Cholera Vaccination Campaign Contributes to Improved Knowledge Regarding Cholera and Improved Practice Relevant to Waterborne Disease in Rural Haiti

Background: Haiti's cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti. Methodology/Principal Findings We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May–June 2012 after which we administered identical surveys to 518 households randomly chosen from the same region in September 2012. We compared responses pre- and post-OCV campaign. Post-vaccination, there was improved knowledge with significant increase in percentage of respondents with ≥3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95% confidence interval[CI] 1.52–2.40), preventive methods (OR 1.83; 95% CI 1.46–2.30), and water treatment modalities (OR 2.75; 95% CI 2.16–3.50). Relative to pre-vaccination, participants were more likely post-OCV to report always treating water (OR 1.62; 95% CI 1.28–2.05). Respondents were also more likely to report hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI 1.03–1.64). Knowledge of treating water as a cholera prevention measure was associated with practice of always treating water (OR 1.47; 95% CI 1.14–1.89). Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47; 95% CI 1.35–4.51). Conclusion: An OCV campaign in rural Haiti was associated with significant improvement in cholera knowledge and practices related to waterborne disease. OCV can be part of comprehensive cholera control and reinforce, not detract from, other control efforts in Haiti

The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete morphogenesis and malaria transmission

Copyright © 2015, The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host cells by Plasmodium falciparum merozoites and Toxoplasma gondii tachyzoites. Using inhibitor studies we show here that palmitoylation is key to transformation of zygotes into ookinetes during initial mosquito infection with P. berghei. We identify DHHC2 as a unique PAT mediating ookinete formation and morphogenesis. Essential for life cycle progression in asexual blood stage parasites and thus refractory to gene deletion analyses, we used promoter swap (ps) methodology to maintain dhhc2 expression in asexual blood stages but down regulate expression in sexual stage parasites and during post-fertilization development of the zygote. The ps mutant showed normal gamete formation, fertilisation and DNA replication to tetraploid cells, but was characterised by a complete block in post-fertilisation development and ookinete formation. Our report highlights the crucial nature of the DHHC2 palmitoyl-S-acyltransferase for transmission of the malaria parasite to the mosquito vector through its essential role for ookinete morphogenesis.FF was supported by European Research Council (ERC-SG 281719) and the EU FP7 research network EVIMalar; JMS by a PhD fellowship grant SFRH/BD/63849/2009 from Fundação para a Ciência e a Tecnologia (FCT) and GRM by FCT grants PTDC/SAU-MIC/122082/2010 and PTDC/BIA-BCM/105610/2008.info:eu-repo/semantics/publishedVersio

Continuous injection synthesis of indium arsenide quantum dots emissive in the short-wavelength infrared

With the emergence of applications based on short-wavelength infrared light, indium arsenide quantum dots are promising candidates to address existing shortcomings of other infrared-emissive nanomaterials. However, III–V quantum dots have historically struggled to match the high-quality optical properties of II–VI quantum dots. Here we present an extensive investigation of the kinetics that govern indium arsenide nanocrystal growth. Based on these insights, we design a synthesis of large indium arsenide quantum dots with narrow emission linewidths. We further synthesize indium arsenide-based core-shell-shell nanocrystals with quantum yields up to 82% and improved photo- and long-term storage stability. We then demonstrate non-invasive through-skull fluorescence imaging of the brain vasculature of murine models, and show that our probes exhibit 2–3 orders of magnitude higher quantum yields than commonly employed infrared emitters across the entire infrared camera sensitivity range. We anticipate that these probes will not only enable new biomedical imaging applications, but also improved infrared nanocrystal-LEDs and photon-upconversion technology.National Science Foundation (U.S.) (EECS-1449291)National Institutes of Health (U.S.) (Massachusetts Institute of Technology. Laser Biomedical Research Center. 9-P41-EB015871-26A1)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (W911NF-13-D-0001)Boehringer Ingelheim FondsEuropean Molecular Biology Organization (Long-term Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramAmerican Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipUnited States. Dept. of Energy. Center for Excitonics (DE- SC0001088)

Eff ectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis

Background Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the eff ectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Methods Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1–4 years, 5–15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. Findings From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine eff ectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine eff ectiveness 63%, 95% CI 8–85). 27 (57%) of 47 cases had certifi ed vaccination versus 147 (78%) of 188 controls (vaccine eff ectiveness 58%, 13–80). Neither self-reported nor verifi ed vaccination was signifi cantly associated with non-cholera diarrhoea (vaccine eff ectiveness 18%, 95% CI –208 to 78 by self-report and –21%, –238 to 57 by verifi ed vaccination). Interpretation Bivalent whole-cell oral cholera vaccine eff ectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of eff orts to control cholera epidemics

Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 to 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a ADHD/typically developing difference with subthreshold cases being intermediate between ADHD and typically developing controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to individuals with ADHD, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity

Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite.

Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid-a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogony-is dependent on the precisely timed expression of the S-acyl-transferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission

Regulatory architecture of the RCA gene cluster captures an intragenic TAD boundary, CTCF-Mediated chromatin looping and a long-range intergenic enhancer

The Regulators of Complement Activation (RCA) gene cluster comprises several tandemly arranged genes with shared functions within the immune system. RCA members, such as complement receptor 2 (CR2), are well-established susceptibility genes in complex autoimmune diseases. Altered expression of RCA genes has been demonstrated at both the functional and genetic level, but the mechanisms underlying their regulation are not fully characterised. We aimed to investigate the structural organisation of the RCA gene cluster to identify key regulatory elements that influence the expression of CR2 and other genes in this immunomodulatory region. Using 4C, we captured extensive CTCF-mediated chromatin looping across the RCA gene cluster in B cells and showed these were organised into two topologically associated domains (TADs). Interestingly, an inter-TAD boundary was located within the CR1 gene at a well-characterised segmental duplication. Additionally, we mapped numerous gene-gene and gene-enhancer interactions across the region, revealing extensive co-regulation. Importantly, we identified an intergenic enhancer and functionally demonstrated this element upregulates two RCA members (CR2 and CD55) in B cells. We have uncovered novel, long-range mechanisms whereby autoimmune disease susceptibility may be influenced by genetic variants, thus highlighting the important contribution of chromatin topology to gene regulation and complex genetic disease.This work was supported by the National Institutes of Health [R01 AI24717 to JH], the Australian Government Research Training Program Scholarship at the University of Western Australia [to JC and JSC], the Spanish Government [BFU2016-74961-P to JG-S] and an institutional grant Unidad de Excelencia María de Maeztu [MDM-206-0687 to the Department of Gene Regulation and Morphogenesis, Centro Andaluz de Biología del Desarrol]

Discrepancies of polygenic effects on symptom dimensions between adolescents and adults with ADHD

A significant proportion of individuals with attention-deficit/hyperactivity disorder (ADHD) show persistence into adulthood. The genetic and neural correlates of ADHD in adolescents versus adults remain poorly characterized. We investigated ADHD polygenic risk score (PRS) in relation to previously identified gray matter (GM) patterns, neurocognitive, and symptom findings in the same ADHD sample (462 adolescents & 422 adults from the NeuroIMAGE and IMpACT cohorts). Significant effects of ADHD PRS were found on hyperactivity and impulsivity symptoms in adolescents, hyperactivity symptom in adults, but not GM volume components. A distinct PRS effect between adolescents and adults on individual ADHD symptoms is suggested

Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti

Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. Methodology/Principal Findings We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6–17 years), and 47 younger children (1–5 years) in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae

Plant and animal endemism in the eastern Andean slope: challenges to conservation

Andean slope: challenges to conservatio