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1.  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
2.  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
3.  Airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in Taiwan 
BMC Infectious Diseases  2012;12:182.
Background
Dengue has not reached an endemic status in Taiwan; nevertheless, we have implemented a fever screening program at airports for the early detection of febrile passengers with a dengue infection. This study is intended to assess the performance of the airport screening procedures for dengue infection.
Methods
We analyzed data from the national surveillance system of the Taiwan Centers for Disease Control. We included the imported dengue cases reported by sentinel airports and clinics as well as the domestic cases from 2007–2010.
Results
Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases with an apparent symptom (febrile) in the viremic stage were detected via the airport fever screening program, with an estimated positive predictive value of 2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%. Fluctuations in the number of the symptomatic imported dengue cases identified in the airports (X) were associated with the total number of imported dengue cases (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104, R2X:Y = 0.61, P < 0.005). Additionally, the fluctuating patterns in the cumulative numbers of the imported dengue cases (X) with a 1–2 month lead time (t) was in parallel with that of the domestic dengue cases (Y) based on a consecutive 4-year surveillance (i.e., n = 48, R2X(t-1):Y = 0.22, R2X(t-2):Y = 0.31, P < 0.001) from 2007–2010.
Conclusions
A moderate sensitivity of detecting dengue at the airports examined in this study indicated some limitations of the fever screening program for the prevention of importation. The screening program could assist in the rapid triage for self-quarantine of some symptomatic dengue cases that were in the viremic stage at the borders and contribute to active sentinel surveillance; however, the blocking of viral transmission to susceptible populations (neighbors or family) from all of the viremic travelers, including those with or without symptoms, is critical to prevent dengue epidemics. Therefore, the reinforcement of mosquito bite prevention and household vector control in dengue-endemic or dengue-competent hotspots during an epidemic season is essential and highly recommended.
doi:10.1186/1471-2334-12-182
PMCID: PMC3462143  PMID: 22867003
Imported dengue; Asymptomatic viremia; Dengue-competent hotspots
4.  Timeliness of contact tracing among flight passengers for influenza A/H1N1 2009 
BMC Infectious Diseases  2011;11:355.
Background
During the initial containment phase of influenza A/H1N1 2009, close contacts of cases were traced to provide antiviral prophylaxis within 48 h after exposure and to alert them on signs of disease for early diagnosis and treatment. Passengers seated on the same row, two rows in front or behind a patient infectious for influenza, during a flight of ≥ 4 h were considered close contacts. This study evaluates the timeliness of flight-contact tracing (CT) as performed following national and international CT requests addressed to the Center of Infectious Disease Control (CIb/RIVM), and implemented by the Municipal Health Services of Schiphol Airport.
Methods
Elapsed days between date of flight arrival and the date passenger lists became available (contact details identified - CI) was used as proxy for timeliness of CT. In a retrospective study, dates of flight arrival, onset of illness, laboratory diagnosis, CT request and identification of contacts details through passenger lists, following CT requests to the RIVM for flights landed at Schiphol Airport were collected and analyzed.
Results
24 requests for CT were identified. Three of these were declined as over 4 days had elapsed since flight arrival. In 17 out of 21 requests, contact details were obtained within 7 days after arrival (81%). The average delay between arrival and CI was 3,9 days (range 2-7), mainly caused by delay in diagnosis of the index patient after arrival (2,6 days). In four flights (19%), contacts were not identified or only after > 7 days. CI involving Dutch airlines was faster than non-Dutch airlines (P < 0,05). Passenger locator cards did not improve timeliness of CI. In only three flights contact details were identified within 2 days after arrival.
Conclusion
CT for influenza A/H1N1 2009 among flight passengers was not successful for timely provision of prophylaxis. CT had little additional value for alerting passengers for disease symptoms, as this information already was provided during and after the flight. Public health authorities should take into account patient delays in seeking medical advise and laboratory confirmation in relation to maximum time to provide postexposure prophylaxis when deciding to install contact tracing measures. International standardization of CT guidelines is recommended.
doi:10.1186/1471-2334-11-355
PMCID: PMC3265549  PMID: 22204494
5.  Genetic Characterization of Human Influenza Viruses in the Pandemic (2009–2010) and Post-Pandemic (2010–2011) Periods in Japan 
PLoS ONE  2012;7(6):e36455.
Background
Pandemic influenza A(H1N1) 2009 virus was first detected in Japan in May 2009 and continued to circulate in the 2010–2011 season. This study aims to characterize human influenza viruses circulating in Japan in the pandemic and post-pandemic periods and to determine the prevalence of antiviral-resistant viruses.
Methods
Respiratory specimens were collected from patients with influenza-like illness on their first visit at outpatient clinics during the 2009–2010 and 2010–2011 influenza seasons. Cycling probe real-time PCR assays were performed to screen for antiviral-resistant strains. Sequencing and phylogenetic analysis of the HA and NA genes were done to characterize circulating strains.
Results and Conclusion
In the pandemic period (2009–2010), the pandemic influenza A(H1N1) 2009 virus was the only circulating strain isolated. None of the 601 A(H1N1)pdm09 virus isolates had the H275Y substitution in NA (oseltamivir resistance) while 599/601 isolates (99.7%) had the S31N substitution in M2 (amantadine resistance). In the post-pandemic period (2010–2011), cocirculation of different types and subtypes of influenza viruses was observed. Of the 1,278 samples analyzed, 414 (42.6%) were A(H1N1)pdm09, 525 (54.0%) were A(H3N2) and 33 (3.4%) were type-B viruses. Among A(H1N1)pdm09 isolates, 2 (0.5%) were oseltamivir-resistant and all were amantadine-resistant. Among A(H3N2) viruses, 520 (99.0%) were amantadine-resistant. Sequence and phylogenetic analyses of A(H1N1)pdm09 viruses from the post-pandemic period showed further evolution from the pandemic period viruses. For viruses that circulated in 2010–2011, strain predominance varied among prefectures. In Hokkaido, Niigata, Gunma and Nagasaki, A(H3N2) viruses (A/Perth/16/2009-like) were predominant whereas, in Kyoto, Hyogo and Osaka, A(H1N1)pdm09 viruses (A/New_York/10/2009-like) were predominant. Influenza B Victoria(HA)-Yamagata(NA) reassortant viruses (B/Brisbane/60/2008-like) were predominant while a small proportion was in Yamagata lineage. Genetic variants with mutations at antigenic sites were identified in A(H1N1)pdm09, A(H3N2) and type-B viruses in the 2010–2011 season but did not show a change in antigenicity when compared with respective vaccine strains.
doi:10.1371/journal.pone.0036455
PMCID: PMC3384667  PMID: 22761651
6.  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
7.  Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1) against A/Narita/1/2009 (H1N1) pandemic influenza virus strain 
Virology Journal  2013;10:47.
Background
The pandemic 2009 (H1N1) influenza virus has spread throughout the world and is now causing seasonal influenza. To prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies.
Methods
Inactivated whole virus particle (WV) and ether-split (ES) vaccines were prepared from an influenza virus strain, A/swine/Hokkaido/2/1981 (H1N1), from the library and from A/Narita/1/2009 (H1N1) pandemic strain. Each of the vaccines was injected subcutaneously into mice and their potencies were evaluated by challenge with A/Narita/1/2009 (H1N1) virus strain in mice.
Results
A/swine/Hokkaido/2/81 (H1N1), which was isolated from the lung of a diseased piglet, was selected on the basis of their antigenicity and growth capacity in embryonated chicken eggs. Two injections of the WV vaccine induced an immune response in mice, decreasing the impact of disease caused by the challenge with A/Narita/1/2009 (H1N1), as did the vaccine prepared from the homologous strain.
Conclusion
The WV vaccine prepared from an influenza virus in the library is useful as an emergency vaccine in the early phase of pandemic influenza.
doi:10.1186/1743-422X-10-47
PMCID: PMC3571931  PMID: 23384324
Influenza A (H1N1)pdm; Vaccine; Swine influenza virus
8.  Critical paths in a metapopulation model of H1N1: Efficiently delaying influenza spreading through flight cancellation 
PLoS Currents  2012;4:e4f8c9a2e1fca8.
Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections.
doi:10.1371/4f8c9a2e1fca8
PMCID: PMC3392097  PMID: 22919563
9.  Transmission of Influenza on International Flights, May 2009 
Emerging Infectious Diseases  2011;17(7):1188-1194.
Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone.
doi:10.3201/eid1707.101135
PMCID: PMC3381396  PMID: 21762571
10.  Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic 
Background
Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic.
Methods
Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels.
Results
Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province.
Interpretation
We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.
doi:10.1503/cmaj.100488
PMCID: PMC2950183  PMID: 20823167
11.  Border Screening for SARS 
Emerging Infectious Diseases  2005;11(1):6-10.
Screening at national borders may not be effective in controlling SARS spread.
With the rapid international spread of severe acute respiratory syndrome (SARS) from March through May 2003, Canada introduced various measures to screen airplane passengers at selected airports for symptoms and signs of SARS. The World Health Organization requested that all affected areas screen departing passengers for SARS symptoms. In spite of intensive screening, no SARS cases were detected. SARS has an extremely low prevalence, and the positive predictive value of screening is essentially zero. Canadian screening results raise questions about the effectiveness of available screening measures for SARS at international borders.
doi:10.3201/eid1101.040835
PMCID: PMC3294328  PMID: 15705315
SARS; airport screening; thermal scanners; Health Alert Notices; quarantine; travelers; research
12.  Clinical Presentation of Novel Influenza A (H1N1) in Hospitalized Children 
Iranian Journal of Pediatrics  2011;21(2):215-219.
Objective
Human pandemic influenza H1N1 virus as the cause of febrile respiratory infection ranging from self-limited to severe illness has spread globally during 2009. Signs and symptoms of upper and lower respiratory tract involvement, fever, sore throat, rhinitis, myalgia, malaise, headache, chills and fatigue are common. In this article we report the clinical presentation of Influenza A (H1N1) in our hospitalized children.
Methods
Between September and October 2009, all children requiring hospitalization for suspected H1N1 infection were transferred to Pediatric Infectious Diseases ward. For all patients the throat swab was taken for PCR testing to confirm or exclude the diagnosis of H1N1 Influenza A. Case patients consisted of H1N1-positive patients. Age, sex, symptoms, signs, laboratory data, CXR changes, details of therapy, duration of admission and patient outcome were documented.
Findings
Twenty patients were H1N1 positive. Mean age of the patients was 65.50±9.8 months. Fever and coughs were with 55% the most commonly reported symptoms. Other presentations included vomiting (55%), abdominal pain (25%), cyanosis and dyspnea (5%), body ache (40%), rhinorrhea (80%), sore throat (35%), head stiffness (5%) and loss of conciousness (5%). The median temperature of the patients was 38.5°C. Chest X-Ray changes were noted in 13 out of 20 patients (65%). Mean leukocyte and platelet was 6475 and 169000 respectively. Seventeen (85%) patients were treated with Oseltamivir, 3 patients received adjuvant antibiotics. The mean duration of admission was 3 days. Three patients required intensive care support and all of them expired due to superinfection.
Conclusion
Our data confirm that the presentation of influenza in children is variable and 2009 H1N1 influenza may cause leucopenia and thrombocytopenia.
PMCID: PMC3446154  PMID: 23056790
Influenza; Infectious Diseases; H1N1; Oseltamivir
13.  Behavior of Adult Influenza Patients during the 2009 Pandemic after Outpatient Clinic Presentations at a Hospital in Tokyo, Japan 
Tropical Medicine and Health  2011;39(3):83-85.
The 2009 pandemic of novel swine-origin influenza A (H1N1) highlighted the importance of community mitigation measures such as voluntary isolation. During the pandemic, we investigated the voluntary isolation behavior of patients with influenza during the 7-day period after they visited an outpatient clinic at a hospital in Tokyo, Japan. A questionnaire-based survey was conducted on patients diagnosed with influenza. Of a total of 14 patients, 13 (93%) visited a workplace, school or other potentially crowded setting at least once in the 7-day period after presentation. Five patients (36%) visited a potentially crowded setting either with a fever or on the day after having a fever. The voluntary isolation behavior of Japanese people with influenza did not necessarily adhere to the Japanese government recommendation that people with influenza-like illness stay home for 7 days following the onset of symptoms.
doi:10.2149/tmh.2011-09
PMCID: PMC3191776  PMID: 22028614
influenza; disease outbreaks; behavior; patient; health policy
14.  Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1) 
Background
After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.
Methods
We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case.
Results
Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays.
Conclusions
Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.
doi:10.1186/1471-2334-10-82
PMCID: PMC3152767  PMID: 20353566
15.  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
16.  Emergence of swine flu in Andhra Pradesh: Facts and future 
Indian Journal of Microbiology  2010;49(4):320-323.
Swine flu is a common term representing the respiratory viral infections caused by influenza A virus strain H1N1. This disease was noticed for the first time in Mexico during early 2009, spread worldwide very soon and took nearly 4000 lives. It is observed that this infection is due to an evolved virulent version of previously existing H1N1. The first report of this infection was noticed in a traveler from USA to India at the Hyderabad international airport. Later, because of its highly contagious and fast-spreading nature through air, many people reported to have the infection throughout the country. In Andhra Pradesh, there were 735 officially confirmed cases of which 44 died. These cases were not only from Hyderabad which is the state capital having frequent travelers from abroad but are also reported from different parts of the state. The incidence and mortality rate is less in Andhra Pradesh compared to some of the other Indian states. This raises a question whether the type of the strain is different or genetic features of the population is playing the role in reducing the severity of the disease. In this review we have discussed about the occurrence, spread and mortality of the current H1N1 pandemic. We have also discussed about the current status of research on H1N1 and efforts in the state of Andhra Pradesh.
doi:10.1007/s12088-009-0057-2
PMCID: PMC3450187  PMID: 23100792
Swine flu; H1N1; Andhra Pradesh; Influenza
17.  The influence of climatic conditions on the transmission dynamics of the 2009 A/H1N1 influenza pandemic in Chile 
BMC Infectious Diseases  2012;12:298.
Background
The role of demographic factors, climatic conditions, school cycles, and connectivity patterns in shaping the spatio-temporal dynamics of pandemic influenza is not clearly understood. Here we analyzed the spatial, age and temporal evolution of the 2009 A/H1N1 influenza pandemic in Chile, a southern hemisphere country covering a long and narrow strip comprising latitudes 17°S to 56°S.
Methods
We analyzed the dissemination patterns of the 2009 A/H1N1 pandemic across 15 regions of Chile based on daily hospitalizations for severe acute respiratory disease and laboratory confirmed A/H1N1 influenza infection from 01-May to 31-December, 2009. We explored the association between timing of pandemic onset and peak pandemic activity and several geographical and demographic indicators, school vacations, climatic factors, and international passengers. We also estimated the reproduction number (R) based on the growth rate of the exponential pandemic phase by date of symptoms onset, estimated using maximum likelihood methods.
Results
While earlier pandemic onset was associated with larger population size, there was no association with connectivity, demographic, school or climatic factors. In contrast, there was a latitudinal gradient in peak pandemic timing, representing a 16-39-day lag in disease activity from the southern regions relative to the northernmost region (P < 0.001). Geographical differences in latitude of Chilean regions, maximum temperature and specific humidity explained 68.5% of the variability in peak timing (P = 0.01). In addition, there was a decreasing gradient in reproduction number from south to north Chile (P < 0.0001). The regional mean R estimates were 1.6-2.0, 1.3-1.5, and 1.2-1.3 for southern, central and northern regions, respectively, which were not affected by the winter vacation period.
Conclusions
There was a lag in the period of most intense 2009 pandemic influenza activity following a South to North traveling pattern across regions of Chile, significantly associated with geographical differences in minimum temperature and specific humidity. The latitudinal gradient in timing of pandemic activity was accompanied by a gradient in reproduction number (P < 0.0001). Intensified surveillance strategies in colder and drier southern regions could lead to earlier detection of pandemic influenza viruses and improved control outcomes.
doi:10.1186/1471-2334-12-298
PMCID: PMC3518181  PMID: 23148597
A/H1N1 influenza pandemic; Acute respiratory infection; Influenza-like-illness; Reproduction number; Spatial heterogeneity; School cycles; Climatological variables, Specific humidity; Temperature; Chile
18.  Outbreaks of Pandemic (H1N1) 2009 and Seasonal Influenza A (H3N2) on Cruise Ship 
Emerging Infectious Diseases  2010;16(11):1731-1737.
Although pandemic virus spread rapidly, especially among children, intensive control measures successfully contained these outbreaks.
To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship’s childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.
doi:10.3201/eid1611.100477
PMCID: PMC3294517  PMID: 21029531
Influenza A virus; subtype H1N1; pandemic; pandemic (H1N1) 2009; disease outbreaks; population health surveillance; influenza; cruise ship; viruses; research
19.  Thermal Image Scanning for Influenza Border Screening: Results of an Airport Screening Study 
PLoS ONE  2011;6(1):e14490.
Background
Infrared thermal image scanners (ITIS) appear an attractive option for the mass screening of travellers for influenza, but there are no published data on their performance in airports.
Methods
ITIS was used to measure cutaneous temperature in 1275 airline travellers who had agreed to tympanic temperature measurement and respiratory sampling. The prediction by ITIS of tympanic temperature (37.8°C and 37.5°C) and of influenza infection was assessed using Receiver Operating Characteristic (ROC) curves and estimated sensitivity, specificity and positive predictive value (PPV).
Findings
Using front of face ITIS for prediction of tympanic temperature ≥37.8°C, the area under the ROC curve was 0.86 (95%CI 0.75–0.97) and setting sensitivity at 86% gave specificity of 71%. The PPV in this population of travellers, of whom 0.5% were febrile using this definition, was 1.5%. We identified influenza virus infection in 30 travellers (3 Type A and 27 Type B). For ITIS prediction of influenza infection the area under the ROC curve was 0.66 (0.56–0.75), a sensitivity of 87% gave specificity of 39%, and PPV of 2.8%. None of the 30 influenza-positive travellers had tympanic temperature ≥37.8°C at screening (95%CI 0% to 12%); three had no influenza symptoms.
Conclusion
ITIS performed moderately well in detecting fever but in this study, during a seasonal epidemic of predominantly influenza type B, the proportion of influenza-infected travellers who were febrile was low and ITIS were not much better than chance at identifying travellers likely to be influenza-infected. Although febrile illness is more common in influenza A infections than influenza B infections, many influenza A infections are afebrile. Our findings therefore suggest that ITIS is unlikely to be effective for entry screening of travellers to detect influenza infection with the intention of preventing entry of the virus into a country.
doi:10.1371/journal.pone.0014490
PMCID: PMC3016318  PMID: 21245928
20.  Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study 
BMC Infectious Diseases  2011;11:225.
Background
There was a pandemic influenza around the world in 2009 including South Korea since last pandemic occurred four decades ago. We aimed to evaluate the epidemiological and clinical characteristics of this infection in childhood.
Methods
We evaluated the epidemiologic characteristics of all the subjects infected with the 2009 H1N1 influenza A virus (2,971 patients, ≤ 15 years of age), and the clinical and laboratory findings of the inpatients (217 patients, 80 had pneumonia) between 1 September 2009 and 31 January 2010 in a single hospital throughout the epidemic.
Results
The age distribution of all the subjects was relatively even. Over 90% of cases occurred during a two-month period. Two hundred and five patients (94.5%) received oseltamivir within 48 h of fever onset, and 97% of inpatients defervesced within 48 h of medication. The group with pneumonia included more males than females, and had higher leukocytes counts with lower lymphocyte differentials than the group without pneumonia. The white blood cell count and lymphocyte differential were associated with the severity of pneumonia. Corticosteroid treatment for severe pneumonia patients was highly effective in preventing disease progression.
Conclusion
Children of all ages affected with even rates of infection, but males were predominant in pneumonia patients. Pneumonia patients showed lymphopenia and its severity was associated with the severity of illness. Our results suggest that the mechanism of lung injury in 2009 H1N1 virus infection may be associated with the host immune response.
doi:10.1186/1471-2334-11-225
PMCID: PMC3176209  PMID: 21864391
21.  Transmission of a 2009 H1N1 Pandemic Influenza Virus Occurs before Fever Is Detected, in the Ferret Model 
PLoS ONE  2012;7(8):e43303.
During the early phase of the 2009 influenza pandemic, attempts were made to contain the spread of the virus. Success of reactive control measures may be compromised if the proportion of transmission that occurs before overt clinical symptoms develop is high. In this study we investigated the timing of transmission of an early prototypic strain of pandemic H1N1 2009 influenza virus in the ferret model. Ferrets are the only animal model in which this can be assessed because they display typical influenza-like clinical signs including fever and sneezing after infection. We assessed transmission from infected animals to sentinels that were placed either in direct contact or in adjacent cages, the latter reflecting the respiratory droplet (RD) transmission route. We found that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed. Three of 3 animals exposed in direct contact between day 1 and 2 after infection of the donor animals became infected, and 2/3 of the animals exposed at this time period by the RD route acquired the infection, with the third animal becoming seropositive indicating either a low level infection or significant exposure. Moreover, this efficient transmission did not temporally correlate with respiratory symptoms, such as coughs and sneezes, but rather with the peak viral titre in the nose. Indeed respiratory droplet transmission did not occur late in infection, even though this was when sneezing and coughing were most apparent. None of the 3 animals exposed at this time by the RD route became infected and these animals remained seronegative at the end of the experiment. These data have important implications for pandemic planning strategies and suggest that successful containment is highly unlikely for a human-adapted influenza virus that transmits efficiently within a population.
doi:10.1371/journal.pone.0043303
PMCID: PMC3430703  PMID: 22952661
22.  Longitudinal molecular microbial analysis of influenza-like illness in New York City, may 2009 through may 2010 
Virology Journal  2011;8:288.
Background
We performed a longitudinal study of viral etiology in samples collected in New York City during May 2009 to May 2010 from outpatients with fever or respiratory disease symptoms in the context of a pilot respiratory virus surveillance system.
Methods
Samples were assessed for the presence of 13 viruses, including influenza A virus, by MassTag PCR.
Results
At least one virus was detected in 52% of 940 samples analyzed, with 3% showing co-infections. The most frequently detected agents were rhinoviruses and influenza A, all representing the 2009 pandemic H1N1 strain. The incidence of influenza H1N1-positive samples was highest in late spring 2009, followed by a decline in summer and early fall, when rhinovirus infections became predominant before H1N1 reemerged in winter. Our study also identified a focal outbreak of enterovirus 68 in the early fall of 2009.
Conclusion
MassTag multiplex PCR affords opportunities to track the epidemiology of infectious diseases and may guide clinicians and public health practitioners in influenza-like illness and outbreak management. Nonetheless, a substantial proportion of influenza-like illness remains unexplained underscoring the need for additional platforms.
doi:10.1186/1743-422X-8-288
PMCID: PMC3121709  PMID: 21658237
23.  Shedding of Pandemic (H1N1) 2009 Virus among Health Care Personnel, Seattle, Washington, USA 
Emerging Infectious Diseases  2011;17(4):639-644.
The Centers for Disease Control and Prevention (CDC) recommends that health care personnel (HCP) infected with pandemic influenza (H1N1) 2009 virus not work until 24 hours after fever subsides without the use of antipyretics. During an influenza outbreak, we examined the association between viral shedding and fever among infected HCP. Participants recorded temperatures daily and provided nasal wash specimens for 2 weeks after symptom onset. Specimens were tested by using PCR and culture. When they met CDC criteria for returning to work, 12 of 16 HCP (75%) (95% confidence interval 48%–93%) had virus detected by PCR, and 9 (56%) (95% confidence interval 30%–80%) had virus detected by culture. Fever was not associated with shedding duration (p = 0.65). HCP might shed virus even when meeting CDC exclusion guidelines. Further research is needed to clarify the association between viral shedding, symptoms, and infectiousness.
doi:10.3201/eid1704.100866
PMCID: PMC3377395  PMID: 21470453
Influenza; virus shedding; pandemic (H1N1) 2009; viruses; PCR; health care personnel; outbreak; Washington; research
24.  Evaluation of Three Commercially Available Influenza A Type-Specific Blocking Enzyme-Linked Immunosorbent Assays for Seroepidemiological Studies of Influenza A Virus Infection in Pigs 
The reverse zoonotic transmission of the pandemic H1N1 2009 influenza virus to swine necessitates enhanced surveillance of swine for influenza virus infection. Using a well-characterized panel of naturally infected swine sera, we evaluated and optimized the performances of three commercially available competitive enzyme-linked immunosorbent assays (ELISAs), namely, the IDEXX Influenza A Ab test, IDEXX AI MultiS-Screen Ab test, and IDVet ID Screen influenza A antibody competition ELISA, for detecting influenza A virus-reactive antibodies in swine. Receiver operating characteristic (ROC) analysis suggests that adjustment of the manufacturer-recommended cutoff values optimizes the sensitivity and specificity of these assays, making them applicable for seroepidemiology studies of swine influenza. Using such optimized cutoff levels, the sensitivity and specificity of the IDEXX Influenza A Ab test were 86% and 89%, respectively; those for the IDEXX AI MultiS-Screen Ab test were 91% and 87%, respectively; and those for the IDVet ID Screen influenza A test were 95% and 79%, respectively.
doi:10.1128/CVI.05358-11
PMCID: PMC3294623  PMID: 22219314
25.  Evaluation of Indirect Fluorescent Antibody Assays Compared to Rapid Influenza Diagnostic Tests for the Detection of Pandemic Influenza A (H1N1) pdm09 
PLoS ONE  2012;7(3):e33097.
Performance of indirect fluorescent antibody (IFA) assays and rapid influenza diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with the relative effects of age and illness severity on test accuracy. Clinicians and laboratories submitted specimens on patients with respiratory illness to public health from April to mid October 2009 for polymerase chain reaction (PCR) testing as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT were performed in clinical settings. Sensitivity and specificity for detection of the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs tested by PCR were falsely negative (sensitivity 71% and 69%, respectively). Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT (84%). Specificity of tests performed on hospitalized children was 94% for IFA and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to previously published studies on pandemic H1N1 influenza and sensitivity of IFA was similar to what has been reported in children for seasonal influenza. Both diagnostic tests produced a high number of false negatives and should not be used to rule out influenza infection.
doi:10.1371/journal.pone.0033097
PMCID: PMC3316561  PMID: 22479360

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