Vector composition, abundance, biting patterns and malaria transmission intensity in Madang, Papua New Guinea: assessment after 7 years of an LLIN-based malaria control programme

Background: A malaria control programme based on distribution of long-lasting insecticidal bed nets (LLINs) and artemisinin combination therapy began in Papua New Guinea in 2009. After implementation of the programme, substantial reductions in vector abundance and malaria transmission intensity occurred. The research reported here investigated whether these reductions remained after seven years of sustained effort. Methods: All-night (18:00 to 06:00) mosquito collections were conducted using human landing catches and barrier screen methods in four villages of Madang Province between September 2016 and March 2017. Anopheles species identification and sporozoite infection with Plasmodium vivax and Plasmodium falciparum were determined with molecular methods. Vector composition was expressed as the relative proportion of different species in villages, and vector abundance was quantified as the number of mosquitoes per barrier screen-night and per person-night. Transmission intensity was quantified as the number of sporozoite-infective vector bites per person-night. Results: Five Anopheles species were present, but vector composition varied greatly among villages. Anopheles koliensis, a strongly anthropophilic species was the most prevalent in Bulal, Matukar and Wasab villages, constituting 63.7–73.8% of all Anopheles, but in Megiar Anopheles farauti was the most prevalent species (97.6%). Vector abundance varied among villages (ranging from 2.8 to 72.3 Anopheles per screen-night and 2.2–31.1 Anopheles per person-night), and spatially within villages. Malaria transmission intensity varied among the villages, with values ranging from 0.03 to 0.5 infective Anopheles bites per person-night. Most (54.1–75.1%) of the Anopheles bites occurred outdoors, with a substantial proportion (25.5–50.8%) occurring before 22:00. Conclusion: The estimates of vector abundance and transmission intensity in the current study were comparable to or higher than estimates in the same villages in 2010–2012, indicating impeded programme effectiveness. Outdoor and early biting behaviours of vectors are some of the likely explanatory factors. Heterogeneity in vector composition, abundance and distribution among and within villages challenge malaria control programmes and must be considered when planning them

Mosquito behavior change after distribution of bednets results in decreased protection against malaria exposure

Behavioral resilience in mosquitoes poses a significant challenge to mosquito control. Although behavior changes in anopheline vectors have been reported over the last decade, there are no empirical data to suggest they compromise the efficacy of vector control in reducing malaria transmission.; In this study, we quantified human exposure to both bites and infective bites of a major malaria vector in Papua New Guinea over the course of 4 years surrounding nationwide bednet distribution. We also quantified malaria infection prevalence in the human population during the same time period.; We observed a shift in mosquito biting to earlier hours of the evening, before individuals are indoors and protected by bednets, followed by a return to preintervention biting rates. As a result, net users and non-net users experienced higher levels of transmission than before the intervention. The personal protection provided by a bednet decreased over the study period and was lowest in the adult population, who may be an important reservoir for transmission. Malaria prevalence decreased in only 1 of 3 study villages after the distribution.; This study highlights the necessity of validating and deploying vector control measures targeting outdoor exposure to control and eliminate malaria

Insecticide Resistance in Areas Under Investigation by the International Centers of Excellence for Malaria Research: A Challenge for Malaria Control and Elimination

Scale-up of the main vector control interventions, residual insecticides sprayed on walls or structures and/or impregnated in bed nets, together with prompt diagnosis and effective treatment, have led to a global reduction in malaria transmission. However, resistance in vectors to almost all classes of insecticides, particularly to the synthetic pyrethroids, is posing a challenge to the recent trend of declining malaria. Ten International Centers of Excellence for Malaria Research (ICEMR) located in the most malaria-endemic regions of the world are currently addressing insecticide resistance in the main vector populations, which not only threaten hope for elimination in malaria-endemic countries but also may lead to reversal where notable reductions in malaria have been documented. This communication illustrates the current status of insecticide resistance with a focus on the countries where activities are ongoing for 9 out of the 10 ICEMRs. Most of the primary malaria vectors in the ICEMR countries exhibit insecticide resistance, albeit of varying magnitude, and spanning all mechanisms of resistance. New alternatives to the insecticides currently available are still to be fully developed for deployment. Integrated vector management principles need to be better understood and encouraged, and viable insecticide resistance management strategies need to be developed and implemented

Investigating differences in village-level heterogeneity of malaria infection and household risk factors in Papua New Guinea

Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control

Limits to Rest-Frame Ultraviolet Emission From Far-Infrared-Luminous z~6 Quasar Hosts

We report on a Hubble Space Telescope search for rest-frame ultraviolet emission from the host galaxies of five far-infrared-luminous $z\simeq{}6$ quasars and the $z=5.85$ hot-dust free quasar SDSS J0005-0006. We perform 2D surface brightness modeling for each quasar using a Markov-Chain Monte-Carlo estimator, to simultaneously fit and subtract the quasar point source in order to constrain the underlying host galaxy emission. We measure upper limits for the quasar host galaxies of $m_J>22.7$ mag and $m_H>22.4$ mag, corresponding to stellar masses of $M_\ast<2\times10^{11}M_\odot$. These stellar mass limits are consistent with the local $M_{\textrm{BH}}$-$M_\ast$ relation. Our flux limits are consistent with those predicted for the UV stellar populations of $z\simeq6$ host galaxies, but likely in the presence of significant dust ($\langle A_{\mathrm{UV}}\rangle\simeq 2.6$ mag). We also detect a total of up to 9 potential $z\simeq6$ quasar companion galaxies surrounding five of the six quasars, separated from the quasars by 1.4''-3.2'', or 8.4-19.4 kpc, which may be interacting with the quasar hosts. These nearby companion galaxies have UV absolute magnitudes of -22.1 to -19.9 mag, and UV spectral slopes $\beta$ of -2.0 to -0.2, consistent with luminous star-forming galaxies at $z\simeq6$. These results suggest that the quasars are in dense environments typical of luminous $z\simeq6$ galaxies. However, we cannot rule out the possibility that some of these companions are foreground interlopers. Infrared observations with the James Webb Space Telescope will be needed to detect the $z\simeq6$ quasar host galaxies and better constrain their stellar mass and dust content.Comment: 22 pages, 13 figures. Accepted for publication in Ap

Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome

<p>Abstract</p> <p>Background</p> <p><it>Clostridium difficile</it>-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting.</p> <p>Methods</p> <p>We performed a historical cohort study on 58 adults with a positive <it>C. difficile </it>cytotoxin assay result occurring in intensive care units.</p> <p>Results</p> <p>Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score ≥3, gender, concurrent infection, and number of days with diarrhea before a positive <it>C. difficile </it>toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13–1.75) and age (per 1-year increment, OR 1.10; CI95 1.02–1.19).</p> <p>Conclusion</p> <p>In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.</p

Crystalline silicates and dust processing in the protoplanetary disks of the Taurus young cluster

We characterize the crystalline silicate content and spatial distribution of small dust grains in a large sample of protoplanetary disks in the Taurus-Auriga young cluster, using Spitzer Space Telescope mid-infrared spectra. In turn we use the results to analyze the evolution of structure and composition of these 1-2 Myr-old disks around Solar- and later-type young stars, and test the standard models of dust processing which result in the conversion of originally amorphous dust into minerals. We find strong evidence of evolution of the dust crystalline mass fraction in parallel with that of the structure of the disks, in the sense that increasing crystalline mass fraction is strongly linked to dust settling to the disk midplane. We also confirm that the crystalline silicates are confined to small radii, r < 10 AU. However, we see no significant correlation of crystalline mass fraction with stellar mass or luminosity, stellar accretion rate, disk mass, or disk/star mass ratio, as would be expected in the standard models of dust processing based upon photo-evaporation and condensation close to the central star, accretion-heating-driven annealing at r < 1 AU, or spiral-shock heating at r < 10 AU, with or without effective radial mixing mechanisms. Either another grain-crystallizing mechanism dominates over these, or another process must be at work within the disks to erase the correlations they produce. We propose one of each sort that seem to be worth further investigation, namely X-ray heating and annealing of dust grains, and modulation of disk structure by giant-planetary formation and migration.Comment: 116 pages, including 11 figures and 4 table

Renal amyloidosis in children

Renal amyloidosis is a detrimental disease caused by the deposition of amyloid fibrils. A child with renal amyloidosis may present with proteinuria or nephrotic syndrome. Chronic renal failure may follow. Amyloid fibrils may deposit in other organs as well. The diagnosis is through the typical appearance on histopathology. Although chronic infections and chronic inflammatory diseases used to be the causes of secondary amyloidosis in children, the most frequent cause is now autoinflammatory diseases. Among this group of diseases, the most frequent one throughout the world is familial Mediterranean fever (FMF). FMF is typically characterized by attacks of clinical inflammation in the form of fever and serositis and high acute-phase reactants. Persisting inflammation in inadequately treated disease is associated with the development of secondary amyloidosis. The main treatment is colchicine. A number of other monogenic autoinflammatory diseases have also been identified. Among them cryopyrin-associated periodic syndrome (CAPS) is outstanding with its clinical features and the predilection to develop secondary amyloidosis in untreated cases. The treatment of secondary amyloidosis mainly depends on the treatment of the disease. However, a number of new treatments for amyloid per se are in the pipeline

Mediator Acts Upstream of the Transcriptional Activator Gal4

We show that Mediator, a protein originally isolated on the basis of its ability to respond to transcriptional activators, and thought to be regulated by an activator, can also be the master that controls the activator