Galeaspid anatomy and the origin of vertebrate paired appendages.

Paired fins are a major innovation1,2 that evolved in the jawed vertebrate lineage after divergence from living jawless vertebrates3. Extinct jawless armoured stem gnathostomes show a diversity of paired body-wall extensions, ranging from skeletal processes to simple flaps4. By contrast, osteostracans (a sister group to jawed vertebrates) are interpreted to have the first true paired appendages in a pectoral position, with pelvic appendages evolving later in association with jaws5. Here we show, on the basis of articulated remains of Tujiaaspis vividus from the Silurian period of China, that galeaspids (a sister group to both osteostracans and jawed vertebrates) possessed three unpaired dorsal fins, an approximately symmetrical hypochordal tail and a pair of continuous, branchial-to-caudal ventrolateral fins. The ventrolateral fins are similar to paired fin flaps in other stem gnathostomes, and specifically to the ventrolateral ridges of cephalaspid osteostracans that also possess differentiated pectoral fins. The ventrolateral fins are compatible with aspects of the fin-fold hypothesis for the origin of vertebrate paired appendages6-10. Galeaspids have a precursor condition to osteostracans and jawed vertebrates in which paired fins arose initially as continuous pectoral-pelvic lateral fins that our computed fluid-dynamics experiments show passively generated lift. Only later in the stem lineage to osteostracans and jawed vertebrates did pectoral fins differentiate anteriorly. This later differentiation was followed by restriction of the remaining field of fin competence to a pelvic position, facilitating active propulsion and steering.

Infrared Photoactivation Enables Improved Native Top-Down Mass Spectrometry of Transmembrane Proteins.

Membrane proteins are often challenging targets for native top-down mass spectrometry experimentation. The requisite use of membrane mimetics to solubilize such proteins necessitates the application of supplementary activation methods to liberate protein ions prior to sequencing, which typically limits the sequence coverage achieved. Recently, infrared photoactivation has emerged as an alternative to collisional activation for the liberation of membrane proteins from surfactant micelles. However, much remains unknown regarding the mechanism by which IR activation liberates membrane protein ions from such micelles, the extent to which such methods can improve membrane protein sequence coverage, and the degree to which such approaches can be extended to support native proteomics. Here, we describe experiments designed to evaluate and probe infrared photoactivation for membrane protein sequencing, proteoform identification, and native proteomics applications. Our data reveal that infrared photoactivation can dissociate micelles composed of a variety of detergent classes, without the need for a strong IR chromophore by leveraging the relatively weak association energies of such detergent clusters in the gas phase. Additionally, our data illustrate how IR photoactivation can be extended to include membrane mimetics beyond micelles and liberate proteins from nanodiscs, liposomes, and bicelles. Finally, our data quantify the improvements in membrane protein sequence coverage produced through the use of IR photoactivation, which typically leads to membrane protein sequence coverage values ranging from 40 to 60%.

Development of an Automated, High-Throughput Methodology for Native Mass Spectrometry and Collision-Induced Unfolding.

Native ion mobility mass spectrometry (nIM-MS) has emerged as a useful technology for the rapid evaluation of biomolecular structures. When combined with collisional activation in a collision-induced unfolding (CIU) experiment, nIM-MS experimentation can be leveraged to gain greater insight into biomolecular conformation and stability. However, nIM-MS and CIU remain throughput limited due to nonautomated sample preparation and introduction. Here, we explore the use of a RapidFire robotic sample handling system to develop an automated, high-throughput methodology for nMS and CIU. We describe native RapidFire-MS (nRapidFire-MS) capable of performing online desalting and sample introduction in as little as 10 s per sample. When combined with CIU, our nRapidFire-MS approach can be used to collect CIU fingerprints in 30 s following desalting by using size exclusion chromatography cartridges. When compared to nMS and CIU data collected using standard approaches, ion signals recorded by nRapidFire-MS exhibit identical ion collision cross sections, indicating that the same conformational populations are tracked by the two approaches. Our data further suggest that nRapidFire-MS can be extended to study a variety of biomolecular classes, including proteins and protein complexes ranging from 5 to 300 kDa and oligonucleotides. Furthermore, nRapidFire-MS data acquired for biotherapeutics suggest that nRapidFire-MS has the potential to enable high-throughput nMS analyses of biopharmaceutical samples. We conclude by discussing the potential of nRapidFire-MS for enabling the development of future CIU assays capable of catalyzing breakthroughs in protein engineering, inhibitor discovery, and formulation development for biotherapeutics.

An insight to better understanding cross border malaria in Saudi Arabia.

BACKGROUND: Border malaria is a major obstacle for the malaria elimination in Saudi Arabia. Today, the southern border of Saudi Arabia is a region where malaria cases are resurging, and malaria control is dwindling mainly due to the humanitarian crisis and the conflict in Yemen. This study analyses the current border malaria epidemiology along the southern border of Saudi Arabia from 2015 to 2018. METHODS: All reported cases maintained by the malaria elimination centres in Aledabi and Baish, Jazan Province, Saudi Arabia, from 2015 to 2018 were analysed to examine the epidemiological changes over time. Pearson's Chi-Square test of differences was utilized to assess differences between the characteristics of imported and local causes and between border cases. A logistic regression model was used to predict imported status was related to living along side of the border area. RESULTS: A total of 3210 malaria cases were reported in Baish and Aledabi malaria centres between 2015 and 2018, of which 170 were classified as local cases and 3040 were classified as imported cases. Reported malaria cases were mainly among males, within the imported cases 61.5% (1868/3039) were residents of the border areas. CONCLUSIONS: Given the complexity of cross-border malaria, creating a malaria buffer zone that covers a certain margin from both sides of the border would allow for a joint force, cross-border malaria elimination programme. To initiate a malaria elimination activity and cases reported as belonging to this zone, rather than being pushed from one country to the other, would allow malaria elimination staff to work collaboratively with local borderland residents and other stakeholders to come up with innovative solutions to combat malaria and reach malaria-free borders.

Durability of long-lasting insecticidal nets (LLINs) in Ethiopia.

BACKGROUND: The functional survival time of long-lasting insecticidal nets (LLINs), which varies across different field contexts, is critical for the successful prevention of malaria transmission. However, there is limited data on LLIN durability in field settings in Ethiopia. METHODS: A three-year longitudinal study was conducted to monitor attrition, physical integrity, and bio-efficacy and residual chemical concentration of LLINs in four regions in Ethiopia. World Health Organization (WHO) guidelines were used to determine sample size, measure physical integrity, and calculate attrition rates, and functional survival time. Yearly bio-efficacy testing was done on randomly selected LLINs. An excel tool developed by vector works project was used to calculate the median functional survival time of the LLINs. Predictors of functional survival were identified by fitting binary and multivariate cox proportional hazards model. RESULTS: A total of 3,396 LLINs were included in the analysis. A total of 3,396 LLINs were included in the analysis. By the end of 36 months, the proportion of LLINs functionally surviving was 12.9% [95% confidence interval (CI) 10.5, 15.6], the rates of attrition due to physical damage and repurposing were 48.8% [95% confidence interval (CI) 45.0, 52.6] and 13.8% [95% confidence interval (CI) 11.6, 14.6], respectively. The estimated median functional survival time was 19 months (95%CI 17, 21). Factors associated with shorter functional survival time include being in a low malaria transmission setting [Adjusted Hazards Ratio (AHR) (95%CI) 1.77 (1.22, 2.55)], rural locations [AHR (95%CI) 1.83 (1.17, 2.84)], and in a room where cooking occurs [AHR (95%CI) 1.28 (1.05, 1.55)]. Bioassay tests revealed that 95.3% (95%CI 86.4, 98.5) of the LLINs met the WHO criteria of bio-efficacy after 24 months of distribution. CONCLUSION: The LLIN survival time was shorter than the expected three years due to high attrition rates and rapid loss of physical integrity. National malaria programmes may consider, procuring more durable LLINs, educating communities on how to prevent damage of LLINs, and revising the current three-year LLIN distribution schedule to ensure sufficient protection is provided by LLINs against malaria transmission. While this paper contributes to the understanding of determinants impacting functional survival, further research is needed to understand factors for the rapid attrition rates and loss of physical integrity of LLINs in field settings.

Livelihood activities, human mobility, and risk of malaria infection in elimination settings: a case-control study.

BACKGROUND: Livelihood activities and human movements participate in the epidemiology of vector-borne diseases and influence malaria risk in elimination settings. In Saudi Arabia, where malaria transmission intensity varies geographically, it is vital to understand the components driving transmission within specific areas. In addition, shared social, behavioural, and occupational characteristics within communities may provoke the risk of malaria infection. This study aims to understand the relationship between human mobility, livelihood activities, and the risk of malaria infection in the border region of Jazan to facilitate further strategic malaria interventions. In addition, the study will complement and reinforce the existing efforts to eliminate malaria on the Saudi and Yemen border by providing a deeper understanding of human movement and livelihood activities. METHODS: An unmatched case-control study was conducted. A total of 261 participants were recruited for the study, including 81 cases of confirmed malaria through rapid diagnostic tests (RDTs) and microscopy and 180 controls in the Baish Governorate in Jazan Provinces, Saudi Arabia. Individuals who received malaria tests were interviewed regarding their livelihood activities and recent movement (travel history). A questionnaire was administered, and the data was captured electronically. STATA software version 16 was used to analyse the data. Bivariate and multivariate analyses were conducted to determine if engaging in agricultural activities such as farming and animal husbandry, recent travel history outside of the home village within the last 30 days and participating in spiritual gatherings were related to malaria infection status. RESULTS: A logistical regression model was used to investigate components associated with malaria infection. After adjusting several confounding factors, individuals who reported travelling away from their home village in the last 30 days OR 11.5 (95% CI 4.43-29.9), and those who attended a seasonal night spiritual gathering OR 3.04 (95% CI 1.10-8.42), involved in animal husbandry OR 2.52 (95% CI 1.10-5.82), and identified as male OR 4.57 (95% CI 1.43-14.7), were more likely to test positive for malaria infection. CONCLUSION: Human movement and livelihood activities, especially at nighttime, should be considered malaria risk factors in malaria elimination settings, mainly when the targeted area is limited to a confined borderland area.

Collagen Sequence Analysis Reveals Evolutionary History of Extinct West Indies Nesophontes (Island-Shrews).

Ancient biomolecule analyses are proving increasingly useful in the study of evolutionary patterns, including extinct organisms. Proteomic sequencing techniques complement genomic approaches, having the potential to examine lineages further back in time than achievable using ancient DNA, given the less stringent preservation requirements. In this study, we demonstrate the ability to use collagen sequence analyses via proteomics to assist species delimitation as a foundation for informing evolutionary patterns. We uncover biogeographic information of an enigmatic and recently extinct lineage of Nesophontes across their range on the Caribbean islands. First, evolutionary relationships reconstructed from collagen sequences reaffirm the affinity of Nesophontes and Solenodon as sister taxa within Solenodonota. This relationship helps lay the foundation for testing geographical isolation hypotheses across islands within the Greater Antilles, including movement from Cuba toward Hispaniola. Second, our results are consistent with Cuba having just two species of Nesophontes (N. micrus and N. major) that exhibit intrapopulation morphological variation. Finally, analysis of the recently described species from the Cayman Islands (N. hemicingulus) indicates that it is a closer relative to N. major rather than N. micrus as previously speculated. This proteomic sequencing improves our understanding of the origin, evolution, and distribution of this extinct mammal lineage, particularly with respect to the approximate timing of speciation. Such knowledge is vital for this biodiversity hotspot, where the magnitude of recent extinctions may obscure true estimates of species richness in the past.

Morphological Phylogenetics Evaluated Using Novel Evolutionary Simulations.

Evolutionary inferences require reliable phylogenies. Morphological data have traditionally been analyzed using maximum parsimony, but recent simulation studies have suggested that Bayesian analyses yield more accurate trees. This debate is ongoing, in part, because of ambiguity over modes of morphological evolution and a lack of appropriate models. Here, we investigate phylogenetic methods using two novel simulation models-one in which morphological characters evolve stochastically along lineages and another in which individuals undergo selection. Both models generate character data and lineage splitting simultaneously: the resulting trees are an emergent property, rather than a fixed parameter. Standard consensus methods for Bayesian searches (Mki) yield fewer incorrect nodes and quartets than the standard consensus trees recovered using equal weighting and implied weighting parsimony searches. Distances between the pool of derived trees (most parsimonious or posterior distribution) and the true trees-measured using Robinson-Foulds (RF), subtree prune and regraft (SPR), and tree bisection reconnection (TBR) metrics-demonstrate that this is related to the search strategy and consensus method of each technique. The amount and structure of homoplasy in character data differ between models. Morphological coherence, which has previously not been considered in this context, proves to be a more important factor for phylogenetic accuracy than homoplasy. Selection-based models exhibit relatively lower homoplasy, lower morphological coherence, and higher inaccuracy in inferred trees. Selection is a dominant driver of morphological evolution, but we demonstrate that it has a confounding effect on numerous character properties which are fundamental to phylogenetic inference. We suggest that the current debate should move beyond considerations of parsimony versus Bayesian, toward identifying modes of morphological evolution and using these to build models for probabilistic search methods. [Bayesian; evolution; morphology; parsimony; phylogenetics; selection; simulation.].

Retrospective evaluation of the effectiveness of indoor residual spray with pirimiphos-methyl (Actellic) on malaria transmission in Zambia.

BACKGROUND: Widespread insecticide resistance to pyrethroids could thwart progress towards elimination. Recently, the World Health Organization has encouraged the use of non-pyrethroid insecticides to reduce the spread of insecticide resistance. An electronic tool for implementing and tracking coverage of IRS campaigns has recently been tested (mSpray), using satellite imagery to improve the accuracy and efficiency of the enumeration process. The purpose of this paper is to retrospectively analyse cross-sectional observational data to provide evidence of the epidemiological effectiveness of having introduced Actellic 300CS and the mSpray platform into IRS programmes across Zambia. METHODS: Health facility catchment areas in 40 high burden districts in 5 selected provinces were initially targeted for spraying. The mSpray platform was used in 7 districts in Luapula Province. An observational study design was used to assess the relationship between IRS exposure and confirmed malaria case incidence. A random effects Poisson model was used to quantify the effect of IRS (with and without use of the mSpray platform) on confirmed malaria case incidence over the period 2013-2017; analysis was restricted to the 4 provinces where IRS was conducted in each year 2014-2016. RESULTS: IRS was conducted in 283 health facility catchment areas from 2014 to 2016; 198 health facilities from the same provinces, that received no IRS during this period, served as a comparison. IRS appears to be associated with reduced confirmed malaria incidence; the incidence rate ratio (IRR) was lower in areas with IRS but without mSpray, compared to areas with no IRS (IRR = 0.91, 95% CI 0.84-0.98). Receiving IRS with mSpray significantly lowered confirmed case incidence (IRR = 0.75, 95% CI 0.66-0.86) compared to no IRS. IRS with mSpray resulted in lower incidence compared to IRS without mSpray (IRR = 0.83, 95% CI 0.72-0.95). CONCLUSIONS: IRS using Actellic-CS appears to substantially reduce malaria incidence in Zambia. The use of the mSpray tool appears to improve the effectiveness of the IRS programme, possibly through improved population level coverage. The results of this study lend credence to the anecdotal evidence of the effectiveness of 3GIRS using Actellic, and the importance of exploring new platforms for improving effective population coverage of areas targeted for spraying.

The effect of long-lasting insecticidal nets (LLINs) physical integrity on utilization.

BACKGROUND: In Ethiopia, despite improvements in coverage and access, utilization of long-lasting insecticidal nets (LLINs) remains a challenge. Different household-level factors have been identified as associated with LLIN use. However, the contribution of LLIN physical integrity to their utilization is not well investigated and documented. This study aimed to assess the association between the physical integrity of LLINs and their use. METHODS: This study employed a nested case-control design using secondary data from the Ethiopian LLIN durability monitoring study conducted from May 2015 to June 2018. LLINs not used the night before the survey were identified as cases, while those used the previous night were categorized as controls. The physical integrity of LLINs was classified as no holes, good, acceptable, and torn using the proportionate hole index (pHI). A Generalized Estimating Equation (GEE) model was used to assess and quantify the association between LLIN physical integrity and use. The model specifications included binomial probabilistic distribution, logit link, exchangeable correlation matrix structure, and robust standard errors. The factors included in the model were selected first by fitting binary regression, and then by including all factors that showed statistical significance at P-value less than 0.25 and conceptually relevant variables into the multivariate regression model. RESULTS: A total of 5277 observations fulfilled the inclusion criteria. Out of these 1767 observations were cases while the remaining 3510 were controls. LLINs that were in torn physical condition had higher odds (AOR [95% CI] = 1.76 [1.41, 2.19]) of not being used compared to LLINs with no holes. Other factors that showed significant association included the age of the LLIN, sleeping place type, washing status of LLINs, perceptions towards net care and repair, LLIN to people ratio, economic status, and study site. CONCLUSION AND RECOMMENDATION: LLINs that have some level of physical damage have a relatively higher likelihood of not being used. Community members need to be educated about proper care and prevention of LLIN damage to delay the development of holes as long as possible and use available LLINs regularly.

Clustering of asymptomatic Plasmodium falciparum infection and the effectiveness of targeted malaria control measures.

BACKGROUND: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. METHODS: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. RESULTS: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. CONCLUSIONS: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.

Parsimony, not Bayesian analysis, recovers more stratigraphically congruent phylogenetic trees.

Reconstructing evolutionary histories requires accurate phylogenetic trees. Recent simulation studies suggest that probabilistic phylogenetic analyses of morphological data are more accurate than traditional parsimony techniques. Here, we use empirical data to compare Bayesian and parsimony phylogenies in terms of their congruence with the distribution of age ranges of the component taxa. Analysis of 167 independent morphological data matrices of fossil tetrapods finds that Bayesian trees exhibit significantly lower stratigraphic congruence than the equivalent parsimony trees. As such, taking stratigraphic data as an independent benchmark indicates that parsimony analyses are more accurate for phylogenetic reconstruction of morphological data. The discrepancy between simulated and empirical studies may result from historic data peaking practices or some complexities of empirical data as yet unaccounted for.

Willingness to pay for small solar powered bed net fans: results of a Becker-DeGroot-Marschak auction in Ghana.

BACKGROUND AND METHODS: Long-lasting insecticidal nets (LLINs) are one of the main interventions recommended by the World Health Organization for malaria vector control. LLINs are ineffective if they are not being used. Subsequent to the completion of a cluster randomized cross over trial conducted in rural Greater Accra where participants were provided with the 'Bɔkɔɔ System'-a set of solar powered net fan and light consoles with a solar panel and battery-or alternative household water filters, all trial participants were invited to participate in a Becker-DeGroot-Marschak auction to determine the mean willingness to pay (WTP) for the fan and light consoles and to estimate the demand curve for the units. RESULTS, DISCUSSION AND CONCLUSIONS: Results demonstraed a mean WTP of approximately 55 Cedis (~13 USD). Demand results suggested that at a price which would support full manufacturing cost recovery, a majority of households in the area would be willing to purchase at least one such unit.

The effect of small solar powered 'Bͻkͻͻ' net fans on mosquito net use: results from a randomized controlled cross-over trial in southern Ghana.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are ineffective malaria transmission prevention tools if they are unused. Discomfort due to heat is the most commonly reported reason for not using nets, but this problem is largely unaddressed. With increasing rural electrification and the dropping price of solar power, fans could improve comfort inside nets and be affordable to populations in malaria endemic areas. Here, results are presented from a pilot randomized controlled cross-over study testing the effect of fans on LLIN use. METHODS: Eighty-three households from two rural communities in Greater Accra, Ghana, randomized into three groups, participated in a 10-month cross-over trial. After a screening survey to identify eligible households, all households received new LLINs. BÍ»kͻͻ net fan systems (one fan per member) were given to households in Group 1 and water filters were given to households in Group 2. At mid-point, Group 1 and 2 crossed over interventions. Households in Group 1 and 2 participated in fortnightly surveys on households' practices related to nets, fans and water filters, while households in Group 3 were surveyed only at screening, mid-point and study end. Entomological and weather data were collected throughout the study. Analysis took both 'per protocol' (PP) and 'intention to treat' (ITT) approaches. The mid- and end-point survey data from Group 1 and 2 were analysed using Firth logistic regressions. Fortnightly survey data from all groups were analysed using logistic regressions with random effects. RESULTS: Provision of fans to households appeared to increase net use in this study. Although the increase in net use explained by fans was not significant in the primary analyses (ITT odds ratio 3.24, p > 0.01; PP odds ratio = 1.17, p > 0.01), it was significant in secondary PP analysis (odds ratio = 1.95, p < 0.01). Net use was high at screening and even higher after provision of new LLINs and with follow up. Fan use was 90-100% depending on the fortnightly visit. CONCLUSIONS: This pilot study could not provide definitive evidence that fans increase net use. A larger study with additional statistical power is needed to assess this association across communities with diverse environmental and socio-demographic characteristics.

Knowledge and perception towards net care and repair practice in Ethiopia.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are a key malaria control intervention. Although LLINs are presumed to be effective for 3 years under field or programmatic conditions, net care and repair approaches by users influence the physical and chemical durability. Understanding how knowledge, perception and practices influence net care and repair practices could guide the development of targeted behavioural change communication interventions related to net care and repair in Ethiopia and elsewhere. METHODS: This population-based, household survey was conducted in four regions of Ethiopia [Amhara, Oromia, Tigray, Southern Nations Nationalities Peoples Region (SNNPR)] in June 2015. A total of 1839 households were selected using multi-stage sampling procedures. The household respondents were the heads of households. A questionnaire was administered and the data were captured electronically. STATA software version 12 was used to analyse the data. Survey commands were used to account for the multi-stage sampling approach. Household descriptive statistics related to characteristics and levels of knowledge and perception on net care and repair are presented. Ordinal logistic regression was used to identify factors associated with net care and repair perceptions. RESULTS: Less than a quarter of the respondents (22.3%: 95% CI 20.4-24.3%) reported adequate knowledge of net care and repair; 24.6% (95% CI 22.7-26.5%) of the respondents reported receiving information on net care and repair in the previous 6 months. Thirty-five per cent of the respondents (35.1%: 95% CI 32.9-37.4%) reported positive perceptions towards net care and repair. Respondents with adequate knowledge on net care and repair (AOR 1.58: 95% CI 1.2-2.02), and those who discussed net care and repair with their family (AOR 1.47: 95% CI 1.14-1.89) had higher odds of having positive perceptions towards net care and repair. CONCLUSIONS: The low level of reported knowledge on net care and repair, as well as the low level of reported positive perception towards net repair need to be addressed. Targeted behavioural change communication campaigns could be used to target specific groups; increased net care and repair would lead to longer lasting nets.

Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

BACKGROUND: Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS: A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence. RESULTS: All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point. CONCLUSIONS: Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas. CLINICAL TRIALS REGISTRATION: NCT02329301.

Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton.

The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected.

Perceptions on the effect of small electric fans on comfort inside bed nets in southern Ghana: a qualitative study.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are known to be highly effective in reducing malaria transmission, morbidity and mortality. However, among those owning an LLIN, use rates are often suboptimal. A reported barrier to bed net use is discomfort due to heat. This qualitative study was part of a larger evaluation conducted in communities without electricity in rural Ghana to assess whether 0.8 W solar powered net fans can increase net use. METHODS: Twenty-three key informant interviews with household heads in the study communities in Shai-Osudoku District, southern Ghana, were conducted from July to August 2015. The purpose of the interviews was to obtain insight into perceptions of participants about the net fan system in relation to LLIN use. RESULTS: While all study participants reported using LLINs, with mosquito nuisance prevention as the prime motivation, heat was also mentioned as a key barrier to net use. Respondents appreciated the net fans because they improved comfort inside bed nets. The LED light on the fan stand became the main source of light at night and positively influenced the perception of the intervention as a whole. CONCLUSION: The general acceptance of the net fan system by the study participants highlights the potential of the intervention to improve comfort inside mosquito nets. This, therefore, has a potential to increase bed net use in areas with low access to electricity.

Malaria vector research and control in Haiti: a systematic review.

BACKGROUND: Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a systematic review of the literature on malaria vector research, bionomics and control in Haiti. METHODS: A systematic search of literature published in French, Spanish and English languages was conducted in 2015 using Pubmed (MEDLINE), Google Scholar, EMBASE, JSTOR WHOLIS and Web of Science databases as well other grey literature sources such as USAID, and PAHO. The following search terms were used: malaria, Haiti, Anopheles, and vector control. RESULTS: A total of 132 references were identified with 40 high quality references deemed relevant and included in this review. Six references dealt with mosquito distribution, seven with larval mosquito ecology, 16 with adult mosquito ecology, three with entomological indicators of malaria transmission, eight with insecticide resistance, one with sero-epidemiology and 16 with vector control. In the last 15 years (2000-2015), there have only been four published papers and three-scientific meeting abstracts on entomology for malaria in Haiti. Overall, the general literature on malaria vector research in Haiti is limited and dated. DISCUSSION: Entomological information generated from past studies in Haiti will contribute to the development of strategies to achieve malaria elimination on Hispaniola. However it is of paramount importance that malaria vector research in Haiti is updated to inform decision-making for vector control strategies in support of malaria elimination.

Strategic roles for behaviour change communication in a changing malaria landscape.

Strong evidence suggests that quality strategic behaviour change communication (BCC) can improve malaria prevention and treatment behaviours. As progress is made towards malaria elimination, BCC becomes an even more important tool. BCC can be used 1) to reach populations who remain at risk as transmission dynamics change (e.g. mobile populations), 2) to facilitate identification of people with asymptomatic infections and their compliance with treatment, 3) to inform communities of the optimal timing of malaria control interventions, and 4) to explain changing diagnostic concerns (e.g. increasing false negatives as parasite density and multiplicity of infections fall) and treatment guidelines. The purpose of this commentary is to highlight the benefits and value for money that BCC brings to all aspects of malaria control, and to discuss areas of operations research needed as transmission dynamics change.