea S.; Gournis, Effie; Heathcote, E. Jenny; Jamieson, Frances B.; Jha, Prabhat; Khan, Kamran M.; Majowicz, Shannon E.; Mazzulli, Tony; McGeer, Allison J.; Muller, Matthew P.; Raut, Abhishek; Rea, Elizabeth; Remis, Robert S.; Shahin, Rita; Wright, Alissa J.; Zagorski, Brandon; Crowcroft, Natasha S.
Background: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.
Potential for the International Spread of Middle East Respiratory Syndrome in Association with Mass Gatherings in Saudi Arabia
(Public Library of Science, 2013) Khan, Kamran; Sears, Jennifer; Hu, Vivian Wei; Brownstein, John S.; Hay, Simon; Kossowsky, David; Eckhardt, Rose; Chim, Tina; Berry, Isha; Bogoch, Isaac; Cetron, Martin
Background: A novel coronavirus (MERS-CoV) causing severe, life-threatening respiratory disease has emerged in the Middle East at a time when two international mass gatherings in Saudi Arabia are imminent. While MERS-CoV has already spread to and within other countries, these mass gatherings could further amplify and/or accelerate its international dissemination, especially since the origins and geographic source of the virus remain poorly understood. Methods: We analyzed 2012 worldwide flight itinerary data and historic Hajj pilgrim data to predict population movements out of Saudi Arabia and the broader Middle East to help cities and countries assess their potential for MERS-CoV importation. We compared the magnitude of travel to countries with their World Bank economic status and per capita healthcare expenditures as surrogate markers of their capacity for timely detection of imported MERS-CoV and their ability to mount an effective public health response. Results: 16.8 million travelers flew on commercial flights out of Saudi Arabia, Jordan, Qatar, and the United Arab Emirates between June and November 2012, of which 51.6% were destined for India (16.3%), Egypt (10.4%), Pakistan (7.8%), the United Kingdom (4.3%), Kuwait (3.6%), Bangladesh (3.1%), Iran (3.1%) and Bahrain (2.9%). Among the 1.74 million foreign pilgrims who performed the Hajj last year, an estimated 65.1% originated from low and lower-middle income countries. Conclusion: MERS-CoV is an emerging pathogen with pandemic potential with its apparent epicenter in Saudi Arabia, where millions of pilgrims will imminently congregate for two international mass gatherings. Understanding global population movements out of the Middle East through the end of this year’s Hajj could help direct anticipatory MERS-CoV surveillance and public health preparedness to mitigate its potential global health and economic impacts.
Exploring the origin and potential for spread of the 2013 dengue outbreak in Luanda, Angola
(Co-Action Publishing, 2013) Sessions, October M.; Khan, Kamran; Hou, Yan’an; Quam, Mikkel; Schwartz, Eli; Gubler, Duane J.; Wilder-Smith, Annelies
Introduction: Dengue in Africa is underreported. Simultaneous reports of travellers with dengue returning from Luanda, Angola, to six countries on four continents suggest that a major dengue outbreak is currently occurring in Angola, South West Africa. Methods: To identify the origin of the imported dengue virus, we sequenced the virus from Angola and investigated the interconnectivity via air travel between dengue-endemic countries and Angola. Results and Conclusion: Our analyses show that the Angola outbreak was most likely caused by an endemic virus strain that had been circulating in West Africa for many years. We also show that Portugal and South Africa are most likely at the highest risk of importation of dengue from Angola due to the large number of air passengers between Angola and these countries.
Mapping the zoonotic niche of Ebola virus disease in Africa
(eLife Sciences Publications, 2014) Pigott, David M.; Golding, Nick; Mylne, Adrian; Huang, Zhi; Henry, Andrew J.; Weiss, Daniel J.; Brady, Oliver J.; Kraemer, Moritz U. G.; Smith, David L.; Moyes, Catherine L.; Bhatt, Samir; Gething, Peter W.; Horby, Peter W.; Bogoch, Isaac I.; Brownstein, John S.; Mekaru, Sumiko R.; Tatem, Andrew J.; Khan, Kamran; Hay, Simon I.
Ebola virus disease (EVD) is a complex zoonosis that is highly virulent in humans. The largest recorded outbreak of EVD is ongoing in West Africa, outside of its previously reported and predicted niche. We assembled location data on all recorded zoonotic transmission to humans and Ebola virus infection in bats and primates (1976–2014). Using species distribution models, these occurrence data were paired with environmental covariates to predict a zoonotic transmission niche covering 22 countries across Central and West Africa. Vegetation, elevation, temperature, evapotranspiration, and suspected reservoir bat distributions define this relationship. At-risk areas are inhabited by 22 million people; however, the rarity of human outbreaks emphasises the very low probability of transmission to humans. Increasing population sizes and international connectivity by air since the first detection of EVD in 1976 suggest that the dynamics of human-to-human secondary transmission in contemporary outbreaks will be very different to those of the past.
The 2012 dengue outbreak in Madeira: Exploring the origins
(European Centre for Disease Prevention and Control, 2014) Wilder-Smith, A.; Quam, M.; Sessions, O.; Rocklov, J.; Liu-Helmersson, J.; Franco, L.; Khan, K.
In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.
International Dispersal of Dengue through Air Travel: Importation Risk for Europe
(Public Library of Science, 2014) Semenza, Jan C.; Sudre, Bertrand; Miniota, Jennifer; Rossi, Massimiliano; Hu, Wei; Kossowsky, David; Suk, Jonathan E.; Van Bortel, Wim; Khan, Kamran
Background: The worldwide distribution of dengue is expanding, in part due to globalized traffic and trade. Aedes albopictus is a competent vector for dengue viruses (DENV) and is now established in numerous regions of Europe. Viremic travellers arriving in Europe from dengue-affected areas of the world can become catalysts of local outbreaks in Europe. Local dengue transmission in Europe is extremely rare, and the last outbreak occurred in 1927–28 in Greece. However, autochthonous transmission was reported from France in September 2010, and from Croatia between August and October 2010. Methodology: We compiled data on areas affected by dengue in 2010 from web resources and surveillance reports, and collected national dengue importation data. We developed a hierarchical regression model to quantify the relationship between the number of reported dengue cases imported into Europe and the volume of airline travellers arriving from dengue-affected areas internationally. Principal Findings: In 2010, over 5.8 million airline travellers entered Europe from dengue-affected areas worldwide, of which 703,396 arrived at 36 airports situated in areas where Ae. albopictus has been recorded. The adjusted incidence rate ratio for imported dengue into European countries was 1.09 (95% CI: 1.01–1.17) for every increase of 10,000 travellers; in August, September, and October the rate ratios were 1.70 (95%CI: 1.23–2.35), 1.46 (95%CI: 1.02–2.10), and 1.35 (95%CI: 1.01–1.81), respectively. Two Italian cities where the vector is present received over 50% of all travellers from dengue-affected areas, yet with the continuing vector expansion more cities will be implicated in the future. In fact, 38% more travellers arrived in 2013 into those parts of Europe where Ae. albopictus has recently been introduced, compared to 2010. Conclusions: The highest risk of dengue importation in 2010 was restricted to three months and can be ranked according to arriving traveller volume from dengue-affected areas into cities where the vector is present. The presence of the vector is a necessary, but not sufficient, prerequisite for DENV onward transmission, which depends on a number of additional factors. However, our empirical model can provide spatio-temporal elements to public health interventions.
Assessing the Origin of and Potential for International Spread of Chikungunya Virus from the Caribbean
(Public Library of Science, 2014) Khan, Kamran; Bogoch, Isaac; Brownstein, John S.; Miniota, Jennifer; Nicolucci, Adrian; Hu, Wei; Nsoesie, Elaine O.; Cetron, Martin; Creatore, Maria Isabella; German, Matthew; Wilder-Smith, Annelies
Background: For the first time, an outbreak of chikungunya has been reported in the Americas. Locally acquired infections have been confirmed in fourteen Caribbean countries and dependent territories, Guyana and French Guiana, in which a large number of North American travelers vacation. Should some travelers become infected with chikungunya virus, they could potentially introduce it into the United States, where there are competent Aedes mosquito vectors, with the possibility of local transmission. Methods: We analyzed historical data on airline travelers departing areas of the Caribbean and South America, where locally acquired cases of chikungunya have been confirmed as of May 12th, 2014. The final destinations of travelers departing these areas between May and July 2012 were determined and overlaid on maps of the reported distribution of Aedes aeygpti and albopictus mosquitoes in the United States, to identify potential areas at risk of autochthonous transmission. Results: The United States alone accounted for 52.1% of the final destinations of all international travelers departing chikungunya indigenous areas of the Caribbean between May and July 2012. Cities in the United States with the highest volume of air travelers were New York City, Miami and San Juan (Puerto Rico). Miami and San Juan were high travel-volume cities where Aedes aeygpti or albopictus are reported and where climatic conditions could be suitable for autochthonous transmission. Conclusion: The rapidly evolving outbreak of chikungunya in the Caribbean poses a growing risk to countries and areas linked by air travel, including the United States where competent Aedes mosquitoes exist. The risk of chikungunya importation into the United States may be elevated following key travel periods in the spring, when large numbers of North American travelers typically vacation in the Caribbean.
Assessment of the potential for international dissemination of Ebola virus via commercial air travel during the 2014 west African outbreak
(Elsevier, 2015) Bogoch, Isaac I.; Creatore, Maria I.; Cetron, Martin S.; Brownstein, John S.; Pesik, Nicki; Miniota, Jennifer; Tam, Theresa; Hu, Wei; Nicolucci, Adriano; Ahmed, Saad; Yoon, James W.; Berryc, Isha; Hay, Simon I.; Anema, Aranka; Tatem, Andrew J.; MacFadden, Derek; German, Matthew; Khan, Kamran
Background: The WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports. Methods: We analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus. Findings: Based on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2·8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91 547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk of exposure to Ebola virus infection. Interpretation: Decision makers must carefully balance the potential harms from travel restrictions imposed on countries that have Ebola virus activity against any potential reductions in risk from Ebola virus importations. Exit screening of travellers at airports in Guinea, Liberia, and Sierra Leone would be the most efficient frontier at which to assess the health status of travellers at risk of Ebola virus exposure, however, this intervention might require international support to implement effectively.
Potential for international spread of wild poliovirus via travelers
(BioMed Central, 2015) Wilder-Smith, Annelies; Leong, Wei-Yee; Lopez, Luis Fernandez; Amaku, Marcos; Quam, Mikkel; Khan, Kamran; Massad, Eduardo
Background: The endgame of polio eradication is hampered by the international spread of poliovirus via travelers. In response to ongoing importations of poliovirus into polio-free countries, on 5 May 2014, WHO’s Director-General declared the international spread of wild poliovirus a public health emergency of international concern. Our objective was to develop a mathematical model to estimate the international spread of polio infections. Methods: Our model took into account polio endemicity in polio-infected countries, population size, polio immunization coverage rates, infectious period, the asymptomatic-to-symptomatic ratio, and also the probability of a traveler being infectious at the time of travel. We applied our model to three scenarios: (1) number of exportations of both symptomatic and asymptomatic polio infections out of currently polio-infected countries, (2) the risk of spread of poliovirus to Saudi Arabia via Hajj pilgrims, and (3) the importation risk of poliovirus into India. Results: Our model estimated 665 polio exportations (>99 % of which were asymptomatic) from nine polio-infected countries in 2014, of which 78.3 % originated from Pakistan. Our model also estimated 21 importations of poliovirus into Saudi Arabia via Hajj pilgrims and 20 poliovirus infections imported to India in the same year. Conclusion: The extent of importations of asymptomatic and symptomatic polio infections is substantial. For countries that are vulnerable to polio outbreaks due to poor national polio immunization coverage rates, our newly developed model may help guide policy-makers to decide whether imposing an entry requirement in terms of proof of vaccination against polio would be justified.
The Effects of Media Reports on Disease Spread and Important Public Health Measurements
(Public Library of Science, 2015) Collinson, Shannon; Khan, Kamran; Heffernan, Jane M.
Controlling the spread of influenza to reduce the effects of infection on a population is an important mandate of public health. Mass media reports on an epidemic or pandemic can provide important information to the public, and in turn, can induce positive healthy behaviour practices (i.e., handwashing, social distancing) in the individuals, that will reduce the probability of contracting the disease. Mass media fatigue, however, can dampen these effects. Mathematical models can be used to study the effects of mass media reports on epidemic/pandemic outcomes. In this study we employ a stochastic agent based model to provide a quantification of mass media reports on the variability in important public health measurements. We also include mass media report data compiled by the Global Public Health Intelligence Network, to study the effects of mass media reports in the 2009 H1N1 pandemic. We find that the report rate and the rate at which individuals relax their healthy behaviours (media fatigue) greatly affect the variability in important public health measurements. When the mass media reporting data is included in the model, two peaks of infection result.
Global travel patterns and risk of measles in Ontario and Quebec, Canada: 2007–2011
(BioMed Central, 2016) Wilson, Sarah E.; Khan, Kamran; Gilca, Vladimir; Miniota, Jennifer; Deeks, Shelley L.; Lim, Gillian; Eckhardt, Rose; Bolotin, Shelly; Crowcroft, Natasha S.
Background: In 2011 the largest measles outbreak in North America in a decade occurred in Quebec, Canada with over 700 cases. In contrast, measles activity in neighbouring province Ontario remained low (8 cases). Our objective was to determine the extent to which the difference could be explained by differing travel patterns. Methods: We explored the relationship between measles cases over 2007–2011, by importation classification, in Quebec and Ontario in relation to global travel patterns to each province using an ecological approach. Global measles exposure was estimated by multiplying the monthly traveler volume for each country of origin into Quebec or Ontario by the yearly measles incidence rate for the corresponding country. Visual inspection of temporal figures and calculation of Pearson correlation coefficients were performed. Results: Global measles exposure was similar in Ontario and Quebec. In Quebec, there was a nearly perfectly linear relationship between annual measles cases and its global measles exposure index over 2007–2011 (r = 0.99, p = 0.001). In contrast, there was a non-significant association in Ontario. The 2011 rise in Quebec’s index was largely driven by a dramatic increase in measles activity in France the same year. Conclusions: Global measles activity was associated with measles epidemiology in Quebec. Global measles exposure risk is higher in Ontario than Quebec. Differences in measles epidemiology between Ontario and Quebec from 2007–2011 are not explained by greater exposure in Quebec. A combination of alternative factors may be responsible, including differences in population susceptibility.
Assessing Seasonal Risks for the Introduction and Mosquito-borne Spread of Zika Virus in Europe
(Elsevier, 2016) Rocklöv, Joacim; Quam, Mikkel Brandon; Sudre, Bertrand; German, Matthew; Kraemer, Moritz U.G.; Brady, Oliver; Bogoch, Isaac I.; Liu-Helmersson, Jing; Wilder-Smith, Annelies; Semenza, Jan C.; Ong, Mark; Aaslav, Kaja Kaasik; Khan, Kamran
The explosive Zika virus epidemic in the Americas is amplifying spread of this emerging pathogen into previously unaffected regions of the world, including Europe (Gulland, 2016), where local populations are immunologically naïve. As summertime approaches in the northern hemisphere, Aedes mosquitoes in Europe may find suitable climatic conditions to acquire and subsequently transmit Zika virus from viremic travellers to local populations. While Aedes albopictus has proven to be a vector for the transmission of dengue and chikungunya viruses in Europe ( Delisle, E., et al., 2015 and ECDC,, n.d) there is growing experimental and ecological evidence to suggest that it may also be competent for Zika virus(Chouin-Carneiro et al., 2016; Grard et al., 2014; Li et al., 2012; Wong et al., 2013). Here we analyze and overlay the monthly flows of airline travellers arriving into European cities from Zika affected areas across the Americas, the predicted monthly estimates of the basic reproduction number of Zika virus in areas where Aedes mosquito populations reside in Europe (Aedes aegypti in Madeira, Portugal and Ae. albopictus in continental Europe), and human populations living within areas where mosquito-borne transmission of Zika virus may be possible. We highlight specific geographic areas and timing of risk for Zika virus introduction and possible spread within Europe to inform the efficient use of human disease surveillance, vector surveillance and control, and public education resources.

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