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1.
Clin Infect Dis ; 78(Supplement_2): S175-S182, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662705

RESUMO

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.


Assuntos
Infecções Assintomáticas , Doença de Chagas , Leishmaniose Visceral , Modelos Teóricos , Doenças Negligenciadas , Humanos , Doenças Negligenciadas/prevenção & controle , Doenças Negligenciadas/epidemiologia , Doença de Chagas/transmissão , Doença de Chagas/prevenção & controle , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Infecções Assintomáticas/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Leishmaniose Visceral/tratamento farmacológico , Tripanossomíase Africana/prevenção & controle , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/transmissão , Tripanossomíase Africana/tratamento farmacológico , Índia/epidemiologia , Animais
2.
Clin Infect Dis ; 78(Supplement_2): S83-S92, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662692

RESUMO

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.


Assuntos
COVID-19 , Doenças Negligenciadas , Medicina Tropical , Doenças Negligenciadas/prevenção & controle , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Modelos Teóricos , Organização Mundial da Saúde , SARS-CoV-2 , Tomada de Decisões , Saúde Global
3.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33649227

RESUMO

The population structure of social species has important consequences for both their demography and transmission of their pathogens. We develop a metapopulation model that tracks two key components of a species' social system: average group size and number of groups within a population. While the model is general, we parameterize it to mimic the dynamics of the Yellowstone wolf population and two associated pathogens: sarcoptic mange and canine distemper. In the initial absence of disease, we show that group size is mainly determined by the birth and death rates and the rates at which groups fission to form new groups. The total number of groups is determined by rates of fission and fusion, as well as environmental resources and rates of intergroup aggression. Incorporating pathogens into the models reduces the size of the host population, predominantly by reducing the number of social groups. Average group size responds in more subtle ways: infected groups decrease in size, but uninfected groups may increase when disease reduces the number of groups and thereby reduces intraspecific aggression. Our modeling approach allows for easy calculation of prevalence at multiple scales (within group, across groups, and population level), illustrating that aggregate population-level prevalence can be misleading for group-living species. The model structure is general, can be applied to other social species, and allows for a dynamic assessment of how pathogens can affect social structure and vice versa.


Assuntos
Cinomose , Modelos Biológicos , Escabiose , Lobos , Animais , Cinomose/epidemiologia , Cinomose/transmissão , Dinâmica Populacional , Prevalência , Escabiose/epidemiologia , Escabiose/transmissão , Escabiose/veterinária
4.
J Adv Nurs ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666414

RESUMO

AIM: To examine healthcare providers' extent of and perceived barriers and facilitators to screening for intimate partner violence in pregnant women attending prenatal clinics. DESIGN: Cross-sectional descriptive design was used to collect data from 130 healthcare providers. METHODS: Seventeen healthcare providers from 17 prenatal clinics in Kanungu district, Uganda, were recruited via convenience sampling to participate in an online survey implementing a modified Normalization Measure Development instrument. Data were collected between February 2023 and March 2023 (02/8/2023 to 03/12/2023) and analysed using descriptive and Mann-Whitney U test and chi-square tests. RESULTS: Slightly more than half (56%) of healthcare providers report screening pregnant women for intimate partner violence. There was a statistically significant relationship between healthcare providers screening for intimate partner violence and having previous training on intimate partner violence screening. The only barrier to screening identified was a lack of understanding of how intimate partner violence screening affects the nature of participant's own work. There were numerous potential facilitators identified for healthcare providers' intimate partner violence screening. CONCLUSION: Although higher-than-expected number of healthcare providers reported screening of pregnant women for intimate partner violence, the extent of screening is still suboptimal. The barrier to screening identified needs to be addressed and facilitators promoted. Receiving training among healthcare providers on intimate partner violence screening was associated with higher levels of screening; thus, this needs to be enhanced to optimize screening rates. Future studies should assess screening practices objectively and implement interventions to improve healthcare providers' intimate partner violence screening rates. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Screening for intimate partner violence should be part of standard care provided by healthcare providers to all pregnant women during prenatal clinic visits. The study supports the need for more training for healthcare providers in aspects related to intimate partner violence screening in order to ensure prompt diagnosis and treatment of those affected, identify those at risk and increase awareness. There is a need to enhance healthcare providers' capacity for intimate partner violence screening through education by integrating intimate partner violence screening pre- and post-registration courses and preparation programs or curriculum. IMPACT: Intimate partner violence (IPV) in pregnancy is a global health problem. Screening for IPV by healthcare providers is suboptimal. This study found that only 56% of healthcare providers were routinely screening for IPV in Ugandan prenatal clinics. This study identified the main facilitators and one barrier to IPV screening. REPORTING METHOD: This study has adhered to the relevant EQUATOR guidelines for quantitative studies. PATIENT AND PUBLIC CONTRIBUTION: No patient was involved in this study.

5.
Ecol Lett ; 25(4): 992-1008, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34967090

RESUMO

Diet composition is among the most important yet least understood dimensions of animal ecology. Inspired by the study of species abundance distributions (SADs), we tested for generalities in the structure of vertebrate diets by characterising them as dietary abundance distributions (DADs). We compiled data on 1167 population-level diets, representing >500 species from six vertebrate classes, spanning all continents and oceans. DADs near-universally (92.5%) followed a hollow-curve shape, with scant support for other plausible rank-abundance-distribution shapes. This strong generality is inherently related to, yet incompletely explained by, the SADs of available food taxa. By quantifying dietary generalisation as the half-saturation point of the cumulative distribution of dietary abundance (sp50, minimum number of foods required to account for 50% of diet), we found that vertebrate populations are surprisingly specialised: in most populations, fewer than three foods accounted for at least half the diet. Variation in sp50 was strongly associated with consumer type, with carnivores being more specialised than herbivores or omnivores. Other methodological (sampling method and effort, taxonomic resolution), biological (body mass, frugivory) and biogeographic (latitude) factors influenced sp50 to varying degrees. Future challenges include identifying the mechanisms underpinning the hollow-curve DAD, its generality beyond vertebrates, and the biological determinants of dietary generalisation.


Assuntos
Ecologia , Herbivoria , Animais , Dieta , Vertebrados
6.
Emerg Infect Dis ; 28(8): 1650-1658, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35876625

RESUMO

Several caribou (Rangifer tarandus) populations have been declining concurrently with increases in infectious diseases in the Arctic. Erysipelothrix rhusiopathiae, a zoonotic bacterium, was first described in 2015 as a notable cause of illness and death among several Arctic wildlife species. We investigated epidemiologic and environmental factors associated with the seroprevalence of E. rhusiopathiae in the Arctic and found that seropositivity was highest during warmer months, peaking in September, and was highest among adult males. Summer seroprevalence increases tracked with the oestrid index from the previous year, icing and snowing events, and precipitation from the same year but decreased with growing degree days in the same year. Seroprevalence of E. rhusiopathiae varied more during the later years of the study. Our findings provide key insights into the influence of environmental factors on disease prevalence that can be instrumental for anticipating and mitigating diseases associated with climate change among Arctic wildlife and human populations.


Assuntos
Erysipelothrix , Rena , Animais , Animais Selvagens , Regiões Árticas , Humanos , Masculino , Estações do Ano , Estudos Soroepidemiológicos
7.
PLoS Biol ; 17(11): e3000526, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31730640

RESUMO

The Amazon is Brazil's greatest natural resource and invaluable to the rest of the world as a buffer against climate change. The recent election of Brazil's president brought disputes over development plans for the region back into the spotlight. Historically, the development model for the Amazon has focused on exploitation of natural resources, resulting in environmental degradation, particularly deforestation. Although considerable attention has focused on the long-term global cost of "losing the Amazon," too little attention has focused on the emergence and reemergence of vector-borne diseases that directly impact the local population, with spillover effects to other neighboring areas. We discuss the impact of Amazon development models on human health, with a focus on vector-borne disease risk. We outline policy actions that could mitigate these negative impacts while creating opportunities for environmentally sensitive economic activities.


Assuntos
Agricultura/métodos , Conservação dos Recursos Naturais/métodos , Doenças Transmitidas por Vetores/epidemiologia , Agricultura/legislação & jurisprudência , Brasil , Mudança Climática , Conservação dos Recursos Naturais/legislação & jurisprudência , Doença/etiologia , Ecossistema , Florestas , Humanos , Doenças Transmitidas por Vetores/transmissão
8.
BMC Med Res Methodol ; 22(1): 13, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027002

RESUMO

Age-stratified serosurvey data are often used to understand spatiotemporal trends in disease incidence and exposure through estimating the Force-of-Infection (FoI). Typically, median or mean FoI estimates are used as the response variable in predictive models, often overlooking the uncertainty in estimated FoI values when fitting models and evaluating their predictive ability. To assess how this uncertainty impact predictions, we compared three approaches with three levels of uncertainty integration. We propose a performance indicator to assess how predictions reflect initial uncertainty.In Colombia, 76 serosurveys (1980-2014) conducted at municipality level provided age-stratified Chagas disease prevalence data. The yearly FoI was estimated at the serosurvey level using a time-varying catalytic model. Environmental, demographic and entomological predictors were used to fit and predict the FoI at municipality level from 1980 to 2010 across Colombia.A stratified bootstrap method was used to fit the models without temporal autocorrelation at the serosurvey level. The predictive ability of each model was evaluated to select the best-fit models within urban, rural and (Amerindian) indigenous settings. Model averaging, with the 10 best-fit models identified, was used to generate predictions.Our analysis shows a risk of overconfidence in model predictions when median estimates of FoI alone are used to fit and evaluate models, failing to account for uncertainty in FoI estimates. Our proposed methodology fully propagates uncertainty in the estimated FoI onto the generated predictions, providing realistic assessments of both central tendency and current uncertainty surrounding exposure to Chagas disease.


Assuntos
Doença de Chagas , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Cidades , Colômbia/epidemiologia , Humanos , Prevalência , Incerteza
9.
Glob Chang Biol ; 27(7): 1319-1321, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33508882

RESUMO

Spillover of novel pathogens from wildlife to people, such as the virus responsible for the COVID-19 pandemic, is increasing and this trend is most strongly associated with tropical deforestation driven by agricultural expansion. This same process is eroding natural capital, reducing forest-associated health co-benefits, and accelerating climate change. Protecting and promoting tropical forests is one of the most immediate steps we can take to simultaneously mitigate climate change while reducing the risk of future pandemics; however, success in this undertaking will require greater connectivity of policy initiatives from local to global, as well as unification of health and environmental policy.


Assuntos
COVID-19 , Política Ambiental , Conservação dos Recursos Naturais , Florestas , Humanos , Pandemias , SARS-CoV-2 , Clima Tropical
10.
J Anim Ecol ; 90(6): 1480-1491, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33821505

RESUMO

Interactions between hosts and pathogens are dynamic at both ecological and evolutionary levels. In the resultant 'eco-evolutionary dynamics' ecological and evolutionary processes affect each other. For example, the house finch Haemorhous mexicanus and its recently emerged pathogen, the bacterium Mycoplasma gallisepticum, form a system in which evidence suggests that changes in bacterial virulence through time enhance levels of host immunity in ways that drive the evolution of virulence in an arms race. We use data from two associated citizen science projects in order to determine whether this arms race has had any detectable effect at the population level in the north-eastern United States. We used data from two citizen science projects, based on observations of birds at bird feeders, which provide information on the long-term changes in sizes of aggregations of house finches (host population density), and the probabilities that these house finches have observable disease (disease prevalence). The initial emergence of M. gallisepticum caused a rapid halving of house finch densities; this was then followed by house finch populations remaining stable or slowly declining. Disease prevalence also decreased sharply after the initial emergence and has remained low, although with fluctuations through time. Surprisingly, while initially higher local disease prevalence was found at sites with higher local densities of finches, this relationship has reversed over time. The ability of a vertebrate host species, with a generation time of at least 1 year, to maintain stable populations in the face of evolved higher virulence of a bacterium, with generation times measurable in minutes, suggests that genetic changes in the host are insufficient to explain the observed population-level patterns. We suggest that acquired immunity plays an important role in the observed interaction between house finches and M. gallisepticum.


Assuntos
Doenças das Aves , Tentilhões , Infecções por Mycoplasma , Mycoplasma gallisepticum , Animais , Doenças das Aves/epidemiologia , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/veterinária , Dinâmica Populacional
11.
Am Nat ; 196(2): E23-E45, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32673097

RESUMO

Environmentally mediated changes in body size often underlie population responses to environmental change, yet this is not a universal phenomenon. Understanding when phenotypic change underlies population responses to environmental change is important for obtaining insights and robust predictions of population dynamics in a changing world. We develop a dynamic integral projection model that mechanistically links environmental conditions to demographic rates and phenotypic traits (body size) via changes in resource availability and individual energetics. We apply the model to the northern Yellowstone elk population and explore population responses to changing patterns of seasonality, incorporating the interdependence of growth, demography, and density-dependent processes operating through population feedback on available resources. We found that small changes in body size distributions can have large impacts on population dynamics but need not cause population responses to environmental change. Environmental changes that altered demographic rates directly, via increasing or decreasing resource availability, led to large population impacts in the absence of substantial changes to body size distributions. In contrast, environmentally driven shifts in body size distributions could occur with little consequence for population dynamics when the effect of environmental change on resource availability was small and seasonally restricted and when strong density-dependent processes counteracted expected population responses. These findings highlight that a robust understanding of how associations between body size and demography influence population responses to environmental change will require knowledge of the shape of the relationship between phenotypic distributions and vital rates, the population status with regard to its carrying capacity, and importantly the nature of the environmentally driven change in body size and carrying capacity.


Assuntos
Peso Corporal , Cervos/fisiologia , Dinâmica Populacional , Animais , Feminino , Modelos Biológicos , Noroeste dos Estados Unidos , Fenótipo , Densidade Demográfica , Estações do Ano
12.
Conserv Biol ; 34(1): 66-79, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30843258

RESUMO

The importance of large reserves has been long maintained in the scientific literature, often leading to dismissal of the conservation potential of small reserves. However, over half the global protected-area inventory is composed of protected areas that are <100 ha, and the median size of added protected area is decreasing. Studies of the conservation value of small reserves and fragments of natural area are relatively uncommon in the literature. We reviewed SCOPUS and WOK for studies on small reserve and fragment contributions to biodiversity conservation and ecosystem services, and fifty-eight taxon-specific studies were included in the review. Small reserves harbored substantial portions (upward of 50%) of regional species diversity for many taxa (birds, plants, amphibians, and small mammals) and even some endemic, specialist bird species. Unfortunately, small reserves and fragments almost always harbored more generalist and exotic species than large reserves. Community composition depended on habitat quality, surrounding land use (agricultural vs. urban), and reserve and fragment size, which presents opportunities for management and improvement. Small reserves also provided ecosystem services, such as pollination and biological pest control, and cultural services, such as recreation and improved human health. Limitations associated with small reserves, such as extinction debt and support of area-sensitive species, necessitate a complement of larger reserves. However, we argue that small reserves can make viable and significant contributions to conservation goals directly as habitat and indirectly by increasing landscape connectivity and quality to the benefit of large reserves. To effectively conserve biodiversity for future generations in landscapes fragmented by human development, small reserves and fragments must be included in conservation planning.


Valor de Conservación de las Pequeñas Reservas Resumen La importancia de las reservas muy extensas se ha mantenido durante mucho tiempo dentro de la literatura científica, lo que comúnmente lleva a la desestimación del potencial de conservación de las reservas pequeñas. Sin embargo, más de la mitad del inventario mundial de áreas protegidas está compuesto por zonas resguardadas con un tamaño menor a las 100 ha, y el tamaño promedio de área protegida añadida está disminuyendo. Los estudios sobre el valor de conservación de las reservas pequeñas y los fragmentos de área natural son relativamente poco comunes en la literatura. Revisamos estudios sobre las contribuciones de las reservas pequeñas y los fragmentos a la conservación de la biodiversidad y los servicios ambientales en SCOPUS y en WOK. Se incluyeron 58 estudios específicos de taxón en la revisión. Las reservas pequeñas albergaron porciones sustanciales (más del 50%) de diversidad de especies regionales para muchos taxones e incluso algunas especies de aves endémicas y especialistas. Desafortunadamente, las reservas pequeñas y los fragmentos casi siempre albergaron más especies exóticas y generalistas que las reservas grandes. La composición de la comunidad dependió de la calidad del hábitat, el uso de suelo (urbano versus agrícola) adyacente y el tamaño de la reserva o el fragmento, lo que presenta oportunidades de manejo y mejora. Las reservas pequeñas también proporcionaron servicios ambientales, como la polinización y el control biológico de plagas, y servicios culturales, como la recreación y una mejor salud humana. Las limitaciones asociadas con las reservas pequeñas, como la deuda de extinción y el respaldo a especies sensibles al área, requieren de un complemento de reservas más grandes. Sin embargo, argumentamos que las reservas pequeñas pueden tener contribuciones viables y significativas para las metas de conservación directamente como hábitat e indirectamente con el incremento de la conectividad y la calidad de paisajes para el beneficio de las reservas más grandes. Para conservar efectivamente a la biodiversidad para generaciones futuras en paisajes fragmentados por el desarrollo humano, se debe incluir a las reservas pequeñas y a los fragmentos en la planeación de la conservación.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Animais , Biodiversidade , Aves , Humanos , Mamíferos
13.
Proc Biol Sci ; 286(1899): 20182772, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30914008

RESUMO

Understanding multi-host pathogen maintenance and transmission dynamics is critical for disease control. However, transmission dynamics remain enigmatic largely because they are difficult to observe directly, particularly in wildlife. Here, we investigate the transmission dynamics of canine parvovirus (CPV) using state-space modelling of 20 years of CPV serology data from domestic dogs and African lions in the Serengeti ecosystem. We show that, although vaccination reduces the probability of infection in dogs, and despite indirect enhancement of population seropositivity as a result of vaccine shedding, the vaccination coverage achieved has been insufficient to prevent CPV from becoming widespread. CPV is maintained by the dog population and has become endemic with approximately 3.5-year cycles and prevalence reaching approximately 80%. While the estimated prevalence in lions is lower, peaks of infection consistently follow those in dogs. Dogs exposed to CPV are also more likely to become infected with a second multi-host pathogen, canine distemper virus. However, vaccination can weaken this coupling, raising questions about the value of monovalent versus polyvalent vaccines against these two pathogens. Our findings highlight the need to consider both pathogen- and host-level community interactions when seeking to understand the dynamics of multi-host pathogens and their implications for conservation, disease surveillance and control programmes.


Assuntos
Doenças do Cão/transmissão , Leões , Infecções por Parvoviridae/veterinária , Parvovirus Canino/fisiologia , Animais , Teorema de Bayes , Doenças do Cão/epidemiologia , Cães , Ecossistema , Modelos Biológicos , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/transmissão , Prevalência , Estudos Soroepidemiológicos , Tanzânia/epidemiologia
14.
Glob Chang Biol ; 25(10): 3406-3423, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31282085

RESUMO

Fire is a key driver in savannah systems and widely used as a land management tool. Intensifying human land uses are leading to rapid changes in the fire regimes, with consequences for ecosystem functioning and composition. We undertake a novel analysis describing spatial patterns in the fire regime of the Serengeti-Mara ecosystem, document multidecadal temporal changes and investigate the factors underlying these patterns. We used MODIS active fire and burned area products from 2001 to 2014 to identify individual fires; summarizing four characteristics for each detected fire: size, ignition date, time since last fire and radiative power. Using satellite imagery, we estimated the rate of change in the density of livestock bomas as a proxy for livestock density. We used these metrics to model drivers of variation in the four fire characteristics, as well as total number of fires and total area burned. Fires in the Serengeti-Mara show high spatial variability-with number of fires and ignition date mirroring mean annual precipitation. The short-term effect of rainfall decreases fire size and intensity but cumulative rainfall over several years leads to increased standing grass biomass and fuel loads, and, therefore, in larger and hotter fires. Our study reveals dramatic changes over time, with a reduction in total number of fires and total area burned, to the point where some areas now experience virtually no fire. We suggest that increasing livestock numbers are driving this decline, presumably by inhibiting fire spread. These temporal patterns are part of a global decline in total area burned, especially in savannahs, and we caution that ecosystem functioning may have been compromised. Land managers and policy formulators need to factor in rapid fire regime modifications to achieve management objectives and maintain the ecological function of savannah ecosystems.


Assuntos
Ecossistema , Incêndios , Biomassa , Humanos , Poaceae , Imagens de Satélites
15.
J Org Chem ; 84(8): 4735-4747, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30352146

RESUMO

A multidisciplinary approach covering synthetic, physical, and analytical chemistry, high-throughput experimentation and experimental design, process engineering, and solid-state chemistry is used to develop a large-scale (kilomole) Suzuki-Miyaura process. Working against clear criteria and targets, a full process investigation and optimization package is described highlighting how and why key decisions are made in the development of large-scale pharmaceutical processes.


Assuntos
Desenho de Fármacos , Indústria Farmacêutica , Pirazinas/síntese química , Triazinas/síntese química , Ensaios de Triagem em Larga Escala , Estrutura Molecular , Pirazinas/química , Triazinas/química
16.
J Anim Ecol ; 88(7): 1001-1016, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30908623

RESUMO

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food. We aimed to (a) document the extent of henipa- and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data. To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa- and filovirus dynamics in three Madagascar fruit bat species. We uncovered serological evidence of exposure to Hendra-/Nipah-related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar-related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola-related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population-level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age-structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult-age bats. Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population-level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.


Assuntos
Quirópteros , Filoviridae , Infecções por Henipavirus , Animais , Feminino , Humanos , Recém-Nascido , Madagáscar , Estudos Soroepidemiológicos
17.
Conserv Biol ; 33(3): 665-675, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30238502

RESUMO

The threat posed to protected areas by the illegal killing of wildlife is countered principally by ranger patrols that aim to detect and deter potential offenders. Deterring poaching is a fundamental conservation objective, but its achievement is difficult to identify, especially when the prime source of information comes in the form of the patrols' own records, which inevitably contain biases. The most common metric of deterrence is a plot of illegal activities detected per unit of patrol effort (CPUE) against patrol effort (CPUE-E). We devised a simple, mechanistic model of law breaking and law enforcement in which we simulated deterrence alongside exogenous changes in the frequency of offences under different temporal patterns of enforcement effort. The CPUE-E plots were not reliable indicators of deterrence. However, plots of change in CPUE over change in effort (ΔCPUE-ΔE) reliably identified deterrence, regardless of the temporal distribution of effort or any exogenous change in illegal activity levels as long as the time lag between patrol effort and subsequent behavioral change among offenders was approximately known. The ΔCPUE-ΔE plots offered a robust, simple metric for monitoring patrol effectiveness; were no more conceptually complicated than the basic CPUE-E plots; and required no specialist knowledge or software to produce. Our findings demonstrate the need to account for temporal autocorrelation in patrol data and to consider appropriate (and poaching-activity-specific) intervals for aggregation. They also reveal important gaps in understanding of deterrence in this context, especially the mechanisms by which it occurs. In practical applications, we recommend the use of ΔCPUE-ΔE plots in preference to other basic metrics and advise that deterrence should be suspected only if there is a clear negative slope. Distinct types of illegal activity should not be grouped together for analysis, especially if the signs of their occurrence have different persistence times in the environment.


Detección de la Disuasión a Partir de Datos de Patrullaje Resumen La amenaza que representa la caza ilegal de fauna para las áreas protegidas está contrarrestada principalmente por las patrullas de guardias que buscan detectar y disuadir a los delincuentes potenciales. La disuasión de la caza furtiva es un objetivo fundamental de la conservación, pero es difícil identificar cuándo se logra, especialmente cuando la fuente principal de información proviene de los propios registros de las patrullas, que inevitablemente contiene sesgos. La medida más común de la disuasión es una parcela de actividades ilegales detectadas por unidad de esfuerzo de patrullaje (CPUE, en inglés) contra el esfuerzo de patrullaje (CPUE-E, en inglés). Diseñamos un modelo simple y mecánico del rompimiento y aplicación de la ley en el cual simulamos la disuasión junto con cambios exógenos en la frecuencia de ofensas bajo diferentes patrones temporales del esfuerzo de aplicación. Las parcelas de CPUE-E no fueron indicadores confiables de la disuasión. Sin embargo, las parcelas de cambio de CPUE sobre cambio en el esfuerzo (ΔCPUE-ΔE) identificaron con seguridad la disuasión sin importar la distribución temporal del esfuerzo o cualquier cambio exógeno en los niveles de actividad ilegal siempre y cuando el retraso en el tiempo entre el esfuerzo de patrullaje y el cambio en comportamiento subsecuente entre los delincuentes se conocía con cierta aproximación. Las parcelas de ΔCPUE-ΔE ofrecieron una medida simple y sólida para el monitoreo de la efectividad del patrullaje; no fueron más complicadas conceptualmente que las parcelas básicas de CPUE-E; y no requirieron de conocimiento de especialistas o algún software para producir. Nuestros hallazgos demuestran la necesidad de dar cuenta de la autocorrelación temporal en los datos de patrullaje y de considerar intervalos apropiados (y específicos a la actividad de caza furtiva) para su agregación. Nuestros hallazgos también revelan vacíos importantes en el entendimiento de la disuasión en este contexto, especialmente para los mecanismos mediante los cuales ocurre. En las aplicaciones prácticas recomendamos el uso de parcelas de ΔCPUE-ΔE por encima de otras medidas básicas y recomendamos que se sospeche de la disuasión sólo si existe una clara pendiente negativa. No se deben agrupar diferentes tipos de actividades ilegales para su análisis, especialmente si las señales de su ocurrencia tienen diferentes momentos de persistencia en el ambiente.


Assuntos
Conservação dos Recursos Naturais , Aplicação da Lei , Animais , Animais Selvagens
18.
Conserv Biol ; 33(1): 99-111, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29896899

RESUMO

Subsistence hunting presents a conservation challenge by which biodiversity preservation must be balanced with safeguarding of human livelihoods. Globally, subsistence hunting threatens primate populations, including Madagascar's endemic lemurs. We used population viability analysis to assess the sustainability of lemur hunting in Makira Natural Park, Madagascar. We identified trends in seasonal hunting of 11 Makira lemur species from household interview data, estimated local lemur densities in populations adjacent to focal villages via transect surveys, and quantified extinction vulnerability for these populations based on species-specific demographic parameters and empirically derived hunting rates. We compared stage-based Lefkovitch with periodic Leslie matrices to evaluate the impact of regional dispersal on persistence trajectories and explored the consequences of perturbations to the timing of peak hunting relative to the lemur birth pulse, under assumptions of density-dependent reproductive compensation. Lemur hunting peaked during the fruit-abundant wet season (March-June). Estimated local lemur densities were roughly inverse to body size across our study area. Life-history modeling indicated that hunting most severely threatened the species with the largest bodies (i.e., Hapalemur occidentalis, Avahi laniger, Daubentonia madagascariensis, and Indri indi), characterized by late-age reproductive onsets and long interbirth intervals. In model simulations, lemur dispersal within a regional metapopulation buffered extinction threats when a majority of local sites supported growth rates above the replacement level but drove regional extirpations when most local sites were overharvested. Hunt simulations were most detrimental when timed to overlap lemur births (a reality for D. madagascariensis and I. indri). In sum, Makira lemurs were overharvested. Regional extirpations, which may contribute to broad-scale extinctions, will be likely if current hunting rates persist. Cessation of anthropogenic lemur harvest is a conservation priority, and development programs are needed to help communities switch from wildlife consumption to domestic protein alternatives.


Assuntos
Lemur , Lemuridae , Animais , Biodiversidade , Conservação dos Recursos Naturais , Humanos , Madagáscar
19.
Biol Conserv ; 234: 165-171, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31937976

RESUMO

Madagascar is home to three endemic species of Old World Fruit Bat, which are important pollinators and seed dispersers. We aimed to quantitatively assess population trajectories for the two largest of these species, the IUCN-listed 'Vulnerable' Eidolon dupreanum and Pteropus rufus. To this end, we conducted a longitudinal field study, in which we live-captured E. dupreanum and P. rufus, estimated species-specific fecundity rates, and generated age-frequency data via histological analysis of cementum annuli layering in tooth samples extracted from a subset of individuals. We fit exponential models to resulting data to estimate annual survival probabilities for adult bats (s A = .794 for E. dupreanum; s A = .511 for P. rufus), then applied Lefkovitch modeling techniques to infer the minimum required juvenile survival rate needed to permit longterm population persistence. Given estimated adult survival, population persistence was only possible for E. dupreanum when field-based fecundity estimates were replaced by higher values reported in the literature for related species. For P. rufus, tooth-derived estimates of adult survival were so low that even assumptions of perfect (100%) juvenile annual survival would not permit stable population trajectories. Age-based survival analyses were further supported by longitudinal exit counts carried out from 2013-2018 at three local P. rufus roost sites, which demonstrated a statistically significant, faintly negative time trend, indicative of subtle regional population declines. These results suggest that Malagasy fruit bat species face significant threats to population viability, with P. rufus particularly imperiled. Immediate conservation interventions, including habitat restoration and cessation of legally sanctioned bat hunting, are needed to protect Madagascar's fruit bats into the future.

20.
Clin Infect Dis ; 66(suppl_4): S293-S300, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29860294

RESUMO

Background: The World Health Organization's 2020 goals for Chagas disease are (1) interrupting vector-borne intradomiciliary transmission and (2) having all infected people under care in endemic countries. Insecticide spraying has proved efficacious for reaching the first goal, but active transmission remains in several regions. For the second, treatment has mostly been restricted to recently infected patients, who comprise only a small proportion of all infected individuals. Methods: We extended our previous dynamic transmission model to simulate a domestic Chagas disease transmission cycle and examined the effects of both vector control and etiological treatment on achieving the operational criterion proposed by the Pan American Health Organization for intradomiciliary, vectorial transmission interruption (ie, <2% seroprevalence in children <5 years of age). Results: Depending on endemicity, an antivectorial intervention that decreases vector density by 90% annually would achieve the transmission interruption criterion in 2-3 years (low endemicity) to >30 years (high endemicity). When this strategy is combined with annual etiological treatment in 10% of the infected human population, the seroprevalence criterion would be achieved, respectively, in 1 and 11 years. Conclusions: Combining highly effective vector control with etiological (trypanocidal) treatment in humans would substantially reduce time to transmission interruption as well as infection incidence and prevalence. However, the success of vector control may depend on prevailing vector species. It will be crucial to improve the coverage of screening programs, the performance of diagnostic tests, the proportion of people treated, and the efficacy of trypanocidal drugs. While screening and access can be incremented as part of strengthening the health systems response, improving diagnostics performance and drug efficacy will require further research.


Assuntos
Doença de Chagas/prevenção & controle , Erradicação de Doenças , Insetos Vetores/efeitos dos fármacos , Inseticidas/administração & dosagem , Modelos Teóricos , Tripanossomicidas/administração & dosagem , Trypanosoma cruzi/imunologia , Animais , Doença de Chagas/tratamento farmacológico , Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Humanos , Incidência , Controle de Insetos , Insetos Vetores/parasitologia , Prevalência , Estudos Soroepidemiológicos
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