The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong

Background. Serial cross-sectional data on antibody levels to the 2009 pandemic H1N1 influenza A virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community. Methods. From April through December 2009, we obtained 12,217 serum specimens from blood donors (aged 16-59 years), 2520 specimens from hospital outpatients (aged 5-59 years), and 917 specimens from subjects involved in a community pediatric cohort study (aged 5-14 years). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired serum samples from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, admission to the intensive care unit (ICU), and death. Results. We found that 3.3% and 14% of persons aged 5-59 years had antibody titers ≥1:40 before and after the first wave, respectively. The overall attack rate was 10.7%, with age stratification as follows: 43.4% in persons aged 5-14 years, 15.8% in persons aged 15-19 years, 11.8% in persons aged 20-29 years, and 4%-4.6% in persons aged 30-59 years. Case-hospitalization rates were 0.47%-0.87% among persons aged 5-59 years. Case-ICU rates were 7.9 cases per 100,000 infections in persons aged 5-14 years and 75 cases per 100,000 infections in persons aged 50-59 years, respectively. Case-fatality rates were 0.4 cases per 100,000 infections in persons aged 5-14 years and 26.5 cases per 100,000 infections in persons aged 50-59 years, respectively. Conclusions. Almost half of all school-aged children in Hong Kong were infected during the first wave. Compared with school children aged 5-14 years, older adults aged 50-59 years had 9.5 and 66 times higher risks of ICU admission and death if infected, respectively. © 2010 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Absence of Detectable Influenza RNA Transmitted via Aerosol during Various Human Respiratory Activities – Experiments from Singapore and Hong Kong

Two independent studies by two separate research teams (from Hong Kong and Singapore) failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin’s mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR) assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing), talk (counting in English/second language), cough (from 1 m/0.1 m away) and laugh, onto a thermal, breathing manikin. The manikin’s face was swabbed at specific points (around both eyes, the nostrils and the mouth) before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team’s in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B) infection with high viral loads, ranging from 105-108 copies/mL (Hong Kong volunteers/assay) and 104–107 copies/mL influenza viral RNA (Singapore volunteers/assay). These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within these exposure time-frames. Various reasons are discussed in an attempt to explain these findings.published_or_final_versio

Seasonal Fluctuations of Astrovirus, But Not Coronavirus Shedding in Bats Inhabiting Human-Modified Tropical Forests

Emerging infectious diseases (EIDs) are considered a major threat to global health. Most EIDs appear to result from increased contact between wildlife and humans, especially when humans encroach into formerly pristine habitats. Habitat deterioration may also negatively affect the physiology and health of wildlife species, which may eventually lead to a higher susceptibility to infectious agents and/or increased shedding of the pathogens causing EIDs. Bats are known to host viruses closely related to important EIDs. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the occurrence of astro- and coronaviruses in eight bat species. In contrast to our hypothesis, anthropogenic habitat disturbance was not associated with corona- and astrovirus detection rates in fecal samples. However, we found that bats infected with either astro- or coronaviruses were likely to be coinfected with the respective other virus. Additionally, we identified two more risk factors influencing astrovirus shedding. First, the detection rate of astroviruses was higher at the beginning of the rainy compared to the dry season. Second, there was a trend that individuals with a poor body condition had a higher probability of shedding astroviruses in their feces. The identification of risk factors for increased viral shedding that may potentially result in increased interspecies transmission is important to prevent viral spillovers from bats to other animals, including humans

Novel coronaviruses and astroviruses in bats

Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses, which can be found from a wide range of mammals, were recently detected in bats. Strikingly, these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families, but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health. © Wuhan Institute of Virology, CAS and Springer-Verlag GmbH 2009.link_to_subscribed_fulltex

Novel astroviruses in insectivorous bats

Bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. They are the reservoir of a number of human zoonotic diseases including Nipah, Ebola, and severe acute respiratory syndrome. We report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in Hong Kong, in particular, bats belonging to the genera Miniopterus and Myotis. Astroviruses are important causes of diarrhea in many animal species, including humans. Many of the bat astroviruses form distinct phylogenetic clusters in the genus Mamastrovirus within the family Astroviridae. Virus detection rates of 36% to 100% and 50% to 70% were found in Miniopterus magnater and Miniopterus pusillus bats, respectively, captured within a single bat habitat during four consecutive visits spanning 1 year. There was high genetic diversity of viruses in bats found within this single habitat. Some bat astroviruses may be phylogenetically related to human astroviruses, and further studies with a wider range of bat species in different geographic locations are warranted. These findings are likely to provide new insights into the ecology and evolution of astroviruses and reinforce the role of bats as a reservoir of viruses with potential to pose a zoonotic threat to human health. Copyright © 2008, American Society for Microbiology. All Rights Reserved.link_to_subscribed_fulltex

Genomic characterizations of bat coronaviruses (1A, 1B and HKU8) and evidence for co-infections in Miniopterus bats

We previously reported the detection of bat coronaviruses (bat CoVs 1A, 1B. HKU7. HKU8 and bat-severe acute respiratory syndrome coronavirus) in Miniopterus,spp. that cohabit a cave in Hong Kong. Here, we report the full genomic s equences of bat CoVs 1A, 1B and HKU8. Bat CoVs 1A and 1B, which are commonly found in the Miniopterus, are phylogenetically closely related. Using species-specific RT-PCR assays, bat CoVs 1A and 1B were confirmed to have distinct host specificities to Miniopterus magnater and Miniopterus pusillus, respectively. Interestingly, co-infections of bat CoVs 1B and HKU8 in M. pusillus are detected in seven of 38 virus-positive specimens collected from 2004 to 2006. These findings highlight that co-infections of some coronaviruses might be common events in nature. The biological basis for the host restriction of bat coronaviruses, however, is yet to be determined. © 2008 SGM.link_to_subscribed_fulltex

Genomic characterizations of bat coronaviruses (1A, 1B and HKU8) and evidence for co-infections in Miniopterus bats

We previously reported the detection of bat coronaviruses (bat CoVs 1A, 1B. HKU7. HKU8 and bat-severe acute respiratory syndrome coronavirus) in Miniopterus,spp. that cohabit a cave in Hong Kong. Here, we report the full genomic s equences of bat CoVs 1A, 1B and HKU8. Bat CoVs 1A and 1B, which are commonly found in the Miniopterus, are phylogenetically closely related. Using species-specific RT-PCR assays, bat CoVs 1A and 1B were confirmed to have distinct host specificities to Miniopterus magnater and Miniopterus pusillus, respectively. Interestingly, co-infections of bat CoVs 1B and HKU8 in M. pusillus are detected in seven of 38 virus-positive specimens collected from 2004 to 2006. These findings highlight that co-infections of some coronaviruses might be common events in nature. The biological basis for the host restriction of bat coronaviruses, however, is yet to be determined. © 2008 SGM.link_to_subscribed_fulltex

Influenza virus infections and immunity in a cohort of school-age children over a 5-year period

Oral Abstract Session - Public Health 2: no. O-26BACKGROUND: School-aged children experience high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection. METHOD: Between August 2009 and February 2010 in Hong Kong, 796 households including 1,182 children were enrolled in a cluster-randomized trial and followed up for approximately for one year. One child in each household was randomized to receive 2009-10 seasonal TIV or saline placebo. We extended follow up of participants through to September 2014, losing approximately 15% of participants each year. Follow-up included serum collection at least once per year, and home visits to collect respiratory specimens from any ill individuals. The primary outcome measure was influenza virus infection in participants indicated by a four-fold or greater increase in antibody titers between paired serum specimens, or by RT-PCR confirmation of influenza on a respiratory specimen. RESULTS: Over the five years of follow-up, we included 4,141 person-years of follow-up of children 6-17 years of age. We identified 12 distinct influenza epidemics across the 5 years. Between 23% and 39% of children experienced laboratory-confirmed influenza virus infections each year, with over 75% of children experiencing at least one infection across the five year period. We found statistically significant evidence of protection against H1N1pdm09 virus infection in year 2 and again in year 4 associated with prior H1N1pdm09 infection in year 1, consistent with homosubtypic immunity lasting multiple years. We also identified a statistically significant protective effect of H3N2 infection in 2010 on H3N2 infection in 2012. There was no evidence that heterosubtypic immunity spanned one or more years. CONCLUSION: Influenza virus infections are common in school-age children in Hong Kong. These results increase our understanding of influenza epidemiology and immunity across multiple years following natural infections

Longitudinal serum quadruples from Hong Kong suggest a key role for middle-aged adults in the transmission of influenza A during the postpandemic period

Poster Presentations: S1-P15BACKGROUND: A number of populations have experienced genuine “follow-up” waves of pandemic H1N1 influenza A (pH1N1) infection (eg, winter waves of 2010-2011 in the United Kingdom and Hong Kong and the 2011-2012 winter wave in Mexico). An upward age shift has been observed in laboratory-confirmed clinical cases in these follow-up waves compared with earlier pandemic waves. Continued circulation of seasonal H3N2 influenza A (sH3N2) in the absence of seasonal H1N1 suggests that sH3N2 and pH1N1 will co-circulate for the foreseeable future. METHODS: We recruited randomly from households in Hong Kong and asked participants to attend a central clinic to answer a questionnaire and provide a blood sample. We conducted 4 rounds: round 1, July 4, 2009-September 19, 2009; round 2, November 11, 2009-February 6, 2010; round 3, December 13, 2010-March 19, 2011; and round 4, August 24, 2011-December 17, 2011. The timing of our rounds relative to waves of clinical cases was assessed using monthly subtype-specific test results from the Center for Health Protection, Hong Kong. Everyone who provided a sample in round 1, who did not explicitly refuse to be contacted again, was invited to participate in subsequent rounds. Serum samples from individuals who participated in all 4 rounds were tested in quadruples using standard hemagglutinin inhibitor assays for pH1N1 and sH3N2. An individual was assumed to have been infected between pairs of waves if the titre for the second sample was ≥4-fold greater than that of the first sample. RESULTS: We obtained quadruples of serum from 445 individuals aged 4-79 years. In general, our rounds of recruitment did not neatly bracket waves of clinical cases: round 1 was taken toward the start of the initial prolonged wave of pH1N1 and round 2 was close to the end of that period. Rounds 2 and 3 did bracket a clear clinical wave of sH3N2. Although rounds 2 and 4 bracketed the follow-up wave of pH1N1, the interval between rounds 2 and 4 was long and contained some infections from the end of the initial wave. Between rounds 1 and 2, 45 of 445 participants were infected with pH1N1. Of these 45, 33% (95% CI, 22%-49%) were aged ≤18 years (children), 24% (95% CI, 15%-40%) were aged 19-44 years (young adults), 22% (95% CI, 13%-37%) were aged 45-64 years (middle-aged adults), and 20% (95% CI, 11%-36%) were ≥65 years (older adults). Between rounds 2 and 4, 123 of 445 participants were infected with pH1N1. Of these 123, 13% (95% CI, 8%-20%) were children, 23% (95% CI, 16%-31%) were young adults, 52% (95% CI, 44%-62%) were middle-aged adults, and 11% (95% CI, 7%-18%) were older adults. Between rounds 2 and 3, 51 of 445 participants were infected with sH3N2. Of these, 13% (95% CI, 7%-26%) were children, 16% (95% CI, 8%-29%) were young adults, 49% (95% CI, 37%-63%) were middle-aged adults, and 22% (95% CI, 13%-35%) were older adults. CONCLUSIONS: There was a substantial shift in infections away from children toward middle-aged adults between the initial and follow-up waves of pH1N1 in Hong Kong. The age distribution of infections in the follow-up wave of pH1N1 was similar to that of sH3N2. Middle-aged adults may be more important for influenza A transmission during nonpandemic periods than was assumed previously. Here, because of the timing of rounds, we focused on the distribution of ages of those infected, rather than on between-round serologic attack rates. However, these data could be combined with catalytic and mechanistic models of transmission to produce accurate estimates of age-specific infection rates for individual waves.link_to_OA_fulltex