Interrupting Malaria Transmission: Quantifying the Impact of Interventions in Regions of Low to Moderate Transmission

Malaria has been eliminated from over 40 countries with an additional 39 currently planning for, or committed to, elimination. Information on the likely impact of available interventions, and the required time, is urgently needed to help plan resource allocation. Mathematical modelling has been used to investigate the impact of various interventions; the strength of the conclusions is boosted when several models with differing formulation produce similar data. Here we predict by using an individual-based stochastic simulation model of seasonal Plasmodium falciparum transmission that transmission can be interrupted and parasite reintroductions controlled in villages of 1,000 individuals where the entomological inoculation rate is <7 infectious bites per person per year using chemotherapy and bed net strategies. Above this transmission intensity bed nets and symptomatic treatment alone were not sufficient to interrupt transmission and control the importation of malaria for at least 150 days. Our model results suggest that 1) stochastic events impact the likelihood of successfully interrupting transmission with large variability in the times required, 2) the relative reduction in morbidity caused by the interventions were age-group specific, changing over time, and 3) the post-intervention changes in morbidity were larger than the corresponding impact on transmission. These results generally agree with the conclusions from previously published models. However the model also predicted changes in parasite population structure as a result of improved treatment of symptomatic individuals; the survival probability of introduced parasites reduced leading to an increase in the prevalence of sub-patent infections in semi-immune individuals. This novel finding requires further investigation in the field because, if confirmed, such a change would have a negative impact on attempts to eliminate the disease from areas of moderate transmission

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Foxp3 and Treg cells in HIV-1 infection and immuno-pathogenesis

FoxP3+CD4+CD25+ regulatory T (Treg) cells are implicated in a number of pathologic processes including elevated levels in cancers and infectious diseases, and reduced levels in autoimmune diseases. Treg cells are activated to modulate immune responses to avoid over-reactive immunity. However, conflicting findings are reported regarding relative levels of Treg cells during HIV-1 infection and disease progression. The role of Treg cells in HIV-1 diseases (aberrant immune activation) is poorly understood due to lack of a robust model. We summarize here the regulation and function of Foxp3 in Treg cells and in modulating HIV-1 replication. Based on recent findings from SIV/monkey and HIV/humanized mouse models, a model of the dual role of Treg cells in HIV-1 infection and immuno-pathogenesis is discussed

Victims of cybercrime in Europe: a review of victim surveys

Objectives: Review the evidence provided by victim surveys in order to provide a rough estimate of the personal crime prevalence of the main types of cybercrime. Methods: We performed a search in databases, searched online, and contacted several Offices for National Statistics in Europe and selected surveys that provided information about individual victims of crime which were representative for a general population. Six types of cybercrime have been distinguished, namely online shopping fraud, online fraud banking/payment, other cyber fraud (such as advanced fee fraud), cyber threats/harassment, malware, and hacking. For every survey the questions on cybercrime are presented and the crime prevalence estimates are compared. Results: Nine surveys were included. Annual crime prevalence rates ranged from 1 to 3% for online shopping fraud, from less than 1 to 2% for online banking/payment fraud. Less than 1% of the population is a victim of other types of fraud and a maximum of 3% of the population experiences some sort of online bullying such as stalking (1%) or threatening (1%). 1–6% is a victim of hacking. The estimates for being a victim of malware range from 2 to 15%. For all offences it cannot be estimated how much of the differences are due to variation in methods and questioning between the studies or real differences between countries or change over time. Conclusions: As yet there have been very few well performed randomised sampled studies on cybercrime amongst the general population. Cybercrime prevalence (and its trend) can only be well measured if the questions are frequently updated and adequately address new aspects of cybercrime. To adequately monitor cybercrime in the future it is advisable to develop some fairly abstract main categories that are of durable validity, whilst allowing for up-to-date illustrations. Furthermore, ideally the questioning in the ongoing surveys in the different countries should be standardised and there should be a uniform categorisation of the different cyber offences. A screening question in order to permit more accurate dating is essential to reduce telescoping bias. Surveys should ask about the impact on or damage to the victims