Host-Specific Evolutionary and Transmission Dynamics Shape the Functional Diversification of Staphylococcus epidermidis in Human Skin.

Metagenomic inferences of bacterial strain diversity and infectious disease transmission studies largely assume a dominant, within-individual haplotype. We hypothesize that within-individual bacterial population diversity is critical for homeostasis of a healthy microbiome and infection risk. We characterized the evolutionary trajectory and functional distribution of Staphylococcus epidermidis-a keystone skin microbe and opportunistic pathogen. Analyzing 1,482 S. epidermidis genomes from 5 healthy individuals, we found that skin S. epidermidis isolates coalesce into multiple founder lineages rather than a single colonizer. Transmission events, natural selection, and pervasive horizontal gene transfer result in population admixture within skin sites and dissemination of antibiotic resistance genes within-individual. We provide experimental evidence for how admixture can modulate virulence and metabolism. Leveraging data on the contextual microbiome, we assess how interspecies interactions can shape genetic diversity and mobile gene elements. Our study provides insights into how within-individual evolution of human skin microbes shapes their functional diversification.

"Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina.

BACKGROUND: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.).

A type IVB pilin influences twitching motility and in vitro adhesion to epithelial cells in Burkholderia pseudomallei.

Type IV pili are involved in adhesion, twitching motility, aggregation, biofilm formation and virulence in a variety of Gram-negative bacteria. Burkholderia pseudomallei, the causative agent of melioidosis and a Tier 1 biological select agent, is a Gram-negative bacterium with eight type IV pili-associated loci (TFP1 to TFP8). Most have not been fully characterized. In this study, we investigated BPSS2185, an uncharacterized TFP8 gene that encodes a type IVB pilus protein subunit. Using genetic deletion and complementation analysis in B. pseudomallei JW270, we demonstrate that BPSS2185 plays an important role in twitching motility and adhesion to A549 human alveolar epithelial cells. Compared to JW270, the JW270 ΔBPSS2185 mutant failed to display twitching motility and did not adhere to the epithelial cells. These phenotypes were partially reversed by the complementation of BPSS2185 in the mutant strain. The study also shows that BPSS2185 is expressed only during the onset of mature biofilm formation and at the dispersal of a biofilm, suggesting that the motility characteristic is required to form a biofilm. Our study is the first to suggest that the BPSS2185 gene in TFP8 contributes to twitching motility, adhesion and biofilm formation, indicating that the gene may contribute to B. pseudomallei virulence.

Toll-like receptor 7 and 8 imidazoquinoline-based agonist/antagonist pairs.

Toll-like receptors (TLRs) 7 and 8 are key targets in the development of immunomodulatory drugs for treating infectious disease, cancer, and autoimmune disorders. These receptors can adopt both agonist and antagonist binding conformations that switch the receptor signal on or off to the downstream production of cytokines. In this study, we examined the effect of simple isomeric substitutions to the C2-butyl group of two imidazoquinoline agonists and evaluated the activity of these analogs using both TLR7 and TLR8 reporter cells and cytokine induction assays. Results are presented showing the C2-isobutyl and C2-cyclopropylmethyl isomers are both mixed TLR7/8 competitive antagonists of the parent agonist [4-Amino-1-(4-(aminomethyl)benzyl)-2-butyl-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline], indicating the conformation of the dimeric receptor complex is highly sensitive to steric perturbations to the ligand binding pocket. This observation is consistent with prior work demonstrating TLR7 and TLR8 activity is directly correlated to C2-alkyl substitutions that project into a hydrophobic pocket at the dimer interface of the receptor. The close structural relationship of the agonist/antagonist pairs identified here highlights the importance of this pocket in tipping the balance between the agonist and antagonist binding states of the receptor which may have significant ramifications to the design of imidazoquinoline-based immunomodulatory agents.

Ambient air pollution and non-communicable respiratory illness in sub-Saharan Africa: a systematic review of the literature.

INTRODUCTION: Aerosol pollutants are known to raise the risk of development of non-communicable respiratory diseases (NCRDs) such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, and allergic rhinitis. Sub-Saharan Africa's rapid pace of urbanization, economic expansion, and population growth raise concerns of increasing incidence of NCRDs. This research characterizes the state of research on pollution and NCRDs in the 46 countries of Sub-Saharan Africa (SSA). This research systematically reviewed the literature on studies of asthma; chronic bronchitis; allergic rhinitis; and air pollutants such as particulate matter, ozone, NOx, and sulfuric oxide. METHODS: We searched three major databases (PubMed, Web of Science, and Scopus) using the key words "asthma", "chronic bronchitis", "allergic rhinitis", and "COPD" with "carbon monoxide (CO)", "sulfuric oxide (SO)", "ozone (O3)", "nitrogen dioxide (NO2)", and "particulate matter (PM)", restricting the search to the 46 countries that comprise SSA. Only papers published in scholarly journals with a defined health outcome in individuals and which tested associations with explicitly measured or modelled air exposures were considered for inclusion. All candidate papers were entered into a database for review. RESULTS: We found a total of 362 unique research papers in the initial search of the three databases. Among these, 14 met the inclusion criteria. These papers comprised studies from just five countries. Nine papers were from South Africa; two from Malawi; and one each from Ghana, Namibia, and Nigeria. Most studies were cross-sectional. Exposures to ambient air pollutants were measured using spectrometry and chromatography. Some studies created composite measures of air pollution using a range of data layers. NCRD outcomes were measured by self-reported health status and measures of lung function (spirometry). Populations of interest were primarily schoolchildren, though a few studies focused on secondary school students and adults. CONCLUSIONS: The paucity of research on NCRDs and ambient air pollutant exposures is pronounced within the African continent. While capacity to measure air quality in SSA is high, studies targeting NCRDs should work to draw attention to questions of outdoor air pollution and health. As the climate changes and SSA economies expand and countries urbanize, these questions will become increasingly important.

Indoor apparent temperature, cognition, and daytime sleepiness among low-income adults in a temperate climate.

The burden of temperature-associated mortality and hospital visits is significant, but temperature's effects on non-emergency health outcomes is less clear. This burden is potentially greater in low-income households unable to afford efficient heating and cooling. We examined short-term associations between indoor temperatures and cognitive function and daytime sleepiness in low-income residents of Detroit, Michigan. Apparent temperature (AT, based on temperature and humidity) was recorded hourly in 34 participant homes between July 2019-March 2020. Between July-October 2019, 18 participants were administered word list immediate (WLL) and delayed (WLD) recall tests (10-point scales) and the Epworth Sleepiness Scale (24-point scale) 2-4 times. We applied longitudinal models with nonlinear distributed lags of temperature up to 7 days prior to testing. Indoor temperatures ranged 8-34°C overall and 15-34°C on survey days. We observed a 0.4 (95% CI: 0.0, 0.7) point increase in WLL and 0.4 (95% CI: 0.0, 0.9) point increase in WLD scores per 2°C increase in AT. Results suggested decreasing sleepiness scores with decreasing nighttime AT below 22°C. Low-income Detroit residents experience uncomfortably high and low indoor temperatures. Indoor temperature may influence cognitive function and sleepiness, although we did not observe deleterious effects of higher temperatures.

A seismically induced onshore surge deposit at the KPg boundary, North Dakota.

The most immediate effects of the terminal-Cretaceous Chicxulub impact, essential to understanding the global-scale environmental and biotic collapses that mark the Cretaceous-Paleogene extinction, are poorly resolved despite extensive previous work. Here, we help to resolve this by describing a rapidly emplaced, high-energy onshore surge deposit from the terrestrial Hell Creek Formation in Montana. Associated ejecta and a cap of iridium-rich impactite reveal that its emplacement coincided with the Chicxulub event. Acipenseriform fish, densely packed in the deposit, contain ejecta spherules in their gills and were buried by an inland-directed surge that inundated a deeply incised river channel before accretion of the fine-grained impactite. Although this deposit displays all of the physical characteristics of a tsunami runup, the timing (<1 hour postimpact) is instead consistent with the arrival of strong seismic waves from the magnitude Mw ∼10 to 11 earthquake generated by the Chicxulub impact, identifying a seismically coupled seiche inundation as the likely cause. Our findings present high-resolution chronology of the immediate aftereffects of the Chicxulub impact event in the Western Interior, and report an impact-triggered onshore mix of marine and terrestrial sedimentation-potentially a significant advancement for eventually resolving both the complex dynamics of debris ejection and the full nature and extent of biotic disruptions that took place in the first moments postimpact.

Hagfish from the Cretaceous Tethys Sea and a reconciliation of the morphological-molecular conflict in early vertebrate phylogeny.

Hagfish depart so much from other fishes anatomically that they were sometimes considered not fully vertebrate. They may represent: (i) an anatomically primitive outgroup of vertebrates (the morphology-based craniate hypothesis); or (ii) an anatomically degenerate vertebrate lineage sister to lampreys (the molecular-based cyclostome hypothesis). This systematic conundrum has become a prominent case of conflict between morphology- and molecular-based phylogenies. To date, the fossil record has offered few insights to this long-branch problem or the evolutionary history of hagfish in general, because unequivocal fossil members of the group are unknown. Here, we report an unequivocal fossil hagfish from the early Late Cretaceous of Lebanon. The soft tissue anatomy includes key attributes of living hagfish: cartilages of barbels, postcranial position of branchial apparatus, and chemical traces of slime glands. This indicates that the suite of characters unique to living hagfish appeared well before Cretaceous times. This new hagfish prompted a reevaluation of morphological characters for interrelationships among jawless vertebrates. By addressing nonindependence of characters, our phylogenetic analyses recovered hagfish and lampreys in a clade of cyclostomes (congruent with the cyclostome hypothesis) using only morphological data. This new phylogeny places the fossil taxon within the hagfish crown group, and resolved other putative fossil cyclostomes to the stem of either hagfish or lamprey crown groups. These results potentially resolve the morphological-molecular conflict at the base of the Vertebrata. Thus, assessment of character nonindependence may help reconcile morphological and molecular inferences for other major discords in animal phylogeny.

Spliced integrated retrotransposed element (SpIRE) formation in the human genome.

Human Long interspersed element-1 (L1) retrotransposons contain an internal RNA polymerase II promoter within their 5' untranslated region (UTR) and encode two proteins, (ORF1p and ORF2p) required for their mobilization (i.e., retrotransposition). The evolutionary success of L1 relies on the continuous retrotransposition of full-length L1 mRNAs. Previous studies identified functional splice donor (SD), splice acceptor (SA), and polyadenylation sequences in L1 mRNA and provided evidence that a small number of spliced L1 mRNAs retrotransposed in the human genome. Here, we demonstrate that the retrotransposition of intra-5'UTR or 5'UTR/ORF1 spliced L1 mRNAs leads to the generation of spliced integrated retrotransposed elements (SpIREs). We identified a new intra-5'UTR SpIRE that is ten times more abundant than previously identified SpIREs. Functional analyses demonstrated that both intra-5'UTR and 5'UTR/ORF1 SpIREs lack Cis-acting transcription factor binding sites and exhibit reduced promoter activity. The 5'UTR/ORF1 SpIREs also produce nonfunctional ORF1p variants. Finally, we demonstrate that sequence changes within the L1 5'UTR over evolutionary time, which permitted L1 to evade the repressive effects of a host protein, can lead to the generation of new L1 splicing events, which, upon retrotransposition, generates a new SpIRE subfamily. We conclude that splicing inhibits L1 retrotransposition, SpIREs generally represent evolutionary "dead-ends" in the L1 retrotransposition process, mutations within the L1 5'UTR alter L1 splicing dynamics, and that retrotransposition of the resultant spliced transcripts can generate interindividual genomic variation.

An urban-to-rural continuum of malaria risk: new analytic approaches characterize patterns in Malawi.

BACKGROUND: The urban-rural designation has been an important risk factor in infectious disease epidemiology. Many studies rely on a politically determined dichotomization of rural versus urban spaces, which fails to capture the complex mosaic of infrastructural, social and environmental factors driving risk. Such evaluation is especially important for Plasmodium transmission and malaria disease. To improve targeting of anti-malarial interventions, a continuous composite measure of urbanicity using spatially-referenced data was developed to evaluate household-level malaria risk from a house-to-house survey of children in Malawi. METHODS: Children from 7564 households from eight districts throughout Malawi were tested for presence of Plasmodium parasites through finger-prick blood sampling and slide microscopy. A survey questionnaire was administered and latitude and longitude coordinates were recorded for each household. Distances from households to features associated with high and low levels of development (health facilities, roads, rivers, lakes) and population density were used to produce a principal component analysis (PCA)-based composite measure for all centroid locations of a fine geo-spatial grid covering Malawi. Regression methods were used to test associations of the urbanicity measure against Plasmodium infection status and to predict parasitaemia risk for all locations in Malawi. RESULTS: Infection probability declined with increasing urbanicity. The new urbanicity metric was more predictive than either a governmentally defined rural/urban dichotomous variable or a population density variable. One reason for this was that 23% of cells within politically defined rural areas exhibited lower risk, more like those normally associated with "urban" locations. CONCLUSIONS: In addition to increasing predictive power, the new continuous urbanicity metric provided a clearer mechanistic understanding than the dichotomous urban/rural designations. Such designations often ignore urban-like, low-risk pockets within traditionally rural areas, as were found in Malawi, along with rural-like, potentially high-risk environments within urban areas. This method of characterizing urbanicity can be applied to other infectious disease processes in rapidly urbanizing contexts.

Short-term exposures to atmospheric evergreen, deciduous, grass, and ragweed aeroallergens and the risk of suicide in Ohio, 2007-2015: Exploring disparities by age, gender, and education level.

BACKGROUND: Seasonal trends in suicide mortality are observed worldwide, potentially aligning with the seasonal release of aeroallergens. However, only a handful of studies have examined whether aeroallergens increase the risk of suicide, with inconclusive results thus far. The goal of this study was to use a time-stratified case-crossover design to test associations of speciated aeroallergens (evergreen, deciduous, grass, and ragweed) with suicide deaths in Ohio, USA (2007-2015). METHODS: Residential addresses for 12,646 persons who died by suicide were linked with environmental data at the 4-25 km grid scale including atmospheric aeroallergen concentrations, maximum temperature, sunlight, particulate matter <2.5 µm, and ozone. A case-crossover design was used to examine same-day and 7-day cumulative lag effects on suicide. Analyses were stratified by age group, gender, and educational level. RESULTS: In general, associations were null between aeroallergens and suicide. Stratified analyses revealed a relationship between grass pollen and same-day suicide for women (OR = 3.84; 95% CI = 1.44, 10.22) and those with a high school degree or less (OR = 2.03; 95% CI = 1.18, 3.49). CONCLUSIONS: While aeroallergens were generally not significantly related to suicide in this sample, these findings provide suggestive evidence for an acute relationship of grass pollen with suicide for women and those with lower education levels. Further research is warranted to determine whether susceptibility to speciated aeroallergens may be driven by underlying biological mechanisms or variation in exposure levels.

Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells.

LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells.

Antimalarial bednet protection of children disappears when shared by three or more people in a high transmission setting of western Kenya.

A sizeable proportion of households is forced to share single long-lasting insecticide treated net (LLIN). However, the relationship between increasing numbers of people sharing a net and the risk for Plasmodium infection is unclear. This study revealed whether risk for Plasmodium falciparum infection is associated with the number of people sharing a LLIN in a holoendemic area of Kenya. Children ⩽5 years of age were tested for P. falciparum infection using polymerase chain reaction. Of 558 children surveyed, 293 (52.5%) tested positive for parasitaemia. Four hundred and fifty-eight (82.1%) reported sleeping under a LLIN. Of those, the number of people sharing a net with the sampled child ranged from 1 to 5 (median = 2). Children using a net alone or with one other person were at lower risk than non-users (OR = 0.29, 95% CI 0.10-0.82 and OR = 0.47, 95% CI 0.22-0.97, respectively). On the other hand, there was no significant difference between non-users and children sharing a net with two (OR = 0.88, 95% CI 0.44-1.77) or more other persons (OR = 0.75, 95% CI 0.32-1.72). LLINs are effective in protecting against Plasmodium infection in children when used alone or with one other person compared with not using them. Public health professionals should inform caretakers of the risks of too many people sharing a net.

Tyrannosauroid integument reveals conflicting patterns of gigantism and feather evolution.

Recent evidence for feathers in theropods has led to speculations that the largest tyrannosaurids, including Tyrannosaurus rex, were extensively feathered. We describe fossil integument from Tyrannosaurus and other tyrannosaurids (Albertosaurus, Daspletosaurus, Gorgosaurus and Tarbosaurus), confirming that these large-bodied forms possessed scaly, reptilian-like skin. Body size evolution in tyrannosauroids reveals two independent occurrences of gigantism; specifically, the large sizes in Yutyrannus and tyrannosaurids were independently derived. These new findings demonstrate that extensive feather coverings observed in some early tyrannosauroids were lost by the Albian, basal to Tyrannosauridae. This loss is unrelated to palaeoclimate but possibly tied to the evolution of gigantism, although other mechanisms exist.

Physical evidence of predatory behavior in Tyrannosaurus rex.

Feeding strategies of the large theropod, Tyrannosaurus rex, either as a predator or a scavenger, have been a topic of debate previously compromised by lack of definitive physical evidence. Tooth drag and bone puncture marks have been documented on suggested prey items, but are often difficult to attribute to a specific theropod. Further, postmortem damage cannot be distinguished from intravital occurrences, unless evidence of healing is present. Here we report definitive evidence of predation by T. rex: a tooth crown embedded in a hadrosaurid caudal centrum, surrounded by healed bone growth. This indicates that the prey escaped and lived for some time after the injury, providing direct evidence of predatory behavior by T. rex. The two traumatically fused hadrosaur vertebrae partially enclosing a T. rex tooth were discovered in the Hell Creek Formation of South Dakota.

A prescription for sustaining community engagement in malaria elimination on Aneityum Island, Vanuatu: an application of Health Empowerment Theory.

BACKGROUND: Community engagement has contributed to disease control and elimination in many countries. Community engagement in malaria elimination (ME) on Aneityum Island has been sustained since its introduction in the early 1990s. Capacity developed within this population has led to a health empowered community response. Health Empowerment Theory (HET) can account for the innovative community actions and capacity development efforts taken to realize and sustain meaningful changes in well-being. This study used the HET framework to investigate participant perceptions of ME efforts on the island focusing on two HET elements, personal and social-contextual resources. The purpose of this study was to explore the role of empowerment as a critical element of community engagement. METHODS: Six focus group discussions, ten key informant interviews and 17 in-depth interviews were conducted in July 2012 on Aneityum. Both deductive and inductive approaches to qualitative content analysis were used to identify themes, which were condensed, coded and classified based on the HET elements above. RESULTS: Awareness and use of personal and social-contextual resources played an important role in ME efforts. Most participants shared their knowledge to prevent malaria reintroduction. Many participants reported their skills needed for behavioral maintenance, problem-solving or leadership. Participants who perceived a threat took preventive actions even in the dry season. Community leaders focused on second generation capacity development. A local health coalition provided ME services. Members of networks were sources of information and assistance. Face-to-face was the preferred method of communication. Barriers to engagement (e.g., financial difficulties, health literacy issues and underdeveloped infrastructure) were minimized through active collaboration and mutual assistance. CONCLUSIONS: In the community engagement continuum, health empowerment develops incrementally overtime as people gain their knowledge and skills, form coalitions and develop collaborative networks (social capital) to make decisions and take action for change. Community engagement, which facilitates local personal and social-contextual resource development, has potential for ME and multilevel empowerment through community-based capacity development processes. These self-empowered communities have written and will continue to write a 'prescription' for sustaining high levels of engagement.

Sleeping on the floor decreases insecticide treated bed net use and increases risk of malaria in children under 5 years of age in Mbita District, Kenya.

Children who sleep on the floor are less likely to use long-lasting insecticidal nets (LLINs); however, the relationship between sleeping location and Plasmodium falciparum infection has not been investigated sufficiently. This study revealed whether sleeping location (bed vs floor) is associated with P. falciparum infection among children 7-59 months old. More than 60% of children slept on the floor. Younger children were significantly more likely to sleep in beds [odds ratio, OR 2.31 (95% confidence interval (CI) 2.02-2.67)]. Nearly 70% of children slept under LLINs the previous night. LLIN use among children who slept on the floor was significantly less than ones sleeping in beds [OR 0.49 (95% CI 0.35-0.68)]. The polymerase chain reaction (PCR) based P. falciparum infection rate and slide based infection rate were 65.2 and 29.7%, respectively. Both infections were significantly higher among children slept on the floor [OR1.51 (95% CI 1.08-2.10) for PCR base, OR 1.62 (95% CI 1.14-2.30) for slide base] while net availability was not significant. Sleeping location was also significant for slide based infection with fever (⩾ 37.5 °C) [2.03 (95% CI 1.14-3.84)] and high parasitemia cases (parasite ⩾ 2500 µL(-1)) [2.07 (95% CI 1.03-4.50)]. The results suggest that sleeping location has a direct bearing on the effectiveness of LLINs.

Insecticide-treated net use before and after mass distribution in a fishing community along Lake Victoria, Kenya: successes and unavoidable pitfalls.

BACKGROUND: Insecticide-treated nets (ITNs) have proven instrumental in the successful reduction of malaria incidence in holoendemic regions during the past decade. As distribution of ITNs throughout sub-Saharan Africa (SSA) is being scaled up, maintaining maximal levels of coverage will be necessary to sustain current gains. The effectiveness of mass distribution of ITNs, requires careful analysis of successes and failures if impacts are to be sustained over the long term. METHODS: Mass distribution of ITNs to a rural Kenyan community along Lake Victoria was performed in early 2011. Surveyors collected data on ITN use both before and one year following this distribution. At both times, household representatives were asked to provide a complete accounting of ITNs within the dwelling, the location of each net, and the ages and genders of each person who slept under that net the previous night. Other data on household material possessions, education levels and occupations were recorded. Information on malaria preventative factors such as ceiling nets and indoor residual spraying was noted. Basic information on malaria knowledge and health-seeking behaviours was also collected. Patterns of ITN use before and one year following net distribution were compared using spatial and multi-variable statistical methods. Associations of ITN use with various individual, household, demographic and malaria related factors were tested using logistic regression. RESULTS: After infancy (<1 year), ITN use sharply declined until the late teenage years then began to rise again, plateauing at 30 years of age. Males were less likely to use ITNs than females. Prior to distribution, socio-economic factors such as parental education and occupation were associated with ITN use. Following distribution, ITN use was similar across social groups. Household factors such as availability of nets and sleeping arrangements still reduced consistent net use, however. CONCLUSIONS: Comprehensive, direct-to-household, mass distribution of ITNs was effective in rapidly scaling up coverage, with use being maintained at a high level at least one year following the intervention. Free distribution of ITNs through direct-to-household distribution method can eliminate important constraints in determining consistent ITN use, thus enhancing the sustainability of effective intervention campaigns.

Determinants of the use of insecticide-treated bed nets on islands of pre- and post-malaria elimination: an application of the health belief model in Vanuatu.

BACKGROUND: Insecticide-treated nets (ITNs) are an integral piece of any malaria elimination strategy, but compliance remains a challenge and determinants of use vary by location and context. The Health Belief Model (HBM) is a tool to explore perceptions and beliefs about malaria and ITN use. Insights from the model can be used to increase coverage to control malaria transmission in island contexts. METHODS: A mixed methods study consisting of a questionnaire and interviews was carried out in July 2012 on two islands of Vanuatu: Ambae Island where malaria transmission continues to occur at low levels, and Aneityum Island, where an elimination programme initiated in 1991 has halted transmission for several years. RESULTS: For most HBM constructs, no significant difference was found in the findings between the two islands: the fear of malaria (99%), severity of malaria (55%), malaria-prevention benefits of ITN use (79%) and willingness to use ITNs (93%). ITN use the previous night on Aneityum (73%) was higher than that on Ambae (68%) though not statistically significant. Results from interviews and group discussions showed that participants on Ambae tended to believe that risk was low due to the perceived absence of malaria, while participants on Aneityum believed that they were still at risk despite the long absence of malaria. On both islands, seasonal variation in perceived risk, thermal discomfort, costs of replacing nets, a lack of money, a lack of nets, nets in poor condition and the inconvenience of hanging had negative influences, while free mass distribution with awareness campaigns and the malaria-prevention benefits had positive influences on ITN use. CONCLUSIONS: The results on Ambae highlight the challenges of motivating communities to engage in elimination efforts when transmission continues to occur, while the results from Aneityum suggest the possibility of continued compliance to malaria elimination efforts given the threat of resurgence. Where a high degree of community engagement is possible, malaria elimination programmes may prove successful.

Drug delivery systems for wound healing treatment of upper airway injury.

INTRODUCTION: Endotracheal intubation is a common procedure to maintain an open airway with risks for traumatic injury. Pathological changes resulting from intubation can cause upper airway complications, including vocal fold scarring, laryngotracheal stenosis, and granulomas and present with symptoms such as dysphonia, dysphagia, and dyspnea. Current intubation-related laryngotracheal injury treatment approaches lack standardized guidelines, relying on individual clinician experience, and surgical and medical interventions have limitations and carry risks. AREAS COVERED: The clinical and preclinical therapeutics for wound healing in the upper airway are described. This review discusses the current developments on local drug delivery systems in the upper airway utilizing particle-based delivery systems, including nanoparticles and microparticles, and bulk-based delivery systems, encompassing hydrogels and polymer-based approaches. EXPERT OPINION: Complex laryngotracheal diseases pose challenges for effective treatment, struggling due to the intricate anatomy, limited access, and recurrence. Symptomatic management often requires invasive surgical procedures or medications that are unable to achieve lasting effects. Recent advances in nanotechnology and biocompatible materials provide potential solutions, enabling precise drug delivery, personalization, and extended treatment efficacy. Combining these technologies could lead to groundbreaking treatments for upper airways diseases, significantly improving patients' quality of life. Research and innovation in this field are crucial for further advancements.