Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

ABSTRACT: BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighbouring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30\% lower with a rate ratio of 0.70 (95\% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20\% and 40\%. DISCUSSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.     

Confronting models with data

Until now, most of the mathematical modelling work on nosocomial infections has used simple models that have permitted qualitative, but not reliable quantitative predictions about the likely effect of different interventions. Increasingly, researchers would like to use models to provide reliable quantitative answers to both scientific and policy questions. This requires confronting models with data. Here, we discuss the importance of this confrontation with data with reference to previous modelling work, and outline the standard methods for doing this. We then describe a powerful new set of tools that promises to allow us to provide better answers to such questions, making far greater use than current methods of the information content of highly detailed hospital infection datasets. These tools should allow us to address questions that would have been impossible to answer using previous analytical techniques.     

Review of the validation of models used in Federal Insecticide,Fungicide, and Rodenticide Act environmental exposure assessments

The first activity of the Federal Insecticide. Fungicide, and Rodenticide Act (FIFRA) Environmental Model Validation Task Force, established to increase confidence in the use of environmental models used in regulatory assessments, was to review the literature information on validation of the pesticide root zone model (PRZM) and the groundwater loading effects of agricultural management systems (GLEAMS). This literature information indicates that these models generally predict the same or greater leaching than observed in actual field measurements, suggesting that these models are suitable for use in regulatory assessments. However, additional validation research conducted using the newest versions of the models would help improve confidence in runoff and leaching predictions because significant revisions have been made in models over the years, few of the literature studies focused on runoff losses, the number of studies having quantitative validation results is minimal, and modelers were aware of the field results in most of the literature studies. Areas for special consideration in conducting model validation research include improving the process for selecting input parameters, developing recommendations for performing calibration simulations, devising appropriate procedures for keeping results of field studies from modelers performing simulations to validate model predictions while providing access for calibration simulations, and developing quantitative statistical procedures for comparing model predictions with experimental results.     

Prediction of epidemic cholera due to Vibrio cholerae O1 in children younger than 10 years using climate data in Bangladesh

To determine if a prediction of epidemic cholera using climate data can be made, we performed autoregression analysis using the data recorded in Dhaka City, Bangladesh over a 20-year period (1983-2002) comparing the number of children aged <10 years who were infected with Vibrio cholerae O1 to the maximum and minimum temperatures and rainfall. We formulated a simple autoregression model that predicts the monthly number of patients using earlier climate variables. The monthly number of patients predicted by this model agreed well with the actual monthly number of patients where the Pearson's correlation coefficient was 0.95. Arbitrarily defined, 39.4% of the predicted numbers during the study period were within 0.8-1.2 times the observed numbers. This prediction model uses the climate data recorded 2-4 months before. Therefore, our approach may be a good basis for establishing a practical early warning system for epidemic cholera.     

Genetic Prediction of Quantitative Lipid Traits: Comparing Shrinkage Models to Gene Scores

Accurate genetic prediction of quantitative traits related to complex disease risk would have potential clinical impact, so investigation of statistical methodology to improve predictive performance is important. We compare a simple approach of polygenic scores using top ranking single nucleotide polymorphisms (SNPs) to a set of shrinkage models, namely Ridge Regression, Lasso and Hyper‐Lasso. These penalised regression methods analyse all genotyped SNPs simultaneously, potentially including much larger sets of SNPs in the models, not only those with the smallest P values. We compare the accuracy of these models for predicting low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) cholesterol, two lipid traits of clinical relevance, in the Whitehall II and British Women's Health and Heart Study cohorts, using SNPs from the HumanCVD BeadChip. For gene scores, the most accurate predictions arise from multivariate weighted scores and include only a small number of SNPs, identified as top hits by the HumanCVD BeadChip. Furthermore, there was little benefit from including external results from published sets of SNPs. We found that shrinkage approaches rarely improved significantly on gene score results. Genetic predictive performance is trait specific, depending on the heritability and genetic architecture of the trait, and is limited by the training data sample size. Our results for lipid traits suggest no current benefit of more complex methods over existing gene score methods. Instead, the most important choice for the prediction model is the number of SNPs and selection of the most predictive SNPs to include. However further comparisons, in larger samples and for other phenotypes, would still be of interest.     

脉冲场凝胶电泳分型方法追溯霍乱传染源

目的　了解四川省 2 0 0 4年霍乱疫情分离菌株与常规监测的外环境和水产品中霍乱弧菌分离株之间的遗传相关性 ,追溯传染源 ,为预测疫情和制定防治措施提供依据。方法　O139群霍乱弧菌编码脂多糖 (LPS)特异性基因引物聚合酶链反应 (PCR)复核菌株 ,霍乱毒素 (CT)基因引物PCR检测霍乱毒力基因 ,脉冲场凝胶电泳 (PFGE)进行菌株的分子分型。结果　 2 5株受试菌株LPS基因 2对引物PCR结果均为阳性。所有 6株河水中分离的菌株均为CT基因阴性 ,其余均具有CT基因。 2 4株菌PFGE可分为 13个型。结论　LPS基因PCR检测结果从分子水平证实受试菌株均为O139群霍乱弧菌。河水中分离的 6株菌是非产毒株 ,其余菌株均具有致病性。环境水分离的O139群非产毒株之间以及产毒株与非产毒株之间遗传相关性较远。产毒株之间具有较高的同源性。四川省从甲鱼分离的O139群霍乱弧菌与同期流行的O139群霍乱弧菌分型的带型一致 ,在国内首次以分子流行病学分析提示甲鱼可能是四川省近年霍乱疫情主要传染来源之一。     

Cost–benefit comparisons of investments in improved water supply and cholera vaccination programs

This paper presents the first cost–benefit comparison of improved water supply investments and cholera vaccination programs. Specifically, we compare two water supply interventions – deep wells with public hand pumps and biosand filters (an in-house, point-of-use water treatment technology) – with two types of cholera immunization programs with new-generation vaccines – general community-based and targeted and school-based programs. In addition to these four stand-alone investments, we also analyze five combinations of water and vaccine interventions: (1) borehole + hand pump and community-based cholera vaccination, (2) borehole + hand pump and school-based cholera vaccination, (3) biosand filter and community-based cholera vaccination, (4) biosand filter and school-based cholera vaccination, and (5) biosand filter and borehole + hand pump. Using recent data applicable to developing country locations for parameters such as disease incidence, the effectiveness of vaccine and water supply interventions against diarrheal diseases, and the value of a statistical life, we construct cost–benefit models for evaluating these interventions. We then employ probabilistic sensitivity analysis to estimate a frequency distribution of benefit–cost ratios for all four interventions, given a wide variety of possible parameter combinations. Our results demonstrate that there are many plausible conditions in developing countries under which these interventions will be attractive, but that the two improved water supply interventions and the targeted cholera vaccination program are much more likely to yield attractive cost–benefit outcomes than a community-based vaccination program. We show that implementing community-based cholera vaccination programs after borehole + hand pump or biosand filters have already been installed will rarely be justified. This is especially true when the biosand filters are already in place, because these achieve substantial cholera risk reductions on their own. On the other hand, implementing school-based cholera vaccination programs after the installation of boreholes with hand pump is more likely to be economically attractive. Also, if policymakers were to first invest in cholera vaccinations, then subsequently investing in water interventions is still likely to yield positive economic outcomes. This is because point-of-use water treatment delivers health benefits other than reduced cholera, and deep boreholes + hand pumps often yield non-health benefits such as time savings.     

Cholera, canals, and contagion: Rediscovering Dr. Beck's report

Cholera first appeared in North America (in Montreal and Quebec) in 1832 and spread rapidly across the eastern half of the continent. The dispatch of American disease control experts to Lower Canada in anticipation of cholera's spread implies that medical professionals expected spread, possibly from contagion, even though the notion that cholera was contagious was disparaged in medical writings of the time, and would be until John Snow's landmark work in London in the 1850s. Snow's insights derived largely from his observations on spatial and temporal patterns of cholera cases. We discuss a document from the 1832 epidemic, the report of Dr. Lewis Beck to New York's Governor Throop, which anticipates Snow in presenting geospatial data that imply cholera's contagiousness. Beck shows that the movements of immigrants along the newly completed New York state canal system resulted in sequential cholera outbreaks along the canal's path. Although aware of the degree to which this suggested contagion, Beck argues strenuously against the contagiousness of cholera. We explore the social context of early nineteenth-century medicine that probably led Beck to disbelieve his own observations, and to favor a medical model inconsistent with his data. Themes that emerge from our inquiry include belief in disease as a physical manifestation of defective morality, stigmatization of the poor and immigrant groups, and reluctance to overturn prevailing medical models that themselves reflected the economic position of medical practitioners. We show that these themes continue to serve as obstacles to innovation in medical and public health practice today.     

Cholera transmission dynamic models for public health practitioners

Great progress has been made in mathematical models of cholera transmission dynamics in recent years. However, little impact, if any, has been made by models upon public health decision-making and day-to-day routine of epidemiologists. This paper provides a brief introduction to the basics of ordinary differential equation models of cholera transmission dynamics. We discuss a basic model adapted from Codeço (2001), and how it can be modified to incorporate different hypotheses, including the importance of asymptomatic or inapparent infections, and hyperinfectious V. cholerae and human-to-human transmission. We highlight three important challenges of cholera models: (1) model misspecification and parameter uncertainty, (2) modeling the impact of water, sanitation and hygiene interventions and (3) model structure. We use published models, especially those related to the 2010 Haitian outbreak as examples. We emphasize that the choice of models should be dictated by the research questions in mind. More collaboration is needed between policy-makers, epidemiologists and modelers in public health.     

Surveillance for epidemic cholera in the Americas: an assessment.

In January 1991, epidemic cholera appeared in Peru and quickly spread to many other Latin American countries. Because reporting of cholera cases was often delayed in some areas, the scope of the epidemic was unclear. An assessment of the conduct of surveillance for cholera in several countries identified some recurrent problems involving surveillance case definitions, laboratory surveillance, surveillance methods, national coordination, and data management. A key conclusion is that a simple, well-communicated cholera surveillance system in place during an epidemic will facilitate prevention and treatment efforts. We recommend the following measures: a) simplify case definitions for cholera; b) focus on laboratory surveillance of patients with diarrhea primarily in the initial stage of the epidemic; c) use predominantly the "suspect" case definition when the number of "confirmed" cases rises; d) transmit weekly the numbers of cases, hospitalized patients, and deaths to regional and central levels; e) analyze data frequently and distribute a weekly or biweekly summary; and f) report the number of cholera cases promptly to the World Health Organization.     

常用艾滋病疫情估计和预测模型研究进展

目的 艾滋病疫情的准确估计和预测,能为艾滋病防控决策和资源配置提供重要的依据。本研究分析和比较了常用的艾滋病疫情估计和预测模型。方法 采用文献综述的方法分析和比较了Workbook模型、亚洲疫情模型（asian epidemic model,AEM）、Spectrum/估计与预测软件包（estimation and projection package, EPP）和传染病动力学模型（susceptible infected recovered model, SIR）对艾滋病疫情估计和预测的特点。结果 通过对归纳和总结Workbook模型、AEM、Spectrum/EPP模型和SIR模型的基本情况、模型原理、适用条件、所需指标、结果产出和劣势分析等,为模型的选择和应用提供了科学依据。结果发现当模型指标要求单一的模型,不能很好地处理各类人群之间的交叉导致的重复估计,导致预测不准确;而指标量要求过多和过全时,数据难以收集和估计,部分数据缺失或质量不佳都会严重影响结果准确性,应根据实际需求进行模型选择。结论 定期有效的对高危人群和普通人群开展艾滋病流行病学监测,获取有效的监测数据,才能够准确的估计和预测艾滋病疫情。     

Invited commentary: The context and challenge of von Pettenkofer's contributions to epidemiology

Max von Pettenkofer is largely remembered for swallowing cholera vibrio, trying thereby to falsify the claim of his rival, the contagionist Robert Koch, that the bacillus he had isolated was cholera's sufficient cause. In this issue of the American Journal of Epidemiology, Alfredo Morabia reminds us that von Pettenkofer was more than this futile gesture. He was a 19th century public health leader whose multifactorial theory of cholera etiology deeply influenced the dominant anticontagionist school of disease transmission. His authority was undercut by the massive 1892 cholera epidemic in Hamburg, Germany. As it took off, the German government sent in Koch, who successfully contained the epidemic through interventions that von Pettenkofer regularly repudiated-quarantine, disinfection, and the boiling of water. The authors situate the antagonism between these two individuals within a broader scientific and political context that includes the evolution of miasma theory and debates over the role of governments confronted by epidemic disease. They also note that Koch's approach, which focused narrowly on the agent and its eradication, was missing key elements required for applying germ theory to public health. As scientists later incorporated biologic, host, and environmental factors into the germ theory paradigm, they reintroduced some of the complexity that had previously characterized the miasma model.     

1981～2006年济南市霍乱疫情分析

[目的]探讨济南市霍乱发病特点,更好地控制霍乱的发生和流行。[方法]对济南市1981~2006年霍乱发病资料进行分析。[结果]26年累计发现霍乱病人55例,检出带菌者14例。其中,1981年市区发生1起因举办结婚宴席引起的食物型暴发,发病22例,检出带菌者8例;1999年天桥区发生1起因婚宴引起的食物型暴发,发病4例,检出带菌者3例;其他均为散发。天桥区发病26例,占47.27%;20~29岁发病24例,占43.64%;工人发病22例,占40.00%;9月发病25例,占45.45%。系统鉴定67株霍乱菌株,其中小川型1b、稻叶型1 d各33株,O139型1株。[结论]济南市的霍乱疫情主要是散发,但有时发生聚餐引起的食物型暴发。     

Accuracy of point predictions in survival analysis

Survival time prediction is important in many applications, particularly for patients diagnosed with terminal diseases. A measure of prediction error taken from the medical literature is advocated as a practicable method of quantifying reliability of point predictions. Optimum predictions are derived for familiar survival models and the accuracy of these predictions is investigated. We argue that poor predictive capability is inherent to standard survival models with realistic parameter values. A lung cancer example is used to illustrate difficulties in prediction in practice.     

Epidemic cholera in a crowded urban environment, Port-au-Prince, Haiti

We conducted a case-control study to investigate factors associated with epidemic cholera. Water treatment and handwashing may have been protective, highlighting the need for personal hygiene for cholera prevention in contaminated urban environments. We also found a diverse diet, a possible proxy for improved nutrition, was protective against cholera.     

Estimation and prediction for a mechanistic model of measles transmission using particle filtering and maximum likelihood estimation

Disease incidence reported directly within health systems frequently reflects a partial observation relative to the true incidence in the population. State-space models present a general framework for inferring both the dynamics of infectious disease processes and the unobserved burden of disease in the population. Here, we present a state-space model of measles transmission and vaccine-based interventions at the country-level and a particle filter-based estimation procedure. Our dynamic transmission model builds on previous work by incorporating population age-structure to allow explicit representation of age-targeted vaccine interventions. We illustrate the performance of estimators of model parameters and predictions of unobserved states on simulated data from two dynamic models: one on the annual time-scale of observations and one on the biweekly time-scale of the epidemiological dynamics. We show that our model results in approximately unbiased estimates of unobserved burden and the underreporting rate. We further illustrate the performance of the fitted model for prediction of future disease burden in the next one to 15 years.     

Random vs. Nonrandom Mixing in Network Epidemic Models

In this paper we compare random and nonrandom mixing patterns for network epidemic models. Several of studies have examined the impact of different mixing patterns using compartmental epidemic models. We extend the work on compartmental models to the case of network epidemic models. We define two nonrandom mixing patterns for a network epidemic model and investigate the impact that these mixing patterns have on a number of epidemic outcomes when compared to random mixing. We find that different mixing assumptions lead to small but statistically significant differences in disease prevalence, cumulative number of new infections, final population size, and network structure. Significant differences in outcomes were more likely to be observed for larger populations and longer time horizons. Sensitivity analysis revealed that greater differences in outcomes between random and nonrandom mixing were associated with a larger incremental mortality rate among infected individuals, a larger average number of partners, and a greater probability of forming new partnerships. When adjusted for the initial population size, differences between random and nonrandom mixing models were approximately constant across all population sizes considered. We also considered the impact that differences between mixing models might have on the cost effectiveness ratio for epidemic control interventions.     

上海市虹口区水环境霍乱弧菌监测分析

目的分析1962—2018年上海市崇明岛域霍乱流行特点,为政府采取相应的干预策略提供依据。方法收集崇明岛1962—2018年的霍乱病例报告资料,采用流行病学方法,对其流行病学特征进行描述性分析。结果1962—2018年,崇明岛共有35个年份发生不同规模的霍乱疫情,共报告霍乱1 812例,年均发病率为5.12/10万;带菌者545例,年均带菌率为1.54/10万。1962—1978年、1984—1987年、1994—1999年以小川1b为优势菌株,1979—1983年、1988—1993年以稻叶1d为优势菌株,2000—2018年以霍乱O139为优势菌株。发病以青壮年为多,流行月份一般为5—10月份。结论加强跨地区、跨部门协作,重视外来水产品监管,规范农村办酒席,强化腹泻病监测和肠道门诊,做好输入性病例早发现与带菌者追踪监测,有助于防控霍乱疫情。