Colonisation resistance in the sand fly gut:Leishmania protects Lutzomyia longipalpis from bacterial infection

BACKGROUND: Phlebotomine sand flies transmit the haemoflagellate Leishmania, the causative agent of human leishmaniasis. The Leishmania promastigotes are confined to the gut lumen and are exposed to the gut microbiota within female sand flies. Here we study the colonisation resistance of yeast and bacteria in preventing the establishment of a Leishmania population in sand flies and the ability of Leishmania to provide colonisation resistance towards the insect bacterial pathogen Serratia marcescens that is also pathogenic towards Leishmania. METHODS: We isolated microorganisms from wild-caught and laboratory-reared female Lutzomyia longipalpis, identified as Pseudozyma sp. Asaia sp. and Ochrobactrum intermedium. We fed the females with a sugar meal containing the microorganisms and then subsequently fed them with a bloodmeal containing Leishmania mexicana and recorded the development of the Leishmania population. Further experiments examined the effect of first colonising the sand fly gut with L. mexicana followed by feeding with, Serratia marcescens, an insect bacterial pathogen. The mortality of the flies due to S. marcescens was recorded in the presence and absence of Leishmania. RESULTS: There was a reduction in the number of flies harbouring a Leishmania population that had been pre-fed with Pseudozyma sp. and Asaia sp. or O. intermedium. Experiments in which L. mexicana colonised the sand fly gut prior to being fed an insect bacterial pathogen, Serratia marcescens, showed that the survival of flies with a Leishmania infection was significantly higher compared to flies without Leishmania infection. CONCLUSIONS: The yeast and bacterial colonisation experiments show that the presence of sand fly gut microorganisms reduce the potential for Leishmania to establish within the sand fly vector. Sand flies infected with Leishmania were able to survive an attack by the bacterial pathogen that would have killed the insect and we concluded that Leishmania may benefit its insect host whilst increasing the potential to establish itself in the sand fly vector. We suggest that the increased ability of the sand fly to withstand a bacterial entomopathogen, due to the presence of the Leishmania, may provide an evolutionary pressure for the maintenance of the Leishmania-vector association

A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

The nonlinear Schroedinger equation for the delta-comb potential: quasi-classical chaos and bifurcations of periodic stationary solutions

The nonlinear Schroedinger equation is studied for a periodic sequence of delta-potentials (a delta-comb) or narrow Gaussian potentials. For the delta-comb the time-independent nonlinear Schroedinger equation can be solved analytically in terms of Jacobi elliptic functions and thus provides useful insight into the features of nonlinear stationary states of periodic potentials. Phenomena well-known from classical chaos are found, such as a bifurcation of periodic stationary states and a transition to spatial chaos. The relation of new features of nonlinear Bloch bands, such as looped and period doubled bands, are analyzed in detail. An analytic expression for the critical nonlinearity for the emergence of looped bands is derived. The results for the delta-comb are generalized to a more realistic potential consisting of a periodic sequence of narrow Gaussian peaks and the dynamical stability of periodic solutions in a Gaussian comb is discussed.Comment: Enhanced and revised version, to appear in J. Nonlin. Math. Phy

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial

BACKGROUND: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia. METHODS: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres). Patients were aged 25-65 years with de-novo BCR-ABL1-negative acute lymphoblastic leukaemia. Patients with de-novo BCR-ABL1-positive acute lymphoblastic leukaemia were eligible if they were aged 19-65 years. Participants were randomly assigned (1:1) to standard-of-care induction therapy or standard-of-care induction therapy plus four doses of intravenous rituximab (375 mg/m2 on days 3, 10, 17, and 24). Randomisation used minimisation and was stratified by sex, age, and white blood cell count. No masking was used for patients, clinicians, or staff (including the trial statistician), although the central laboratory analysing minimal residual disease and CD20 was masked to treatment allocation. The primary endpoint was event-free survival in the intention-to-treat population. Safety was assessed in all participants who started trial treatment. This study is registered with ClincialTrials.gov, NCT01085617. FINDINGS: Between April 19, 2012, and July 10, 2017, 586 patients were randomly assigned to standard of care (n=292) or standard of care plus rituximab (n=294). Nine patients were excluded from the final analysis due to misdiagnosis (standard of care n=4, standard of care plus rituximab n=5). In the standard-of-care group, median age was 45 years (IQR 22-65), 159 (55%) of 292 participants were male, 128 (44%) were female, one (<1%) was intersex, and 143 (59%) of 244 participants had high-risk cytogenetics. In the standard-of-care plus rituximab group, median age was 46 years (IQR 23-65), 159 (55%) of 294 participants were male, 130 (45%) were female, and 140 (60%) of 235 participants had high-risk cytogenetics. After a median follow-up of 53·7 months (IQR 40·3-70·4), 3-year event-free survival was 43·7% (95% CI 37·8-49·5) for standard of care versus 51·4% (45·4-57·1) for standard of care plus rituximab (hazard ratio [HR] 0·85 [95% CI 0·69-1·06]; p=0·14). The most common adverse events were infections and cytopenias, with no difference between the groups in the rates of adverse events. There were 11 (4%) fatal (grade 5) events in induction phases 1 and 2 in the standard-of-care group and 13 (5%) events in the standard-of-care plus rituximab group). 3-year non-relapse mortality was 23·7% (95% CI 19·0-29·4) in the standard-of-care group versus 20·6% (16·2-25·9) in the standard-of-care plus rituximab group (HR 0·88 [95% CI 0·62-1·26]; p=0·49). INTERPRETATION: Standard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient. FUNDING: Cancer Research UK and Blood Cancer UK

Vegetation of Europe: hierarchical floristic classification system of vascular plant, bryophyte, lichen, and algal communities

Vegetation classification consistent with the Braun-Blanquet approach is widely used in Europe for applied vegetation science, conservation planning and land management. During the long history of syntaxonomy, many concepts and names of vegetation units have been proposed, but there has been no single classification system integrating these units. Here we (1) present a comprehensive, hierarchical, syntaxonomic system of alliances, orders and classes of Braun-Blanquet syntaxonomy for vascular plant, bryophyte and lichen, and algal communities of Europe; (2) briefly characterize in ecological and geographic terms accepted syntaxonomic concepts; (3) link available synonyms to these accepted concepts; and (4) provide a list of diagnostic species for all classes. Location: European mainland, Greenland, Arctic archipelagos (including Iceland, Svalbard, Novaya Zemlya), Canary Islands, Madeira, Azores, Caucasus, Cyprus. Methods: We evaluated approximately 10 000 bibliographic sources to create a comprehensive list of previously proposed syntaxonomic units. These units were evaluated by experts for their floristic and ecological distinctness, clarity of geographic distribution and compliance with the nomenclature code. Accepted units were compiled into three systems of classes, orders and alliances (EuroVegChecklist, EVC) for communities dominated by vascular plants (EVC1), bryophytes and lichens (EVC2) and algae (EVC3). Results: EVC1 includes 109 classes, 300 orders and 1108 alliances; EVC2 includes 27 classes, 53 orders and 137 alliances, and EVC3 includes 13 classes, 24 orders and 53 alliances. In total 13 448 taxa were assigned as indicator species to classes of EVC1, 2087 to classes of EVC2 and 368 to classes of EVC3. Accepted syntaxonomic concepts are summarized in a series of appendices, and detailed information on each is accessible through the software tool EuroVegBrowser. Conclusions: This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists. It aims to document and stabilize the concepts and nomenclature of syntaxa for practical uses, such as calibration of habitat classification used by the European Union, standardization of terminology for environmental assessment, management and conservation of nature areas, landscape planning and education. The presented classification systems provide a baseline for future development and revision of European syntaxonomy.info:eu-repo/semantics/publishedVersio

After the epidemic: Zika virus projections for Latin America and the Caribbean

Background: Zika is one of the most challenging emergent vector-borne diseases, yet its future public health impact remains unclear. Zika was of little public health concern until recent reports of its association with congenital syndromes. By 3 August 2017 ~217,000 Zika cases and ~3,400 cases of associated congenital syndrome were reported in Latin America and the Caribbean. Some modelling exercises suggest that Zika virus infection could become endemic in agreement with recent declarations from the The World Health Organisation. Methodology/Principal findings: We produced high-resolution spatially-explicit projections of Zika cases, associated congenital syndromes and monetary costs for Latin America and the Caribbean now that the epidemic phase of the disease appears to be over. In contrast to previous studies which have adopted a modelling approach to map Zika potential, we project case numbers using a statistical approach based upon reported dengue case data as a Zika surrogate. Our results indicate that ~12.3 (0.7–162.3) million Zika cases could be expected across Latin America and the Caribbean every year, leading to ~64.4 (0.2–5159.3) thousand cases of Guillain-Barré syndrome and ~4.7 (0.0–116.3) thousand cases of microcephaly. The economic burden of these neurological sequelae are estimated to be USD ~2.3 (USD 0–159.3) billion per annum. Conclusions/Significance: Zika is likely to have significant public health consequences across Latin America and the Caribbean in years to come. Our projections inform regional and federal health authorities, offering an opportunity to adapt to this public health challenge

Obstetric Outcomes in Women with Rheumatic Disease and COVID-19 in the Context of Vaccination Status

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi -square or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2%(n = 2). CONCLUSION: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy