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1.

Background

Snakebites are a public health problem in Nicaragua: it is a tropical developing country, venomous snakes are present and there are reports of snakebites treated both in the formal and informal health care system. We aimed to produce an incidence map using data reported by the health care system that would be used to allocate resources. However, this map may suffer from case detection bias and decisions based on this map will neglect snakebite victims who do not receive healthcare. To avoid this error, we try to identify where underreporting is likely based on available information.

Method and Findings

The Nicaraguan municipalities are categorized by precipitation, altitude and geographical location into regions of assumed homogenous snake prevalence. Socio-economic and healthcare variables hypothesized to be related to underreporting of snakebites are aggregated into an index. The environmental region variable, the underreporting index and three demographic variables (rurality, sex and age distribution) are entered in a Poisson regression model of municipality-level snakebite incidence. In this model, the underreporting index is non-linearly associated with snakebite incidence, a finding we attribute to underreporting in the most deprived municipalities. The municipalities with the worst scoring on the underreporting index and those with combined low reported incidence and large rural population are identified as likely underreporting. 3,286 snakebite cases were reported in 2005–2009, corresponding to a 5-year incidence of 56 bites per 100,000 inhabitants (municipality range: 0–600 cases per 100,000 inhabitants).

Conclusions

Using publicly available data, we identified areas likely to be underreporting snakebites and highlighted these areas instead of leaving them “white” on the incidence map. The effects of the case detection bias on the distribution of resources against snakebites could decrease. Although not yet verified empirically, our study provides an example of how snake bite epidemiology may be investigated in similar settings worldwide at a low cost.  相似文献   

2.
In epidemic models, the effective reproduction number is of central importance to assess the transmission dynamics of an infectious disease and to orient health intervention strategies. Publicly shared data during an outbreak often suffers from two sources of misreporting (underreporting and delay in reporting) that should not be overlooked when estimating epidemiological parameters. The main statistical challenge in models that intrinsically account for a misreporting process lies in the joint estimation of the time-varying reproduction number and the delay/underreporting parameters. Existing Bayesian approaches typically rely on Markov chain Monte Carlo algorithms that are extremely costly from a computational perspective. We propose a much faster alternative based on Laplacian-P-splines (LPS) that combines Bayesian penalized B-splines for flexible and smooth estimation of the instantaneous reproduction number and Laplace approximations to selected posterior distributions for fast computation. Assuming a known generation interval distribution, the incidence at a given calendar time is governed by the epidemic renewal equation and the delay structure is specified through a composite link framework. Laplace approximations to the conditional posterior of the spline vector are obtained from analytical versions of the gradient and Hessian of the log-likelihood, implying a drastic speed-up in the computation of posterior estimates. Furthermore, the proposed LPS approach can be used to obtain point estimates and approximate credible intervals for the delay and reporting probabilities. Simulation of epidemics with different combinations for the underreporting rate and delay structure (one-day, two-day, and weekend delays) show that the proposed LPS methodology delivers fast and accurate estimates outperforming existing methods that do not take into account underreporting and delay patterns. Finally, LPS is illustrated in two real case studies of epidemic outbreaks.  相似文献   

3.
BackgroundEffective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India’s most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence.MethodsExpenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider’s perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD.ResultsDuring 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81, $4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from $1.6–4 million, depending on the extent to which blanket and camp ACD was relied upon.ConclusionCost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India.  相似文献   

4.
An analysis of T cell responsiveness in Indian kala-azar   总被引:30,自引:0,他引:30  
The inability of most untreated patients with Kala-azar to control their visceral infections with Leishmania donovani has been attributed to a defective cell-mediated immune response to leishmanial antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of Kala-azar, there is an absence of Leishmania-specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of asymptomatic infection than is ELISA. Identification of such an exposed, Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals.  相似文献   

5.
BackgroundLeprosy remains concentrated among the poorest communities in low-and middle-income countries and it is one of the primary infectious causes of disability. Although there have been increasing advances in leprosy surveillance worldwide, leprosy underreporting is still common and can hinder decision-making regarding the distribution of financial and health resources and thereby limit the effectiveness of interventions. In this study, we estimated the proportion of unreported cases of leprosy in Brazilian microregions.Methodology/Principal findingsUsing data collected between 2007 to 2015 from each of the 557 Brazilian microregions, we applied a Bayesian hierarchical model that used the presence of grade 2 leprosy-related physical disabilities as a direct indicator of delayed diagnosis and a proxy for the effectiveness of local leprosy surveillance program. We also analyzed some relevant factors that influence spatial variability in the observed mean incidence rate in the Brazilian microregions, highlighting the importance of socioeconomic factors and how they affect the levels of underreporting. We corrected leprosy incidence rates for each Brazilian microregion and estimated that, on average, 33,252 (9.6%) new leprosy cases went unreported in the country between 2007 to 2015, with this proportion varying from 8.4% to 14.1% across the Brazilian States.Conclusions/SignificanceThe magnitude and distribution of leprosy underreporting were adequately explained by a model using Grade 2 disability as a marker for the ability of the system to detect new missing cases. The percentage of missed cases was significant, and efforts are warranted to improve leprosy case detection. Our estimates in Brazilian microregions can be used to guide effective interventions, efficient resource allocation, and target actions to mitigate transmission.  相似文献   

6.
Background: Population-based cancer registries (PBCR) are important in cancer epidemiology as they provide the basis for monitoring cancer incidence. Childhood acute lymphoblastic leukemia (ALL) is said to have lower incidence in developing countries, which has implications for its pathogenesis, but there are few studies concerning the completeness of cancer registries in developing countries. This study analyzes the number of cases and incidence of childhood acute lymphoblastic leukemia in three different cities in Brazil and estimates underreporting cases and possible PBCR failures. Methods: We evaluated the completeness of PBCR and the incidence rates of childhood ALL from three different Brazilian cities using the two-source capture–recapture method. The sources used were a population-based registry and databases from a diagnosis reference laboratory in 2001 and the Chapman's formula was used to calculate the estimates. Results: The estimated incidence was 5.76, 6.32 and 5.48 per 100,000 inhabitants for Salvador, Recife and Belo Horizonte, respectively. The estimated completeness of childhood ALL in PBCRs was 15.5%, 35.4% and 29.2%, respectively, for Salvador, Recife and Belo Horizonte. Conclusions: There was a high estimated underreporting of childhood leukemia cases in some Brazilian cities. The relationship between information systems and the capture–recapture method application improved epidemiological estimates. Childhood acute lymphoblastic leukemia incidence rates are similar to those of developed countries.  相似文献   

7.
Background: Currently, only 7 out of 16 Federal States of Germany provide testicular cancer incidence rates with an estimated completeness of at least 90% which complicates the regional comparison of incidence rates. The aim of this study was to provide a novel approach to estimate the testicular cancer incidence in Germany by using nationwide hospitalization data. Methods: We used the nationwide hospitalization data (DRG statistics) of the years 2005–2006 including 16,6 million hospitalizations among men. We identified incident testicular cancer cases by the combination of a diagnosis of testicular cancer and an orchiectomy during the same hospitalization and estimated the age-specific and age-standardized (World Standard Population) incidence of testicular cancer across Federal States. We also analyzed available cancer registry data from 2005 to 2006. Results: A total of 8544 hospitalizations indicated incident testicular cancer cases in 2005–2006. The nationwide crude incidence rate of testicular cancer was 10,6 per 100.000 person-years. The ratio of the number of registered cases (cancer registry) to the estimated number of cases based on the hospitalization statistics ranged between 79% and 100%. There was only little variation of the age-standardized DRG-based incidence estimates across Federal States (range: 8,2–10,6 per 100.000 person-years). Discussion: We provided testicular cancer incidence estimates for each of the 16 Federal States of Germany based on hospitalization data for the first time. The low within-population incidence variability in Germany and high between-population incidence variability in Europe may indicate that ecologic factors play a causal role in the European variation of testicular cancer.  相似文献   

8.

Introduction

In 2005, Bangladesh, India, and Nepal joined forces to eliminate Visceral Leishmaniasis (or kala-azar) from the region by 2015. In Bangladesh the elimination target is set at less than one new case per 10,000 population per year at upazila (sub-district) level. As the deadline approaches, we review the status of the elimination initiative in this country.

Methods

We collected all available disease surveillance data at the Disease Control Unit of the Directorate General of Health Services, Government of Bangladesh from 1994 to 2013. Additionally, we retrieved data from the Civil Surgeon Office from the Mymensingh district, one of the most heavily affected areas in Bangladesh.

Results

Between 1994 and 2013, 109,266 kala-azar cases causing 329 deaths were reported from 37 endemic districts in Bangladesh. Only 16 districts reported cases every year. The Mymensingh district was the most affected with 53,582 (49.04%) cases. Between 2008 and 2013 only 16 upazilas showed incidence rates above the elimination target in which they ranged from 1.06 to 18.25 per 10,000 people per year.

Discussion

While clear progress has been made towards eliminating VL, 16 upazilas in Bangladesh had not yet reached the target in 2013, based on official notification data that probably suffered from under-reporting bias. The elimination initiative urgently needs to establish methods to ascertain and monitor the elimination target.  相似文献   

9.

Background

Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India—an area highly endemic for Leishmania donovani—using this regimen as first-line treatment.

Methods and Principal Findings

Intravenous Ambisome 20 mg/kg was administered in four doses of 5 mg/kg over 4–10 days, depending on the severity of disease. Initial clinical cure at discharge was defined as improved symptoms, cessation of fever, and recession of spleen enlargement. This observational retrospective cohort study describes 8749 patients with laboratory-confirmed primary VL treated over a 5-year period: 1396 at primary healthcare centers, 7189 at hospital, and 164 at treatment camps. Initial clinical cure was achieved in 99.3% of patients (8692/8749); 0.3% of patients (26/8749) defaulted from treatment and 0.4% (31/8749) died. Overall, 1.8% of patients (161/8749) were co-infected with HIV and 0.6% (51/8749) with tuberculosis. Treatment was discontinued because of severe allergic reactions in 0.1% of patients (7/8749). Overall, 27 patients (0.3%) were readmitted with post Kala-azar dermal leishmaniasis (PKDL). Risk factors for late presentation included female sex, age >15 years and being from a scheduled caste.In 2012, a long-term efficacy survey in the same area of Bihar determined relapse rates of VL after 5 years'' intervention with Ambisome. Of 984 immunocompetent patients discharged between September 2010 and December 2011, 827 (84.0%) were traced in order to determine their long-term outcomes. Of these, 20 patients (2.4%) had relapsed or received further treatment for VL. Of those completing 6, 12, and 15 month follow-up, 0.3% (2/767), 3.7% (14/383), and 2.4% (4/164), respectively, had relapsed. The mean ±SD time-to-relapse was 9.6±3.0 months.

Significance

This is the largest cohort of VL patients treated with 20 mg/kg Ambisome worldwide. The drug has high initial and long-term efficacy, and a low rate of adverse reactions when administered under field conditions in Bihar, India. Although challenging, its use as first line treatment in rural settings in Bihar is safe and feasible.  相似文献   

10.
Colombia announced the first case of severe acute respiratory syndrome coronavirus 2 on March 6, 2020. Since then, the country has reported a total of 5,002,387 cases and 127,258 deaths as of October 31, 2021. The aggressive transmission dynamics of SARS-CoV-2 motivate an investigation of COVID-19 at the national and regional levels in Colombia. We utilize the case incidence and mortality data to estimate the transmission potential and generate short-term forecasts of the COVID-19 pandemic to inform the public health policies using previously validated mathematical models. The analysis is augmented by the examination of geographic heterogeneity of COVID-19 at the departmental level along with the investigation of mobility and social media trends. Overall, the national and regional reproduction numbers show sustained disease transmission during the early phase of the pandemic, exhibiting sub-exponential growth dynamics. Whereas the most recent estimates of reproduction number indicate disease containment, with Rt<1.0 as of October 31, 2021. On the forecasting front, the sub-epidemic model performs best at capturing the 30-day ahead COVID-19 trajectory compared to the Richards and generalized logistic growth model. Nevertheless, the spatial variability in the incidence rate patterns across different departments can be grouped into four distinct clusters. As the case incidence surged in July 2020, an increase in mobility patterns was also observed. On the contrary, a spike in the number of tweets indicating the stay-at-home orders was observed in November 2020 when the case incidence had already plateaued, indicating the pandemic fatigue in the country.  相似文献   

11.
The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden.  相似文献   

12.
Exceptional climatic events from 2003 to 2005 (scorching heat and drought) affected the whole of the vegetation in the French Mediterranean region and in particular the Scots pine (Pinus sylvestris L.), one of the most important forest tree species in this area. To understand its response to these extreme conditions, we investigated its radial growth, branch length growth, architectural development and reproduction for the period 1995–2005, and linked these variables to climatic parameters. We used four plots situated in southeastern France and presenting different levels of site quality and potential forest productivity. The results show that: (1) the climatic episode 2003–2005 was highly detrimental to the growth (bole and branches), crown development, and cone production but favored the production of male flowers; (2) these variables depend on climatic factors of both the current and previous years; (3) the 2003 scorching heat impact was strong but was mainly apparent from 2004; it was part of a 6-year-long unfavorable cycle beginning in 2000, characterized by high minimum and maximum temperatures and very dry springs; (4) in spite of a significant effect of site quality, the Scots pine’s response to extreme climatic conditions was homogeneous in the French Mediterranean area; and (5) the stress induced by poor site conditions generally resulted in the same consequences for tree growth, architecture, and reproduction as in unfavorable climatic conditions.  相似文献   

13.

Background

Dengue virus infection is the most common arthropod-borne disease of humans and its geographical range and infection rates are increasing. Health policy decisions require information about the disease burden, but surveillance systems usually underreport the total number of cases. These may be estimated by multiplying reported cases by an expansion factor (EF).

Methods and Findings

As a key step to estimate the economic and disease burden of dengue in Southeast Asia (SEA), we projected dengue cases from 2001 through 2010 using EFs. We conducted a systematic literature review (1995–2011) and identified 11 published articles reporting original, empirically derived EFs or the necessary data, and 11 additional relevant studies. To estimate EFs for total cases in countries where no empirical studies were available, we extrapolated data based on the statistically significant inverse relationship between an index of a country''s health system quality and its observed reporting rate. We compiled an average 386,000 dengue episodes reported annually to surveillance systems in the region, and projected about 2.92 million dengue episodes. We conducted a probabilistic sensitivity analysis, simultaneously varying the most important parameters in 20,000 Monte Carlo simulations, and derived 95% certainty level of 2.73–3.38 million dengue episodes. We estimated an overall EF in SEA of 7.6 (95% certainty level: 7.0–8.8) dengue cases for every case reported, with an EF range of 3.8 for Malaysia to 19.0 in East Timor.

Conclusion

Studies that make no adjustment for underreporting would seriously understate the burden and cost of dengue in SEA and elsewhere. As the sites of the empirical studies we identified were not randomly chosen, the exact extent of underreporting remains uncertain. Nevertheless, the results reported here, based on a systematic analysis of the available literature, show general consistency and provide a reasonable empirical basis to adjust for underreporting.  相似文献   

14.

Background

Several approaches have been used for measuring HIV incidence in large areas, yet each presents specific challenges in incidence estimation.

Methodology/Principal Findings

We present a comparison of incidence estimates for Kenya and Uganda using multiple methods: 1) Epidemic Projections Package (EPP) and Spectrum models fitted to HIV prevalence from antenatal clinics (ANC) and national population-based surveys (NPS) in Kenya (2003, 2007) and Uganda (2004/2005); 2) a survey-derived model to infer age-specific incidence between two sequential NPS; 3) an assay-derived measurement in NPS using the BED IgG capture enzyme immunoassay, adjusted for misclassification using a locally derived false-recent rate (FRR) for the assay; (4) community cohorts in Uganda; (5) prevalence trends in young ANC attendees. EPP/Spectrum-derived and survey-derived modeled estimates were similar: 0.67 [uncertainty range: 0.60, 0.74] and 0.6 [confidence interval: (CI) 0.4, 0.9], respectively, for Uganda (2005) and 0.72 [uncertainty range: 0.70, 0.74] and 0.7 [CI 0.3, 1.1], respectively, for Kenya (2007). Using a local FRR, assay-derived incidence estimates were 0.3 [CI 0.0, 0.9] for Uganda (2004/2005) and 0.6 [CI 0, 1.3] for Kenya (2007). Incidence trends were similar for all methods for both Uganda and Kenya.

Conclusions/Significance

Triangulation of methods is recommended to determine best-supported estimates of incidence to guide programs. Assay-derived incidence estimates are sensitive to the level of the assay''s FRR, and uncertainty around high FRRs can significantly impact the validity of the estimate. Systematic evaluations of new and existing incidence assays are needed to the study the level, distribution, and determinants of the FRR to guide whether incidence assays can produce reliable estimates of national HIV incidence.  相似文献   

15.

Background

Visceral Leishmaniasis (VL) is a vector-borne disease transmitted by Phlebotomus argentipes. To understand the VL seasonality, annual and monthly variations of VL incidence and its relationship to meteorological variables, the numbers of VL cases reported in Muzaffarpur district, Bihar, India from 1990 to 2008 were studied.

Methods

Annual VL incidence per 10,000 and the total number of annual VL cases reported at block Community Health Centres (CHC), Public Hospitals or Non-Governmental Organisations (NGO) and the number of VL cases per month from 2000 to 2008 as well as the monthly average of cases for 2000–08, 2000–04 and 2005–08 periods along with the monthly averages of temperature, rainfall and relative humidity were plotted. VL Standardised Incidence Ratios per block were computed for the periods of 1990–1993, 1994–1998, 1999–2004 and 2005–2008 and month wise from 2002 to 2008. A negative binomial regression model was used to evaluate the association between meteorological variables and the number of VL cases per month from 2000 to 2008.

Results

A total of 68,358 VL cases were reported in Muzaffarpur district from 1990 to 2008, ranging from 1,2481 in 1992 to 1,161 in 2001. The blocks with the highest number of cases shifted from East (1990–98) to West (1999–2008). Monthly averages of cases ranged from 149 to 309, highest peak in March–April and another one in July. Monthly VL incidence was associated positively to rainfall and negatively to relative humidity and the numbers of VL cases in the previous month.

Interpretation

The number of cases reported to the public health sector allowed the describing of the spatial distribution and temporal variations in the Muzaffarpur from 1990 to 2008. However, to assess the actual VL burden, as well as the efficacy of the control measures applied in the district, reporting from private practices and NGOs should be encouraged.  相似文献   

16.
Length frequency data collected from artisanal fisheries in Lake Ayamé I (Côte d'Ivoire) from August 2004 to 2005 were analysed with F isat software using the E lefan package to estimate the population parameters of 11 fish species. Asymptotic values for total length ( L∞ ) ranged from 20.5 cm for Brycinus imberi to 78 cm for Mormyrops anguilloides . Growth rates ( k ) varied from 0.24 year−1 for Chrysichthys nigrodigitatus to 0.57 year−1 for Hemichromis fasciatus . The growth performance estimates were close to the values found by others authors and reported in FishBase 2008. Fishing mortality ( F ) and exploitation rate ( E ) were found to be below optimum levels of exploitation for most fish species. Recruitment was noted as year–round and bimodal for most studied populations. The data sets were limited in most cases, thus this study provides preliminary population parameters only, but for species for which information is scarce. For application in stock assessment, the growth parameters and especially the natural mortality data require further confirmation.  相似文献   

17.
In order to estimate the level of under-reporting and to improve estimates of the incidence of tuberculosis (TB) in the vicinity of Cayenne, French Guiana, we performed capture-recapture analysis from 1996 through 2003. We cross-linked data from the Institut Pasteur, the Département d'Information Médicale of Cayenne Hospital, and the Service de Lutte Anti-Tuberculeuse. The estimate of 381 TB cases obtained after matching those three sources was revised to 425 (95% confidence interval: 407, 453) using the capture-recapture model based on sample coverage. The corresponding average annual incidence was 63.1 TB cases per 100,000 population. The evaluated sensitivity of the compulsory notification system was 35.3%, indicating wide under-notification of TB in the vicinity of Cayenne. The estimated coverage reported by the three sources was fairly accurate (i.e. 85.9%), but not sufficient to evaluate the risk of transmission of TB in the Ile-de-Cayenne (Cayenne and its suburbs).  相似文献   

18.
Personal genome tests are now offered direct-to-consumer (DTC) via genetic variants identified by genome-wide association studies (GWAS) for common diseases. Tests report risk estimates (age-specific and lifetime) for various diseases based on genotypes at multiple loci. However, uncertainty surrounding such risk estimates has not been systematically investigated. With breast cancer as an example, we examined the combined effect of uncertainties in population incidence rates, genotype frequency, effect sizes, and models of joint effects among genetic variants on lifetime risk estimates. We performed simulations to estimate lifetime breast cancer risk for carriers and noncarriers of genetic variants. We derived population-based cancer incidence rates from Surveillance, Epidemiology, and End Results (SEER) Program and comparative international data. We used data for non-Hispanic white women from 2003 to 2005. We derived genotype frequencies and effect sizes from published GWAS and meta-analyses. For a single genetic variant in FGFR2 gene (rs2981582), combination of uncertainty in these parameters produced risk estimates where upper and lower 95% simulation intervals differed by more than 3-fold. Difference in population incidence rates was the largest contributor to variation in risk estimates. For a panel of five genetic variants, estimated lifetime risk of developing breast cancer before age 80 for a woman that carried all risk variants ranged from 6.1% to 21%, depending on assumptions of additive or multiplicative joint effects and breast cancer incidence rates. Epidemiologic parameters involved in computation of disease risk have substantial uncertainty, and cumulative uncertainty should be properly recognized. Reliance on point estimates alone could be seriously misleading.  相似文献   

19.
Large carnivores are elusive and use large areas, which causes monitoring to be challenging and costly. Moreover, management to reduce conflicts and simultaneously ensure long-term population viability require precise population estimates. In Scandinavia, the monitoring of wolves (Canis lupus) is primarily based on counting packs, identifying reproduction, and genetically identifying territorial wolves from noninvasive DNA samples. We assessed the reliability of wolf monitoring in Scandinavia by estimating the detectability of territorial pairs, packs, and reproduction. Our data, comprising snow-tracking data and DNA-identified individuals from 2005–2016, covered 11 consecutive winter monitoring seasons (Oct–Mar). Among 343 cases where we identified a wolf pack, territorial wolves were also detected in the same area during the previous season in 323 (94.2%) cases. In only 6 of the remaining 20 cases, there was no prior knowledge of territorial wolves in the area. Among the 328 detected reproduction events (litter born to a pack), we detected 97% during the monitoring period and identified the rest ≥1 year later from kinship assessments of all DNA-detected individuals. These results suggest that we failed to detect only few packs with reproduction events during the monitoring season that followed breeding. Yearly monitoring of territorial individuals and continuous updates of the pedigree allowed us to retrospectively identify reproduction events and packs that were not identified earlier.  相似文献   

20.
Incidence of cholera outbreak is a serious issue in underdeveloped and developing countries. In Zimbabwe, after the massive outbreak in 2008–09, cholera cases and deaths are reported every year from some provinces. Substantial number of reported cholera cases in some provinces during and after the epidemic in 2008–09 indicates a plausible presence of seasonality in cholera incidence in those regions. We formulate a compartmental mathematical model with periodic slow-fast transmission rate to study such recurrent occurrences and fitted the model to cumulative cholera cases and deaths for different provinces of Zimbabwe from the beginning of cholera outbreak in 2008–09 to June 2011. Daily and weekly reported cholera incidence data were collected from Zimbabwe epidemiological bulletin, Zimbabwe Daily cholera updates and Office for the Coordination of Humanitarian Affairs Zimbabwe (OCHA, Zimbabwe). For each province, the basic reproduction number () in periodic environment is estimated. To the best of our knowledge, this is probably a pioneering attempt to estimate in periodic environment using real-life data set of cholera epidemic for Zimbabwe. Our estimates of agree with the previous estimate for some provinces but differ significantly for Bulawayo, Mashonaland West, Manicaland, Matabeleland South and Matabeleland North. Seasonal trend in cholera incidence is observed in Harare, Mashonaland West, Mashonaland East, Manicaland and Matabeleland South. Our result suggests that, slow transmission is a dominating factor for cholera transmission in most of these provinces. Our model projects cholera cases and cholera deaths during the end of the epidemic in 2008–09 to January 1, 2012. We also determine an optimal cost-effective control strategy among the four government undertaken interventions namely promoting hand-hygiene & clean water distribution, vaccination, treatment and sanitation for each province.  相似文献   

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