Comparing the estimates of effect obtained from statistical causal inference methods: An example using bovine respiratory disease in feedlot cattle

The causal effect of an exposure on an outcome of interest in an observational study cannot be estimated directly if the confounding variables are not controlled. Many approaches are available for estimating the causal effect of an exposure. In this manuscript, we demonstrate the advantages associated with using inverse probability weighting (IPW) and doubly robust estimation of the odds ratio in terms of reduced bias. IPW approach can be used to adjust for confounding variables and provide unbiased estimates of the exposure’s causal effect. For cluster-structured data, as is common in animal populations, inverse conditional probability weighting (ICPW) approach can provide a robust estimation of the causal effect. Doubly robust estimation can provide a robust method even when the specification of the model form is uncertain. In this paper, the usage of IPW, ICPW, and doubly robust approaches are illustrated with a subset of data with complete covariates from the Australian-based National Bovine Respiratory Disease Initiative as well as simulated data. We evaluate the causal effect of prior bovine viral diarrhea exposure on bovine respiratory disease in feedlot cattle. The results show that the IPW, ICPW and doubly robust approaches would provide a more accurate estimation of the exposure effect than the traditional outcome regression model, and doubly robust approaches are the most preferable overall

Impact of anthropogenic and natural environmental changes on Echinococcus transmission in Ningxia Hui Autonomous Region, the People’s Republic of China

Echinococcus transmission is known to be affected by various environmental factors, which may be modified by human influence or natural events including global warming. Considerable population growth in the last fifty years in Ningxia Hui Autonomous Region (NHAR), the People's Republic of China (PRC), has led to dramatic increases in deforestation and modified agricultural practices. In turn, this has resulted in many changes in the habitats for the definitive and intermediate hosts of both Echinococcus granulosus and E. multilocularis, which have increased the risks for transmission of both parasites, affecting echinococcosis prevalence and human disease. Ecological environmental changes due to anthropogenic activities and natural events drive Echinococcus transmission and NHAR provides a notable example illustrating how human activity can impact on a parasitic infection of major public health significance. It is very important to continually monitor these environmental (including climatic) factors that drive the distribution of Echinococcus spp. and their impact on transmission to humans because such information is necessary to formulate reliable future public health policy for echinococcosis control programs and to prevent disease spread.We acknowledge financial support by the National Health and Medical Research Council (NHMRC) of Australia (APP1009539) and the Natural Science Foundation of China (NSFC) (30960339) for our studies on echinococcosis. DJG is an Australian Research Council Fellow (DECRA); DPM is a NHMRC Senior Principal Research Fellow; ACAC is a NHMRC Career Development Fellow

Estimating the prevalence of Echinococcus in domestic dogs in highly endemic for echinococcosis

Background: Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly endemic in Xiji County of Ningxia Hui Autonomous Region (NHAR) in China where the control campaign based on dog de-worming with praziquantel has been undertaken over preceding decades. This study is to determine the current prevalence of Echinococcus granulosus and E. multilocularis in domestic dogs and monitor the echinococcosis transmission dynamics. Methods: Study villages were selected using landscape patterns (Geographic Information System, GIS) for Echinococcus transmission "hot spots", combined with hospital records identifying risk areas for AE and CE. A survey of 750 domestic dogs, including copro-sampling and owner questionnaires, from 25 selected villages, was undertaken in 2012. A copro-multiplex PCR assay was used for the specific diagnosis of E. granulosus and E. multilocularis in the dogs. Data analysis, using IBM SPSS Statistics, was undertaken, to compare the prevalence of the two Echinococcus spp. in dogs between four geographical areas of Xiji by the χ 2 test. Univariate analysis of the combinations of outcomes from the questionnaire and copro-PCR assay data was carried out to determine the significant risk factors for dog infection. Results: The highest de-worming rate of 84.0% was found in the northwest area of Xiji County, and significant differences (P 0.05) in the prevalence of E. granulosus in dogs from the northwest, southwest, northeast, and southeast of Xiji, but there were significant differences (P< 0.05) between dogs infected with E. multilocularis from the four areas. None of the other independent variables was statistically significant. Conclusions: The results from this study indicate a high prevalence of both E. granulosus and E. muiltilocularis in dogs in Xiji County, NHAR. Transmission of E. multilocularis was more impacted by geographical risk-factors in Xiji County than that of E. granulosus. Dogs have the potential to maintain the transmission of both species of Echinococcus within local Xiji communities, and the current praziquantel dosing of dogs appears to be ineffective or poorly implemented in this area.This study was funded by the Science Fund for Gansu Provincial Key Science and Technology Projects (No. 1203NKDA039); Special Fund for Agro-scientific Research in the Public Interest (No. 200903036–07; 201303037); West China Top Class Discipline Project in Basic Medical Sciences, Ningxia Medical University; The National Natural Science Foundation of China (No. 30960339; 81460311) and the Australian National Health and Medical Research Council (NHMRC) (project grant No. APP 1009539)

Spatial prediction of the risk of exposure to Echinococcus spp. among schoolchildren and dogs in Ningxia Hui Autonomous Region, People's Republic of China

The geographical distribution of Echinococcus spp. infections in Ningxia Hui Autonomous Region (NHAR) has been reported to be expanding in response to environmental change. The aim of the present study was to predict and compare the spatial distribution of human seropositivity for Echinococcus granulosus and Echinococcus multilocularis and infections with these parasites in dogs in four counties in the south of NHAR to identify communities where targeted prevention and control efforts are required. Predicted seroprevalence of E. granulosus in schoolchildren and E. granulosus infections in dogs concurred spatially, whereas predicted seroprevalence of E. multilocularis in schoolchildren and E. multilocularis infections in dogs differed spatially. Enhanced vegetation index was significantly associated with E. multilocularis seropositivity among schoolchildren, and infections with E. granulosus and E. multilocularis in dogs. A positive association was also found between dog infection with E. granulosus and cultivated land, and a negative association between human seropositivity for E. granulosus and bare-land/artificial surfaces. The findings of this study support the importance of land cover and climatic variables in determining habitat suitability for Echinococcus spp. infections, and suggest that definitive hosts other than dogs (e.g. foxes) are important in defining the geographical risk of human seropositivity for E. multilocularis in NHAR.the authors acknowledge financial support by the National Health and Medical Research Council (NHMRC) of Australia (APP1009539)

Environmental risk factors and changing spatial patterns of human seropositivity for Echinococcus spp. in Xiji County, Ningxia Hui Autonomous Region, China

Background: Human echinococcoses are parasitic helminth infections that constitute a serious public health concern in several regions across the world. Cystic (CE) and alveolar echinococcosis (AE) in China represent a high proportion of the total global burden of these infections. This study was conducted to predict the spatial distribution of human seropositivity for Echinococcus species in Xiji County, Ningxia Hui Autonomous Region (NHAR), with the aim of identifying communities where targeted prevention and control efforts are required. Methods: Bayesian geostatistical models with environmental and demographic covariates were developed to predict spatial variation in the risk of human seropositivity for Echinococcus granulosus (the cause of CE) and E. multilocularis (the cause of AE). Data were collected from three cross-sectional surveys of school children conducted in Xiji County in 2002-2003, 2006-2007 and 2012-2013. Environmental data were derived from high-resolution satellite images and meteorological data. Results: The overall seroprevalence of E. granulosus and E. multilocularis was 33.4 and 12.2%, respectively, across the three surveys. Seropositivity for E. granulosus was significantly associated with summer and winter precipitation, landscape fragmentation variables and the extent of areas covered by forest, shrubland, water and bareland/artificial surfaces. Seropositivity for E. multilocularis was significantly associated with summer and winter precipitations, landscape fragmentation variables and the extent of shrubland and water bodies. Spatial correlation occurred over greater distances for E. granulosus than for E. multilocularis. The predictive maps showed that the risk of seropositivity for E. granulosus expanded across Xiji during the three surveys, while the risk of seropositivity for E. multilocularis became more confined in communities located in the south. Conclusions: The identification of high-risk areas for seropositivity for these parasites, and a better understanding of the role of the environment in determining the transmission dynamics of Echinococcus spp. may help to guide and monitor improvements in human echinococcosis control strategies by allowing targeted allocation of resources.We acknowledge financial support by the National Health and Medical Research Council (NHMRC) of Australia (APP1009539). AMCR is a PhD Candidate supported by a Postgraduate Award from The Australian National University and ACAC is a NHMRC Senior Research Fellow. DPM is a NHMRC Senior Principal Research Fellow and DJG is a NHMRC Career Development Fello

Spatiotemporal patterns and environmental drivers of human echinococcoses over a twenty-year period in Ningxia Hui Autonomous Region, China

Background Human cystic (CE) and alveolar (AE) echinococcoses are zoonotic parasitic diseases that can be influenced by environmental variability and change through effects on the parasites, animal intermediate and definitive hosts, and human populations. We aimed to assess and quantify the spatiotemporal patterns of human echinococcoses in Ningxia Hui Autonomous Region (NHAR), China between January 1994 and December 2013, and examine associations between these infections and indicators of environmental variability and change, including large-scale landscape regeneration undertaken by the Chinese authorities. Methods Data on the number of human echinococcosis cases were obtained from a hospital-based retrospective survey conducted in NHAR for the period 1 January 1994 through 31 December 2013. High-resolution imagery from Landsat 4/5-TM and 8-OLI was used to create single date land cover maps. Meteorological data were also collected for the period January 1980 to December 2013 to derive time series of bioclimatic variables. A Bayesian spatio-temporal conditional autoregressive model was used to quantify the relationship between annual cases of CE and AE and environmental variables. Results Annual CE incidence demonstrated a negative temporal trend and was positively associated with winter mean temperature at a 10-year lag. There was also a significant, nonlinear effect of annual mean temperature at 13-year lag. The findings also revealed a negative association between AE incidence with temporal moving averages of bareland/artificial surface coverage and annual mean temperature calculated for the period 11–15 years before diagnosis and winter mean temperature for the period 0–4 years. Unlike CE risk, the selected environmental covariates accounted for some of the spatial variation in the risk of AE. Conclusions The present study contributes towards efforts to understand the role of environmental factors in determining the spatial heterogeneity of human echinococcoses. The identification of areas with high incidence of CE and AE may assist in the development and refinement of interventions for these diseases, and enhanced environmental change risk assessment.We acknowledge financial support by the National Health and Medical Research Council (NHMRC) of Australia (APP1009539). AMCR is a PhD Candidate supported by a Postgraduate Award from The Australian National University, ACAC is a NHMRC Senior Research Fellow, DPM is a NHMRC Senior Principal Research Fellow and DJG is a NHMRC Career Development Fellow

Spatial prediction of the risk of exposure to Echinococcus spp. among schoolchildren and dogs in Ningxia Hui Autonomous Region, People’s Republic of China

The geographical distribution of Echinococcus spp. infections in Ningxia Hui Autonomous Region (NHAR) has been reported to be expanding in response to environmental change. The aim of the present study was to predict and compare the spatial distribution of human seropositivity for Echinococcus granulosus and Echinococcus multilocularis and infections with these parasites in dogs in four counties in the south of NHAR to identify communities where targeted prevention and control efforts are required. Predicted seroprevalence of E. granulosus in schoolchildren and E. granulosus infections in dogs concurred spatially, whereas predicted seroprevalence of E. multilocularis in schoolchildren and E. multilocularis infections in dogs differed spatially. Enhanced vegetation index was significantly associated with E. multilocularis seropositivity among schoolchildren, and infections with E. granulosus and E. multilocularis in dogs. A positive association was also found between dog infection with E. granulosus and cultivated land, and a negative association between human seropositivity for E. granulosus and bare-land/artificial surfaces. The findings of this study support the importance of land cover and climatic variables in determining habitat suitability for Echinococcus spp. infections, and suggest that definitive hosts other than dogs (e.g. foxes) are important in defining the geographical risk of human seropositivity for E. multilocularis in NHAR

Northern Australia beef fertility project: Cash Cow

The causes of poor reproductive performance in northern Australian beef herds are multi-factorial and uantification of the impact of individual factors on performance of breeding mobs is lacking. The reproductive performance of ~78,000 cows managed in 142 breeding mobs located on 72 commercial beef cattle properties was measured over three to four consecutive years (2008-11) using a crush-side electronic data capture system. Percentage of lactating cows pregnant within four months of calving, annual pregnancy rate, percentage foetal/calf loss between pregnancy diagnosis and weaning, and annual percentage of pregnant cows missing (mortality) were used to define performance, with the commercially achievable level of performance proposed as the performance of the 75th percentile mob or cow for each measure. Also, methods of estimating liveweight production from breeding herds were developed, and an achievable level determined for each country type. The impacts of 83 property, environmental, nutritional, management, and infectious disease factors on performance were investigated. The major factors affecting performance included country type, time of previous calving, wet season phosphorous status, cow body condition, hip-height, cow age class, cow reproductive history, severity of environmental conditions, and occurrence of mustering events around the time of calving. Producer/manager opinion that wild dogs were a problem, evidence of recent pestivirus infection and vibriosis were factors that did not contribute to the final model, but did significantly affect animal performance when present. A framework was developed for conducting economic analyses to assess the impact of factors affecting performance

Impact of “Grain to Green” Programme on echinococcosis infection in Ningxia Hui Autonomous Region of China

Cystic echinococcosis (CE) is endemic among the human population of Xiji County, Ningxia Hui Autonomous Region, China, where the prevalence is estimated to be between 2.2% and 3.6%. Government-run sheep abattoirs in Xiji County have closed in recent years and, as a consequence, slaughter is carried out mostly at rural market places. The market place in Xinglong Township, Xiji County, is home to an increasing number of stray dogs and the lack of government control over slaughter practices potentially favours Echinococcus granulosus transmission. A survey of sheep, goats and cattle reared in Xiji County was conducted in Xinglong Market and Xinglong Township to determine prevalence and transmission dynamics of E. granulosus infection. The liver and lungs of all livestock aged one year and older were examined macroscopically post mortem; visual examination and palpation of organs determined overall prevalence of E. granulosus. Cysts consistent in appearance with E. granulosus were observed in 2/184 sheep (prevalence 1.0%) and 1/55 of the cattle examined (prevalence 1.8%); 0/13 goats were found to be infected. However, microscopic examination of these suspected cysts failed to confirm these samples as E. granulosus, giving a prevalence of confirmed infection of zero percent in all three species. The prevalence of liver fluke was 61.3% in sheep and 12.7% in cattle with a significant difference between males and females (p ≤ 0.001). Considering the high prevalence of echinococcosis in the local human population, the absence of CE observed among commercially slaughtered livestock was surprising. Several explanations for this discrepancy and their implications are proposed.The study was supported by funds of NNSFC, China (30960339), NHMRC, Australia (APP1009539). DJG is an Australian Research Council Fellow (DECRA); ACAC is NHMRC Senior Research Fellow; DPM is NHMRC Senior Principal Research Fellow; YRY is Griffith University Research Fellow

Spatiotemporal patterns and environmental drivers of human echinococcoses over a twenty-year period in Ningxia Hui Autonomous Region, China

Background Human cystic (CE) and alveolar (AE) echinococcoses are zoonotic parasitic diseases that can be influenced by environmental variability and change through effects on the parasites, animal intermediate and definitive hosts, and human populations. We aimed to assess and quantify the spatiotemporal patterns of human echinococcoses in Ningxia Hui Autonomous Region (NHAR), China between January 1994 and December 2013, and examine associations between these infections and indicators of environmental variability and change, including large-scale landscape regeneration undertaken by the Chinese authorities. Methods Data on the number of human echinococcosis cases were obtained from a hospital-based retrospective survey conducted in NHAR for the period 1 January 1994 through 31 December 2013. High-resolution imagery from Landsat 4/5-TM and 8-OLI was used to create single date land cover maps. Meteorological data were also collected for the period January 1980 to December 2013 to derive time series of bioclimatic variables. A Bayesian spatio-temporal conditional autoregressive model was used to quantify the relationship between annual cases of CE and AE and environmental variables. Results Annual CE incidence demonstrated a negative temporal trend and was positively associated with winter mean temperature at a 10-year lag. There was also a significant, nonlinear effect of annual mean temperature at 13-year lag. The findings also revealed a negative association between AE incidence with temporal moving averages of bareland/artificial surface coverage and annual mean temperature calculated for the period 11–15 years before diagnosis and winter mean temperature for the period 0–4 years. Unlike CE risk, the selected environmental covariates accounted for some of the spatial variation in the risk of AE. Conclusions The present study contributes towards efforts to understand the role of environmental factors in determining the spatial heterogeneity of human echinococcoses. The identification of areas with high incidence of CE and AE may assist in the development and refinement of interventions for these diseases, and enhanced environmental change risk assessment