Trade, travel and disease : the role of law in pandemic preparedness

In 2009 the world experienced an influenza pandemic caused by the H1N1 virus. While the pandemic was milder then expected, it nonetheless provided the world with an opportunity to do real-time testing of pandemic preparedness. This paper examines the threats to human health posed by infectious diseases and the challenges for the global community in development of effective surveillance systems for emerging infectious diseases. In 2005 a new revised version of the International Health Regulations (IHR) was adopted. The requirements of the IHR (2005) are outlined and considered in light of the constraints facing resource-poor countries. Finally, the paper addresses the role of domestic law-making in supporting public health preparedness and articulates a number of ethical principles that should be considered when developing new public health laws.

Geographical distribution of human Schistosoma japonicum infection in the Philippines : tools to support disease control and further elimination

S. japonicum infection is believed to be endemic in 28 of the 80 provinces of the Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small scale spatial variation in S. japonicum prevalence across the Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children <5 years. The role of the environmental variables differed between regions of the Philippines. S. japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in prevalence of S. japonicum infection in the Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized to areas identified to be at high risk, but which were underrepresented in our dataset.

Spatial analysis of risk factors for transmission of the Barmah forest virus in Queensland, Australia

Barmah Forest virus (BFV) disease is the second most common mosquito-borne disease in Australia but few data are available on the risk factors. We assessed the impact of spatial climatic, socioeconomic and ecological factors on the transmission of BFV disease in Queensland, Australia, using spatial regression. All our analyses indicate that spatial lag models provide a superior fit to the data compared to spatial error and ordinary least square models. The residuals of the spatial lag models were found to be uncorrelated, indicating that the models adequately account for spatial and temporal autocorrelation. Our results revealed that minimum temperature, distance from coast and low tide were negatively and rainfall was positively associated with BFV disease in coastal areas, whereas minimum temperature and high tide were negatively and rainfall was positively associated with BFV disease (all P-value.

Ross River virus disease activity associated with naturally occurring non-tidal flood events in Australia : A systematic review

Ross River virus (RRV) disease is the most common and widespread mosquito-borne disease in Australia, resulting in considerable health and economic cost to communities. While naturally occurring non-tidal flood events may enhance mosquito abundance, little is known about the impact of such events on RRV transmission. This paper critically reviews the existing evidence for an association between naturally occurring non-tidal flood events and RRV transmission. A systematic literature search was conducted on RRV transmission related to flooding and inundation from rain and riverine overflow. Overall, the evidence to support a positive association between flooding and RRV outbreaks is largely circumstantial, with the literature mostly reporting only coincidental occurrence between the two. However, for the Murray River, river flow and height (surrogates of flooding) were positively and significantly associated with RRV transmission. The association between non-tidal flooding and RRV transmission has not been studied comprehensively. More frequent flood events arising from climate change may result in increased outbreaks of RRV disease. Understanding the link between flood events and RRV transmission is necessary if resources for mosquito spraying and public health warnings are to be utilized more effectively and efficiently.

Sub-genomic RNA of defective interfering (D.I.) dengue viral particles is replicated in the same manner as full length genomes

The predicted secondary structure of sub-genomic RNA in dengue virus defective interfering (D.I.) particles from patients, or generated in vitro, resembled that of the 3′ and 5′ regions of wild type dengue virus (DENV) genomes. While these structures in the sub-genomic RNA were found to be essential for its replication, their nucleotide sequences were not, so long as any new sequences maintained wild type RNA secondary structure. These observations suggested that these sub-genomic fragments of RNA from dengue viruses were replicated in the same manner as the full length genomes of their wild type, “helper”, viruses and that they probably represent the smallest fragments of DENV RNA that can be replicated during a natural infection. While D.I. particles containing sub-genomic RNA are completely parasitic, the relationship between wild type and D.I. DENV may be symbiotic, with the D.I. particles enhancing the transmission of infectious DENV.

Role of big data in the early detection of Ebola and other emerging infectious diseases

The lack of adequate disease surveillance systems in Ebola-affected areas has both reduced the ability to respond locally and has increased global risk. There is a need to improve disease surveillance in vulnerable regions, and digital surveillance could present a viable approach.

Estimating the burden of disease attributable to childhood and maternal undernutrition in South Africa in 2000

OBJECTIVES To estimate the disease burden attributable to being underweight as an indicator of undernutrition in children under 5 years of age and in pregnant women for the year 2000. DESIGN World Health Organization comparative risk assessment (CRA) methodology was followed. The 1999 National Food Consumption Survey prevalence of underweight classified in three low weight-for-age categories was compared with standard growth charts to estimate population-attributable fractions for mortality and morbidity outcomes, based on increased risk for each category and applied to revised burden of disease estimates for South Africa in 2000. Maternal underweight, leading to an increased risk of intra-uterine growth retardation and further risk of low birth weight (LBW), was also assessed using the approach adopted by the global assessment. Monte Carlo simulation-modeling techniques were used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years of age and pregnant women. OUTCOME MEASURES Mortality and disability-adjusted life years (DALYs) from protein- energy malnutrition and a fraction of those from diarrhoeal disease, pneumonia, malaria, other non- HIV/AIDS infectious and parasitic conditions in children aged 0 - 4 years, and LBW. RESULTS Among children under 5 years, 11.8% were underweight. In the same age group, 11,808 deaths (95% uncertainty interval 11,100 - 12,642) or 12.3% (95% uncertainty interval 11.5 - 13.1%) were attributable to being underweight. Protein-energy malnutrition contributed 44.7% and diarrhoeal disease 29.6% of the total attributable burden. Childhood and maternal underweight accounted for 2.7% (95% uncertainty interval 2.6 - 2.9%) of all DALYs in South Africa in 2000 and 10.8% (95% uncertainty interval 10.2 - 11.5%) of DALYs in children under 5. CONCLUSIONS The study shows that reduction of the occurrence of underweight would have a substantial impact on child mortality, and also highlights the need to monitor this important indicator of child health.

Introduction: Epitope mimicry as a component cause of autoimmune disease

The causes of autoimmune diseases have yet to be fully elucidated. Autoantibodies, autoreactive T cell responses, the presence of a predisposing major histocompatibility complex (MHC) haplotype and responsiveness to corticosteroids are features, and some are possibly contributory causes of autoimmune disease. The most challenging question is how autoimmune diseases are triggered. Molecular mimicry of host cell determinants by epitopes of infectious agents with ensuing cross-reactivity is one of the most popular yet still controversial theories for the initiation of autoimmune diseases [1]. Throughout the 1990s, hundreds of research articles focusing to various extents on epitope mimicry, as it is more accurately described in an immunological context, were published annually. Many of these articles presented data that were consistent with the hypothesis of mimicry but that did not actually prove the theory. Other equally convincing reports indicated that epitope mimicry was not the cause of the autoimmune disease despite sequence similarity between molecules of infectious agents and the host. Some 20 years ago, Rothman [2] proposed a model for disease causation and I have used this as a framework to examine the role of epitope mimicry in the development of autoimmune disease. The thesis of Rothman’s model is that an effect, in this instance autoimmune disease, arises as a result of a cause. In most cases, multiple-component causes contribute synergistically to yield the effect, and each of these components alone is insufficient as a cause. Logically, some component causes, such as the presence of a particular autoimmune response, are also necessary causes.

Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Mimicry of host antigens by infectious agents may induce cross-reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post-viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin-dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross-reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC-peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012

Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. Methods Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. Results A total of 100,868 cases were reported during 2005–2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. Conclusions This study identified significant space-time clusters of HFRS in China during 2005–2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Chlamydial infections of fish: Diverse pathogens and emerging causes of disease in aquaculture species

Chlamydial infections of fish are emerging as an important cause of disease in new and established aquaculture industries. To date, epitheliocystis, a skin and gill disease associated with infection by these obligate intracellular pathogens, has been described in over 90 fish species, including hosts from marine and fresh water environments. Aided by advances in molecular detection and typing, recent years have seen an explosion in the description of these epitheliocystis-related chlamydial pathogens of fish, significantly broadening our knowledge of the genetic diversity of the order Chlamydiales. Remarkably, in most cases, it seems that each new piscine host studied has revealed the presence of a phylogenetically unique and novel chlamydial pathogen, providing researchers with a fascinating opportunity to understand the origin, evolution and adaptation of their traditional terrestrial chlamydial relatives. Despite the advances in this area, much still needs to be learnt about the epidemiology of chlamydial infections in fish if these pathogens are to be controlled in farmed environments. The lack of in vitro methods for culturing of chlamydial pathogens of fish is a major hindrance to this field. This review provides an update on our current knowledge of the taxonomy and diversity of chlamydial pathogens of fish, discusses the impact of these infections on the health, and highlights further areas of research required to understand the biology and epidemiology of this important emerging group of fish pathogens of aquaculture species.

5-year Chlamydia vaccination programme could reverse disease-related koala population decline: Predictions from a mathematical model using field data

BACKGROUND Many koala populations around Australia are in serious decline, with a substantial component of this decline in some Southeast Queensland populations attributed to the impact of Chlamydia. A Chlamydia vaccine for koalas is in development and has shown promise in early trials. This study contributes to implementation preparedness by simulating vaccination strategies designed to reverse population decline and by identifying which age and sex category it would be most effective to target. METHODS We used field data to inform the development and parameterisation of an individual-based stochastic simulation model of a koala population endemic with Chlamydia. The model took into account transmission, morbidity and mortality caused by Chlamydia infections. We calibrated the model to characteristics of typical Southeast Queensland koala populations. As there is uncertainty about the effectiveness of the vaccine in real-world settings, a variety of potential vaccine efficacies, half-lives and dosing schedules were simulated. RESULTS Assuming other threats remain constant, it is expected that current population declines could be reversed in around 5-6 years if female koalas aged 1-2 years are targeted, average vaccine protective efficacy is 75%, and vaccine coverage is around 10% per year. At lower vaccine efficacies the immunological effects of boosting become important: at 45% vaccine efficacy population decline is predicted to reverse in 6 years under optimistic boosting assumptions but in 9 years under pessimistic boosting assumptions. Terminating a successful vaccination programme at 5 years would lead to a rise in Chlamydia prevalence towards pre-vaccination levels. CONCLUSION For a range of vaccine efficacy levels it is projected that population decline due to endemic Chlamydia can be reversed under realistic dosing schedules, potentially in just 5 years. However, a vaccination programme might need to continue indefinitely in order to maintain Chlamydia prevalence at a sufficiently low level for population growth to continue.

Lung disease in indigenous children

Children in indigenous populations have substantially higher respiratory morbidity than non-indigenous children. Indigenous children have more frequent respiratory infections that are, more severe and, associated with long-term sequelae. Post-infectious sequelae such as chronic suppurative lung disease and bronchiectasis are especially prevalent among indigenous groups and have lifelong impact on lung function. Also, although estimates of asthma prevalence among indigenous children are similar to non-indigenous groups the morbidity of asthma is higher in indigenous children. To reduce the morbidity of respiratory illness, best-practice medicine is essential in addition to improving socio-economic factors, (eg household crowding), tobacco smoke exposure, and access to health care and illness prevention programs that likely contribute to these issues. Although each indigenous group may have unique health beliefs and interfaces with modern health care, a culturally sensitive and community-based comprehensive care system of preventive and long term care can improve outcomes for all these conditions. This article focuses on common respiratory conditions encountered by indigenous children living in affluent countries where data is available.

Wolbachia reduces the transmission potential of Dengue-infected Aedes aegypti

BACKGROUND: Dengue viruses (DENV) are the causative agents of dengue, the world's most prevalent arthropod-borne disease with around 40% of the world's population at risk of infection annually. Wolbachia pipientis, an obligate intracellular bacterium, is being developed as a biocontrol strategy against dengue because it limits replication of the virus in the mosquito. The Wolbachia strain wMel, which has been introduced into the mosquito vector, Aedes aegypti, has been shown to invade and spread to near fixation in field releases. Standard measures of Wolbachia's efficacy for blocking virus replication focus on the detection and quantification of virus in mosquito tissues. Examining the saliva provides a more accurate measure of transmission potential and can reveal the extrinsic incubation period (EIP), that is, the time it takes virus to arrive in the saliva following the consumption of DENV viremic blood. EIP is a key determinant of a mosquito's ability to transmit DENVs, as the earlier the virus appears in the saliva the more opportunities the mosquito will have to infect humans on subsequent bites. METHODOLOGY/PRINCIPAL FINDINGS: We used a non-destructive assay to repeatedly quantify DENV in saliva from wMel-infected and Wolbachia-free wild-type control mosquitoes following the consumption of a DENV-infected blood meal. We show that wMel lengthens the EIP, reduces the frequency at which the virus is expectorated and decreases the dengue copy number in mosquito saliva as compared to wild-type mosquitoes. These observations can at least be partially explained by an overall reduction in saliva produced by wMel mosquitoes. More generally, we found that the concentration of DENV in a blood meal is a determinant of the length of EIP, saliva virus titer and mosquito survival. CONCLUSIONS/SIGNIFICANCE: The saliva-based traits reported here offer more disease-relevant measures of Wolbachia's effects on the vector and the virus. The lengthening of EIP highlights another means, in addition to the reduction of infection frequencies and DENV titers in mosquitoes, by which Wolbachia should operate to reduce DENV transmission in the field.

Acute infectious diarrhea lessons learned from the past?

The Journal of Pediatric Gastroenterology and Nutrition (JPGN) has been at the forefront of many of the seminal advances into research on infectious diarrhea. In 1982, the first article of the JPGN was entitled “Oral Therapy for Dehydration in Diarrheal Diseases as a Global Problem” and has set the scene for several thousand subsequent articles. In his initial editorial, Finberg (1) posed several questions, which still have relevance 30 years later: 1. When is oral rehydration not appropriate, if ever? 2. What should be the composition of the oral solution and should there be more than one? 3. Should recommended practice be different in lesser-developed countries from those in developed countries? 4. Should the salts and glucose be prepackaged or should home supplies be used by instructed mothers? 5. When should standard feedings be resumed?