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INTRODUCTION: The CoronaVirus Disease 2019 (COVID-19) pandemic remains a formidable threat to populations around the world. The U.S. Military, in particular, represents a unique and distinguishable subset of the population, primarily due to the age and gender of active duty personnel. Current investigations have focused on health outcome forecasts for civilian populations, making them of limited value for military planning. MATERIALS AND METHODS: We have developed and applied an age-structured susceptible, exposed, infectious, recovered, or dead compartmental model for both civilian and military populations, driven by estimates of the time-dependent reproduction number, R(t), which can be both fit to available data and also forecast future cases, intensive care unit (ICU) patients, and deaths. RESULTS: We show that the expected health outcomes for active duty military populations are substantially different than for civilian populations of the same size. Specifically, while the number of cases is not expected to differ dramatically, severity, both in terms of ICU burdens and deaths, is substantially lower. CONCLUSIONS: Our results confirm that the burden placed on military health centers will be substantially lower than that for equivalent-sized civilian populations. More practically, the tool we have developed to investigate this (https://q.predsci.com/covid19/) can be used by military health planners to estimate the resources needed in particular locations based on current estimates of the transmission profiles of COVID-19 within the surrounding civilian population in which the military installation is embedded. As this tool continues to be developed, it can be used to assess the likely impact of different intervention strategies, as well as vaccine policies; both for the current pandemic as well as future ones.
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COVID-19 , Personal Militar , Humanos , COVID-19/epidemiologíaRESUMEN
Terahertz emission from ferromagnetic/non-magnetic spintronic heterostructures had been demonstrated as pump wavelength-independent. We report, however, the pump wavelength dependence of terahertz emission from an optimized Fe/Pt spintronic bilayer on MgO substrate. Maximum terahertz generation per total pump power was observed in the 1200- to 1800-nm pump wavelength range, and a marked decrease in the terahertz emission efficiency beyond 2500 nm (pump photon energies <0.5 eV) suggests a â¼0.35-eV threshold pump photon energy for effective spintronic terahertz emission. The inferred threshold is supported by previous theoretical results on the onset energy of significant spin-filtering at the Fe-Pt interface, and confirmed by Fe/Pt electronic structure calculations in this present work. The results of terahertz time-domain emission spectroscopy show the sensitivity of spintronic terahertz emission to both the optical absorptance of the heterostructure and the energy-dependent spin transport, as dictated by the properties of the metallic thin films.
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Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.
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An exciton, a two-body composite quasiparticle formed of an electron and hole, is a fundamental optical excitation in condensed matter systems. Since its discovery nearly a century ago, a measurement of the excitonic wave function has remained beyond experimental reach. Here, we directly image the excitonic wave function in reciprocal space by measuring the momentum distribution of electrons photoemitted from excitons in monolayer tungsten diselenide. By transforming to real space, we obtain a visual of the distribution of the electron around the hole in an exciton. Further, by also resolving the energy coordinate, we confirm the elusive theoretical prediction that the photoemitted electron exhibits an inverted energy-momentum dispersion relationship reflecting the valence band where the partner hole remains, rather than that of conduction band states of the electron.
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We report on the design, fabrication and characterisation of large-area photoconductive THz array structures, consisting of a thin LT-GaAs active region transferred to an insulating substrate using a wafer-scale bonding process. The electrically insulating, transparent substrate reduces the parasitic currents in the devices, allowing peak THz-fields as high as 120 kV cm-1 to be generated over a bandwidth >5 THz. These results are achieved using lower pulse energies than demanded by conventional photoconductive arrays and other popular methods of generating high-field THz radiation. Two device sizes are fully characterised and the emission properties are compared to generation by optical rectification in ZnTe. The device can be operated in an optically saturated regime in order to suppress laser noise.
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Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.
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Epidemias , Predicción/métodos , Gripe Humana/epidemiología , Centers for Disease Control and Prevention, U.S. , Biología Computacional , Epidemias/estadística & datos numéricos , Humanos , Humedad , Cadenas de Markov , Modelos Biológicos , Modelos Estadísticos , Método de Montecarlo , Estudios Prospectivos , Estudios Retrospectivos , Estaciones del Año , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: Every year millions of people in developing countries suffer from snakebite, causing a large number of deaths and long term complications. Prevention and appropriate first aid could reduce the incidence and improve the health outcomes for those who suffer bites. However, many communities where snakebite is a major issue suffer from a lack of information about prevention and first aid measures that a family or community member could take to prevent severe envenoming, complications and poor outcomes. Myanmar suffers from a high burden of snakebites with a large number of deaths. As part of a health services and community development program, a community survey was conducted to identify communities' knowledge about snakebite and their sequelae, and knowledge and practice about first aid and health services use. METHOD: 4,276 rural residents of Kyaukse and Madaya townships in the Mandalay region were recruited by cluster sampling, involving random selection of 144 villages and random sampling of 30 households from each village. One adult member of each household was interviewed using a structured questionnaire. RESULTS: The incidence of snakebite was 116/100,000 people. Respondents reported 15 different types of snakes in the area, with Russell's Viper, Cobra and Green snakes as the most common. 88% of the people informed that working in the fields and forests was when most of the bites occur. A majority knew about snakebite prevention methods such as wearing long boots. However, only a few people knew about the specific symptoms caused by snakebites. Only 39% knew about the correct methods of first aid. More than 60% mentioned tourniquet as a first aid method, though this may cause significant complications such as ischaemia of the limb. 88% said that they would take a snakebite victim to a government hospital, and 58% mentioned availability of antivenom as the reason for doing this. At the same time, the majority mentioned that traditional methods existed for first aid and treatment and 25% mentioned at least one harmful traditional method as an effective measure that they might use. CONCLUSION: The community is aware of snakebites as a major public health issue and know how to prevent them. However, the high incidence of snakebites point to lack of application of preventive methods. The community recognise the need for treatment with antivenom. However, inadequate knowledge about appropriate first aid methods, and a reliance on using tourniquets require a targeted education program. Existing knowledge in communities, albeit insufficient, provides a good starting point for mass media educational campaigns.
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Primeros Auxilios , Conocimientos, Actitudes y Práctica en Salud , Mordeduras de Serpientes/epidemiología , Mordeduras de Serpientes/terapia , Adolescente , Adulto , Animales , Antivenenos , Femenino , Primeros Auxilios/efectos adversos , Primeros Auxilios/métodos , Humanos , Incidencia , Masculino , Mianmar/epidemiología , Serpientes/clasificación , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Snakebite is predominantly an occupational disease affecting poor rural farmers in tropical regions and was recently added to the World Health Organisation list of Neglected Tropical Diseases (NTD). We document an overview of methodologies developed and deployed in the Myanmar Snakebite Project, a foreign aid project largely funded by the Australian Government, with the core aim to "improve outcomes for snakebite patients". A multidisciplinary team of experts was assembled that worked in a collaborative manner with colleagues in Myanmar, first to identify problems related to managing snakebite and then develop interventions aimed to improve selected problem areas. A broad approach was adopted, covering antivenom production, antivenom distribution and health system management of snakebite. Problems identified in antivenom production included poor snake husbandry resulting in poor survival of captive specimens, lack of geographical diversity; poor horse husbandry, resulting in high mortality, inadequate stock acquisition protocols and data collection, and inappropriate immunisation and bleeding techniques; and inadequate production capacity for freeze dried antivenoms and quality control systems. These problems were addressed in various ways, resulting in some substantial improvements. Antivenom distribution is being reorganised to achieve better availability and utilisation of stock. Health system management of snakebite was assessed across all levels within the area selected for the study, in Mandalay region. A comprehensive community survey indicated that hospital statistics substantially underestimated the snakebite burden, and that access to care by local villagers was delayed by transport and cost issues compounded by lack of antivenom at the most peripheral level of the health service. A health system survey confirmed under-resourcing at the local village level. Prospective case data collection initiated at tertiary hospitals indicated the extent of the snakebite burden on health resources. Interventions initiated or planned include training of health staff, development of a core of senior trainers who can "train the trainers" nationwide in a sustainable way, development and deployment of management guidelines and algorithms for snakebite and a distribution of solar powered fridges to remote health facilities to allow storage of antivenom and prompt treatment of snakebite cases before transfer to major hospitals, thereby reducing the "bite to needle" time.
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INTRODUCTION: The global incidence of snakebite is estimated at more than 2.5 million cases annually, with greater than 100,000 deaths. Historically, Myanmar has one of the highest incidences of venomous snakebites. In order to improve the health outcomes of snakebite patients in Myanmar, access to accurate snakebite incidence data is crucial. The last population-based study in Myanmar was conducted more than a decade ago. In 2014, the Ministry of Health and Sports data from health facilities indicated an incidence of about 29.5 bites/ 100,000 population/year (a total of 15,079 bites). Since data from health facilities lack information about those who do not seek health care from government health services, a new population-based survey was conducted in 2 rural areas of Mandalay region. The survey data were compared to those obtained from healthcare services. METHOD: 4,276 rural respondents in Kyaukse and Madaya townships in Mandalay Division were recruited using cluster sampling that involved random selection of 150 villages and random sampling of 30 households from each village. One adult member of each household was interviewed using a structured questionnaire. RESULTS: One respondent from each of 4,276 households represented 19,877 residents from 144 villages. 24 people in these households had suffered snakebite during the last one year giving an annual incidence of 116/100,000. During the last ten years, 252 people suffered snakebites. 44.1% of the victims were women. 14% of the villages reported 4 or more bites during the last ten years, whereas 27% villages reported no snakebites. 92.4% of the victims recovered fully, 5.4% died, and 2% suffered long term health issues. One victim was reported to have died from causes unrelated to the snakebite. While there was no statistically significant difference between outcomes for children and adults, 4 of 38 of those under 18 years of age died compared to 7 of 133 adults between 19 to 40 years of age. CONCLUSION: This incidence reported by the community members points to substantially more snakebites than the number of snakebite patients attending health facilities. This higher incidence points to the need for a nation-wide population-based survey, community education about gaining access to care where antivenom is available, and to the potential need for a larger supply of antivenom and expansion of medical care in rural areas.
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Mordeduras de Serpientes/epidemiología , Adolescente , Adulto , Animales , Antivenenos/administración & dosificación , Niño , Femenino , Humanos , Incidencia , Masculino , Mianmar/epidemiología , Población Rural/estadística & datos numéricos , Mordeduras de Serpientes/tratamiento farmacológico , Mordeduras de Serpientes/parasitología , Serpientes/fisiología , Adulto JovenRESUMEN
Einstein's theory of gravity, General Relativity, has been precisely tested on Solar System scales, but the long-range nature of gravity is still poorly constrained. The nearby strong gravitational lens ESO 325-G004 provides a laboratory to probe the weak-field regime of gravity and measure the spatial curvature generated per unit mass, γ. By reconstructing the observed light profile of the lensed arcs and the observed spatially resolved stellar kinematics with a single self-consistent model, we conclude that γ = 0.97 ± 0.09 at 68% confidence. Our result is consistent with the prediction of 1 from General Relativity and provides a strong extragalactic constraint on the weak-field metric of gravity.
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Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
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BACKGROUND: Snakebite is a major public health problem in many developing countries. Farmers are particularly exposed to snakes, and due to their rural location often experience delays in accessing formal healthcare. The reasons to use traditional healers may include difficulties in accessing formal healthcare, certain beliefs about snakes and snake venom, tradition, and trust in the capacity of traditional healers. Traditional healing, however, may have serious consequences in terms of delays or added complications. There is little in-depth current information about the reasons for its continued use for snakebite. As part of a health services development project to improve health outcomes for snakebite patients, community attitudes to the use of traditional healers were explored in the Mandalay region of Myanmar. METHODOLOGY & FINDINGS: With the objective of learning from local communities, information was generated in three communities using participatory appraisal methods with the communities, and focus group discussions with the local healthcare staff. Many snakebite victims in these communities use traditional healing. Reasons include transport difficulties, low cost for traditional healing, inadequacy of anti-snake venom in the formal healthcare sector, and traditional beliefs, as traditional healing practices are rooted in many cultural and traditional factors. The communities reported that even if access to medical care were improved, traditional healing would continue to be used. CONCLUSION: These findings point to the need for working with traditional healers for prevention, appropriate first aid and timely access to effective treatment for snakebite.
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Conocimientos, Actitudes y Práctica en Salud , Medicina Tradicional de Asia Oriental , Aceptación de la Atención de Salud , Mordeduras de Serpientes/terapia , Adolescente , Adulto , Niño , Femenino , Primeros Auxilios , Accesibilidad a los Servicios de Salud/economía , Humanos , Masculino , Persona de Mediana Edad , Mianmar , Enfermedades Desatendidas/terapia , Grupos de Población , Población Rural , Mordeduras de Serpientes/complicaciones , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Pertussis is a highly contagious, vaccine preventable upper respiratory disease. The incidence of the disease has been rising in the past few decades. During the winter of 2015, an upper respiratory outbreak occurred in one of Israel Defense Forces basic training bases in northern Israel. Following the detection of the first primary cases, a suspected outbreak investigation was initiated in conjunction with more rigorous clinical and laboratory testing efforts to include specific antibody enzyme-linked immunosorbent assay assays and polymerase chain reaction to diagnose pertussis. Initially, 1,596 soldiers were surveyed clinically using a questionnaire and physicians' interviews for upper respiratory disease symptoms. A total of 158 soldiers were further evaluated and 38.6% (61) of those were diagnosed as having pertussis (with laboratory evidence). Based on the protocol that we developed during the course of this outbreak, a postexposure prophylaxis was given to every soldier for whom there was a high level of suspicion for infection and met the inclusion criteria for the postexposure prophylaxis protocol. The effects of the postvaccination waning immunity among a vaccinated population were demonstrated, thus the need of maintaining a high index of suspicion of Brodetella pertussis as a causative agent during respiratory diseases outbreaks in young soldiers.
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Brotes de Enfermedades/prevención & control , Guías como Asunto/normas , Personal Militar , Tos Ferina/prevención & control , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Educación/métodos , Educación/organización & administración , Ensayo de Inmunoadsorción Enzimática/métodos , Israel , Reacción en Cadena de la Polimerasa/métodos , Encuestas y CuestionariosRESUMEN
Probing the relative speeds of gravitational waves and light acts as an important test of general relativity and alternative theories of gravity. Measuring the arrival time of gravitational waves (GWs) and electromagnetic (EM) counterparts can be used to measure the relative speeds, but only if the intrinsic time lag between emission of the photons and gravitational waves is well understood. Here we suggest a method that does not make such an assumption, using future strongly lensed GW events and EM counterparts; Biesiada et al. [J. Cosmol. Astropart. Phys.10 (2014) 080JCAPBP1475-751610.1088/1475-7516/2014/10/080] forecast that 50-100 strongly lensed GW events will be observed each year with the Einstein Telescope. A single strongly lensed GW event would produce robust constraints on c_{GW}/c_{γ} at the 10^{-7} level, if a high-energy EM counterpart is observed within the field of view of an observing γ-ray burst monitor.
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We report on large-area photoconductive terahertz (THz) emitters with a low-temperature-grown GaAs (LT-GaAs) active layer fabricated on quartz substrates using a lift-off transfer process. These devices are compared to the same LT-GaAs emitters when fabricated on the growth substrate. We find that the transferred devices show higher optical-to-THz conversion efficiencies and significantly larger breakdown fields, which we attribute to reduced parasitic current in the substrate. Through these improvements, we demonstrate a factor of ~8 increase in emitted THz field strength at the maximum operating voltage. In addition we find improved performance when these devices are used for photoconductive detection, which we explain through a combination of reduced parasitic substrate currents and reduced space-charge build-up in the device.
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The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133-0.150 and R0, 1.09-2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics.
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Biología Computacional/métodos , Bases de Datos Factuales , Gripe Humana , Modelos Biológicos , Pandemias , Humanos , Gripe Humana/epidemiología , Gripe Humana/transmisión , Pandemias/prevención & control , Pandemias/estadística & datos numéricosRESUMEN
We evaluated the efficacy of three primaquine (PQ) regimes to prevent relapses with Plasmodium vivax through an open-label randomized trial in Loreto, Peru. Vivax monoinfections were treated with chloroquine for 3 days and PQ in three different regimes: 0.5 mg/kg per day for 5 days (150 mg total), 0.5 mg/kg per day for 7 days (210 mg total), or 0.25 mg/kg per day for 14 days (210 mg total). Biweekly fever assessments and bimonthly thick smears were taken for 210 days. Recurrences after 35 days were considered relapses. One hundred eighty cases were enrolled in each group; 90% of cases completed follow-up. There were no group-related differences in age, sex, or parasitemia. Relapse rates were similar in the 7- and 14-day regimes (16/156 = 10.3% and 22/162 = 13.6%, P = 0.361) and higher in the 5-day group (48/169 = 28.4%, P < 0.001 and P = 0.001, respectively). The 7-day PQ regimen used in Peru is as efficacious as the recommended 14-day regimen and superior to 5 treatment days.
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Antimaláricos/farmacología , Cloroquina/farmacología , Malaria Vivax/tratamiento farmacológico , Primaquina/farmacología , Adolescente , Adulto , Anciano , Niño , Preescolar , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Malaria Vivax/parasitología , Masculino , Persona de Mediana Edad , Perú , Plasmodium vivax/fisiología , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Plasmodium vivax is a predominant species of malaria in parts of South America and there is increasing resistance to drugs to treat infections by P. vivax. The existence of latent hypnozoites further complicates the ability to classify recurrent infections as treatment failures due to relapse, recrudescence of hyponozoites or re-infections. Antigen loci are putatively under natural selection and may not be an optimal molecular marker to define parasite haplotypes in paired samples. Putatively neutral microsatellite loci, however, offer an assessment of neutral haplotypes. The objective here was to assess the utility of neutral microsatellite loci to reconcile cases of recurrent parasitaemia in Amazonian P. vivax populations in Peru. METHODS: Patient blood samples were collected from three locations in or around Iquitos in the Peruvian Amazon. Five putatively neutral microsatellite loci were characterized from 445 samples to ascertain the within and amongst population variation. A total of 30 day 0 and day of recurrent parasitaemia samples were characterized at microsatellite loci and five polymorphic antigen loci for haplotype classification. RESULTS: The genetic diversity at microsatellite loci was consistent with neutral levels of variation measured in other South American P. vivax populations. Results between antigen and microsatellite loci for the 30 day 0 and day of recurrent parasitaemia samples were the same for 80% of the pairs. The majority of non-concordant results were the result of differing alleles at microsatellite loci. This analysis estimates that 90% of the paired samples with the same microsatellite haplotype are unlikely to be due to a new infection. CONCLUSIONS: A population-level approach was used to yield a better estimate of the probability of a new infection versus relapse or recrudescence of homologous hypnozoites; hypnozoite activation was common for this cohort. Population studies are critical with the evaluation of genetic markers to assess P. vivax biology and epidemiology. The additional demonstration of microsatellite loci as neutral markers capable of distinguishing the origin of the recurrent parasites (new infection or originating from the patient) lends support to their use in assessment of treatment outcomes.
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Variación Genética , Malaria Vivax/epidemiología , Malaria Vivax/parasitología , Parasitemia/epidemiología , Parasitemia/parasitología , Plasmodium vivax/clasificación , Plasmodium vivax/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , ADN Protozoario/genética , Femenino , Haplotipos , Humanos , Lactante , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Perú/epidemiología , Recurrencia , Adulto JovenRESUMEN
The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times.
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Antígenos de Protozoos/genética , Eliminación de Gen , Parásitos/genética , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Animales , Teorema de Bayes , Análisis por Conglomerados , Haplotipos/genética , Humanos , Repeticiones de Microsatélite/genética , Perú , Fenotipo , PrevalenciaRESUMEN
The merozoite surface protein-9 (MSP-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. Orthologs encoding this antigen have been found in all known species of Plasmodium parasitic to primates. In order to characterize and investigate the extent and maintenance of MSP-9 genetic diversity, we analyzed DNA sequences of the following malaria parasite species: Plasmodium falciparum, Plasmodium reichenowi, Plasmodium chabaudi, Plasmodium yoelii, Plasmodium berghei, Plasmodium coatneyi, Plasmodium gonderi, Plasmodium knowlesi, Plasmodium inui, Plasmodium simiovale, Plasmodium fieldi, Plasmodium cynomolgi and Plasmodium vivax and evaluated the signature of natural selection in all MSP-9 orthologs. Our findings suggest that the gene encoding MSP-9 is under purifying selection in P. vivax and closely related species. We further explored how selection affected different regions of MSP-9 by comparing the polymorphisms in P. vivax and P. falciparum, and found contrasting patterns between these two species that suggest differences in functional constraints. This observation implies that the MSP-9 orthologs in human parasites may interact differently with the host immune response. Thus, studies carried out in one species cannot be directly translated into the other.