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[Modelling the impact of pandemic influenza].

The impact of the next influenza pandemic is difficult to predict. It is dependent on how virulent the virus is, how rapidly it spreads from population to population, and the effectiveness of prevention and response efforts. Despite the uncertainty about the magnitude of the next pandemic, estimates of the health and economic impact remain important to aid public health policy decisions and guide pandemic planning for health and emergency sectors. Planning ahead in preparation for an influenza pandemic, with its potentially very high morbidity and mortality rates, is essential for hospital administrators and public health officials. The estimation of pandemic impact is based on the previous pandemics--we had experienced at least 3 pandemics in 20th century. But the epidemiological characteristics--ie, start season, the impact of 1st wave, pathogenicity and virulence of the viruses and the primary victims of population were quite different from one another. I reviewed methodology for estimation and modelling of pandemic impact and described some nations's results using them in their national preparedness plans. And then I showed the estimates of pandemic influenza impact in Korea with FluSurge and FluAid. And, I described the results of pandemic modelling with parameters of 1918 pandemic for the sake of education and training of the first-line responder health officials to the epidemics. In preparing influenza pandemics, the simulation and modelling are the keys to reduce the uncertainty of the future and to make proper policies to manage and control the pandemics.

Computer Simulation↗

A hypothesis: Sunspot cycles may detect pandemic influenza A in 1700-2000 A.D.

BACKGROUND: Influenza pandemics in this century (1946-1947, 1957 and 1968) have fascinated some people for the idea of 11-year pattern pandemic cycles. In solar physics, it is well known that sunspot cycles also have regular periods of around 11 years. This study therefore aims to investigate the association between sunspot cycles and the occurrences of pandemic influenza. The hypothesis here states that sunspot numbers can detect pandemic influenza A between 1700 and 2000 A.D. PRESENTATION OF THE HYPOTHESIS: Antigenic shift of influenza occurs is a result of genetic reassortment between animal and human influenza A viruses. It is suggested the viruses spread from the migratory birds to other avian species such as chicken or ducks along their migratory pathways. Solar activity has an influence on terrestrial climate in terms of temperature, rainfall, storms and finally the biological systems. It was shown that the arrival dates of some migratory birds were delayed with increased sunspot numbers. This delay arrival may be associated with increased contacts with other susceptible birds in their migratory routes that facilitate genetic reassortment of the circulating influenza viruses. TEST THE HYPOTHESIS: Comprehensive reviews on both pandemics and possible pandemics of influenza were searched. International sunspot numbers were obtained from the World Data Center for Sunspot Index, Belgium and used to detect pandemics by binomial test. Five comprehensive reviews were found and the agreements on pandemics were good to excellent. Sensitivity of using Sunspot Number more than 50 (SSN>50) to detect pandemics increased as the levels of agreements increased. In stringent criteria, two pandemics might have occurred in the 18th century (1729-1733 and 1781-1782), two in the 19th century (1830-1833 and 1889-1892) and three in the 20th century (1918-1920, 1957-1958 and 1968-1969). The sensitivity of using SSN>50 to detect influenza pandemics was 85.7% (95%CI=59.8-100%, p=0.019). The specificity was 51.2% (95%CI=35.9-66.5%). IMPLICATIONS OF THE HYPOTHESIS: On top of virological and epidemiological surveillance, sunspot cycles may be an inexpensive and easy method to detect influenza pandemics. The next high risk period will be around 2008-2013 and it may suggest us to be more alert and be prepared in order to minimize unnecessary deaths as a result of influenza.

Disease Outbreaks↗

The GP's response to pandemic influenza: a qualitative study.

BACKGROUND: Current pandemic influenza plans to place GPs at the front line of a pandemic influenza response. However, little is known about GPs' perceptions of their role and preparedness in the event of a pandemic occurring. OBJECTIVE: Our aim was to assess general practice preparedness to respond to pandemic influenza and to identify issues that need to be addressed to enhance preparedness for the next pandemic. METHODS: We conducted a series of semi-structured interviews to explore GPs' views regarding their role in responding to pandemic influenza, practice preparedness and planning issues, and the expectations and requirements of GPs for provision of professional services during a pandemic. The subjects were 60 Australian GPs, purposively selected to maximize diversity within the sample. RESULTS: GPs in this study expressed a willingness to provide professional services in a pandemic. The motivation for this was largely altruistic and was in the context of high personal risk of becoming infected. Participants did not have stockpiles of antivirals or personal protective equipment within their practices and felt that government had a duty of care to stockpile on behalf of the general practice workforce. Participants were enthusiastic about receiving further information and training in pandemic preparedness. The most appropriate setting for this was within practices. CONCLUSIONS: GPs were willing to provide clinical services in a pandemic. However, appropriate education, training and supply of equipment were necessary to support them in this role. This information will inform further planning for the public health response to pandemic influenza.

Adult↗

Avian influenza: an omnipresent pandemic threat.

BACKGROUND: Humans have faced 3 major influenza pandemics in the 20th century. In recent years, it has become evident that domestic poultry play an important role in the generation of novel influenza strains with the capacity to cross the species barrier and infect and kill humans at an alarming rate. There is particular concern that avian influenza viruses of the H5N1 subtype could cause a pandemic. METHODS: A better understanding of the genetic factors that lead to interspecies transmission is essential to prevent the emergence of influenza pandemics. In addition, the stockpiling of antiviral drugs and development of vaccines against potentially pandemic viruses must be considered under the umbrella of pandemic plans. RESULTS: The world is ill-prepared to face an influenza pandemic. Only a handful of countries have developed influenza pandemic plans, and even fewer are developing vaccines or stockpiling antiinfluenza drugs to ameliorate the impact of a potential pandemic. Currently the major undertaking in several at risk nations is to implement effective control measures to stop the spread of the virus at its source, that is, avian species. These measures include the culling of domestic poultry to contain the virus, a practice that could eventually bring these countries to a financial and social breaking point. CONCLUSIONS: Avian influenza disease is preventable in humans and birds with the concerted effort of governments and poultry producers, large and small, to improve biosecurity and education programs. Pandemic plans can reduce the impact of the pandemic; however, preventing avian influenza in poultry can avert a pandemic altogether.

Amino Acid Sequence↗

[The preparedness plan for influenza pandemic].

Influenza A viruses periodically cause worldwide epidemics, or pandemics, with high rates of illness and death. A pandemic can occur at any time, with the potential to cause serious illness, death and social and economic disruption throughout the world. Historic evidence suggests that pandemics occurred three to four times per century. In the last century there were three influenza pandemics. The circumstances still exist for a new influenza virus with pandemic potential to emerge and spread. The unpredictability of the timing of the next pandemic is underlined by the occurrence of several large outbreaks of highly pathogenic avian influenza since the early 1980s. In 1999, the World Health Organization published the Influenza pandemic plan. The role of WHO and guidelines for national and regional planning. And in 2005, WHO revised the global influenza preparedness plan for new national measures before and during pandemics. This document outlines briefly the Korean Centers for Disease Control's plan for responding to an influenza pandemic. According to the new pandemic phases of WHO, we set up the 4 national levels of preparedness and made guidelines for preventing and control the epidemics in each phase. And also we described the future plans to antiviral stockpiles and pandemic vaccine development.

Disease Outbreaks↗

Cases and deaths during influenza pandemics in the United States.

OBJECTIVE: To assess how numbers and age distributions of cases and deaths during an influenza pandemic in the United States would potentially vary from those during the 1918-1919 pandemic, given the same virulence of the pandemic strain. METHODS: Influenza cases and deaths in two referent populations (U.S. residents in 1917 and 2006) were calculated using clinical case rates from three pandemics (1918-like, 1957-like, and 1968-like) and case fatality rates from the 1918-1919 pandemic. RESULTS: Across pandemic scenarios, overall case ("attack") rates ranged from 24.7% to 34.2%, and overall death rates ranged from 4.4 to 6.7 per 1000. In both referent populations, total cases and deaths were significantly higher when using 1957-like and 1968-like, compared to 1918-like, case rates. Under all pandemic scenarios, the most deaths occurred among those aged 25 to 29 years. However, in the 2006 referent population, there were large numbers and high proportions of deaths in middle-aged and elderly adults (unlike during the 1918-1919 pandemic). CONCLUSIONS: Numbers and distributions of cases and deaths during influenza pandemics depend on numbers of individuals, clinical case rates, and case fatality rates in relation to age. During a future pandemic in the United States, influenza deaths will likely not be as sharply focused in young adults as in 1918-1919 (even if case fatality rates are similar) because of larger proportions of middle-aged and elderly adults and potentially higher case rates among adults older than 30.

Adolescent↗

Influenza pandemic planning.

Periodically, novel influenza viruses emerge and spread rapidly through susceptible populations, resulting in worldwide epidemics or pandemics. Three pandemics occurred in the 20th century. The first and most devastating of these, the "Spanish Flu" (A/H1N1) pandemic of 1918-1919, is estimated to have resulted in 20-50 million or more deaths worldwide, with unusually high mortality among young adults [C.W. Potter, Chronicle of influenza pandemics, in: K.G. Nicholson, R.G. Webster, A.J. Hay (Eds.), Textbook of Influenza, Blackwell Science, Oxford, 1998, p. 3]. Mortality associated with the 1957 "Asian Flu" (A/H2N2) and the 1968 "Hong Kong Flu" (A/H3N2) pandemics was less severe, with the highest excess mortality in the elderly and persons with chronic diseases [J. Infect. Dis. 178 (1998) 53]. However, considerable morbidity, social disruption and economic loss occurred during both of these pandemics [J. Infect. Dis. 176 (Suppl. 1) (1997) S4]. It is reasonable to assume that future influenza pandemics will occur, given historical evidence and current understanding of the biology, ecology, and epidemiology of influenza. Influenza viruses are impossible to eradicate, as there is a large reservoir of all subtypes of influenza A viruses in wild aquatic birds. In agricultural-based communities with high human population density such as are found in China, conditions exist for the emergence and spread of pandemic viruses. It is also impossible to predict when the next pandemic will occur. Moreover, the severity of illness is also unpredictable, so contingency plans must be put in place now during the inter-pandemic period. These plans must be flexible enough to respond to different levels of disease.

Bioterrorism↗

The epidemiology and clinical impact of pandemic influenza.

It is impossible to predict when the next pandemic of influenza will occur; however, it is almost 35 years since the last pandemic, and the longest inter-pandemic interval recorded with certainty is 39 years. The next pandemic virus is likely to emerge in southeast Asia, as have two of the last three pandemic viruses. Complete global spread is likely to occur in 6 months or less, due to increased travel and urbanisation. It is likely that the usual inter-pandemic pattern of age-specific mortality will deviate temporarily towards higher mortality in younger adults. The extent to which this will happen is unclear, as the shift was extreme in 1918-1919 but less so in subsequent pandemics. Nevertheless, this may have important implications for the protection of essential workers such as health care, emergency service and military personnel. The extent to which elderly persons will be affected will depend upon previous exposure to similar influenza viruses. It is impossible to predict the likely increase in excess mortality that will occur when a new pandemic virus emerges. However, whilst mortality on the scale experienced in 1918-1919 is probably unlikely, there was a high level of mortality among those infected with the A/H5N1 virus in 1997, so it cannot be assumed that a future pandemic will be as mild as those in 1957-1958 or 1968-1969. There is likely to be more than one wave of infection and health services in most countries will be hard pressed to provide vaccines or to manage populations with clinical attack rates of approximately 25-30% and concomitant increases in demand for both primary and secondary health care services.

Age Factors↗

Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness.

It is commonly believed that the clinical and epidemiological characteristics of the next influenza pandemic will mimic those of the 1918 pandemic. Determinative beliefs regarding the 1918 pandemic include that infections were expressed as primary viral pneumonias and/or acute respiratory distress syndrome, that pandemic-related deaths were the end states of the natural progression of disease caused by the pandemic strain, and that bacterial superinfections caused relatively fewer deaths in 1918 than in subsequent pandemics. In turn, response plans are focused on developing and/or increasing inventories of a strain-specific vaccine, antivirals, intensive care beds, mechanical ventilators, and so on. Yet, there is strong and consistent evidence of epidemiologically and clinically important interactions between influenza and secondary bacterial respiratory pathogens, including during the 1918 pandemic. Countermeasures (eg, vaccination against pneumococcal and meningococcal disease before a pandemic; mass uses of antibiotic(s) with broad spectrums of activity against common bacterial respiratory pathogens during local epidemics) designed to prevent or mitigate the effects of influenza-bacterial interactions should be major focuses of pandemic-related research, prevention, and response planning.

Bacterial Infections↗

The next influenza pandemic: lessons from Hong Kong.

Pandemic influenza is a zoonosis. Studies on influenza ecology conducted in Hong Kong since the 1970s in which Hong Kong essentially functioned as an influenza sentinel post indicated that it might be possible, for the first time, to have influenza preparedness at the baseline avian level. This appreciation of influenza ecology facilitated recognition of the H5N1 'bird flu' incident in Hong Kong in 1997 in what was considered to be an incipient pandemic situation, the chicken being the source of virus for humans and, if so, was the first instance where a pandemic may have been averted. The 2001 and 2002 H5N1 incidents demonstrated that it was possible to have an even higher order of baseline preparedness with the recognition in chicken of a range of genotypes of H5N1-like viruses before they had the opportunity to infect humans. Investigations of these incidents revealed a complex ecology involving variously precursor avian H5N1 virus in geese and ducks, and H9N2 and H6N1 viruses in quail, the quail possibly functioning as an avian 'mixing vessel' for key genetic reassortment events for onward transmission of H5N1 viruses highly pathogenic for chicken and humans. These findings highlight the importance of systematic virus surveillance of domestic poultry in recognizing changes in virus occurrence, host range and pathogenicity as signals at the avian level that could presage a pandemic. For example, there is now an increasing prevalence of avian influenza viruses in terrestrial (in contrast to aquatic) poultry. Prior to 1997, no particular virus subtype other than H4N6 would have been considered a candidate for pandemicity and this was based, in the absence of any other data, on its high frequency of occurrence in ducks in southern China. Now,with the isolation of H5N1 and H9N2 viruses from humans supported by genetic, molecular and biological studies on these and other avian isolates, there is credible evidence for the candidacy, in order, of H5N1, H9N2 and H6N1 viruses. These viruses have been made available for the production of diagnostic reagents and exploratory vaccines. The 1997 incident upheld the hypothesis that southern China is an epicentre for the emergence of pandemic influenza viruses. However, the intensification of the poultry (chicken) industry worldwide coupled with the spread of viruses such as the Eurasian lineage of H9N2 suggest that the genesis of a pandemic could take place elsewhere in the world. This re-emphasizes the importance of systematic virus surveillance of poultry globally for international public health and for economic and food concerns. Faced with an incipient pandemic in 1997, Hong Kong brought in international experts to join the investigative effort. Good teamwork at all levels is essential in dealing with the many facets. The threat of a pandemic should not be minimized, nor should governments be lulled into a sense of false security. The media is a powerful channel and has the responsibility and the avenues to convey and influence public perception of events. Close liaison between the media and those on the operational side ensures effective, accurate and timely dissemination of information. This will enhance public confidence in the investigative process and in steps taken for its safety and health.

Animals↗

The evolutionary emergence of pandemic influenza.

Pandemic influenza remains a serious public health threat and the processes involved in the evolutionary emergence of pandemic influenza strains remain incompletely understood. Here, we develop a stochastic model for the evolutionary emergence of pandemic influenza, and use it to address three main questions. (i) What is the minimum annual number of avian influenza virus infections required in humans to explain the historical rate of pandemic emergence? (ii) Are such avian influenza infections in humans more likely to give rise to pandemic strains if they are driven by repeated cross-species introductions, or by low-level transmission of avian influenza viruses between humans? (iii) What are the most effective interventions for reducing the probability that an influenza strain with pandemic potential will evolve? Our results suggest that if evolutionary emergence of past pandemics has occurred primarily through viral reassortment in humans, then thousands of avian influenza virus infections in humans must have occurred each year for the past 250 years. Analyses also show that if there is epidemiologically significant variation among avian influenza virus genotypes, then avian virus outbreaks stemming from repeated cross-species transmission events result in a greater likelihood of a pandemic strain evolving than those caused by low-level transmission between humans. Finally, public health interventions aimed at reducing the duration of avian virus infections in humans give the greatest reduction in the probability that a pandemic strain will evolve.

Animals↗

Avian influenza pandemic threat and health systems response.

Avian influenza is a panzootic and recurring human epidemic with pandemic potential. Pandemic requirements for a viral pathogen are: a novel virus must emerge against which the general population has little or no immunity; the new virus must be able to replicate in humans and cause serious illness; and the new virus must be efficiently transmitted from person to person. At present, only the first two conditions have been met. Nonetheless, influenza pandemics are considered inevitable. Expected worldwide human mortality from a moderate pandemic scenario is 45 million people or more than 75% of the current annual global death burden. Although mathematical models have predicted that an emerging pandemic could be contained at its source, this conclusion remains controversial among public health experts. The Terrestrial Animal Health Code and International Health Regulations are enforceable legal instruments integral to pandemic preparedness. Donor support in financial, material and technical assistance remains critical to disease control efforts - particularly in developing countries where avian influenza predominately occurs at present. Personal protective equipment kits, decontamination kits and specimen collection kits in lightweight, portable packages are becoming standardized. Air transport border control measures purporting to delay importation and spread of human avian influenza are scientifically controversial. National pandemic plans prioritize beneficiary access to antiviral drugs and vaccines for some countries. Other medical commodities including ventilators, hospital beds and intensive care units remain less well prioritized in national plans. These resources will play virtually no role in care of the overwhelming majority of patients worldwide in a pandemic. Prehospital care, triage and acute care all require additional professional standardization for the high patient volumes anticipated in a pandemic.

Cluster Analysis↗

Genotypic analyses of Vibrio parahaemolyticus and development of a pandemic group-specific multiplex PCR assay.

A total of 54 Vibrio parahaemolyticus strains including pandemic O3:K6 strains and newly emerged O4:K68, O1:K25, O1:K26, and O1:K untypeable strains (collectively referred to as the "pandemic group") were examined for their pulsed-field gel electrophoresis (PFGE) and arbitrarily primed PCR (AP-PCR) profiles and for the presence or absence of genetic marker DNA sequences, toxRS/new or orf8, that had been reported elsewhere to be specific for the pandemic group. Both PFGE and AP-PCR analyses indicated that all strains of the pandemic group formed a distinct genotypic cluster, suggesting that they originated from the same clone. In addition to the pandemic group, four O3:K6 strains that did not possess the thermostable direct hemolysin (tdh) gene also belonged to this cluster and possessed the toxRS/new sequence. However, three O3:K6 strains that clearly belonged to the pandemic group by PFGE and AP-PCR did not possess the orf8 sequence. The evidence suggests that neither the toxRS/new nor the orf8 sequence is a reliable gene marker for definite identification of the pandemic group. We therefore developed a novel multiplex PCR assay specific for the pandemic group. The assay successfully distinguished pandemic group strains from other V. parahaemolyticus strains by yielding two distinct PCR products for tdh (263 bp) and the toxRS/new sequence (651 bp).

Bacterial Proteins↗

Pandemics, avian influenza A (H5N1), and a strategy for pharmacists.

Epidemics of influenza occur annually and account for more morbidity in the developed world than all other respiratory diseases combined. On average, 36,000 Americans die from influenza or its complications each year. Pandemics occur when influenza viruses undergo either antigenic drift or antigenic shift that results in a new viral strain that infects humans, when they are capable of sustained transmission from person-to-person, and when they are introduced in populations with little or no preexisting immunity. The influenza pandemic of 1918 caused an estimated 20-40 million deaths worldwide. An avian influenza A (H5N1) virus, currently circulating in Asia, has pandemic potential. However, no evidence currently exists that a pandemic is occurring. Pharmacists are uniquely positioned to initiate nearterm practice changes that may positively impact both seasonal and potential pandemic morbidity and mortality. Pharmacists must be immunization advocates and provide pharmaceutical care that includes evaluation of immunization status. Increasing immunization to prevent invasive pneumococcal disease, as well as seasonal influenza immunization, is encouraged. A pandemic vaccine represents the most effective strategy to mitigate the effects of a pandemic. Antiviral agents represent a treatment bridge until a pandemic-specific vaccine is available. The neuraminidase inhibitors oseltamivir and zanamivir are active against H5N1, although oseltamivir resistance has been reported. Advances in vaccine research, development, and production through the use of reverse-genetics systems represent the most effective technology to rapidly produce a pandemic influenza vaccine.

Antiviral Agents↗

Assessment of evolution of pandemic Vibrio parahaemolyticus by multilocus sequence typing.

The genetic relatedness of 81 isolates of Vibrio parahaemolyticus was assessed by multilocus sequence typing. The strain with serotype O3:K6 emerged as a pandemic pathogen in 1996, with subsequent expansion to include strains having serotypes O1:KUT, O4:K68, and O1:K25. Sequence data from gyrB, recA, dnaE, and gnd revealed that 16 distinct serogroups isolated prior to the pandemic were highly variable and only isolates of serogroup O3:K6 shared two alleles with the pandemic strains. The pandemic strains regardless of serotype were clonal, with 51 of 54 isolates having the identical allelic profile (AP). Serotype alone did not adequately define a pandemic strain: among O1:KUT strains tested, seven strains with the identical pandemic AP carried previously described pandemic markers, while five nonpandemic strains had five distinct APs. Our sequence data provide strong molecular support for the clonal origin of pandemic V. parahaemolyticus O3:K6 and suggest that strains within such a clonal group may acquire previously identified serotypes.

Genes, Bacterial↗

Surge capacity associated with restrictions on nonurgent hospital utilization and expected admissions during an influenza pandemic: lessons from the Toronto severe acute respiratory syndrome outbreak.

BACKGROUND: Current influenza pandemic models predict a surge in influenza-related hospitalizations in affected jurisdictions. One proposed strategy to increase hospital surge capacity is to restrict elective hospitalizations, yet the degree to which this measure would meet the anticipated is unknown. OBJECTIVES: To compare the reduction in hospitalizations resulting from widespread nonurgent hospital admission restrictions during the Toronto severe acute respiratory syndrome (SARS) outbreak with the expected increase in admissions resulting from an influenza pandemic in Toronto. METHODS: The authors compared the expected influenza-related hospitalizations in the first eight weeks of a mild, moderate, or severe pandemic with the actual reduction in the number of hospital admissions in Toronto, Ontario, during the first eight weeks of the SARS-related restrictions. RESULTS: Influenza modeling for Toronto predicts that there will be 4,819, 8,032, or 11,245 influenza-related admissions in the first eight weeks of a mild, moderate, or severe pandemic, respectively. In the first eight weeks of SARS-related hospital admission restrictions, there were 3,654 fewer hospitalizations than expected in Toronto, representing a modest 12% decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000 population). Therefore, influenza-related admissions could exceed the reduction in admissions resulting from restricted hospital utilization by 1,165 to 7,591 patient admissions, depending on pandemic severity, which corresponds to an excess of 0.44 to 2.91 influenza-related admissions per 1,000 population per eight weeks, and an increase of 4% to 25% in the overall number of admissions, when compared with nonpandemic conditions. CONCLUSIONS: Pandemic modeling for Toronto suggests that influenza-related admissions would exceed the reduction in hospitalizations seen during SARS-related nonurgent hospital admission restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic will likely require the implementation of other measures, including possibly stricter implementation of hospital utilization restrictions.

Bed Occupancy↗

The threat and prospects for control of an influenza pandemic.

Influenza constitutes the most widespread and significant respiratory infectious disease in the world, resulting in increased morbidity, mortality and economic loss each epidemic year. Pandemic influenza is a worldwide epidemic usually caused by a new virus variant to which the majority of the population has no immunity. As demonstrated in the devastating pandemic of 1918 to 1919, a pandemic virus may infect 30 to 50% of the worlds population and kill 1 to 2% of those infected. Pandemic control must be a concerted and co-ordinated world strategy and under the auspices of the World Health Organization, pandemic preparedness plans have been formulated, including: intensified surveillance for more rapid identification of new reassortant viruses with potential human virulence and infectivity, laboratory characterization of the new viruses so that vaccine may be prepared, development of techniques for more rapid vaccine production and the manufacture and stock piling of antiviral drugs. The H5N1 outbreak of virulent chicken influenza in 1997 in Hong Kong which resulted in the deaths of six of 18 infected persons serves as a wake-up call. Should such a virus attain high transmissibility in humans, a pandemic of tragic proportions might ensue. Even though the timing of onset of the next pandemic cannot be precisely predicted, world governments must understand the urgency of the problem and increase funding for influenza pandemic control.

Adjuvants, Immunologic↗

Reconstructing the early spatial spread of pandemic respiratory viruses in the United States.

Understanding the geographic spread of emerging respiratory viruses is critical for pandemic preparedness, yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic influenza and severe acute respiratory syndrome coronavirus 2 in the United States remain unclear. While mobility and genomic data have revealed important aspects of pandemic spatial spread, several key questions remain: Did the two pandemics follow similar spatial transmission routes? How rapidly did they spread across the United States? What role did stochastic processes play in early spatial transmission? To address these questions, we integrated high-resolution disease data with a robust, data-efficient inference framework combining air travel, commuting flows, and pathogen superspreading potentials to reconstruct their spatial spread across US metropolitan areas. The two pandemics exhibited distinct transmission pathways across locations; however, both pandemics established local circulation in most metropolitan areas within weeks, driven by several shared transmission hubs. Early spatial spread was more strongly associated with air travel than with commuting, though stochastic dynamics introduced substantial uncertainty in transmission routes, creating challenges for timely detection and control. Simulations indicate that broad wastewater surveillance coverage beyond top transmission hubs coupled with effective infection control may slow initial spatial expansion. Our findings highlight the rapid, stochastic spread of pandemic respiratory pathogens and the difficulties of early outbreak containment.

Humans↗