Dingmei Zhang

Rabies trend in China (1990–2007) and post-exposure prophylaxis in the Guangdong province

BackgroundRabies is a major public-health problem in developing countries such as China. Although the recent re-emergence of human rabies in China was noted in several epidemiological studies, little attention was paid to the reasons behind this phenomenon paralleling the findings of the previous reports. The purpose of this study is thus first to characterize the current trends of human rabies in China from 1990 to 2007, and then to define better recommendations for improving the post-exposure prophylaxis (PEP) schedules delivered to rabies patients.MethodsThe most updated epidemiological data for 22527 human rabies cases from January 1990 to July 2007, retrieved from the surveillance database of reportable diseases managed by the Ministry of Health of China, were analysed. To investigate the efficiency for the post-exposure treatment of rabies, the details of 244 rabies patients, including their anti-rabies treatment of injuries or related incidents, were ascertained in Guangdong provincial jurisdiction. The risk factors to which the patients were predisposed or the regimens given to 80 patients who received any type of PEP were analysed to identify the reasons for the PEP failures.ResultsThe results from analysis of the large number of human rabies cases showed that rabies in China was largely under control during the period 1990–1996. However, there has been a large jump in the number of reported rabies cases since 2001 up to a new peak (with an incidence rate of 0.20 per 100000 people) that was reached in 2004, and where the level has remained until present. Then, we analysed the PEP in 244 rabies cases collected in the Guangdong province in 2003 and 2004, and found that 67.2% of the patients did not seek medical services or did not receive any PEP. Further analysis of PEP for the 80 rabies patients who received any type of PEP indicated that almost all of the patients did not receive proper or timely treatment on the wounds or post-exposure vaccination or rabies immunoglobulins.ConclusionWhile the issue of under-reporting of rabies in previous years may well be a factor in the apparent upwards trend of human rabies in recent years, the analysis of PEP in the Guangdong province provides evidence that suggests that the failure to receive PEP was a major factor in the number of human cases in China. Thus, the data underline the need for greatly improved availability and timely application of high-quality anti-rabies biologicals, both vaccines and immunoglobulins, in the treatment of human bite victims. Controlling dog rabies through pet vaccination schemes may also play a huge role in reducing the rate of human exposure. Education of the public, health care staff and veterinarians will also help to change the current situation.

Enterovirus 71 vaccine: close but still far.

Summary Background Enterovirus 71 (EV71), a member of the Enterovirus genus of the Picornaviridae family, is one of the causative pathogens of hand-foot-and-mouth disease (HFMD) and the most common etiological agent isolated from HFMD patients complicated with neurological disorders. EV71 has become an increasingly important neurotropic enterovirus in the post-poliomyelitis eradication era. Effective antiviral agents and vaccines against this virus are currently still under development. We reviewed publications on the development of EV71 vaccines in order to provide an overview of the field. Methods Fifty-five articles on EV71 vaccine development, published from 1974 to 2009, were collected from Sun Yat-sen University library and reviewed. Results Various types of vaccine have been developed for EV71. In results published to date, all vaccines for EV71 under development appear to elicit an immune response in rodents or in monkeys. According to the established regulatory standards, it may be relatively easy to acquire a license to use the inactivated virus in order to meet the immediate demands for EV71 control . With regard to the attenuated vaccine, it is critical to increase the genetic stability before clinical use, due to the risk of virulent revertants. The virus-like particle (VLP) vaccine, not only conserving the conformational epitopes, but also having no risk of virulent revertants, is another promising vaccine candidate for EV71, but needs further development. The VP1 capsid protein is the backbone antigen protein for developing subunit vaccine and epitope vaccine; these remain viable potential vaccine strategies worthy of further study and development. Conclusions The conservation of the three-dimensional structure is important for the EV71 inactivated vaccine and VLP vaccine to induce a strong immune response. To develop EV71 vaccines with a high protection efficacy, strategies such as the use of adjuvant, strong promoters, tissue-specific promoters, and addition of mucosal immune adjuvant should be considered.

Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in BALB/c mice

The development of novel antiviral drugs is necessary for the prevention and treatment of a potential avian influenza pandemic. The aim of this study was to evaluate the efficacy and safety of a novel statin/caffeine combination against H5N1, H3N2 and H1N1 virus infection in a murine model. In H5N1-, H3N2- and H1N1-infected BALB/c mice, 50mug statin/200mug caffeine effectively ameliorated lung damage and inhibited viral replication and was at least as effective as oseltamivir and ribavirin. The statin/caffeine combination also appeared to be more effective when administered preventatively rather than as treatment. These findings provide justification for further research into this novel antiviral formulation.

Epidemiology characteristics of respiratory viruses found in children and adults with respiratory tract infections in southern China

Summary Background The World Health Organization (WHO) ranks respiratory tract infection (RTI) as the second leading cause of death worldwide for children under 5 years of age. The aim of this work was to evaluate the epidemiology characteristics of respiratory viruses found in children and adults with RTI from July 2009 to June 2012 in southern China. Methods In this work, a total of 14 237 nasopharyngeal swabs (14 237 patients from 25 hospitals) were analyzed, and seven respiratory viruses (influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human metapneumovirus, human coronavirus, human bocavirus) were detected using PCR/RT-PCR from nasopharyngeal swabs. Results The demographic characteristics, viral prevalence, age distribution, seasonal distribution, and pathogen spectrum of the patients with RTIs were analyzed. Co-infection was observed in 483 specimens, but it was more common in male patients, inpatients, children, and young adults. It varied by season, being more prevalent in the spring and summer and less so in the winter. Human coronavirus and human bocavirus were the most common pathogens, tending to occur in co-infection with other respiratory viruses. Conclusions This work adds to our knowledge of the epidemiology characteristics of these seven common respiratory viruses among patients with RTI in southern China. The detection of the specific viral causes of infection provides a useful starting point for an understanding of illness attributable to respiratory infection, and might also provide data relevant to the development of prevention strategies.

Boosted regression tree model-based assessment of the impacts of meteorological drivers of hand, foot and mouth disease in Guangdong, China.

BACKGROUND Hand, foot and mouth disease (HFMD) is a common childhood infection and has become a major public health issue in China. Considerable research has focused on the role of meteorological factors in HFMD development. Nonlinear relationship, delayed effects and collinearity problems are key issues for achieving robust and accurate estimations in this kind of weather-health relationship explorations. The current study was designed to address these issues and assess the impact of meteorological factors on HFMD in Guangdong, China. METHODS Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from China CDC and the National Meteorological Information Center, respectively. After a preliminary variable selection, for each dataset boosted regression tree (BRT) models were applied to determine the optimal lag for meteorological factors at which the variance of HFMD cases was most explained, and to assess the impacts of these meteorological factors at the optimal lag. RESULTS Variance of HFMD cases was explained most by meteorological factors about 1 week ago. Younger children and those from the Pearl-River Delta Region were more sensitive to weather changes. Temperature had the largest contribution to HFMD epidemics (28.99-71.93%), followed by precipitation (6.52-16.11%), humidity (3.92-17.66%), wind speed (3.84-11.37%) and sunshine (6.21-10.36%). Temperature between 10°C and 25°C, as well as humidity between 70% and 90%, had a facilitating effect on the epidemic of HFMD. Sunshine duration above 9h and wind speed below 2.5m/s also contributed to an elevated risk of HFMD. The positive relationship between HFMD and precipitation reversed when the daily amount of rainfall exceeded 25 mm. CONCLUSIONS This study indicated significantly facilitating effects of five meteorological factors within some range on the epidemic of HFMD. Results from the current study were particularly important for developing early warning and response system on HFMD in the context of global climate change.

Protective effect of fluvastatin on influenza virus infection

Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and have pleiotropic effects. It has been suggested that statins may be a potential treatment during the next influenza pandemic. In a previous study we found that a statin/caffeine combination protects BALB/c mice against Influenza A, subtypes haemagglutinin type 5 and neuraminidase type 1 (H5N1), H3N2 and H1N1 infection. The effect of statins alone on influenza virus infection, however, is not known. In this study, it was investigated whether fluvastatin is capable of inhibiting influenza A virus replication in vitro. The results demonstrated that the synthesis of viral RNA and protein was affected by fluvastatin treatment. Virus production was markedly reduced when fluvastatin was administered simultaneously with the virus; however, a greater inhibition was observed when fluvastatin was added following viral adsorption. The selectivity index [SI; 50% cytotoxic concentration (CC50)/50% inhibition concentration (IC50)], however, was only 21. It was further demonstrated that fluvastatin protects host cells against influenza-induced inflammation by reducing the production of tumour necrosis factor-α, interleukin 8 and interferon γ. In conclusion, the results demonstrated that fluvastatin exerted a minor inhibitory effect on influenza virus infection, which involved anti-inflammatory activities.

Mandibular reconstruction with the vascularized fibula flap: comparison of virtual planning surgery and conventional surgery.

This study evaluated the accuracy of mandibular reconstruction and assessed clinical outcomes in both virtual planning and conventional surgery patients. ProPlan CMF surgical planning software was used preoperatively in the virtual planning group. In the virtual planning group, fibula flaps were harvested and osteotomized, and the mandibles were resected and reconstructed assisted by the prefabricated cutting guides and templates. The main outcome measures included the operative time, postoperative computed tomography (CT) scans, facial appearance, and occlusal function. The ischemia time and total operation time were shorter in the virtual planning group than in the conventional surgery group. High precision with the use of the cutting guides and templates was found for both the fibula and mandible, and a good fit was noted among the pre-bent plate, mandible, and fibula segments in the virtual planning group. Postoperative CT scans also showed excellent mandibular contours of the fibula flaps in accordance with virtual plans in the virtual planning group. This study demonstrated that virtual surgical planning was able to achieve more accurate mandibular reconstruction than conventional surgery. The use of prefabricated cutting guides and plates makes fibula flap moulding and placement easier, minimizes the operating time, and improves clinical outcomes.

Quantifying the adverse effect of excessive heat on children: An elevated risk of hand, foot and mouth disease in hot days.

BACKGROUND Hand, foot and mouth disease (HFMD) is a common childhood infection and has become a major public health issue in China. Considerable research has focused on the role of meteorological factors such as temperature and relative humidity in HFMD development. However, no studies have specifically quantified the impact of another major environmental agent, excessive heat, on HFMD. The current study was designed to help address this research gap. METHODS Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from China CDC and the National Meteorological Information Center, respectively. Distributed lag nonlinear models were applied to assess the impact of excessive heat on HFMD and its variability across social-economic status and age groups. RESULTS After controlling the effects of several potential confounders, the commonly hot days were found to positively affect the HFMD burdens with the relative risk (RR) peaking at around 6 days of lag. The RR of HFMD in the Pearl-River Delta Region was generally higher and persisted longer than that in the remaining developing areas. Regarding the inter-age group discrepancy, children aged 3-6 years old had the highest risk of HFMD under conditions of excessive heat whereas those greater than 6 years old had the lowest. The lag structure of the impact of the extremely hot days was quite similar to that of the commonly hot days, although the relative effect of these two kinds of conditions of excessive heat might vary across regions. CONCLUSIONS This study indicated significantly facilitating effects of excessive heat on HFMD especially among those aged 3-6 and from developed areas. Results from the current study were particularly practical and important for developing area-and-age-targeted control programs in the context of climate change and urbanization.

Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an Application to Assessing Hepatitis B Infection Relevant Factors in Community Residents.

Objectives In epidemiological studies, it is important to identify independent associations between collective exposures and a health outcome. The current stepwise selection technique ignores stochastic errors and suffers from a lack of stability. The alternative LASSO-penalized regression model can be applied to detect significant predictors from a pool of candidate variables. However, this technique is prone to false positives and tends to create excessive biases. It remains challenging to develop robust variable selection methods and enhance predictability. Material and methods Two improved algorithms denoted the two-stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty, were developed for epidemiological association analysis. The performance of the proposed procedures and other methods including conventional LASSO, Bolasso, stepwise and stability selection models were evaluated using intensive simulation. In addition, methods were compared by using an empirical analysis based on large-scale survey data of hepatitis B infection-relevant factors among Guangdong residents. Results The proposed procedures produced comparable or less biased selection results when compared to conventional variable selection models. In total, the two newly proposed procedures were stable with respect to various scenarios of simulation, demonstrating a higher power and a lower false positive rate during variable selection than the compared methods. In empirical analysis, the proposed procedures yielding a sparse set of hepatitis B infection-relevant factors gave the best predictive performance and showed that the procedures were able to select a more stringent set of factors. The individual history of hepatitis B vaccination, family and individual history of hepatitis B infection were associated with hepatitis B infection in the studied residents according to the proposed procedures. Conclusions The newly proposed procedures improve the identification of significant variables and enable us to derive a new insight into epidemiological association analysis.

Clinical epidemiology and molecular profiling of human bocavirus in faecal samples from children with diarrhoea in Guangzhou, China.

To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.