Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

A simulation model of the within-host dynamics of Plasmodium vivax infection

Background The benign reputation of Plasmodium vivax is at odds with the burden and severity of the disease. This reputation, combined with restricted in vitro techniques, has slowed efforts to gain an understanding of the parasite biology and interaction with its human host. Methods A simulation model of the within-host dynamics of P. vivax infection is described, incorporating distinctive characteristics of the parasite such as the preferential invasion of reticulocytes and hypnozoite production. The developed model is fitted using digitized time-series’ from historic neurosyphilis studies, and subsequently validated against summary statistics from a larger study of the same population. The Chesson relapse pattern was used to demonstrate the impact of released hypnozoites. Results The typical pattern for dynamics of the parasite population is a rapid exponential increase in the first 10 days, followed by a gradual decline. Gametocyte counts follow a similar trend, but are approximately two orders of magnitude lower. The model predicts that, on average, an infected naïve host in the absence of treatment becomes infectious 7.9 days post patency and is infectious for a mean of 34.4 days. In the absence of treatment, the effect of hypnozoite release was not apparent as newly released parasites were obscured by the existing infection. Conclusions The results from the model provides useful insights into the dynamics of P. vivax infection in human hosts, in particular the timing of host infectiousness and the role of the hypnozoite in perpetuating infection.

Inorganic-organic composite particle as a staged delivery platform for plasmid DNA-based biopharmaceuticals

Infectious diseases such as SARS, influenza and bird flu may spread exponentially throughout communities. In fact, most infectious diseases remain major health risks due to the lack of vaccine or the lack of facilities to deliver the vaccines. Conventional vaccinations are based on damaged pathogens, live attenuated viruses and viral vectors. If the damage was not complete, the vaccination itself may cause adverse effects. Therefore, researchers have been prompted to prepare viable replacements for the attenuated vaccines that would be more effective and safer to use. DNA vaccines are generally composed of a double stranded plasmid that includes a gene encoding the target antigen under the transcriptional directory and control of a promoter region which is active in cells. Plasmid DNA (pDNA) vaccines allow the foreign genes to be expressed transiently in cells, mimicking intracellular pathogenic infection and inducing both humoral and cellular immune responses. Currently, because of their highly evolved and specialized components, viral systems are the most effective means for DNA delivery, and they achieve high efficiencies (generally >90%), for both DNA delivery and expression. As yet, viral-mediated deliveries have several limitations, including toxicity, limited DNA carrying capacity, restricted target to specific cell types, production and packing problems, and high cost. Thus, nonviral systems, particularly a synthetic DNA delivery system, are highly desirable in both research and clinical applications.

Process engineering aspects of plasmid-based biopharmaceuticals production : tackling the threatening vaccine shortages to prevent global pandemics

Infectious diseases such as SARS, influenza and bird flu have the potential to cause global pandemics; a key intervention will be vaccination. Hence, it is imperative to have in place the capacity to create vaccines against new diseases in the shortest time possible. In 2004, The Institute of Medicine asserted that the world is tottering on the verge of a colossal influenza outbreak. The institute stated that, inadequate production system for influenza vaccines is a major obstruction in the preparation towards influenza outbreaks. Because of production issues, the vaccine industry is facing financial and technological bottlenecks: In October 2004, the FDA was caught off guard by the shortage of flu vaccine, caused by a contamination in a US-based plant (Chiron Corporation), one of the only two suppliers of US flu vaccine. Due to difficulties in production and long processing times, the bulk of the world's vaccine production comes from very small number of companies compared to the number of companies producing drugs. Conventional vaccines are made of attenuated or modified forms of viruses. Relatively high and continuous doses are administered when a non-viable vaccine is used and the overall protective immunity obtained is ephemeral. The safety concerns of viral vaccines have propelled interest in creating a viable replacement that would be more effective and safer to use.

Rapid-response vaccines - does DNA offer a solution?

In responding to future influenza pandemics and other infectious agents, plasmid DNA overcomes many of the limitations of conventional vaccine production approaches.

Materials, methods and systems for purification and/or seperation

Materials, methods and systems are provided for the purifn., filtration and​/or sepn. of certain mols. such as certain size biomols. Certain embodiments relate to supports contg. at least one polymethacrylate polymer engineered to have certain pore diams. and other properties, and which can be functionally adapted to for certain purifications, filtrations and​/or sepns. Biomols. are selected from a group consisting of: polynucleotide mols., oligonucleotide mols. including antisense oligonucleotide mols. such as antisense RNA and other oligonucleotide mols. that are inhibitory of gene function such as small interfering RNA (siRNA)​, polypeptides including proteinaceous infective agents such as prions, for example, the infectious agent for CJD, and infectious agents such as viruses and phage.

How costs change with infection prevention efforts

Purpose of review: To describe articles since January 2013 that include information on how costs change with infection prevention efforts. Recent findings: Three articles described only the costs imposed by nosocomial infection and so provided limited information about whether or not infection prevention efforts should be changed. One article was found that described the costs of supplying alcohol-based hand run in low-income countries. Eight articles showed the extra costs and cost savings from changing infection prevention programmes and discussed the health benefits. All concluded that the changes are economically worthwhile. There was a systematic review of the costs of methicillin-resistant Staphylococcus aureus control programmes and a methods article for how to make cost estimates for infection prevention programmes. Summary: The balance has shifted away from studies that report the high cost of nosocomial infections toward articles that address the value for money of infection prevention. This is good as simply showing a disease is high cost does not inform decisions to reduce it. More research, done well, on the costs of implementation, cost savings and change to health benefits in this area needs to be done as many gaps exist in our knowledge.

Impact of mobility and topology on information diffusion in MANETs

In some delay-tolerant communication systems such as vehicular ad-hoc networks, information flow can be represented as an infectious process, where each entity having already received the information will try to share it with its neighbours. The random walk and random waypoint models are popular analysis tools for these epidemic broadcasts, and represent two types of random mobility. In this paper, we introduce a simulation framework investigating the impact of a gradual increase of bias in path selection (i.e. reduction of randomness), when moving from the former to the latter. Randomness in path selection can significantly alter the system performances, in both regular and irregular network structures. The implications of these results for real systems are discussed in details.

Hand, foot and mouth disease in China: Evaluating an automated system for the detection of outbreaks

Objective To evaluate the performance of China’s infectious disease automated alert and response system in the detection of outbreaks of hand, foot and mouth (HFM) disease. Methods We estimated size, duration and delay in reporting HFM disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and between 1 May 2010 and 30 April 2012, before and after automatic alert and response included HFM disease. Sensitivity, specificity and timeliness of detection of aberrations in the incidence of HFM disease outbreaks were estimated by comparing automated detections to observations of public health staff. Findings The alert and response system recorded 106 005 aberrations in the incidence of HFM disease between 1 May 2010 and 30 April 2012 – a mean of 5.6 aberrations per 100 days in each county that reported HFM disease. The response system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay between the reporting of the first case of an outbreak and detection of that outbreak by the response system was 2.1 days. Between the first and second study periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8 cases and the mean interval between the onset and initial reporting of such an outbreak to the public health emergency reporting system decreased from 10.0 to 9.1 days. Conclusion The automated alert and response system shows good sensitivity in the detection of HFM disease outbreaks and appears to be relatively rapid. Continued use of this system should allow more effective prevention and limitation of such outbreaks in China.

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.

Exploration of diarrhoea seasonality and its drivers in China

This study investigated the diarrhoea seasonality and its potential drivers as well as potential opportunities for future diarrhoea control and prevention in China. Data on weekly infectious diarrhoea cases in 31 provinces of China from 2005 to 2012, and data on demographic and geographic characteristics, as well as climatic factors, were complied. A cosinor function combined with a Poisson regression was used to calculate the three seasonal parameters of diarrhoea in different provinces. Regression tree analysis was used to identify the predictors of diarrhoea seasonality. Diarrhoea cases in China showed a bimodal distribution. Diarrhoea in children <5 years was more likely to peak in fall-winter seasons, while diarrhoea in persons > = 5 years peaked in summer. Latitude was significantly associated with spatial pattern of diarrhoea seasonality, with peak and trough times occurring earlier at high latitudes (northern areas), and later at low latitudes (southern areas). The annual amplitudes of diarrhoea in persons > = 5 years increased with latitude (r = 0.62, P<0.001). Latitude 27.8° N and 38.65° N were the latitudinal thresholds for diarrhoea seasonality in China. Regional-specific diarrhoea control and prevention strategies may be optimal for China. More attention should be paid to diarrhoea in children <5 years during fall-winter seasons.

Spatiotemporal analysis of indigenous and imported dengue fever cases in Guangdong province, China

Background Dengue fever has been a major public health concern in China since it re-emerged in Guangdong province in 1978. This study aimed to explore spatiotemporal characteristics of dengue fever cases for both indigenous and imported cases during recent years in Guangdong province, so as to identify high-risk areas of the province and thereby help plan resource allocation for dengue interventions. Methods Notifiable cases of dengue fever were collected from all 123 counties of Guangdong province from 2005 to 2010. Descriptive temporal and spatial analysis were conducted, including plotting of seasonal distribution of cases, and creating choropleth maps of cumulative incidence by county. The space-time scan statistic was used to determine space-time clusters of dengue fever cases at the county level, and a geographical information system was used to visualize the location of the clusters. Analysis were stratified by imported and indigenous origin. Results 1658 dengue fever cases were recorded in Guangdong province during the study period, including 94 imported cases and 1564 indigenous cases. Both imported and indigenous cases occurred more frequently in autumn. The areas affected by the indigenous and imported cases presented a geographically expanding trend over the study period. The results showed that the most likely cluster of imported cases (relative risk = 7.52, p < 0.001) and indigenous cases (relative risk = 153.56, p < 0.001) occurred in the Pearl River Delta Area; while a secondary cluster of indigenous cases occurred in one district of the Chao Shan Area (relative risk = 471.25, p < 0.001). Conclusions This study demonstrated that the geographic range of imported and indigenous dengue fever cases has expanded over recent years, and cases were significantly clustered in two heavily urbanised areas of Guangdong province. This provides the foundation for further investigation of risk factors and interventions in these high-risk areas.

A nationwide web-based automated system for early outbreak detection and rapid response in China

Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

Ambient temperature and the rates of adverse reactions of pertussis vaccines

To the Editor—Diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines are the 2 main pertussis-contained vaccines. DTwP, developed in the 1930s, has contributed to the reduction of pertussis, but has often been associated with vaccine-related adverse reactions (ARs) [1]. This had severely affected the public confidence in immunization programs, followed by decreased vaccine coverage and pertussis outbreaks in many industrialized countries in the 1970s [2]. DTaP, which was developed in the 1980s and replaced DTwP in developed countries in the 1990s, has been associated with fewer ARs due to removal/reduction of endotoxin [1]. China began replacing DTwP with DTaP in its national immunization programs in December 2007, and its passive Adverse Events Following Immunization (AEFI) surveillance system was established in 2005 [3]. The Intergovernmental Panel on Climate Change Fifth Assessment Report indicates that the planet is warming at...

Developing an epidemic forecasting model for Influenza A in Brisbane, Australia, based on climate and Hong Kong Influenza A surveillance data

Influenza is associated with substantial disease burden [ 1]. Development of a climate-based early warning system for in fluenza epidemics has been recommended given the signi fi - cant association between climate variability and influenza activity [2]. Brisbane is a subtropical city in Australia and offers free in fluenza vaccines to residents aged ≥65 years considering their high risks in developing life-threatening complications, especially for in fluenza A predominant seasons. Hong Kong is an international subtropical city in Eastern Asia and plays a crucial role in global infectious diseases transmission dynamics via the international air transportation network [3, 4]. We hypothesized that Hong Kong in fluenza surveillance data could provide a signal for in fluenza epidemics in Brisbane [ 4]. This study aims to develop an epidemic forecasting model for influenza A in Brisbane elders, by combining climate variability and Hong Kong in fluenza A surveillance data. Weekly numbers of laboratoryconfirmed influenza A positive isolates for people aged ≥65 years from 2004 to 2009 were obtained for Brisbane from Queensland Health, Australia, and for Hong Kong from Queen Mary Hospital (QMH). QMH is the largest public hospital located in Hong Kong Island, and in fluenza surveillance data from this hospital have been demonstrated to be representative for influenza circulation in the entirety of Hong Kong [ 5]. The Brisbane in fluenza A epidemics occurred during July –September, whereas the Hong Kong in fluenza A epidemics occurred during February –March and May –August.