Validation of statistical models for estimating hospitalization associated with influenza and other respiratory viruses

Background

Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza and adenovirus.

Methods and Findings

We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization.

Conclusion

The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong.     

A possible geographic origin of endemic hepatitis C virus 6a in Hong Kong: evidences for the association with Vietnamese immigration

Background

Hepatitis C virus (HCV) 6a accounts for 23.6% of all HCV infections of the general population and 58.5% of intravenous drug users in Hong Kong. However, the geographical origin of this highly predominant HCV subgenotype is largely unknown. This study explores a hypothesis for one possible transmission route of HCV 6a to Hong Kong.

Methods

NS5A sequences derived from 26 HCV 6a samples were chosen from a five year period (1999–2004) from epidemiologically unrelated patients from Hong Kong. Partial-NS5A sequences (513-bp from nt 6728 to 7240) were adopted for Bayesian coalescent analysis to reconstruct the evolutionary history of HCV infections in Hong Kong using the BEAST v1.3 program. A rooted phylogenetic tree was drawn for these sequences by alignment with reference Vietnamese sequences. Demographic data were accessed from “The Statistic Yearbooks of Hong Kong”.

Results

Bayesian coalescent analysis showed that the rapid increase in 6a infections, which had increased more than 90-fold in Hong Kong from 1986 to 1994 correlated to two peaks of Vietnamese immigration to Hong Kong from 1978 to 1997. The second peak, which occurred from 1987 through 1997, overlapped with the rapid increase of HCV 6a occurrence in Hong Kong. Phylogenetic analyses have further revealed that HCV 6a strains from Vietnam may be ancestral to Hong Kong counterparts.

Conclusions

The high predominance of HCV 6a infections in Hong Kong was possibly associated with Vietnamese immigration during 1987–1997.     

Latitudinal Variations in Seasonal Activity of Influenza and Respiratory Syncytial Virus (RSV): A Global Comparative Review

Background

There is limited information on influenza and respiratory syncytial virus (RSV) seasonal patterns in tropical areas, although there is renewed interest in understanding the seasonal drivers of respiratory viruses.

Methods

We review geographic variations in seasonality of laboratory-confirmed influenza and RSV epidemics in 137 global locations based on literature review and electronic sources. We assessed peak timing and epidemic duration and explored their association with geography and study settings. We fitted time series model to weekly national data available from the WHO influenza surveillance system (FluNet) to further characterize seasonal parameters.

Results

Influenza and RSV activity consistently peaked during winter months in temperate locales, while there was greater diversity in the tropics. Several temperate locations experienced semi-annual influenza activity with peaks occurring in winter and summer. Semi-annual activity was relatively common in tropical areas of Southeast Asia for both viruses. Biennial cycles of RSV activity were identified in Northern Europe. Both viruses exhibited weak latitudinal gradients in the timing of epidemics by hemisphere, with peak timing occurring later in the calendar year with increasing latitude (P<0.03). Time series model applied to influenza data from 85 countries confirmed the presence of latitudinal gradients in timing, duration, seasonal amplitude, and between-year variability of epidemics. Overall, 80% of tropical locations experienced distinct RSV seasons lasting 6 months or less, while the percentage was 50% for influenza.

Conclusion

Our review combining literature and electronic data sources suggests that a large fraction of tropical locations experience focused seasons of respiratory virus activity in individual years. Information on seasonal patterns remains limited in large undersampled regions, included Africa and Central America. Future studies should attempt to link the observed latitudinal gradients in seasonality of viral epidemics with climatic and population factors, and explore regional differences in disease transmission dynamics and attack rates.     

Influenza virus in human exhaled breath: an observational study

Background

Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection.

Methodology/Principal Findings

We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter.

Conclusions

These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission.     

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong

Background

Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong.

Methods

We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: “immunofluorescence-assay” (IFA) or “polymerase-chain-reaction” (PCR)-guided oseltamivir treatment, “empirical treatment plus PCR” and “empirical treatment alone”. Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010–2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers'' perspective.

Results

In base-case analysis, “empirical treatment alone” was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that “PCR-guided treatment” would dominate “empirical treatment alone” when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, “empirical treatment alone” and “PCR-guided treatment” were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations.

Conclusions

During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.     

Seasonality of influenza A(H3N2) virus: a Hong Kong perspective (1997-2006)

Background

The underlying basis for the seasonality of influenza A viruses is still uncertain. Phylogenetic studies investigated this phenomenon but have lacked sequences from more subtropical and tropical regions, particularly from Southeast Asia.

Methodology/Principal Findings

281 complete hemagglutinin (HA) and neuraminidase (NA) sequences were obtained from influenza A(H3N2) viruses, collected over 10 years (1997–2006) from Hong Kong. These dated sequences were analyzed with influenza A(H3N2) vaccine strain sequences (Syd/5/97, Mos/10/99, Fuj/411/02, Cal/7/04) and 315 other publicly available dated sequences from elsewhere, worldwide. In addition, the NA sequence alignment was inspected for the presence of any naturally occurring, known, neuraminidase inhibitor (NAI) resistance-associated amino acid mutations (R292K and E119V). Before 2001, the Hong Kong HA and NA sequences clustered more closely with the older vaccine sequences (Syd/5/97, Mos/10/99) than did sequences from elsewhere. After 2001, this trend reversed with significant clusters containing HA and NA sequences from different locations, isolated at different times, suggesting that viral migration may account for much of the influenza A(H3N2) seasonality during this 10-year period. However, at least one example from Hong Kong was found suggesting that in some years, influenza A(H3N2) viruses may persist in the same location, perhaps continuing to circulate, sub-clinically, at low levels between seasons, to re-emerge in the influenza season the following year, relatively unchanged. None of these Hong Kong influenza A(H3N2) NA sequences contained any of the known NAI-resistance associated mutations.

Conclusions/Significance

The seasonality of influenza A(H3N2) may be largely due to global migration, with similar viruses appearing in different countries at different times. However, occasionally, some viruses may remain within a single location and continue to circulate within that population, to re-emerge during the next influenza season, with relatively little genetic change. Naturally occurring NAI resistance mutations were absent or, at least, very rare in this population.     

Cross-Sectional Study on Attitudes among General Practitioners towards Pneumococcal Vaccination for Middle-Aged and Elderly Population in Hong Kong

Objective

To study the attitudes among general practitioners towards pneumococcal vaccination for middle-aged (50–64) and elderly population (over 65) in Hong Kong and the factors affecting their decision to advise pneumococcal vaccination for those age groups.

Design

Cross-sectional study of general practitioners in private practice in Hong Kong.

Participants

Members of Hong Kong Medical Association delivering general practice services in private sector.

Measuring Tool

Self-administered questionnaire.

Main Outcome Measures

Intention to recommend pneumococcal vaccination, barriers against pneumococcal vaccination.

Results

53.4% of the respondents would actively recommend pneumococcal vaccination to elderly patients but only 18.8% would recommend for middle-aged patients. Consultation not related to pneumococcal vaccine was the main reason for not recommending pneumococcal vaccine (43.6%). Rarity of pneumonia in their daily practice was another reason with 68.4% of respondents attending five or less patients with pneumonia each year. In multivariate analysis, factors such as respondents would get vaccination when reaching age 50 (OR_m 10.1), and attending 6 pneumonia cases or more per year (OR_m 2.28) were found to be associated with increasing likelihood for recommending vaccination to the middle-aged. While concerns of marketing a product (OR_m 0.41), consultation not related to vaccination (OR_m 0.45) and limited time (OR_m 0.38) were factors that reduced the likelihood.

Conclusion

Public policy is needed to increase the awareness of impact of pneumococcal pneumonia and the availability of preventive measures.     

Regional Impact of Climate on Japanese Encephalitis in Areas Located near the Three Gorges Dam

Background

In this study, we aim to identify key climatic factors that are associated with the transmission of Japanese encephalitis virus in areas located near the Three Gorges Dam, between 1997 and 2008.

Methods

We identified three geographical regions of Chongqing, based on their distance from the Three Gorges Dam. Collectively, the three regions consisted of 12 districts from which study information was collected. Zero-Inflated Poisson Regression models were run to identify key climatic factors of the transmission of Japanese encephalitis virus for both the whole study area and for each individual region; linear regression models were conducted to examine the fluctuation of climatic variables over time during the construction of the Three Gorges Dam.

Results

Between 1997 and 2008, the incidence of Japanese encephalitis decreased throughout the entire city of Chongqing, with noticeable variations taking place in 2000, 2001 and 2006. The eastern region, which is closest to the Three Gorges Dam, suffered the highest incidence of Japanese encephalitis, while the western region experienced the lowest incidence. Linear regression models revealed that there were seasonal fluctuations of climatic variables during this period. Zero-Inflated Poisson Regression models indicated a significant positive association between temperature (with a lag of 1 and 3 months) and Japanese encephalitis incidence, and a significant negative association between rainfall (with a lag of 0 and 4 months) and Japanese encephalitis incidence.

Conclusion

The spatial and temporal trends of Japanese encephalitis incidence that occurred in the City of Chongqing were associated with temperature and rainfall. Seasonal fluctuations of climatic variables during this period were also observed. Additional studies that focus on long-term data collection are needed to validate the findings of this study and to further explore the effects of the Three Gorges Dam on Japanese encephalitis and other related diseases.     

Synchrony of clinical and laboratory surveillance for influenza in Hong Kong

Background

Consultation rates of influenza-like illness (ILI) in an outpatient setting have been regarded as a good indicator of influenza virus activity in the community. As ILI-like symptoms may be caused by etiologies other than influenza, and influenza virus activity in the tropics and subtropics is less predictable than in temperate regions, the correlation between of ILI and influenza virus activity in tropical and subtropical regions is less well defined.

Methodology and Principal Findings

In this study, we used wavelet analysis to investigate the relationship between seasonality of influenza virus activity and consultation rates of ILI reported separately by General Out-patient Clinics (GOPC) and General Practitioners (GP). During the periods 1998–2000 and 2002–2003, influenza virus activity exhibited both annual and semiannual cycles, with one peak in the winter and another in late spring or early summer. But during 2001 and 2004–2006, only annual cycles could be clearly identified. ILI consultation rates in both GOPC and GP settings share a similar non-stationary seasonal pattern. We found high coherence between ILI in GOPC and influenza virus activity for the annual cycle, but this was only significant (p<0.05) during the periods 1998–1999 and 2002–2006. For the semiannual cycle high coherence (p<0.05) was also found significant during the period 1998–1999 and year 2003 when two peaks of influenza were evident. Similarly, ILI in GP setting is also associated with influenza virus activity for both the annual and semiannual cycles. On average, oscillation of ILI in GP and of ILI in GOPC preceded influenza virus isolation by approximately four and two weeks, respectively.

Conclusions

Our findings suggest that consultation rates of ILI precede the oscillations of laboratory surveillance by at least two weeks and can be used as a predictor for influenza epidemics in Hong Kong. The validity of our model for other tropical regions needs to be explored.     

A Comparison of Functional Outcome in Patients Sustaining Major Trauma: A Multicentre,Prospective, International Study

Objectives

To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia.

Summary Background Data

Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR).

Methods

Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE) functional outcome and risk-adjusted Short-Form 12 (SF-12) health status at 6 and 12 months after injury.

Results

261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17), and at 12 months was 0.83 (95% CI: 0.60, 1.12). Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: −1.2, 3.6) and 12-months (adjusted mean difference: −0.4, 95% CI: −3.2, 2.4) compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: −2.1, 2.8) or 12-months (adjusted mean difference: 1.8, 95% CI: −0.8, 4.5).

Conclusion

The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions.     

The Role of Climate Variability in the Spread of Malaria in Bangladeshi Highlands

Background

Malaria is a major public health problem in Bangladesh, frequently occurring as epidemics since the 1990s. Many factors affect increases in malaria cases, including changes in land use, drug resistance, malaria control programs, socioeconomic issues, and climatic factors. No study has examined the relationship between malaria epidemics and climatic factors in Bangladesh. Here, we investigate the relationship between climatic parameters [rainfall, temperature, humidity, sea surface temperature (SST), El Niño-Southern Oscillation (ENSO), the normalized difference vegetation index (NDVI)], and malaria cases over the last 20 years in the malaria endemic district of Chittagong Hill Tracts (CHT).

Methods and Principal Findings

Monthly malaria case data from January 1989 to December 2008, monthly rainfall, temperature, humidity sea surface temperature in the Bay of Bengal and ENSO index at the Niño Region 3 (NIÑO3) were used. A generalized linear negative binomial regression model was developed using the number of monthly malaria cases and each of the climatic parameters. After adjusting for potential mutual confounding between climatic factors there was no evidence for any association between the number of malaria cases and temperature, rainfall and humidity. Only a low NDVI was associated with an increase in the number of malaria cases. There was no evidence of an association between malaria cases and SST in the Bay of Bengal and NIÑO3.

Conclusion and Significance

It seems counterintuitive that a low NDVI, an indicator of low vegetation greenness, is associated with increases in malaria cases, since the primary vectors in Bangladesh, such as An. dirus, are associated with forests. This relationship can be explained by the drying up of rivers and streams creating suitable breeding sites for the vector fauna. Bangladesh has very high vector species diversity and vectors suited to these habitats may be responsible for the observed results.     

Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine

Background

Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.

Methods

We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.

Results

We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.

Conclusions

Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.     

Socioeconomic Disparity in Breast Cancer Detection in Hong Kong – A High Income City: Retrospective Epidemiological Study Using the Breast Cancer Registry

Background

It is not known whether socioeconomic disparities affect the detection of breast cancer in Asian countries where the incidence of breast cancer is a rising trend. In this study, we explore the socioeconomic profiles of women and the stage of the disease at the time of diagnosis in breast cancer patients aged 40 or over in Hong Kong.

Method

During the period 2008 to 2011, 5393 breast cancer patients registered with the Hong Kong Breast Cancer Registry. Participants and their clinicians were asked to complete standardised questionnaires including patient socio-demographics, health history and risk factors, the course of the disease, post-treatment physical discomfort and psychosocial impact, follow-up recurrence and survival status.

Results

Monthly household incomes, educational levels and the practice of regular screening are independently associated with the stage of the disease at diagnosis. Higher socioeconomic status and a higher educational level were associated with an earlier stage of the disease at the time of diagnosis. Yearly clinical examinations, ultrasound and mammographic screening every 2 to 3 years were significantly associated with the earlier detection of breast cancer.

Conclusion

There were socioeconomic disparities among Hong Kong women who were found to have breast cancer. Population-based screening policies, including raising awareness among women at risk, should be implemented.     

Comparison of Different Risk Perception Measures in Predicting Seasonal Influenza Vaccination among Healthy Chinese Adults in Hong Kong: A Prospective Longitudinal Study

Background

Risk perception is a reported predictor of vaccination uptake, but which measures of risk perception best predict influenza vaccination uptake remain unclear.

Methodology

During the main influenza seasons (between January and March) of 2009 (Wave 1) and 2010 (Wave 2),505 Chinese students and employees from a Hong Kong university completed an online survey. Multivariate logistic regression models were conducted to assess how well different risk perceptions measures in Wave 1 predicted vaccination uptake against seasonal influenza in Wave 2.

Principal Findings

The results of the multivariate logistic regression models showed that feeling at risk (β = 0.25, p = 0.021) was the better predictor compared with probability judgment while probability judgment (β = 0.25, p = 0.029 ) was better than beliefs about risk in predicting subsequent influenza vaccination uptake. Beliefs about risk and feeling at risk seemed to predict the same aspect of subsequent vaccination uptake because their associations with vaccination uptake became insignificant when paired into the logistic regression model. Similarly, to compare the four scales for assessing probability judgment in predicting vaccination uptake, the 7-point verbal scale remained a significant and stronger predictor for vaccination uptake when paired with other three scales; the 6-point verbal scale was a significant and stronger predictor when paired with the percentage scale or the 2-point verbal scale; and the percentage scale was a significant and stronger predictor only when paired with the 2-point verbal scale.

Conclusions/Significance

Beliefs about risk and feeling at risk are not well differentiated by Hong Kong Chinese people. Feeling at risk, an affective-cognitive dimension of risk perception predicts subsequent vaccination uptake better than do probability judgments. Among the four scales for assessing risk probability judgment, the 7-point verbal scale offered the best predictive power for subsequent vaccination uptake.     

High Humidity Leads to Loss of Infectious Influenza Virus from Simulated Coughs

Background

The role of relative humidity in the aerosol transmission of influenza was examined in a simulated examination room containing coughing and breathing manikins.

Methods

Nebulized influenza was coughed into the examination room and Bioaerosol samplers collected size-fractionated aerosols (<1 µM, 1–4 µM, and >4 µM aerodynamic diameters) adjacent to the breathing manikin’s mouth and also at other locations within the room. At constant temperature, the RH was varied from 7–73% and infectivity was assessed by the viral plaque assay.

Results

Total virus collected for 60 minutes retained 70.6–77.3% infectivity at relative humidity ≤23% but only 14.6–22.2% at relative humidity ≥43%. Analysis of the individual aerosol fractions showed a similar loss in infectivity among the fractions. Time interval analysis showed that most of the loss in infectivity within each aerosol fraction occurred 0–15 minutes after coughing. Thereafter, losses in infectivity continued up to 5 hours after coughing, however, the rate of decline at 45% relative humidity was not statistically different than that at 20% regardless of the aerosol fraction analyzed.

Conclusion

At low relative humidity, influenza retains maximal infectivity and inactivation of the virus at higher relative humidity occurs rapidly after coughing. Although virus carried on aerosol particles <4 µM have the potential for remaining suspended in air currents longer and traveling further distances than those on larger particles, their rapid inactivation at high humidity tempers this concern. Maintaining indoor relative humidity >40% will significantly reduce the infectivity of aerosolized virus.     

A Prospective Study of Romanian Agriculture Workers for Zoonotic Influenza Infections

Background

In this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among Romanian agricultural workers.

Methods

Sera were drawn upon enrollment (2009) and again at 12 and 24 months from 312 adult agriculture workers and 51 age-group matched controls. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members meeting ILI criteria permitted respiratory swab collections as well as acute and convalescent serum collection. Serologic assays were performed against 9 avian, 3 swine, and 3 human influenza viruses.

Results

During the two-year follow-up, a total of 23 ILI events were reported. Two subjects'' specimens were identified as influenza A by rRT-PCR. During the follow-up period, three individuals experienced elevated microneutralization antibody titers ≥1∶80 against three (one each) avian influenza viruses: A/Teal/Hong Kong/w312/97(H6N1), A/Hong Kong/1073/1999(H9N2), or A/Duck/Alberta/60/1976(H12N5). However, none of these participants met the criteria for poultry exposure. A number of subjects demonstrated four-fold increases over time in hemagglutination inhibition (HI) assay titers for at least one of the three swine influenza viruses (SIVs); however, it seems likely that two of these three responses were due to cross-reacting antibody against human influenza. Only elevated antibody titers against A/Swine/Flanders/1/1998(H3N2) lacked evidence for such confounding. In examining risk factors for elevated antibody against this SIV with multiple logistic regression, swine exposure (adjusted OR = 1.8, 95% CI 1.1–2.8) and tobacco use (adjusted OR = 1.8; 95% CI 1.1–2.9) were important predictors.

Conclusions

While Romania has recently experienced multiple incursions of highly pathogenic avian influenza among domestic poultry, this cohort of Romanian agriculture workers had sparse evidence of avian influenza virus infections. In contrast, there was evidence, especially among the swine exposed participants, of infections with human and one swine H3N2 influenza virus.     

Prospective Study of Avian Influenza Virus Infections among Rural Thai Villagers

Background

In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses.

Methods

After enrollment, participants were contacted weekly for 24mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses.

Results

Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1∶80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04–5.2) at the 24-month encounter. One subject had an elevated titer (1∶20) against H5N1 during follow-up.

Conclusions

From 2008–10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.