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1.  Transmission Dynamics, Border Entry Screening, and School Holidays during the 2009 Influenza A (H1N1) Pandemic, China 
Emerging Infectious Diseases  2012;18(5):758-766.
Screening delayed spread by <4 days; autumn school holidays reduced the effective reproduction number by ≈40%.
Pandemic influenza A (H1N1) 2009 virus spread rapidly around the world in 2009. We used multiple data sources from surveillance systems and specific investigations to characterize the transmission patterns of this virus in China during May–November 2009 and analyze the effectiveness of border entry screening and holiday-related school closures on transmission. In China, age distribution and transmission dynamic characteristics were similar to those in Northern Hemisphere temperate countries. The epidemic was focused in children, with an effective reproduction number of ≈1.2–1.3. The 8 days of national holidays in October reduced the effective reproduction number by 37% (95% credible interval 28%–45%) and increased underreporting by ≈20%–30%. Border entry screening detected at most 37% of international travel–related cases, with most (89%) persons identified as having fever at time of entry. These findings suggest that border entry screening was unlikely to have delayed spread in China by >4 days.
doi:10.3201/eid1805.110356
PMCID: PMC3358060  PMID: 22515989
transmission; school closure; border screening; influenza A; pandemic (H1N1) 2009; People’s Republic of China; influenza; viruses
2.  The Waiting Time for Inter-Country Spread of Pandemic Influenza 
PLoS ONE  2007;2(1):e143.
Background
The time delay between the start of an influenza pandemic and its subsequent initiation in other countries is highly relevant to preparedness planning. We quantify the distribution of this random time in terms of the separate components of this delay, and assess how the delay may be extended by non-pharmaceutical interventions.
Methods and Findings
The model constructed for this time delay accounts for: (i) epidemic growth in the source region, (ii) the delay until an infected individual from the source region seeks to travel to an at-risk country, (iii) the chance that infected travelers are detected by screening at exit and entry borders, (iv) the possibility of in-flight transmission, (v) the chance that an infected arrival might not initiate an epidemic, and (vi) the delay until infection in the at-risk country gathers momentum. Efforts that reduce the disease reproduction number in the source region below two and severe travel restrictions are most effective for delaying a local epidemic, and under favourable circumstances, could add several months to the delay. On the other hand, the model predicts that border screening for symptomatic infection, wearing a protective mask during travel, promoting early presentation of cases arising among arriving passengers and moderate reduction in travel volumes increase the delay only by a matter of days or weeks. Elevated in-flight transmission reduces the delay only minimally.
Conclusions
The delay until an epidemic of pandemic strain influenza is imported into an at-risk country is largely determined by the course of the epidemic in the source region and the number of travelers attempting to enter the at-risk country, and is little affected by non-pharmaceutical interventions targeting these travelers. Short of preventing international travel altogether, eradicating a nascent pandemic in the source region appears to be the only reliable method of preventing country-to-country spread of a pandemic strain of influenza.
doi:10.1371/journal.pone.0000143
PMCID: PMC1764036  PMID: 17206278
3.  Fever screening during the influenza (H1N1-2009) pandemic at Narita International Airport, Japan 
BMC Infectious Diseases  2011;11:111.
Background
Entry screening tends to start with a search for febrile international passengers, and infrared thermoscanners have been employed for fever screening in Japan. We aimed to retrospectively assess the feasibility of detecting influenza cases based on fever screening as a sole measure.
Methods
Two datasets were collected at Narita International Airport during the 2009 pandemic. The first contained confirmed influenza cases (n = 16) whose diagnosis took place at the airport during the early stages of the pandemic, and the second contained a selected and suspected fraction of passengers (self-reported or detected by an infrared thermoscanner; n = 1,049) screened from September 2009 to January 2010. The sensitivity of fever (38.0°C) for detecting H1N1-2009 was estimated, and the diagnostic performances of the infrared thermoscanners in detecting hyperthermia at cut-off levels of 37.5°C, 38.0°C and 38.5°C were also estimated.
Results
The sensitivity of fever for detecting H1N1-2009 cases upon arrival was estimated to be 22.2% (95% confidence interval: 0, 55.6) among nine confirmed H1N1-2009 cases, and 55.6% of the H1N1-2009 cases were under antipyretic medications upon arrival. The sensitivity and specificity of the infrared thermoscanners in detecting hyperthermia ranged from 50.8-70.4% and 63.6-81.7%, respectively. The positive predictive value appeared to be as low as 37.3-68.0%.
Conclusions
The sensitivity of entry screening is a product of the sensitivity of fever for detecting influenza cases and the sensitivity of the infrared thermoscanners in detecting fever. Given the additional presence of confounding factors and unrestricted medications among passengers, reliance on fever alone is unlikely to be feasible as an entry screening measure.
doi:10.1186/1471-2334-11-111
PMCID: PMC3096599  PMID: 21539735
4.  Screening for Influenza A(H1N1)pdm09, Auckland International Airport, New Zealand 
Emerging Infectious Diseases  2012;18(5):866-868.
Entry screening for influenza A(H1N1)pdm09 at Auckland International Airport, New Zealand, detected 4 cases, which were later confirmed, among 456,518 passengers arriving April 27–June 22, 2009. On the basis of national influenza surveillance data, which suggest that ≈69 infected travelers passed through the airport, sensitivity for screening was only 5.8%.
doi:10.3201/eid1805.111080
PMCID: PMC3358051  PMID: 22516105
pandemic; communicable diseases; influenza; viruses; emigration and immigration; mass screening; sensitivity; program evaluation; airport; influenza; New Zealand; influenza A(H1N1)pdm09; pandemic (H1N1) 2009; H1N1; pH1N1
5.  Nonpharmaceutical Interventions for Pandemic Influenza, International Measures 
Emerging Infectious Diseases  2006;12(1):81-87.
Closing international borders was usually ineffective in past pandemics and would be less effective today.
Since global availability of vaccine and antiviral agents against influenza caused by novel human subtypes is insufficient, the World Health Organization (WHO) recommends nonpharmaceutical public health interventions to contain infection, delay spread, and reduce the impact of pandemic disease. Virus transmission characteristics will not be completely known in advance, but difficulties in influenza control typically include peak infectivity early in illness, a short interval between cases, and to a lesser extent, transmission from persons with incubating or asymptomatic infection. Screening and quarantining entering travelers at international borders did not substantially delay virus introduction in past pandemics, except in some island countries, and will likely be even less effective in the modern era. Instead, WHO recommends providing information to international travelers and possibly screening travelers departing countries with transmissible human infection. The principal focus of interventions against pandemic influenza spread should be at national and community levels rather than international borders.
doi:10.3201/eid1201.051370
PMCID: PMC3291414  PMID: 16494722
influenza; World Health Organization; quarantine
6.  Assessment of Border Control Measures and Community Containment Measures Used in Japan during the Early Stages of Pandemic (H1N1) 2009 
PLoS ONE  2012;7(2):e31289.
Background
In the early stages of Pandemic (H1N1) 2009, border control measures were taken by quarantine stations to block the entry of infected individuals into Japan and community containment measures were implemented to prevent the spreading. The objectives of this study were to describe these measures and the characteristics of infected individuals, and to assess the measures' effectiveness.
Methodology/Principal Findings
Border control and community containment measures implemented from April to June (Period I: April 28–May 21, Period II: May 22–June 18) 2009 were described. Number of individuals identified and disease characteristics were analyzed. For entry screening, a health declaration form and an infrared thermoscanner were used to detect symptomatic passengers. Passengers indicated for the rapid influenza test underwent the test followed by RT-PCR. Patients positive for H1N1 were isolated, and close contacts were quarantined. Entry cards were handed out to all asymptomatic passengers informing them about how to contact a health center in case they developed symptoms. Nine individuals were identified by entry screening and 1 during quarantine to have Pandemic (H1N1) 2009. Health monitoring by health centers was performed in period I for passengers arriving from affected countries and in period II for those who had come into contact with the individuals identified by entry screening. Health monitoring identified 3 infected individuals among 129,546 in Period I and 5 among 746 in Period II. Enhanced surveillance, which included mandatory reporting of details of the infected individuals, identified 812 individuals, 141 (18%) of whom had a history of international travel. Twenty-four of these 141 passengers picked up by enhanced surveillance had been developing symptoms on entry and were missed at screening.
Conclusion/Significance
Symptomatic passengers were detected by the various entry screening measures put in place. Enhanced surveillance provided data for the improvement of public health measures in future pandemics.
doi:10.1371/journal.pone.0031289
PMCID: PMC3280294  PMID: 22355354
7.  The effective reproduction number of pandemic influenza: Prospective estimation 
Epidemiology (Cambridge, Mass.)  2010;21(6):842-846.
Background
Timely estimation of the transmissibility of a novel pandemic influenza virus was a public health priority in 2009.
Methods
We extended methods for prospective estimation of the effective reproduction number, (Rt), over time in an emerging epidemic to allow for reporting delays and repeated importations. We estimated Rt based on case notifications and hospitalizations associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in Hong Kong from June through October 2009
Results
Rt declined from around 1.4–1.5 at the start of the local epidemic to around 1.1–1.2 later in the summer, suggesting changes in transmissibility perhaps related to school vacations or seasonality. Estimates of Rt based on hospitalizations of confirmed H1N1 cases closely matched estimates based on case notifications.
Conclusion
Real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and calibration of mitigation strategies.
doi:10.1097/EDE.0b013e3181f20977
PMCID: PMC3084966  PMID: 20805752
8.  The feasibility of age-specific travel restrictions during influenza pandemics 
Background
Epidemiological studies have shown that imposing travel restrictions to prevent or delay an influenza pandemic may not be feasible. To delay an epidemic substantially, an extremely high proportion of trips (~99%) would have to be restricted in a homogeneously mixing population. Influenza is, however, strongly influenced by age-dependent transmission dynamics, and the effectiveness of age-specific travel restrictions, such as the selective restriction of travel by children, has yet to be examined.
Methods
A simple stochastic model was developed to describe the importation of infectious cases into a population and to model local chains of transmission seeded by imported cases. The probability of a local epidemic, and the time period until a major epidemic takes off, were used as outcome measures, and travel restriction policies in which children or adults were preferentially restricted were compared to age-blind restriction policies using an age-dependent next generation matrix parameterized for influenza H1N1-2009.
Results
Restricting children from travelling would yield greater reductions to the short-term risk of the epidemic being established locally than other policy options considered, and potentially could delay an epidemic for a few weeks. However, given a scenario with a total of 500 imported cases over a period of a few months, a substantial reduction in the probability of an epidemic in this time period is possible only if the transmission potential were low and assortativity (i.e. the proportion of contacts within-group) were unrealistically high. In all other scenarios considered, age-structured travel restrictions would not prevent an epidemic and would not delay the epidemic for longer than a few weeks.
Conclusions
Selectively restricting children from traveling overseas during a pandemic may potentially delay its arrival for a few weeks, depending on the characteristics of the pandemic strain, but could have less of an impact on the economy compared to restricting adult travelers. However, as long as adults have at least a moderate potential to trigger an epidemic, selectively restricting the higher risk group (children) may not be a practical option to delay the arrival of an epidemic substantially.
doi:10.1186/1742-4682-8-44
PMCID: PMC3278369  PMID: 22078655
9.  Transmission of pandemic A/H1N1 2009 influenza on passenger aircraft: retrospective cohort study 
Objectives To assess the risk of transmission of pandemic A/H1N1 2009 influenza (pandemic A/H1N1) from an infected high school group to other passengers on an airline flight and the effectiveness of screening and follow-up of exposed passengers.
Design Retrospective cohort investigation using a questionnaire administered to passengers and laboratory investigation of those with symptoms.
Setting Auckland, New Zealand, with national and international follow-up of passengers.
Participants Passengers seated in the rear section of a Boeing 747-400 long haul flight that arrived on 25 April 2009, including a group of 24 students and teachers and 97 (out of 102) other passengers in the same section of the plane who agreed to be interviewed.
Main outcome measures Laboratory confirmed pandemic A/H1N1 infection in susceptible passengers within 3.2 days of arrival; sensitivity and specificity of influenza symptoms for confirmed infection; and completeness and timeliness of contact tracing.
Results Nine members of the school group were laboratory confirmed cases of pandemic A/H1N1 infection and had symptoms during the flight. Two other passengers developed confirmed pandemic A/H1N1 infection, 12 and 48 hours after the flight. They reported no other potential sources of infection. Their seating was within two rows of infected passengers, implying a risk of infection of about 3.5% for the 57 passengers in those rows. All but one of the confirmed pandemic A/H1N1 infected travellers reported cough, but more complex definitions of influenza cases had relatively low sensitivity. Rigorous follow-up by public health workers located 93% of passengers, but only 52% were contacted within 72 hours of arrival.
Conclusions A low but measurable risk of transmission of pandemic A/H1N1 exists during modern commercial air travel. This risk is concentrated close to infected passengers with symptoms. Follow-up and screening of exposed passengers is slow and difficult once they have left the airport.
doi:10.1136/bmj.c2424
PMCID: PMC2874661  PMID: 20495017
10.  Distribution and Risk Factors of 2009 Pandemic Influenza A (H1N1) in Mainland China 
American Journal of Epidemiology  2012;175(9):890-897.
Data from all reported cases of 2009 pandemic influenza A (H1N1) were obtained from the China Information System for Disease Control and Prevention. The spatiotemporal distribution patterns of cases were characterized through spatial analysis. The impact of travel-related risk factors on invasion of the disease was analyzed using survival analysis, and climatic factors related to local transmission were identified using multilevel Poisson regression, both at the county level. The results showed that the epidemic spanned a large geographic area, with the most affected areas being in western China. Significant differences in incidence were found among age groups, with incidences peaking in school-age children. Overall, the epidemic spread from southeast to northwest. Proximity to airports and being intersected by national highways or freeways but not railways were variables associated with the presence of the disease in a county. Lower temperature and lower relative humidity were the climatic factors facilitating local transmission after correction for the effects of school summer vacation and public holidays, as well as population density and the density of medical facilities. These findings indicate that interventions focused on domestic travel, population density, and climatic factors could play a role in mitigating the public health impact of future influenza pandemics.
doi:10.1093/aje/kwr411
PMCID: PMC3339311  PMID: 22491083
China; disease outbreaks; disease transmission, infectious; influenza, human; invasion process; pandemics
11.  Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures 
Emerging Infectious Diseases  2006;12(1):88-94.
Recommended interventions vary by transmission pattern, pandemic phase, and disease severity.
The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights.
doi:10.3201/eid1201.051371
PMCID: PMC3291415  PMID: 16494723
influenza; World Health Organization; quarantine
12.  Assessing secondary attack rates among household contacts at the beginning of the influenza A (H1N1) pandemic in Ontario, Canada, April-June 2009: A prospective, observational study 
BMC Public Health  2011;11:234.
Background
Understanding transmission dynamics of the pandemic influenza A (H1N1) virus in various exposure settings and determining whether transmissibility differed from seasonal influenza viruses was a priority for decision making on mitigation strategies at the beginning of the pandemic. The objective of this study was to estimate household secondary attack rates for pandemic influenza in a susceptible population where control measures had yet to be implemented.
Methods
All Ontario local health units were invited to participate; seven health units volunteered. For all laboratory-confirmed cases reported between April 24 and June 18, 2009, participating health units performed contact tracing to detect secondary cases among household contacts. In total, 87 cases and 266 household contacts were included in this study. Secondary cases were defined as any household member with new onset of acute respiratory illness (fever or two or more respiratory symptoms) or influenza-like illness (fever plus one additional respiratory symptom). Attack rates were estimated using both case definitions.
Results
Secondary attack rates were estimated at 10.3% (95% CI 6.8-14.7) for secondary cases with influenza-like illness and 20.2% (95% CI 15.4-25.6) for secondary cases with acute respiratory illness. For both case definitions, attack rates were significantly higher in children under 16 years than adults (25.4% and 42.4% compared to 7.6% and 17.2%). The median time between symptom onset in the primary case and the secondary case was estimated at 3.0 days.
Conclusions
Secondary attack rates for pandemic influenza A (H1N1) were comparable to seasonal influenza estimates suggesting similarities in transmission. High secondary attack rates in children provide additional support for increased susceptibility to infection.
doi:10.1186/1471-2458-11-234
PMCID: PMC3095560  PMID: 21492445
13.  Effects of Internal Border Control on Spread of Pandemic Influenza 
Emerging Infectious Diseases  2007;13(7):1038-1045.
Population size, travel rates, and residence of travelers can aid in determining travel restrictions as a control policy.
We investigated the capacity of internal border control to limit influenza spread in an emergent pandemic in the context of Australia, a country with a low-population density and geopolitical boundaries that may facilitate restrictions. Mathematical models were used to study the time delay between epidemics in 2 population centers when travel restrictions were imposed. The models demonstrated that population size, travel rates, and places where travelers reside can strongly influence delay. The model simulations suggested that moderate delays in geographic spread may be possible with stringent restrictions and a low reproduction number, but results will be sensitive to the reproduction number and timing of restrictions. Model limitations include the absence of further importations and additional control measures. Internal border control may have a role in protecting domestic centers early in a pandemic, when importations are sparse. Our results may be useful for policymakers.
doi:10.3201/eid1307.060740
PMCID: PMC2878213  PMID: 18214176
Influenza; modeling; travel; pandemic; epidemiology; research
14.  Recent Advances in the Diagnosis and Treatment of Influenza Pneumonia 
A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure. Confirmation of etiology by laboratory testing is warranted in such cases. Rapid antigen and immunofluorescence testing are useful screening tests, but have limited sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture. The most effective preventive measure is annual influenza vaccination in selected individuals. Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results. Neuraminidase inhibitors (NI) are the agents of choice.
doi:10.1007/s11908-012-0257-5
PMCID: PMC3342505  PMID: 22477036
Influenza pneumonia; Diagnosis; Treatment; Prevention; Swine influenza; Avian influenza; H1N1; Pandemic; Medicine & Public Health; Infectious Diseases
15.  Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico 
PLoS Medicine  2011;8(5):e1000436.
Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states.
Background
Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.
Methods and Findings
We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.
Conclusions
We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
From June 2009 to August 2010, the world was officially (according to specific World Health Organization [WHO] criteria—WHO phase 6 pandemic alert) in the grip of an Influenza A pandemic with a new strain of the H1N1 virus. The epidemic in Mexico, which had the second confirmed global case of H1N1 virus was first noted in early April 2009, when reports of respiratory hospitalizations and deaths among 62 young adults in Mexico alerted local health officials to the occurrence of atypical rates of respiratory illness. In line with its inter-institutional National Pandemic Influenza Preparedness and Response Plan, the Ministry of Health cancelled school attendance in the greater Mexico City area on April 24 and expanded these measures to the rest the country three days later. The Ministry of Health then implemented in Mexico City other “social distancing” strategies such as closing cinemas and restaurants and cancelling large public gatherings.
Why Was This Study Done?
School closures and other intense social distancing strategies can be very disruptive to the population, but as yet it is uncertain whether these measures were successful in reducing disease transmission. In addition, there have been no studies concentrating on recurrent pandemic waves in Mexico. So in this study the authors addressed these issues by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican States and quantified the association between local influenza transmission rates, school cycles, and demographic factors.
What Did the Researchers Do and Find?
The researchers used the epidemiological surveillance system of the Mexican Institute for Social Security—a Mexican health system that covers private sector workers and their families, a group representative of the general population, that comprises roughly 40% of the Mexican population (107 million individuals), with a network of 1,099 primary health care units and 259 hospitals nationwide. Then the researchers compiled state- and age-specific time series of incident influenza-like illness and H1N1 influenza cases by day of symptom onset to analyze the geographic dissemination patterns of the pandemic across Mexico and defined three temporally distinct pandemic waves in 2009: spring (April 1–May 20), summer (May 21–August 1), and fall (August 2–December 31). The researchers then applied a mathematical model of influenza transmission to daily case data to assess the effectiveness of mandatory school closures and other social distancing measures implemented during April 24–May 11, in reducing influenza transmission rates.
The Mexican Institute for Social Security reported a total of 117,626 people with influenza-like illness from April 1 to December 31, 2009, of which 36,044 were laboratory tested (30.6%) and 27,440 (23.3%) were confirmed with H1N1 influenza. During this period, 1,370 people with influenza-like illness died of which 585 (1.5 per 100,000) were confirmed to have H1N1 influenza. The median age of people with laboratory confirmed influenza like illness (H1N1) was 18 years overall but increased to 31 years during the autumn wave. The overall case-fatality ratio among people with influenza like illness was 1.2%, but highest (5.5%) among people over 60 years. The researchers found that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a substantial (29%–37%) reduction in influenza transmission in spring 2009 but increased in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.
What Do These Findings Mean?
These findings show that the age distribution of pandemic influenza morbidity was greater in younger age groups, while the risk of severe disease was skewed towards older age groups, and that there were substantial geographical variation in pandemic patterns across Mexico, in part related to population size. But most importantly, these findings support the effectiveness of early mitigation efforts including mandatory school closures and cancellation of large public gatherings, reinforcing the importance of school cycles in the transmission of pandemic influenza. This analysis increases understanding of the age and transmission patterns of the Mexican 2009 influenza pandemic at various geographic scales, which is crucial for designing more efficient public health interventions against future influenza pandemics.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000436.
The World Health Organization provides information about the global response to the 2009 H1N1 pandemic
doi:10.1371/journal.pmed.1000436
PMCID: PMC3101203  PMID: 21629683
16.  Identification and epidemiology of severe respiratory disease due to novel swine-origin influenza A (H1N1) virus infection in Alberta 
BACKGROUND:
In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada.
METHODS:
Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods.
RESULTS:
The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain.
CONCLUSION:
Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.
PMCID: PMC3009582  PMID: 22132007
Influenza; Pandemic; pH1N1
17.  Threat of an influenza pandemic: family physicians in the front line 
BMC Family Practice  2009;10:11.
Background
The chance of an influenza pandemic is real and clinicians should keep themselves informed about the rationale and science behind preventive and therapeutic principles relating to an (impending) influenza pandemic.
Discussion
Vaccination is considered the best prevention in case of a pandemic threat and first choice to contain the impact of a pandemic. Pending the availability of an effective pandemic vaccine, antivirals are likely the only effective agents for prevention and treatment. When an influenza pandemic is impending, all interventions aim to prevent people becoming infected and to suppress replication and transmission of the virus as much as possible. Antivirals will be prescribed to patients with laboratory confirmed pre-pandemic influenza as well as to their contacts (post-exposure prophylaxis) which may delay development of or even prevent a pandemic. During a manifest influenza pandemic, however, there is large-scale spreading of the influenza virus. Therefore, preventive use of antivirals is less efficient to prevent transmission. Delaying the pandemic is then important in order to prevent exhausting public health resources and disruption of society. Thus, during a manifest pandemic everyone with influenza symptoms should receive antivirals as quickly as possible, regardless of virological confirmation. To ensure optimal effectiveness of antivirals and to minimize development of drug resistant viral strains, the use of antivirals for annual influenza should be restrictive. The crucial position of family physicians during an (impending) influenza pandemic necessitates the development of primary health care guidelines on this topic for all countries.
Summary
Family physicians will play a key role in assessing and treating victims of a new influenza virus, and in reassuring the worried well. We outline various possible interventions in the event of an impending and a manifest influenza pandemic, such as non-medial measures, prescription of antivirals, and vaccination, and emphasize the need for pandemic influenza preparedness.
doi:10.1186/1471-2296-10-11
PMCID: PMC2656465  PMID: 19192304
18.  Outbreak of pandemic influenza A/H1N1 2009 in Nepal 
Virology Journal  2011;8:133.
Background
The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009.
Results
Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type.
Conclusion
The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.
doi:10.1186/1743-422X-8-133
PMCID: PMC3072927  PMID: 21426589
19.  The novel influenza A (H1N1) virus pandemic: An update 
Annals of Thoracic Medicine  2009;4(4):163-172.
In the 4 months since it was first recognized, the pandemic strain of a novel influenza A (H1N1) virus has spread to all continents and, after documentation of human-to-human transmission of the virus in at least three countries in two separate World Health Organization (WHO) regions, the pandemic alert was raised to level 6. The agent responsible for this pandemic, a swine-origin influenza A (H1N1) virus (S-OIV), is characterized by a unique combination of gene segments that has not previously been identified among human or swine influenza A viruses. As of 31th July 2009, 168 countries and overseas territories/communities have each reported at least one laboratory-confirmed case of pandemic H1N1 infection. There have been a total of 162,380 reported cases and 1154 associated deaths. Influenza epidemics usually take off in autumn, and it is important to prepare for an earlier start this season. Estimates from Europe indicate that 230 millions Europe inhabitants will have clinical signs and symptoms of S-OIV this autumn, and 7–35% of the clinical cases will have a fatal outcome, which means that there will be 160,000–750,000 H1N1-related deaths. A vaccine against H1N1 is expected to be the most effective tool for controlling influenza A (H1N1) infection in terms of reducing morbidity and mortality and limiting diffusion. However, there are several issues with regard to vaccine manufacture and approval, as well as production capacity, that remain unsettled. We searched the literature indexed in PubMed as well as the websites of major international health agencies to obtain the material presented in this update on the current S-OIV pandemic.
doi:10.4103/1817-1737.56008
PMCID: PMC2801040  PMID: 19881161
Epidemiology; H1N1; influenza
20.  Point of Care Strategy for Rapid Diagnosis of Novel A/H1N1 Influenza Virus 
PLoS ONE  2010;5(2):e9215.
Background
Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v), systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC) strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic.
Methodology/Principal Findings
Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT) and real-time RT-PCR assay (rtRT-PCR). This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours.
Conclusions/Significance
The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay), because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the epidemiology of the pandemic.
doi:10.1371/journal.pone.0009215
PMCID: PMC2822848  PMID: 20174646
21.  Implementation of Non-Pharmaceutical Interventions by New York City Public Schools to Prevent 2009 Influenza A 
PLoS ONE  2013;8(1):e50916.
Introduction
Children are important transmitters of influenza in the community and a number of non-pharmaceutical interventions (NPIs), including hand washing and use of hand sanitizer, have been recommended to mitigate the transmission of influenza, but limited information is available regarding schools' ability to implement these NPIs during an influenza outbreak. We evaluated implementation of NPIs during fall 2009 in response to H1N1 pandemic influenza (pH1N1) by New York City (NYC) public schools.
Methods
From January 25 through February 9, 2010, an online survey was sent to all the 1,632 NYC public schools and principals were asked to participate in the survey or to designate a school nurse or other school official with knowledge of school policies and characteristics to do so.
Results
Of 1,633 schools, 376(23%) accessed and completed the survey. Nearly all respondents (99%) implemented at least two NPIs. Schools that had a Flu Response Team (FRT) as a part of school emergency preparedness plan were more likely to implement the NPI guidelines recommended by NYC public health officials than schools that did not have a FRT. Designation of a room for isolating ill students, for example, was more common in schools with a FRT (72%) than those without (53%) (p<0.001).
Conclusions
Implementing an NPI program in a large school system to mitigate the effects of an influenza outbreak is feasible, but there is potential need for additional resources in some schools to increase capacity and adherence to all recommendations. Public health influenza-preparedness plans should include school preparedness planning and FRTs.
doi:10.1371/journal.pone.0050916
PMCID: PMC3546112  PMID: 23341877
22.  Household Transmission of Pandemic (H1N1) 2009, San Antonio, Texas, USA, April–May 2009 
Emerging Infectious Diseases  2010;16(4):631-637.
Transmission rates were lower than those for seasonal influenza.
To assess household transmission of pandemic (H1N1) 2009 in San Antonio, Texas, USA, during April 15–May 8, 2009, we investigated 77 households. The index case-patient was defined as the household member with the earliest onset date of symptoms of acute respiratory infection (ARI), influenza-like illness (ILI), or laboratory-confirmed pandemic (H1N1) 2009. Median interval between illness onset in index and secondary case-patients was 4 days (range 1–9 days); the index case-patient was likely to be <18 years of age (p = 0.034). The secondary attack rate was 4% for pandemic (H1N1) 2009, 9% for ILI, and 13% for ARI. The secondary attack rate was highest for children <5 years of age (8%–19%) and lowest for adults >50 years of age (4%–12%). Early in the outbreak, household transmission primarily occurred from children to other household members and was lower than the transmission rate for seasonal influenza.
doi:10.3201/eid1604.091658
PMCID: PMC3321969  PMID: 20350377
Human influenza; viruses; pandemic (H1N1) 2009; household transmission; Texas; research
23.  Delaying the International Spread of Pandemic Influenza 
PLoS Medicine  2006;3(6):e212.
Background
The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics.
Methods and Findings
To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected.
Conclusions
Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.
Air travel might contribute to the spread of influenza in future pandemics. However, this modelling study concluded that restrictions on air travel would not provide effective control.
doi:10.1371/journal.pmed.0030212
PMCID: PMC1450020  PMID: 16640458
24.  Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity 
PLoS Currents  2012;4:RRN1306.
Background
A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time.
Methods
We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset.
Results
A total of 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The reproduction number of the winter 2011-12 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009.
Conclusions
We have documented a substantial and ongoing increase in the number of ARI hospitalizations during the period December 2011-February 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths, relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is reminiscent of historical pandemics and indicates either a gradual drift in the A/H1N1 virus, and/or a build-up of immunity among younger populations.
doi:10.1371/currents.RRN1306
PMCID: PMC3286879  PMID: 22485199
25.  Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity 
PLoS Currents  2012;4:RRN1306.
Background
A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time.
Methods
We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset.
Results
A total of 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The reproduction number of the winter 2011-12 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009.
Conclusions
We have documented a substantial and ongoing increase in the number of ARI hospitalizations during the period December 2011-February 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths, relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is reminiscent of historical pandemics and indicates either a gradual drift in the A/H1N1 virus, and/or a build-up of immunity among younger populations.
doi:10.1371/currents.RRN1306
PMCID: PMC3286879  PMID: 22485199

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