Disease Control Perspective Research Articles

A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS).

Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition. The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5). iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes. A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity. This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes. Number 2018-004967-30.

Prevalence of Active Pouch Symptoms and Patient Perception of Symptom Control and Quality of Life in an Outpatient Practice

Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life. We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant. We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% weremale. Average treatment satisfaction score (scale of 0-10) was6.4 and quality of life score was 5.8. A majority (64.9%)expressed interest in fecal microbiota transplant. Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.

Interaction between self-perceived disease control and self-management behaviours among Chinese middle-aged and older hypertensive patients: the role of subjective life expectancy

BackgroundOne of the effective ways to control hypertension is long-term self-management, which is difficult to maintain. Therefore, understanding how people engage in the process of self-management behaviour change is necessary. In this study, we aimed to examine the dynamic relationship between self-perceived disease control and self-management behaviours in Chinese middle-aged and older hypertensive patients, namely, medication use, self-monitoring, physical activity, tobacco and alcohol avoidance, and to explore the mediating role of subjective life expectancy (SLE) on this relationship.MethodsData were obtained from a nationally representative sample of 508 middle-aged and older hypertensive patients (aged 45+) from the 2013, 2015, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. A cross-lagged panel model combined with mediation analysis was used to determine the dynamic relationship between self-perceived disease control and self-management behaviours and to clarify the mediating effect of SLE on this ascertained relationship.ResultsGood self-perceived disease control subsequently predicted good medication use, self-monitoring and physical activity, and vice versa. Subjective life expectancy (SLE) partially mediated the prospective reciprocal relationships between self-perceived disease control and these self-management behaviours, which accounted for 37.11, 25.88, and 19.39% of the total effect of self-perceived disease control on medication use, self-monitoring and physical activity, respectively. These self-management behaviours had a significant and positive feedback effect on self-perceived disease control. However, neither the direct and indirect effects (via SLE) of self-perceived disease control on tobacco and alcohol avoidance were revealed.ConclusionsPositive feedback loops of present self-perceived disease control, future SLE and self-management behaviours (medication use, self-monitoring, and physical activity) help middle-aged and older hypertensive patients adhere to these behaviours but are useless for the avoidance of addictive behaviours. Interventions aimed at enhancing the effect perception of general self-management behaviours (e.g., medication use, self-monitoring and physical activity) on the present disease control perspective, and future lifespan perspective would be beneficial for the consistent self-management behaviours of middle-aged and older hypertensive patients. The utility of present disease control perception to these self-management behaviours was much higher than the utility of future expectations. Alternative stress relief strategies may be conducive to long-term changes in addictive behaviours.

Patient-Reported Control of Asthma, Nasal Polyposis, and Middle-Ear Symptoms in NSAID-Exacerbated Respiratory Disease.

Non-steroidal anti-inflammatory drug (NSAID)—exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD.

Mayaro Virus: The Potential Role of Microbiota and Wolbachia.

The Mayaro virus (MAYV) is an arbovirus that circulates mainly in tropical forests or rural areas in Latin America and is transmitted mainly by Haemagogus mosquitoes. The objective of this study was to evaluate the vector competence, microbiome, and the presence of Wolbachia in three Aedes albopictus populations infected with MAYV. The vector competence was assessed based on viral infection and transmission by RT-qPCR. In addition, the microbiome was evaluated by amplification of the 16S rRNA V4 region and PCR to detect the presence of Wolbachia (strain wAlbA/wAlbB). Our results show that all three populations were susceptible to MAYV infection. The potential transmission of the MAYV was consistent in all populations of naïve mosquitoes injected (more than 50%). The microbiome analysis revealed 118 OTUs (operational taxonomic unit) from the three populations, 8 phyla, 15 classes, 26 orders, 35 families, 65 genera, and 53 species. All populations had Pseudomonas and Wolbachia as predominant genera. There was no difference between the variables for MAYV and Wolbachia (wAlbA or wAlbB) in the abdomen. However, in the head + thorax samples at 14 dpi, there was a difference between the two populations, indicating a possible correlation between the presence of Wolbachia (wAlbB) and infection. Overall, we show evidence that Ae. albopictus displays significant infection and transmission competence for the MAYV in the laboratory, and its bacterial microbiota play an important role in the host, mainly the strains of Wolbachia. The influence of the intestinal microbiota of Ae. albopictus is poorly known, and a better understanding of these interactions would open new perspectives for disease control through the manipulation of microbial communities. The exact contribution of this mosquito species to the transmission of the MAYV in the field remains to be confirmed.

Measuring the contribution of human mobility to malaria persistence

BackgroundTo achieve malaria elimination, it is important to determine the role of human mobility in parasite transmission maintenance. The Alto Juruá basin (Brazil) exhibits one of the largest vivax and falciparum malaria prevalence in the Amazon. The goal of this study was to estimate the contribution of human commutes to malaria persistence in this region, using data from an origin-destination survey.MethodsData from an origin-destination survey were used to describe the intensity and motivation for commutations between rural and urban areas in two Alto Juruá basin (Brazil) municipalities, Mâncio Lima and Rodrigues Alves. The relative time-person spent in each locality per household was estimated. A logistic model was developed to estimate the effect of commuting on the probability of contracting malaria for a certain residence zone inhabitant commuting to another zone.ResultsThe main results suggest that the assessed population is not very mobile. A total of 96% households reported spending over 90% of their annual person-hour in areas within the same residence zone. Study and work were the most prevalent commuting motivations, calculated at 40.5% and 29.5% respectively. Spending person-hours in urban Rodrigues Alves conferred relative protection to urban Mâncio Lima residents. The opposite effect was observed for those spending time in rural areas of both municipalities.ConclusionResidence area is a stronger determinant for contracting malaria than commuting zones in the Alto Juruá region. As these municipalities are a hotspot for Plasmodium transmission, understanding the main local human fluxes is essential for planning control strategies, since the probability of contracting malaria is dependent on the transmission intensity of both the origin and the displacement area. The natural conditions for the circulation of certain pathogens, such as Plasmodium spp., combined with the Amazon human mobility pattern indicate the need for disease control perspective changes. Therefore, intersectoral public policies should become the basis for health mitigation actions.

Infection\xa0of highly insecticide-resistant malaria vector Anopheles coluzzii with entomopathogenic bacteria Chromobacterium violaceum reduces its survival, blood feeding propensity and fecundity

BackgroundThis is now a concern that malaria eradication will not be achieved without the introduction of novel control tools. Microbiological control might be able to make a greater contribution to vector control in the future. The interactions between bacteria and mosquito make mosquito microbiota really promising from a disease control perspective. Here, the impact of Chromobacterium violaceum infections, isolated from both larvae and adult of wild-caught Anopheles gambiae sensu lato mosquitoes in Burkina Faso, was evaluated on mosquito survival, blood feeding and fecundity.MethodsTo assess entomopathogenic effects of C. violaceum infection on mosquitoes, three different types of bioassays were performed in laboratory. These bioassays aimed to evaluate the impact of C. violaceum infection on mosquito survival, blood feeding and fecundity, respectively. During bioassays mosquitoes were infected through the well-established system of cotton ball soaked with 6% glucose containing C. violaceum.ResultsChromobacterium violaceum kills pyrethroid resistant Anopheles coluzzii (LT80 of 8.78 days ± 0.18 at 108 bacteria cell/ml of sugar meal). Interestingly, this bacterium had other negative effects on mosquito lifespan by significantly reducing (~ 59%, P < 0.001) the mosquito feeding willingness from day 4-post infection (~ 81% would seek a host to blood feed) to 9- day post infection (22 ± 4.62% would seek a host to blood feed). Moreover, C. violaceum considerably jeopardized the egg laying (~ 16 eggs laid/mosquito with C. violaceum infected mosquitoes vs ~ 129 eggs laid/mosquito with control mosquitoes) and hatching of mosquitoes (a reduction of ~ 22% of hatching rate with C. violaceum infected mosquitoes). Compared to the bacterial uninfected mosquitoes, mosquitoes infected with C. violaceum showed significantly higher retention rates of immature eggs and follicles.ConclusionThese data showed important properties of Burkina Faso C. violaceum strains, which are highly virulent against insecticide-resistant An. coluzzii, and reduce both mosquito blood feeding and fecundity propensities. However, additional studies as the sequencing of C. violaceum genome and the potential toxins secreted will provide useful information render it a potential candidate for the biological control strategies of malaria and other disease vectors.

Settling and feeding behavior of sharpshooter vectors of Xylella fastidiosa on plum genotypes resistant to leaf scald disease

Plum leaf scald (PLS) is a serious disease caused by Xylella fastidiosa subsp. multiplex, a pathogenic bacterium transmitted by xylem-sap feeding leafhoppers, commonly named sharpshooters (Hemiptera: Cicadellidae: Cicadellinae). In Brazil, the development of plum genotypes that apparently are not infected under field conditions has opened new perspectives for disease control based on host plant resistance. For example, PLS incidence on ‘SC13’ and ‘SC7’ genotypes is almost null under field conditions, although ‘SC13’ is infected by graft inoculation. Thus, we hypothesized that the performance of these genotypes in the field may be related to vector behavior. To verify this hypothesis, we investigated the settling preference and probing and feeding behavior of the sharpshooters Bucephalogonia xanthophis (Berg) and Sibovia sagata (Signoret) on the PLS-resistant plum genotypes, ‘SC7’ and ‘SC13’, and on the naturally infected cultivar, ‘Laetitia’. In the settling experiments, ‘SC7’ was less preferred by both vector species. For S. sagata held on ‘SC13’, reduced sap ingestion rates were observed. For B. xanthophis, probing and feeding activities differed between individuals held on ‘SC13’ and ‘Laetitia’. Specifically, duration of the stylet pathway phase, duration of xylem sap ingestion events, and number of interruptions of the xylem phase differed for B. xanthophis held on ‘SC13’ and ‘Laetitia’. The results show that the resistant genotypes affected host plant selection by the sharpshooters and highlight the importance of incorporating vector behavior into studies aimed at identifying or developing X. fastidiosa-resistant genotypes.

Invasive Densification as a Pandemic Generator – Extreme Case in Uppsala

Deliberate density planning was investigated in Eriksberg - a suburban development project in Western Uppsala, where an existing district was proposed by the municipality to double its population and its housing capacity over a period of 20 years. The intensive densification was proposed as a response to fast population growth in the city. But such invasive densification can be shown to threaten to eradicate existing internal green areas, to increase traffic movements strongly and challenge half-a-century-old social networks in the area. The intensive densification is likely to destroy the original plan, where housing, green structure, activity arenas and transport infrastructure are today well integrated, and where there is currently a good balance between density and spaciousness. Such densification levels would also be highly problematic from a disease control perspective, with increased social contacts, less opportunities to access courtyard and district green areas, higher popular density in shops, buses, schools and other service functions. As an alternative to intensifying existing near-suburbs we suggest a new strategy – DOSSIER [1] – where existing secondary settlements (satellite communities) outside the city of Uppsala are supplemented with new homes and new job opportunities. This approach – together with a modest in-fill densification within the cityscape, could create a fruitful balance and a new sustainable alliance between urban and rural areas – a fundamental strategy for abating climate change. [1] Densification Of Secondary Settlements Environmental Regeneration

Positioning Quebec ORF5 sequences of porcine reproductive and respiratory syndrome virus (PRRSV) within Canada and worldwide diversity

Sequencing of ORF5 gene is widely used and considered essential for diagnostics and control of porcine reproductive and respiratory syndrome (PRRS) in Canada. The objective of this study was to position Quebec ORF5 sequences of PRRS virus within Canada and worldwide diversity. Overall, 76.8% of the 5204 sequences gathered from Quebec (n = 5031), Ontario (n = 151) and Manitoba (n = 18) were classified into one of 34 genetic clusters defined as groupings including ≥15 sequences and having ≥70% rapid bootstrap support value from a maximum likelihood (ML)-phylogeny. Following the addition of PRRSV 2 international reference dataset from Shi et al. (2010), the most predominant lineages in our dataset were wild-type 1 and vaccine-like 5.1 (MLV) and 8.9 (ATP). No strains or only a very few (1 or 2) were assigned to lineages 1.3–1.5, 3, 4, 5.2, 6, 7 or 9. Most wild-type clusters (97%) detected in a dataset from Canada did not include any sequence from the international reference dataset. It might reflect recent subpopulations that were absent at the time of Shi's publication. As an example, cluster #25 first appeared in 2007, but since then had expanded considerably and is now the most prevalent wild-type cluster found in Quebec. A total of 117 RFLP patterns were identified and those were poorly correlated with genetic clusters based on phylogeny. Factors modulating PRRSV diversity such as pig movement that occurred within and between provinces should be further investigated in a perspective of disease control.

The contact structure of Great Britain’s salmon and trout aquaculture industry

We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh nodes and 72% of Scottish nodes are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers.

Visceral leishmaniasis: situation diagnosis from the perspective of disease control in Brazil

Leishmaniasis is a group of neglected diseases that are highly prevalent worldwide, mainly in the developing world, and can take on severe forms. They are transmitted to the man by the bite of phlebotomines, existing a range of animal reservoirs, among which the dog is considered the main urban host. In this context, leishmaniasis, mainly the visceral form, has been urbanized in Brazil, reaching large urban centers throughout the country. In addition, recently, new areas previously unaffected started to present autochthonous cases of human visceral leishmaniasis. The expansion of the disease to new areas has demonstrated the failure of the measures recommended by national health agencies and calls for a new control model in which popular awareness and environmental management are priority actions.

Towards comprehensive and effective strategies to address sexual health

Sexual health is an important global public health concern. Planning effective strategies to improve sexual health requires a high degree of attention to the local epidemiological trends and cultural context where the strategy is to be implemented. The paper by Chemtob et al. describes the process to develop a plan that aims to reduce the burden of Sexually Transmitted Infections in Israel by 2025. This commentary argues that increased attention to planning and implementation of sexual health policy is required in order to address the real burden of disease. Sexual health should not be merely addressed from a communicable disease control perspective but should comprehensively address health and wellbeing of all population groups through a positive approach in line with the WHO current definition of sexual health. As even traditionally culturally conservative societies are experiencing rapid changes in attitudes and practices towards sexual lifestyles, the challenge is to ensure that sexual health strategies combine evidence-informed measures and good practices with culturally appropriate communication and implementation approaches.

Aedes-Borne Virus-Mosquito Interactions: Mass Spectrometry Strategies and Findings.

Aedes-borne viruses are responsible for high-impact neglected tropical diseases and unpredictable outbreaks such as the ongoing Zika epidemics. Aedes mosquitoes spread different arboviruses such as Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus, among others, and are responsible for the continuous emergence and reemergence of these pathogens. These viruses have complex transmission cycles that include two hosts, namely the Aedes mosquito as a vector and susceptible vertebrate hosts. Human infection with arboviruses causes diseases that range from subclinical or mild to febrile diseases, encephalitis, and hemorrhagic fever. Infected mosquitoes do not show detectable signs of disease, even though the virus maintains a lifelong persistent infection. The infection of the Aedes mosquito by viruses involves a molecular crosstalk between cell and viral proteins. An understanding of how mosquito vectors and viruses interact is of fundamental interest, and it also offers novel perspectives for disease control. In recent years, mass spectrometry (MS)-based strategies in combination with bioinformatics have been successfully applied to identify and quantify global changes in cellular proteins, lipids, peptides, and metabolites in response to viral infection. Although the information about proteomics in the Aedes mosquito is limited, the information that has been reported can set up the basis for future studies. This review reflects how MS-based approaches have extended our understanding of Aedes mosquito biology and the development of DENV and CHIKV infection in the vector. Finally, this review discusses future challenges in the field.

Mycotoxins in harvested fruits and vegetables: Insights in producing fungi, biological role, conducive conditions, and tools to manage postharvest contamination

The postharvest life of fruits and vegetables is influenced by several parameters, such as physiological properties and biotic/abiotic stresses. In particular, a consistent portion of the product is lost, mainly due to fungal diseases, which represent a concern not only to retailers but also to consumers, due to the presence of mycotoxins. Indeed, some species of postharvest genera, i.e. Aspergillus, Penicillium, and Alternaria, produce toxic secondary metabolites, which pose a health risk to humans and animals, so that maximum content in harvested commodities and derived products have been established for certain toxins by national and international organizations. Although some mycotoxins are poisonous to competing microorganisms or plants, their biological role is still unclear. Recent studies support their involvement in disease onset/development, so that a reduction in mycotoxin production might have a disease control perspective. Indeed, the use of synthetic fungicides is not always possible or effective in postharvest, because of restrictions on residue content and the appearance of resistant strains. Moreover, the application of suboptimal concentrations of fungicides may even increase mycotoxin biosynthesis. Thus, the demand for alternative control means (e.g. microbial antagonists, natural or generally regarded as safe compounds, and physical means) is growing. In this review, a synopsis of the main postharvest mycotoxigenic genera is given with particular reference to their control.

Intra-epidemic evolutionary dynamics of a Dengue virus type 1 population reveal mutant spectra that correlate with disease transmission.

Dengue virus (DENV) is currently the most prevalent mosquito-borne viral pathogen. DENVs naturally exist as highly heterogeneous populations. Even though the descriptions on DENV diversity are plentiful, only a few studies have narrated the dynamics of intra-epidemic virus diversity at a fine scale. Such accounts are important to decipher the reciprocal relationship between viral evolutionary dynamics and disease transmission that shape dengue epidemiology. In the current study, we present a micro-scale genetic analysis of a monophyletic lineage of DENV-1 genotype III (epidemic lineage) detected from November 2012 to May 2014. The lineage was involved in an unprecedented dengue epidemic in Singapore during 2013–2014. Our findings showed that the epidemic lineage was an ensemble of mutants (variants) originated from an initial mixed viral population. The composition of mutant spectrum was dynamic and positively correlated with case load. The close interaction between viral evolution and transmission intensity indicated that tracking genetic diversity through time is potentially a useful tool to infer DENV transmission dynamics and thereby, to assess the epidemic risk in a disease control perspective. Moreover, such information is salient to understand the viral basis of clinical outcome and immune response variations that is imperative to effective vaccine design.

Chromobacterium Csp_P reduces malaria and dengue infection in vector mosquitoes and has entomopathogenic and in vitro anti-pathogen activities.

Plasmodium and dengue virus, the causative agents of the two most devastating vector-borne diseases, malaria and dengue, are transmitted by the two most important mosquito vectors, Anopheles gambiae and Aedes aegypti, respectively. Insect-bacteria associations have been shown to influence vector competence for human pathogens through multi-faceted actions that include the elicitation of the insect immune system, pathogen sequestration by microbes, and bacteria-produced anti-pathogenic factors. These influences make the mosquito microbiota highly interesting from a disease control perspective. Here we present a bacterium of the genus Chromobacterium (Csp_P), which was isolated from the midgut of field-caught Aedes aegypti. Csp_P can effectively colonize the mosquito midgut when introduced through an artificial nectar meal, and it also inhibits the growth of other members of the midgut microbiota. Csp_P colonization of the midgut tissue activates mosquito immune responses, and Csp_P exposure dramatically reduces the survival of both the larval and adult stages. Ingestion of Csp_P by the mosquito significantly reduces its susceptibility to Plasmodium falciparum and dengue virus infection, thereby compromising the mosquito's vector competence. This bacterium also exerts in vitro anti-Plasmodium and anti-dengue activities, which appear to be mediated through Csp_P -produced stable bioactive factors with transmission-blocking and therapeutic potential. The anti-pathogen and entomopathogenic properties of Csp_P render it a potential candidate for the development of malaria and dengue control strategies.

Population structure and temporal maintenance of the multihost fungal pathogen Botrytis cinerea: causes and implications for disease management

Understanding the causes of population subdivision is of fundamental importance, as studying barriers to gene flow between populations may reveal key aspects of the process of adaptive divergence and, for pathogens, may help forecasting disease emergence and implementing sound management strategies. Here, we investigated population subdivision in the multihost fungus Botrytis cinerea based on comprehensive multiyear sampling on different hosts in three French regions. Analyses revealed a weak association between population structure and geography, but a clear differentiation according to the host plant of origin. This was consistent with adaptation to hosts, but the distribution of inferred genetic clusters and the frequency of admixed individuals indicated a lack of strict host specificity. Differentiation between individuals collected in the greenhouse (on Solanum) and outdoor (on Vitis and Rubus) was stronger than that observed between individuals from the two outdoor hosts, probably reflecting an additional isolating effect associated with the cropping system. Three genetic clusters coexisted on Vitis but did not persist over time. Linkage disequilibrium analysis indicated that outdoor populations were regularly recombining, whereas clonality was predominant in the greenhouse. Our findings open up new perspectives for disease control by managing plant debris in outdoor conditions and reinforcing prophylactic measures indoor.

Cervical cancer screening at crossroads.

Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT) demonstrated that HPV testing provides better protection against cervical cancer than cytology, but it requires extra repeated testing. HPV vaccination RCTs, furthermore, have proved that HPV vaccination protects against vaccine-type high-grade CIN in women vaccinated prior to sexual activity, but less so in women vaccinated later. The challenge now is therefore to find an algorithm for screening of a heterogeneous population including non-vaccinated women; women vaccinated prior to start of sexual activity; and women vaccinated later.

Qualitative analysis and optimal control of an epidemic model with vaccination and treatment

We focus on an epidemic model which incorporates a non-linear force of infection and two controls: an imperfect preventive vaccine given to susceptible individuals and therapeutic treatment given to infectious. We study both the cases of constant and non constant controls. In the case of constant controls we perform a qualitative analysis based on Lyapunov stability which allows to integrate the bifurcation analysis performed in a previous paper. The occurrence of a backward bifurcation is discussed in the perspective of disease control. The case of time-dependent controls is studied by means of the optimal control theory. The strategy is to minimize both the disease burden and the intervention costs. We derive the optimality system and solve it numerically. The characterization of the optimal time profile of the controls, together with the qualitative analysis provides a rather complete picture of the possible outcomes of the model.