Mutans Streptococci and Lactobacilli Colonization in Predentate Children from the Neonatal Period to Seven Months of Age

Background/Aims: The aim of this study was to investigate the colonization of mutans streptococci (MS) and lactobacilli (LB) in predentate children from the neonatal period to 7 months. Methods: A total of 957 mother-and-child pairs were recruited from birth and followed up at 7 months. The 283 children who did not have erupted teeth at the second visit were included in the study. Oral mucosal swabs were taken, and the presence of MS and LB was determined using a commercial microbiological culture kit. Results: At mean ages of 34 days and 7 months, 9 and 11% of the infants, respectively, showed the presence of MS. In contrast, LB presence increased from 24 to 47% (p < 0.0001). MS presence in the neonatal period was associated with maternal MS counts of >105 CFU/ml (p = 0.05), while LB presence was associated with natural birth (p = 0.03) and maternal LB presence (p = 0.02). At 7 months, MS presence was associated with maternal MS counts (p = 0.02) and LB counts of >105 CFU/ml (p = 0.007). Additional predictors of MS presence at 7 months were a child’s MS counts of >105 CFU/ml at the neonatal visit (p = 0.019) and nighttime bottle feeding (p = 0.024). LB presence at 7 months was associated with maternal LB (p < 0.001) and MS presence (p = 0.02). Conclusions: MS and LB can be detected by culture in the oral cavity as early as 34 days after birth. Their infection rates increase to 11 and 47%, respectively, by the time the children reach the end of the predentate stage of oral development.

Expression of HPV-11 L1 protein in transgenic Arabidopsis thaliana and Nicotiana tabacum

Background We have investigated the possibility and feasibility of producing the HPV-11 L1 major capsid protein in transgenic Arabidopsis thaliana ecotype Columbia and Nicotiana tabacum cv. Xanthi as potential sources for an inexpensive subunit vaccine. Results Transformation of plants was only achieved with the HPV-11 L1 gene with the C-terminal nuclear localization signal (NLS-) encoding region removed, and not with the full-length gene. The HPV-11 L1 NLS- gene was stably integrated and inherited through several generations of transgenic plants. Plant-derived HPV-11 L1 protein was capable of assembling into virus-like particles (VLPs), although resulting particles displayed a pleomorphic phenotype. Neutralising monoclonal antibodies binding both surface-linear and conformation-specific epitopes bound the A. thaliana-derived particles and - to a lesser degree - the N. tabacum-derived particles, suggesting that plant-derived and insect cell-derived VLPs displayed similar antigenic properties. Yields of up to 12 μg/g of HPV-11 L1 NLS- protein were harvested from transgenic A. thaliana plants, and 2 μg/g from N. tabacum plants - a significant increase over previous efforts. Immunization of New Zealand white rabbits with ∼50 μg of plant-derived HPV-11 L1 NLS- protein induced an antibody response that predominantly recognized insect cell-produced HPV-11 L1 NLS- and not NLS+ VLPs. Evaluation of the same sera concluded that none of them were able to neutralise pseudovirion in vitro. Conclusion We expressed the wild-type HPV-11 L1 NLS- gene in two different plant species and increased yields of HPV-11 L1 protein by between 500 and 1000-fold compared to previous reports. Inoculation of rabbits with extracts from both plant types resulted in a weak immune response, and antisera neither reacted with native HPV-11 L1 VLPs, nor did they neutralise HPV-11 pseudovirion infectivity. This has important and potentially negative implications for the production of HPV-11 vaccines in plants. © 2007 Kohl et al; licensee BioMed Central Ltd.

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

Vaccination strategies for the prevention of cervical cancer

Infection with high-risk human papillomaviruses (HPVs) is an essential step in the multistep process leading to cervical cancer. There are approximately 120 different types of HPV identified: of these, 18 are high-risk types associated with cervical cancer, with HPV-16 being the dominant type in most parts of the world. The major capsid protein of papillomavirus, produced in a number of expression systems, self assembles to form virus-like particles. Virus-like particles are the basis of the first generation of HPV vaccines presently being tested in clinical trials. Virus-like particles are highly immunogenic and afford protection from infection both in animal models and in Phase IIb clinical trials. A number of Phase III trials are in progress to determine if the vaccine will protect against cervical disease and, in some cases, genital warts. However, it is predicted that these vaccines will be too expensive for the developing world, where they are desperately needed. Another problem is that they will be type specific. Novel approaches to the production of virus-like particles in plants, second-generation vaccine approaches including viral and bacterial vaccine vectors and DNA vaccines, as well as different routes of immunization, are also reviewed. © 2005 Future Drugs Ltd.

Report on the AIDS Vaccine 2008 Conference

The "AIDS Vaccine 2008" Conference was held in Cape Town, South Africa (October 13 to 16, 2008) and organized, under the aegis of the Global HIV Vaccine Enterprise, by Dr. Lynn Morris (Chair of the Conference) National Institute of Communicable Diseases; Dr. Koleka Mlisana from CAPRISA, University KwaZulu-Natal, Durban, Dr. Glenda Gray from Perinatal HIV Research Unit, University Witwatersrand, Johannesburg and Dr. Carolyn Williamson from Institute of Infectious Diseses. and Molecular Medicine, UCT, Cape Town (Co-Chairs of the Conference). Since the first AIDS Vaccine conference, organized in Paris in 2000, this was the first time it was held outside of the U.S. and Europe, and involved nearly 1,000 participants. Besides three Plenary Sessions with ten state-of-the-art plenary lectures and one Keynote Lecture given by Dr. A.S. Fauci (Director of NIAID, NIH, USA), the Conference was organized in nine oral sessions, four poster discussion groups covering a wide spectrum of scientific information relating to HIV vaccine research and development. Moreover three Symposia, two Special Sessions, one Roundtable as well as two Debates were held, the latter focusing on current controversial topics. The conference opening was memorable for a number of reasons: among these was the presence of South Africa's new Minister of Health, Barbara Hogan who, in her first speech in a major forum as a senior member of the SA Government, affirmed that HIV causes AIDS, and that the search for a vaccine is of paramount importance to SA and the rest of the world. A scientific summary of the Conference is reported in the present article, divided into four major topics: (1) vaccine concepts and design; (2) T-cell immunology and innate immunity; (3) B-cell immunology, neutralizing antibodies and mucosal immunology; and (4) clinical trials. © 2009 Landes Bioscience.

Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner

Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls  were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.

Characterization of in vitro Chlamydia muridarum persistence and utilization in an in vivo mouse model of Chlamydia vaccine

Problem: Chlamydia trachomatis genital tract infections are easily treated with antibiotics, however the majority of infections are asymptomatic and therefore untreated, highlighting the need for a vaccine. Because most infections are asymptomatic, vaccination could potentially be administered to individuals who may have an acute infection at that time. In such individuals the effect of vaccination on the existing infection is unknown; however one potential outcome could be the development of a persistent infection. In vitro chlamydial persistence has been well characterized in various strains, however there have been no reported studies in C. muridarum. Method of Study: We performed ultrastructural characterization, and transcriptome analysis of selected genes. We then used the transcriptional profiles of the selected genes to examine whether intranasal immunization of mice during an active genital infection would induce persistence in the upper reproductive tract of female mice. Results and Conclusions: We found that persistence developed in the oviducts of mice as a result of immunization. This is a significant finding, not only because it is the first time that C. muridarum persistence has been characterized in vitro, but also due to the fact that there is minimal characterization of in vivo persistence of any chlamydial species. This highlights the importance of the timing of vaccination in individuals.

Development status and future prospects for a vaccine against Chlamydia trachomatis infection

Chlamydia trachomatis continues to be the most commonly reported sexually transmitted bacterial infection in many countries with more than 100 million new cases estimated annually. These acute infections translate into significant downstream health care costs, particularly for women, where complications can include pelvic inflammatory disease and other disease sequelae such as tubal factor infertility. Despite years of research, the immunological mechanisms responsible for protective immunity versus immunopathology are still not well understood, although it is widely accepted that T cell driven IFN-g and Th17 responses are critical for clearing infection. While antibodies are able to neutralize infections in vitro, alone they are not protective, indicating that any successful vaccine will need to elicit both arms of the immune response. In recent years, there has been an expansion in the number and types of antigens that have been evaluated as vaccines, and combined with the new array of mucosal adjuvants, this aspect of chlamydial vaccinology is showing promise. Most recently, the opportunities to develop successful vaccines have been given a significant boost with the development of a genetic transformation system for Chlamydia, as well as the identification of the key role of the chlamydial plasmid in virulence. While still remaining a major challenge, the development of a successful C.trachomatis vaccine is starting to look more likely.

Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease

Deleterious responses to pathogens during infancy may contribute to infection and associated asthma. Chlamydia respiratory infections in early life are common causes of pneumonia and lead to reduced lung function and asthma. We investigated the role of interleukin-13 (IL-13) in promoting early-life Chlamydia respiratory infection, infection-induced airway hyperresponsiveness (AHR), and severe allergic airway disease (AAD). Infected infant Il13−/− mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13−/− mice induced persistent AHR. Infection and associated pathology were restored in infected Il13−/− mice by reconstitution with IL-13. Stat6−/− mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

Epidemiological trend of hepatitis B, liver cirrhosis and liver cancer during 1990 - 2007 in Shandong province, China [山东省乙型肝炎、肝硬化及肝癌流行趋势分析]

Objective To analyze the epidemiological trend of hepatitis B, liver cirrhosis and liver cancer during 1990 to 2007 in Shandong province, and to evaluate the effectiveness of hepatitis B prevention and control measures, so as to provide evidence for policy-making. Methods Based on the routine incidence data of hepatitis B, mortality data of hepatitis B, liver cirrhosis, liver cancer and demographic data, the incidence rate, mortality rate and age-specific mortality rate were calculated and analyzed with simple linear regression model. Results A total of 437094 cases of hepatitis B were reported during 1990 - 2007 with an average yearly morbidity of 27.32 per 100 000 persons and a decreased trend for the 0-9 years old children. At the same time, the adjusted mortality rate for hepatitis B and liver cirrhosis showed a decreased trend and the combined mortality rate decreased from 17.55 /100 000 in 1990 to 4.01 /100 000 in 2007. The mortality of liver cancer was stable during this time (P = 0. 9998). Conclusion Immunization of hepatitis B vaccine may have lowered the incidence of hepatitis B in the target population and the overall mortality rates of liver cirrhosis and liver cancer. Abstract in Chinese 目的 了解山东省1990～2007年乙肝、肝硬化和肝癌的流行状况及变化趋势,初步评价乙肝预防控制措施的效果,为今后防治决策制定提供参考. 方法 根据报告的乙肝发病资料和乙肝、肝硬化、肝癌死亡资料以及历年人口资料,利用发病率、死亡率、年龄别死亡率等指标对上述3种疾病进行流行趋势的分析,并建立简单线性回归模型进行统计分析. 结果 1990～2007年山东省共报告乙肝病例437 094例,年均总发病率为27.32/10万,并呈上升趋势,而0～9岁年龄组的发病率呈显著下降趋势.乙肝和肝硬化调整死亡率下降趋势明显,两者合并死亡率由1990年的17.55/10万下降到2007年的4.01/10万.肝癌调整死亡率基本稳定(P=0.999 8). 结论 做好乙肝疫苗的免疫接种不仅可降低目标人群乙肝的发病,并将最终降低与此相关的肝硬化和肝癌的死亡率.

Epidemiological Trend of Hepatitis B in Shandong Province of China, 1990 - 2007 []

Objective To analyze the epidemiological trend of hepatitis B from 1990 to 2007 in Shandong province, and to find the high risk population so as to explore the further control strategy. Methods Based on the routine reporting incidence data of hepatitis B and demographic data of Shandong province, the incidence rates and sex - specific, age - specific incidence rates of hepatitis B were calculated and statistically analyzed in the simple linear regression model. Results The total number of hepatitis B was 437 094, the annual average morbidity was 27132 per 100 000 population during 1990 to 2007. The incidence of men (38142 per 100 000) was higher than that for women (15183 per 100 000) 1The annual incidence rate of hepatitis B indicated an increasing trend for the whole population, while a decreased trend for the 0～9 year - old children p resented in the past 18 years. It showed that the average age of onset moved to the older. Conclusion Young adult men are the high-risk groups for the onset of hepatitis B. For the prevention of hepatitis B, the immunization of hepatitis B vaccine should be enhanced for other groups, especially for the high - risk population on the basis of imp roving the immunization coverage rate for newborns.

Problems in the current vaccination assurance policy and possible solutions [试述现行计划免疫保偿制存在的问题与改进对策]

Vaccination assurance was developed in 1980s to increase vaccine uptake. However, there have been problems in the concept, scope, management and claim. Possible solutions include regulating vaccination fee and developing vaccination insurance. Abstract in Chinese 计划免疫保偿制是20世纪80年代初我国卫生事业改革中出现的一种新生事物,为促进计划免疫工作开展发挥了重要作用.但随着人们对健康需求的不断提高和计划免疫工作的深入开展,计划免疫保偿制中的许多内容已经不适应当前的预防接种工作,亟待规范和提高.

Quality demand in vaccination and how to improve service quality under Total Quality Control [论全面质量管理模式下预防接种工作的质量要求与改进对策]

Under the concept of Total Quality Control, based on their experience, the authors discussed potential demand for quality of immunization services and possible solutions to these demands. Abstract in Chinese 全面质量管理(total quality control,TQC)是在20世纪60年代由美国人V,Feigonbaum和J.unan先后提出的新的质量管理观念,众所周知的ISO9000族标准即建立在TQC理念下的质量管理标准,该标准已成为当今世界全球一致、最具权威的质量管理和质量保证的国际规则[1-2].21世纪是质量世纪,推行TQC,不断改进产品和服务质量,目前已成为我国各行各业在不断激烈的市场竞争下完善自我、保证生存和发展的重要手段.实施预防接种是预防和控制传染病,保护人群健康的重要措施,预防接种工作中,产品即预防接种服务,需方(顾客)为接受预防接种服务的广大人群,是产品的消费者.随社会的迅速发展,人们对健康需求的不断提高,对预防接种工作也提出了更高的质量要求.本文对TQC模式下顾客对预防接种服务的质量要求进行了综合分析,并对如何改进服务质量进行了初步探讨.

Immunisation coverage in Australian Indigenous children : time to move the goal posts

Childhood immunisation coverage reported at 12 to <15 months and 2 years of age, may mask deficiencies in the timeliness of vaccines designed to protect against diseases in infancy. This study aimed to evaluate immunisation timeliness in Indigenous infants in the Northern Territory, Australia. Coverage was analysed at the date children turned 7, 13 and 18 months of age. By 7 months of age, 45.2% of children had completed the recommended schedule, increasing to 49.5% and 81.2% at 13 and 18 months of age, respectively. Immunisation performance benchmarks must focus on improving the timeliness in these children in the first year of life.