A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and Rationale

Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages

Using Risk Assessment as Part of a Systems Approach to the Control and Prevention of HPAIV H5N1

Since its emergence in China in 1996, highly pathogenic avian influenza virus subtype H5N1 has spread across Asia, Africa, and Europe. Countries had to promptly implement control and prevention measures. Numerous research and capacity building initiatives were conducted in the affected regions to improve the capacity of national animal health services to support the development of risk-based mitigation strategies. This paper reviews and discusses risk assessments initiated in several South-East Asian and African countries under one of these projects. Despite important data gaps, the risk assessment results improved the ability of policy makers to design appropriate risk management policies. Disease risk was strongly influenced by various human behavioral factors. The ongoing circulation of HPAIV H5N1 in several Asian countries and in Egypt, despite major disease control efforts, supports the need for an interdisciplinary approach to development of tailored risk management policies, in accordance with the EcoHealth paradigm and the broad concept of risk governance. In particular, active stakeholders engagement and integration of economic and social studies into the policy making process are needed to optimize compliance and sustainable behavioral changes, thereby increasing the effectiveness of mitigation strategies

Global mapping of highly pathogenic avian influenza H5N1 and H5Nx clade 2.3.4.4 viruses with spatial cross-validation.

Global disease suitability models are essential tools to inform surveillance systems and enable early detection. We present the first global suitability model of highly pathogenic avian influenza (HPAI) H5N1 and demonstrate that reliable predictions can be obtained at global scale. Best predictions are obtained using spatial predictor variables describing host distributions, rather than land use or eco-climatic spatial predictor variables, with a strong association with domestic duck and extensively raised chicken densities. Our results also support a more systematic use of spatial cross-validation in large-scale disease suitability modelling compared to standard random cross-validation that can lead to unreliable measure of extrapolation accuracy. A global suitability model of the H5 clade 2.3.4.4 viruses, a group of viruses that recently spread extensively in Asia and the US, shows in comparison a lower spatial extrapolation capacity than the HPAI H5N1 models, with a stronger association with intensively raised chicken densities and anthropogenic factors

Seasonal Oscillation of Human Infection with Influenza A/H5N1 in Egypt and Indonesia

As of June 22, 2011, influenza A/H5N1 has caused a reported 329 deaths and 562 cases in humans, typically attributed to contact with infected poultry. Influenza H5N1 has been described as seasonal. Although several studies have evaluated environmental risk factors for H5N1 in poultry, none have considered seasonality of H5N1 in humans. In addition, temperature and humidity are suspected to drive influenza in temperate regions, but drivers in the tropics are unknown, for H5N1 as well as other influenza viruses. An analysis was conducted to determine whether human H5N1 cases occur seasonally in association with changes in temperature, precipitation and humidity. Data analyzed were H5N1 human cases in Indonesia (n = 135) and Egypt (n = 50), from January 1, 2005 (Indonesia) or 2006 (Egypt) through May 1, 2008 obtained from WHO case reports, and average daily weather conditions obtained from NOAA's National Climatic Data Center. Fourier time series analysis was used to determine seasonality of cases and associations between weather conditions and human H5N1 incidence. Human H5N1 cases in Indonesia occurred with a period of 1.67 years/cycle (p<0.05) and in Egypt, a period of 1.18 years/cycle (p≅0.10). Human H5N1 incidence in Egypt, but not Indonesia, was strongly associated with meteorological variables (κ2≥0.94) and peaked in Egypt when precipitation was low, and temperature, absolute humidity and relative humidity were moderate compared to the average daily conditions in Egypt. Weather conditions coinciding with peak human H5N1 incidence in Egypt suggest that human infection may be occurring primarily via droplet transmission from close contact with infected poultry

Leptospirosis in dairy herds : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, School of Veterinary Science, Massey University, Palmerston North, New Zealand

The introduction and adoption of Leptospira vaccination in most New Zealand dairy herds in the 1980s was associated with a substantial reduction of the incidence of notified human leptospirosis cases in the population and notably among dairy farm workers. However, 80% of cases notified from 1999 to 2016 with a “farmer-type” occupation were dairy farmers, hence this occupational group continues to be at risk for leptospirosis. Failure to vaccinate dairy herds can have serious public health consequences. An example is described in an opportunistic case study, chapter 3 of this thesis. Within the space of three months in early 2015, three workers from a dairy farm with an unvaccinated dairy herd were hospitalised with leptospirosis caused by serovars Hardjo and Pomona. In young and adult dairy cattle from this farm, Hardjo, Pomona, Copenhageni, Ballum and Tarassovi serovars were all detected serologically. While two of the diseased workers recovered, one remains affected four years after the event being unable to return to work. These circumstances – the continuation of dairy workers among notified human cases and the potentially serious consequences from failure to vaccinate or to achieve effective immunity – have raised concerns about the effectiveness of the long–term vaccination programme in dairy herds. The concerns were further substantiated by an opportunistic pilot study (2011) that found evidence of Leptospira shedding in vaccinated dairy cattle. Therefore, a large cross-sectional study of New Zealand dairy farms was conducted involving 200 dairy farms and 4,000 cows. Farms were randomly selected from the national database and blood and urine was collected from 20 cows per herd. Non- response (30%) was investigated by personal interview which indicated that selection bias (e.g. by selecting only farmers with vaccinated herds) was minimal, if not absent. Shedding was indicated by a positive qPCR at cow-level and by one or more shedders per herd at herd-level. A serological response was considered positive when titres of the microscopic agglutination test (MAT) were at or above 48. Overall shedding rates were 2.4% at cow- and 26.5% at herd-level. Seropositivity to Hardjo, Pomona and, when trivalent vaccines were used, Copenhageni, was most likely a response to vaccination. None of the vaccinal serovars were associated with urine shedding. However, there was a strong linear association at the cow-level between increasing MAT titres to Tarassovi and the likelihood of shedding. Serological evidence for exposure to Tarassovi was observed in 17% of cows and 74% of the herds. Few cows (1%) and 16% herds were sero-positive to Copenhageni when not vaccinated against this serovar which, however, was not associated with cow-level shedding. Similarly, the rodent-related serovar Ballum was not associated with shedding; with positive titres observed in 3% of cows and 38% of herds. Studies in the 1970s and 1980s found little serological evidence of Tarassovi, so we conclude that this serovar has emerged, became endemic and is now probably causing most of the shedding in the dairy cattle population. Considering published evidence that a large proportion of notified cases in dairy farmers were Tarassovi, there is strong corroborative evidence that this serovar poses a public health risk for workers on dairy farms. Our survey administered a questionnaire about vaccination practices and putative risk factors. All but one of the farmers had regular vaccination programmes for calves, heifers and cows using mostly bivalent (80%, 69%, 68% of farms, respectively) and some trivalent vaccines (20%, 31%, 32% of farms, respectively). Regardless of the almost universal practice of Leptospira vaccination in dairy cattle, fewer than 40% famers conformed with Best Practice Guidelines (2012) developed and propagated by the New Zealand Veterinary Association. A further objective was a risk factor analysis (Chapter 6). One cow-level (age) and three herd-level (presence of sheep or dogs, herd size) factors were significantly associated with the risk of shedding. As 93% of the potential factors evaluated were at herd level, and with only 200 herds included in the study, and the shedding rate being relatively low, the statistical power might have been too low to identify other herd-level determinants related to the management and environment of the farms. Nevertheless, a linear negative effect of age suggested that young cows were more likely to shed Leptospira than adult cows, and therefore increase the risk of infection for dairy workers. Evidence from this thesis suggests that current Leptospira vaccination practices are effective for preventing the exposure of farm workers against the serovars most commonly incorporated in vaccines (Hardjo and Pomona), and the less common serovar Copenhageni. Thus, continuation with vaccination is supported. The public health risk arising from Tarassovi that has emerged, and evidence here that this serovar is widely present in the dairy cattle population, justifies raised awareness, the adoption of protection measures additional to vaccination, further research into the epidemiology of Tarassovi and an evaluation of the justification for its inclusion into vaccines. Dairy workers are advised to take extra care and precautions when milking and handling cows, especially first calving heifers irrespective of their vaccination status

Risk factors of poultry outbreaks and human cases of H5N1 avian influenza virus infection in West Java Province, Indonesia

Background: The purpose of this study was to determine the association of potential risk factors to the spread and maintenance of the highly pathogenic avian influenza (HPAI) H5N1 virus in poultry and humans at the district level in West Java Province, Indonesia. Methods: The association of demography and environmental risk factors including poultry density, human density, road density, percentage of paddy field, and percentage of swamp, dyke and pond with both HPAI human cases and HPAI outbreaks in poultry were assessed using a descriptive epidemiological design. We also assessed the association of HPAI outbreaks in poultry with HPAI human cases. Poisson regression (generalized linear modeling and generalized estimating equations) was used to analyze the data corrected for over-dispersion. Results: There were 794 HPAI outbreaks in poultry covering 24 of the 25 districts in our study during 2003-2008 and 34 HPAI human cases involving 12 districts during 2005-2008. We found that two risk factors - poultry density and road density - had a statistically significant correlation with the number of HPAI outbreaks in poultry. The number of poultry outbreaks had a negative association with poultry density (29% effect) and a positive association with road density (67% effect). The number of human cases was significantly associated with the number of poultry outbreaks (34% effect), but with none of the other risk factors considered. Conclusions: We conclude that the most effective way to prevent human HPAI cases is to intervene directly in the poultry sector. Our study further suggests that implementing preventive measures in backyard chicken farming and limiting transport of live poultry and their products are promising options to this end. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Risk factors of poultry outbreaks and human cases of H5N1 avian influenza virus infection in West Java Province, Indonesia

Background: The purpose of this study was to determine the association of potential risk factors to the spread and maintenance of the highly pathogenic avian influenza (HPAI) H5N1 virus in poultry and humans at the district level in West Java Province, Indonesia. Methods: The association of demography and environmental risk factors including poultry density, human density, road density, percentage of paddy field, and percentage of swamp, dyke and pond with both HPAI human cases and HPAI outbreaks in poultry were assessed using a descriptive epidemiological design. We also assessed the association of HPAI outbreaks in poultry with HPAI human cases. Poisson regression (generalized linear modeling and generalized estimating equations) was used to analyze the data corrected for over-dispersion. Results: There were 794 HPAI outbreaks in poultry covering 24 of the 25 districts in our study during 2003-2008 and 34 HPAI human cases involving 12 districts during 2005-2008. We found that two risk factors - poultry density and road density - had a statistically significant correlation with the number of HPAI outbreaks in poultry. The number of poultry outbreaks had a negative association with poultry density (29% effect) and a positive association with road density (67% effect). The number of human cases was significantly associated with the number of poultry outbreaks (34% effect), but with none of the other risk factors considered. Conclusions: We conclude that the most effective way to prevent human HPAI cases is to intervene directly in the poultry sector. Our study further suggests that implementing preventive measures in backyard chicken farming and limiting transport of live poultry and their products are promising options to this end. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Interventions for avian influenza A (H5N1) risk management in live bird market networks.

Highly pathogenic avian influenza virus subtype H5N1 is endemic in Asia, with live bird trade as a major disease transmission pathway. A cross-sectional survey was undertaken in northern Vietnam to investigate the structure of the live bird market (LBM) contact network and the implications for virus spread. Based on the movements of traders between LBMs, weighted and directed networks were constructed and used for social network analysis and individual-based modeling. Most LBMs were connected to one another, suggesting that the LBM network may support large-scale disease spread. Because of cross-border trade, it also may promote transboundary virus circulation. However, opportunities for disease control do exist. The implementation of thorough, daily disinfection of the market environment as well as of traders' vehicles and equipment in only a small number of hubs can disconnect the network dramatically, preventing disease spread. These targeted interventions would be an effective alternative to the current policy of a complete ban of LBMs in some areas. Some LBMs that have been banned still are very active, and they likely have a substantial impact on disease dynamics, exhibiting the highest levels of susceptibility and infectiousness. The number of trader visits to markets, information that can be collected quickly and easily, may be used to identify LBMs suitable for implementing interventions. This would not require prior knowledge of the force of infection, for which laboratory-confirmed surveillance would be necessary. These findings are of particular relevance for policy development in resource-scarce settings