Dengue and dengue haemorrhagic fever: implications of host genetics

Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.     

我国登革2/4型病毒株Pr-M-E基因的双表达质粒构建及在真核细胞中的共表达

将我国登革 2、4型病毒分离株PrM E基因通过RT PCR以病毒RNA为模板扩增我国登革 2型 4 3株和 4型B5株的PrM E基因 .并分别克隆至pGEM TEasy载体 ,然后亚克隆至双顺反子表达质粒的两个多克隆位点 ,获得同时含有登革 2型 4 3株和 4型B5株PrM E基因的双顺反子重组表达质粒pIDME2 4 .在用该重组质粒转染的BHK2 1细胞中 ,不但可检测到PrM E基因的转录产物 ,而且采用间接免疫荧光法还可观察到针对登革 2型 4型病毒的特异荧光 .研究结果表明 ,重组的双顺反子表达质粒在真核细胞中可共表达登革两个血清型PrM E基因 ,为双价登革核酸疫苗的研究奠定基础     

禽白血病病毒研究的过去、现在和将来

简要介绍了鸡的重要的肿瘤性病毒禽白血病病毒（ALV）研究的历史及其在现代分子生物学研究进展中的作用。对近10多年来,ALV在国内外鸡群中,特别是我国鸡群中的流行动态及相关研究做了综述。在此基础上,对ALV及其相关肿瘤方面有待进一步深入研究的目标和内容提出了展望。     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Evaluation in mice of the immunogenicity and protective efficacy of a tetravalent subunit vaccine candidate against dengue virus

A dengue vaccine must induce protective immunity against the four serotypes of the virus. Our group has developed chimeric proteins consisting of the protein P64k from Neisseria meningitidis and the domain III from the four viral envelope proteins. In this study, the immunogenicity of a tetravalent vaccine formulation using aluminum hydroxide as adjuvant was evaluated in mice. After three doses, neutralizing antibody titers were detected against the four viral serotypes, the lowest seroconversion rate being against dengue virus serotype 4. One month after the last dose, immunized animals were challenged with infective virus, and partial but statistically significant protection was found to have been achieved. Based on these results, further studies in mice and non‐human primates using this tetravalent formulation in a prime‐boost strategy with attenuated viruses are strongly recommended.     

The past,present and future of reproductive skew theory and experiments

A major evolutionary question is how reproductive sharing arises in cooperatively breeding species despite the inherent reproductive conflicts in social groups. Reproductive skew theory offers one potential solution: each group member gains or is allotted inclusive fitness equal to or exceeding their expectation from reproducing on their own. Unfortunately, a multitude of skew models with conflicting predictions has led to confusion in both testing and evaluating skew theory. The confusion arises partly because one set of models (the ‘transactional’ type) answer the ultimate evolutionary question of what ranges of reproductive skew can yield fitness‐enhancing solutions for all group members. The second set of models (‘compromise’) give an evolutionarily proximate, game‐theoretic evolutionarily stable state (ESS) solution that determines reproductive shares based on relative competitive abilities. However, several predictions arising from compromise models require a linear payoff to increased competition and do not hold with non‐linear payoffs. Given that for most species it may be very difficult or impossible to determine the true relationship between effort devoted to competition and reproductive share gained, compromise models are much less predictive than previously appreciated. Almost all skew models make one quantitative prediction (e.g. realized skew must fall within ranges predicted by transactional models), and two qualitative predictions (e.g. variation in relatedness or competitive ability across groups affects skew). A thorough review of the data finds that these three predictions are relatively rarely supported. As a general rule, therefore, the evolution of cooperative breeding appears not to be dependent on the ability of group members to monitor relatedness or competitive ability in order to adjust their behaviour dynamically to gain reproductive share. Although reproductive skew theory fails to predict within‐group dynamics consistently, it does better at predicting quantitative differences in skew across populations or species. This suggests that kin selection can play a significant role in the evolution of sociality. To advance our understanding of reproductive skew will require focusing on a broader array of factors, such as the frequency of mistaken identity, delayed fitness payoffs, and selection pressures arising from across‐group competition. We furthermore suggest a novel approach to investigate the sharing of reproduction that focuses on the underlying genetics of skew. A quantitative genetics approach allows the partitioning of variance in reproductive share itself or that of traits closely associated with skew into genetic and non‐genetic sources. Thus, we can determine the heritability of reproductive share and infer whether it actually is the focus of natural selection. We view the ‘animal model’ as the most promising empirical method where the genetics of reproductive share can be directly analyzed in wild populations. In the quest to assess whether skew theory can provide a framework for understanding the evolution of sociality, quantitative genetics will be a central tool in future research.     

Programmed cell death and the pathogenesis of tissue injury induced by type A Francisella tularensis

The protein Pal (peptidoglycan-associated lipoprotein) is anchored in the outer membrane (OM) of Gram-negative bacteria and interacts with Tol proteins. Tol–Pal proteins form two complexes: the first is composed of three inner membrane Tol proteins (TolA, TolQ and TolR); the second consists of the TolB and Pal proteins linked to the cell's OM. These complexes interact with one another forming a multiprotein membrane-spanning system. It has recently been demonstrated that Pal is essential for bacterial survival and pathogenesis, although its role in virulence has not been clearly defined. This review summarizes the available data concerning the structure and function of Pal and its role in pathogenesis.     

Effect of dengue vector control interventions on entomological parameters in developing countries: a systematic review and meta-analysis

The aim of this review was to compare the effects of different dengue vector control interventions (i.e. biological control, chemical control, environmental management and integrated vector management) with respect to the following entomological parameters: Breteau index (BI), container index (CI), and house index (HI). We systematically searched PubMed, ISI Web of Science, Science Direct, the Dengue Bulletin of the World Health Organization and reference lists of retrieved articles on dengue vector control interventions in developing countries. We extracted data on the effectiveness of different dengue vector control interventions (defined as the relative reduction of an entomological measure caused by the intervention compared with the control or pre-intervention phase) and calculated a measure of combined relative effectiveness, with 95% confidence intervals (95% c.i.). We identified 56 publications covering 61 dengue vector control interventions. Integrated vector management was found to be the most effective method to reduce the CI, HI and BI, resulting in random combined relative effectiveness values of 0.12 (95% c.i. 0.02-0.62), 0.17 (95% c.i. 0.02-1.28) and 0.33 (95% c.i. 0.22-0.48), respectively. Environmental management showed a relatively low effectiveness of 0.71 (95% c.i. 0.55-0.90) for the BI, 0.49 (95% c.i. 0.30-0.79) for the CI and 0.43 (95% c.i. 0.31-0.59) for the HI. Biological control (relative effectiveness for the CI: 0.18) usually targeted a small number of people (median population size: 200; range 20-2500), whereas integrated vector management focused on larger populations (median: 12 450; range: 210-9 600 000). In conclusion, dengue vector control is effective in reducing vector populations, particularly when interventions use a community-based, integrated approach, which is tailored to local eco-epidemiological and sociocultural settings and combined with educational programmes to increase knowledge and understanding of best practice. New research should assess the density-dependent effectiveness of each control measure in order to estimate whether reducing vector numbers has an impact on dengue transmission when populations are at a critical threshold.     

人工模拟胃肠道模型在食源性致病菌耐受及致病机理中的应用

人工模拟胃肠道模型是研究食源性致病菌耐受及致病机理的一种重要工具,其本质是在实验室模拟的条件下,重现人体消化过程中的化学、物理及生物作用,以研究食源性致病菌的耐受性、致病机理、肠道菌群互作及疫苗开发,对食源性致病菌的控制和治疗具有十分重要的意义。文中综述了人工模拟胃肠道模型在食源性致病菌研究中的应用,将现有胃肠道模型系统地划分为体外静态模型、体外动态模型、普通动物模型及人源化动物模型,并详细介绍了各类模型的概念及特性。在此基础之上,进一步分析了现有模型的不足,并对未来人工模拟胃肠道模型的研究方向进行了展望,以期为食源性致病菌耐受及致病机理的研究奠定扎实的研究基础。     

Malaria on the Guiana Shield: a review of the situation in French Guiana

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.     

Experimental validation of a statistical model for evaluating the past or future magnetic field exposures of a population living near power lines

This study was designed to provide an experimental validation for a statistical model predicting past or future exposures to magnetic fields (MF) from power lines. The model estimates exposure, combining the distribution of ambient MF in the absence of power lines with the distribution of past or future MF produced by power lines. In the study, validation is carried out by comparing exposures predicted by the model with the actual measurements obtained from a large-scale epidemiological study. The comparison was made for a group of 220 women living near a 735 kV power line. Knowing that the individual arithmetic means of MF exposures follow a log-normal distribution, the Pearson correlation between the log-transformed measured means and the calculated ones was determined and found to be 0.77. Predicted values of MF exposures were slightly lower than measured values. The calculated geometric mean of the group was 0.33 microT, compared to 0.38 microT for the measured geometric mean. The present study shows good agreement between the measured MF exposure of an individual inside a house near a 735 kV line and the MF exposure calculated using a statistical model.     

The effect of shade on the container index and pupal productivity of the mosquitoes Aedes aegypti and Culex pipiens breeding in artificial containers

Abstract The aim of this study was to assess whether certain attributes of larval breeding sites are correlated with pupal productivity (i.e. numbers of pupae collected per sampling period), so that these could be used as the focus for control measures to enhance control efficiency. Therefore, the objectives were to identify the months of highest pupal productivity of Aedes aegypti (L.) and Culex pipiens L. (Diptera: Culicidae) in an urban temperate cemetery in Argentina where artificial containers of < 6 L (flower vases) were the predominant breeding habitats, to compare various measures of the productivity of sunlit and shaded containers and to determine whether the composition of the containers affected pupal productivity. Over a period of 9 months, 200 randomly chosen water‐filled containers (100 sunlit and 100 shaded), out of ～ 3738 containers present (～ 54% in shade), were examined each month within a cemetery (5 ha) in Buenos Aires (October 2006 to June 2007). In total, 3440 immatures of Cx pipiens and 1974 of Ae. aegypti were collected. The larvae : pupae ratio was 10 times greater for the former, indicating that larval mortality was greater for Cx pipiens. Both mosquito species showed a higher container index (CI) in shaded than in sunlit containers (Ae. aegypti: 12.8% vs. 6.9% [χ² = 17.6, P < 0.001]; Cx pipiens: 6.3% vs. 1.8% [χ² = 24, P < 0.001]). However, the number and the density of immatures per infested container and the number of pupae per pupa‐positive container did not differ significantly between sunlit and shaded containers for either species. Therefore, the overall relative productivity of pupae per ha of Ae. aegypti and Cx pipiens was 2.3 and 1.8 times greater, respectively, in shaded than in sunlit areas as a result of the greater CIs of containers in shaded areas. Neither the CI nor the number of immatures per infested container differed significantly among container types of different materials in either lighting condition. The maximum CI and total pupal counts occurred in March for Ae. aegypti and in January and February for Cx pipiens. The estimated peak abundance of pupae in the whole cemetery reached a total of ～ 4388 in the middle of March for Ae. aegypti and ～ 1059 in the middle of January for Cx pipiens. Spearman’s correlations between monthly total productivity and monthly CI were significant at P < 0.001 for Ae. aegypti (r_s = 0.975) and P < 0.01 for Cx pipiens (r_s = 0.869). Our findings indicate that the efficacy of control campaigns against the two most important mosquito vectors in temperate Argentina could be improved by targeting containers in shaded areas, with maximum effort during species‐specific times of year when pupal productivity is at its peak.     

Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti

Aedes aegypti mosquitoes carrying the wAlbB Wolbachia strain show a reduced capacity to transmit dengue virus. wAlbB has been introduced into wild Ae. aegypti populations in several field sites in Kuala Lumpur, Malaysia, where it has persisted at high frequency for more than 2 years and significantly reduced dengue incidence. Although these encouraging results indicate that wAlbB releases can be an effective dengue control strategy, the long-term success depends on wAlbB maintaining high population frequencies and virus transmission inhibition, and both could be compromised by Wolbachia–host coevolution in the field. Here, wAlbB-carrying Ae. aegypti collected from the field 20 months after the cessation of releases showed no reduction in Wolbachia density or tissue distribution changes compared to a wAlbB laboratory colony. The wAlbB strain continued to induce complete unidirectional cytoplasmic incompatibility, showed perfect maternal transmission under laboratory conditions, and retained its capacity to inhibit dengue. Additionally, a field-collected wAlbB line was challenged with Malaysian dengue patient blood, and showed significant blocking of virus dissemination to the salivary glands. These results indicate that wAlbB continues to inhibit currently circulating strains of dengue in field populations of Ae. aegypti, and provides additional support for the continued scale-up of Wolbachia wAlbB releases for dengue control.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.     

Summary of aromatase inhibitor trials: the past and future

Antagonizing estrogen by inhibition of aromatase has become a mainstay of adjuvant endocrine therapy in women with hormone receptor positive (ER+) breast cancer. Recent trials have shown an incremental gain for the AIs over tamoxifen when given as an up-front alternative to tamoxifen, but additionally added benefit is achieved by giving them in sequence with tamoxifen after either an early switch (2–3 years) or as a late switch (5 years). The true clinical implications of accelerated bone resorption from AIs is becoming better understood and its management defined. AI minimally effect quality of life. The chronic relapsing nature of ER+ breast cancer implies long term therapy will be of benefit in selected patients. Outstanding issues under investigation include optimal duration of endocrine therapy, optimal sequence, optimal agents and whether combining anti-estrogens will yield advantage. The role of AIs is also under investigation in premenopausal women in combination with ovarian function suppression. Identifying prognostic and predictive factors of endocrine therapy is important as is the identification and overcoming of resistance mechanisms. Both tumor and host signatures are being pursued to this end. Optimizing, expanding and extending endocrine therapy is likely to add further to patient outcome.     

Endothelial cells and the pathogenesis of lepromatous neuritis:insights from the armadillo model

Selective infection of peripheral nerves is a unique property of Mycobacterium leprae that results in serious injury, but its basis is unexplained. Recent evidence from infected armadillos suggests that endothelial cells of peripheral nerve vasculature may be the gatekeepers by which M. leprae infects nerves. The pathogenesis of neuropathy in leprosy may thus entail a dynamic sequence of adhesion, immunologic, and inflammatory processes involving peripheral nerve endothelial cells.     

The baboon model (Papio hamadryas) of fetal loss: maternal weight,age, reproductive history and pregnancy outcome

Background Several risk factors are associated with the incidence of human stillbirths. The prevention of stillbirths in women is a pressing clinical problem. Methods We reviewed 402 pathology records of fetal loss occurring in a large baboon (Papio spp.) colony during a 15‐year period. Clinical histories of 565 female baboons with one or more fetal losses during a 20‐year period were analyzed for weight, age, and reproductive history. Results Fetal loss was most common at term (35.57%) and preterm (28.61%) and less common in the first half of gestation (11.20%) and post‐term (5.22%). Greater maternal weight, older age, history of stillbirth and higher parity were independent predictors for stillbirth. An exponential increase in the incidence of fetal loss was observed beginning at age 14 years in baboons. Conclusions Fetal loss and maternal risk factors associated with stillbirths in baboons were similar to those documented in women.     

Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines

At the end of 2005, six European countries had implemented public immunization campaigns with serogroup C conjugate vaccines, and all had experienced substantial declines in the incidence of serogroup C disease. A quadrivalent ACWY meningococcal vaccine is in use in the USA, but serogroup A is extremely rare in Europe and serogroups Y and W135 are infrequent causes of disease. This paper outlines recommendations on the use of conjugate vaccines in Europe based on the experience with meningococcal C conjugate (MCC) vaccines so far.