Geneva–Seattle collaboration in support of developing country vaccine manufacturing

Vaccines were once produced almost exclusively by state-supported entities. While they remain essential tools for public health protection, the majority of the world’s governments have allowed industry to assume responsibility for this function. This is significant because while the international harmonisation of quality assurance standards have effectively increased vaccine safety, they have also reduced the number of developing country vaccine producers, and Northern multinational pharmaceutical companies have shown little interest in offering the range of low-priced products needed in low and middle-income-country contexts. This article examines how public–private collaboration is relevant to contemporary efforts aimed at strengthening developing country manufacturers’ capacity to produce high-quality, low-priced vaccines. Specifically, it casts light on the important and largely complimentary roles of the World Health Organization, The Bill and Melinda Gates Foundation, and the Seattle-based non-profit PATH, in this process. The take away message is that external support remains critical to ensuring that developing country vaccine manufacturers have the tools needed to produce for both domestic and global markets, and the United Nations supply chain, and collaboration at the public–private interface is driving organisational innovation focused on meeting these goals.     

End-stage periventricular leukomalacia: MR evaluation

A prospective study was performed to assess the capabilities of magnetic resonance (MR) imaging in evaluation of end-stage periventricular leukomalacia (PVL) in six children, aged 31-54 months, in whom PVL had been documented by neurologic ultrasonography during the neonatal period. Eight children of similar age (four premature infants and four full-term infants) with normal neurologic development served as controls. A characteristic triad of PVL abnormalities was seen on MR images: (a) abnormally increased periventricular white-matter signal intensity on the first and second echo images of a T2-weighted sequence (repetition time = 2,000-2,400 msec, echo times = 20 or 30 and 80 msec), most commonly observed in the trigone regions of the lateral ventricles bilaterally; (b) marked loss of periventricular white matter in these regions of abnormal signal intensity, predominantly in the periatrial regions; and (c) compensatory focal ventricular enlargement adjacent to regions of abnormal signal intensity. In patients with the classic periatrial distribution of PVL lesions, general correlation between the degree of neurologic impairment and the severity of MR abnormalities was demonstrated. MR imaging was useful in detecting subtle forms of PVL in cases in which neurologic damage was subclinical.     

The burden of disease and injury in Australia.

An overview of the results of the Australian Burden of Disease (ABD) study is presented. The ABD study was the first to use methodology developed for the Global Burden of Disease study to measure the burden of disease and injury in a developed country. In 1996, mental disorders were the main causes of disability burden, responsible for nearly 30% of total years of life lost to disability (YLD), with depression accounting for 8% of the total YLD. Ischaemic heart disease and stroke were the main contributors to the disease burden disability-adjusted life years (DALYs), together causing nearly 18% of the total disease burden. Risk factors such as smoking, alcohol consumption, physical inactivity, hypertension, high blood cholesterol, obesity and inadequate fruit and vegetable consumption were responsible for much of the overall disease burden in Australia. The lessons learnt from the ABD study are discussed, together with methodological issues that require further attention.     

Report of the xenotransplantation advisory committee of the international society for heart and lung transplantation:: The present status of xenotransplantation and its potential role in the treatment of end-stage cardiac and pulmonary diseases

An urgent and steadily increasing need exists world-wide for a greater supply of donor thoracic organs. Xenotransplantation offers the possibility of an unlimited supply of hearts and lungs that could be available electively when required. However, anti-body- mediated mechanisms cause the rejection of pig organs transplanted into non-human primates, and these mechanisms provide major immunologic barriers that have not yet been overcome. Having reviewed the literature on xenotransplantation, we present a number of conclusions on its present status with regard to thoracic organs, and we make a number of recommendations relating to eventual clinical trials. Although pig hearts have functioned in heterotopic sites in non-human primates for periods of several weeks, median survival of orthotopically transplanted hearts is currently ,1 month. No transplanted pig lung has functioned for even 24 hours. Current experimental results indicate that a clinical trial would be premature. A potential risk exists, hitherto undetermined, of transferring infectious organisms along with the donor pig organ to the recipient, and possibly to other members of the community. A clinical trial of xeno-transplantation should not be undertaken until experts in microbiology and the relevant regulatory authorities consider this risk to be minimal. A clinical trial should be considered when approximately 60% survival of life-supporting pig organs in non-human primates has been achieved for a minimum of 3 months, with at least 10 animals surviving for this minimum period. Furthermore, evidence should suggest that longer survival (.6 months) can be achieved. These results should be achieved in the absence of life-threatening complications caused by the immunosuppressive regimen used. The relationship between the presence of anti-HLA antibody and anti-pig antibody and their cross-reactivity, and the outcome of pig-organ xenotransplantation in recipients previously sensitized to HLA antigens require further investigation. We recommend that the patients who initially enter into a clinical trial of cardiac xenotransplantation be unacceptable for allotransplantation, or acceptable for allotransplantation but unlikely to survive until a human cadaveric organ becomes available, and in whom mechanical assist-device bridging is not possible. National bodies that have wide-reaching government-backed control over all aspects of the trials should regulate the initial clinical trial and all subsequent clinical xenotransplantation procedures for the foreseeable future. We recommend coordination and monitoring of these trials through an international body, such as the International Society for Heart and Lung Transplantation, and setting up a registry to record and widely disperse the results of these trials. Xenotransplantation has the potential to solve the problem of donor-organ supply, and therefore research in this field should be actively encouraged and supported.     

The effect of military clothing on gunshot wounding patterns in gelatine

With no two gunshot wounds (GSW) being the same, novel research into wound ballistics is challenging. It is evident that the majority of previous wound ballistic research has been conducted without the presence of clothing. Whilst the effect of clothing on wound contamination has been explored, there is a paucity of literature examining the effect of clothing on GSW patterns. The aim of this study was to test the effect of Multi-Terrain Pattern (MTP) UK military clothing on GSW patterns within calibrated blocks of 10% by mass gelatine, using two types of ammunition commonly used in recent conflicts—7.62 × 39 mm and 5.45 × 39 mm. In total, 36 blocks were shot, 18 by each projectile type, further divided into 6 with no clothing layers (C_nil), 6 with a single clothing layer (C_min) and 6 with maximum clothing layers (C_max) worn on active duty. Blocks were analysed with high-speed video and dissection to capture measurements of damage, and results compared using analysis of variance (ANOVA). Results showed significantly different damage measurements within blocks with C_max for both ammunition types compared to the other clothing states. This may result in GSWs that require more extensive surgical management, inviting further study.

     

Methicillin-Resistant Staphylococcus aureus Sequence Type 239-III, Ohio, USA, 2007�C2009

Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen that has diverse molecular heterogeneity. Most MRSA strains in the United States are pulsed-field gel electrophoresis USA100 sequence type (ST) 5 and USA300 ST8. Infections with MRSA ST239-III are common and found during health care–associated outbreaks. However, this strain has been rarely reported in the United States. As part of a study supported by the Prevention Epicenter Program of the Centers for Disease Control and Prevention (Atlanta, GA, USA), which evaluated transmission of MRSA among hospitals in Ohio, molecular typing identified 78 (6%) of 1,286 patients with MRSA ST239-III infections. Ninety-five percent (74/78) of these infections were health care associated, and 65% (51/78) of patients had histories of invasive device use. The crude case-fatality rate was 22% (17/78). Identification of these strains, which belong to a virulent clonal group, emphasizes the need for molecular surveillance.Staphylococcus aureus is a major human pathogen that possesses multiple toxins and virulence mechanisms (1). Antimicrobial drug resistance in S. aureus has added to the complexity of treating serious infections caused by this bacteria, and methicillin-resistant S. aureus (MRSA) appears to have greater virulence than methicillin-susceptible strains (2,3). Most MRSA strains in the United States are pulsed-field gel electrophoresis (PFGE) types USA100 and USA300, corresponding to multilocus sequence typing (MLST) ST5 and ST8, respectively (4). MRSA belonging to MLST ST239 and harboring staphylococcal cassette chromosome mec (SCCmec) type III (MRSA ST239-III) are associated with infections in health care settings, outbreaks, increased resistance to antimicrobial drugs, and capacity for invasive disease (5–7).MRSA ST239-III has a history of successful dissemination in many regions, leading to a diverse array of regionally prevalent clones. These clones include the Brazilian; British Epidemic 1, 4, 7, 9, and 11; Canadian Epidemic 3/Punjab; Czech; Eastern Australian 2 and 3; Georgian; Hungarian; Lublin; Nanjing/Taipei (ST241); Portuguese; and Vienna clones (8,9). Although it is common worldwide, MRSA ST239-III has not played any predominant role in the United States; infections with MRSA ST239-III have been rarely reported in the United States since the 1990s (9–13). Recently, only 2 reports of this strain in the United States involving sporadic nasal colonization and bloodstream infections have been published (13,14).In this study, we describe clinical epidemiologic characteristics and molecular analysis of clinical infections with MRSA ST239-III in the midwestern United States. Identification of a strain from such a virulent clonal group in the United States with wide dissemination in other parts of the world represents a potential public health concern.     

Effect of muscle strength and movement speed on the biomechanics of rising from a chair in healthy elderly and young women

The ability to rise from a chair is an important task of daily living that is difficult for many elderly individuals to perform, and is particularly challenging when performed quickly. It is important to understand what factors limit performance of the task in older people, so that effective remedial approaches can be developed. In this study, we quantified lower-extremity muscle strength and chair-rise biomechanics in 12 young and 26 healthy elderly women during chair rise at normal and fast speeds without use of the hands. We found that hip and knee extensor torques, vertical and horizontal momentum, and vertical and horizontal ground reaction forces increased in the same way with speed for all subjects. All subjects increased their speed from normal to fast trials, but the young subjects were able to rise more quickly in the fast trials. In the normal speed trials, elderly subjects generated more trunk flexion and horizontal momentum while still in contact with the chair. Muscle activity patterns were similar for all subjects except that the elderly activated the ankle extensors earlier than the young. Although the elderly subjects were much weaker relative to body weight than the young subjects (48.5±14.1%), they were able to generate sufficient torques to perform the task. However, age-related differences suggest that chair-rise biomechanics were affected by the reduction in muscle strength, and that strength training regimens, particularly for the hip musculature, may be important to maintain chair-rise ability in the elderly.     

A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope

DNA vaccines induce CTL attack on target tumor epitopes, but tumor elimination in vivo also requires sufficient effector CTL to enter the site, guided by inflammatory chemokines. Many herpesviruses contain genes for chemokine and chemokine receptor-like proteins to protect infected cells from immune attack. To assess if this evasion strategy could protect tumor cells, we used a model where CTL specific for a single epitope were the only effectors. Following DNA vaccination, CTL eliminated tumor cells from a subcutaneous site. However, introducing a viral gene encoding a secreted broad-spectrum chemokine-binding protein (M3) into tumor cells completely blocked CTL attack. Transduced tumor cells also protected neighboring non-transduced tumor. These findings confirm the importance of chemokines for migration of CTL to a non-lymphoid site. They may have relevance for escape of human virus-associated malignancies, and raise the question of whether analogous molecules might contribute to the failure of CTL to eliminate tumors.     

Gamma hydroxybutyric acid (GHB): an increasing trend in drug abuse.

The use of recreational drugs in society is becoming a widespread problem increasing the workload of all the emergency services. Gamma hydroxybutyric acid (GHB) is one of these, a drug used primarily for its euphoric effect. Toxic effects of ingestion include bradycardia, slow respiration or apnoea, coma and death. We present seven cases, all of which had consumed GHB either alone or in conjunction with other drugs and alcohol. The presentation, clinical features and management of these cases are described. All health care personnel involved in the emergency setting need to know of its existence, toxic effects and initial management with particular reference to airway control and possible assisted ventilation.