Epidemiological Concepts Regarding Disease Monitoring and Surveillance

Definitions of epidemiological concepts regarding disease monitoring and surveillance can be found in textbooks on veterinary epidemiology. This paper gives a review of how the concepts: monitoring, surveillance, and disease control strategies are defined. Monitoring and surveillance systems (MO&SS) involve measurements of disease occurrence, and the design of the monitoring determines which types of disease occurrence measures can be applied. However, the knowledge of the performance of diagnostic tests (sensitivity and specificity) is essential to estimate the true occurrence of the disease. The terms, disease control programme (DCP) or disease eradication programme (DEP), are defined, and the steps of DCP/DEP are described to illustrate that they are a process rather than a static MO&SS.

     

Relationships Between Animal Health Monitoring and the Risk Assessment Process

Risk assessment is part of the risk analysis process as it is used in veterinary medicine to estimate risks related to international trade and food safety. Data from monitoring and surveillance systems (MO&SS) are used throughout the risk assessment process for hazard identification, release assessment, exposure assessment and consequence assessment. As the quality of risk assessments depends to a large extent on the availability and quality of input data, there is a close relationship between MO&SS and risk assessment. In order to improve the quality of risk assessments, MO&SS should be designed according to minimum quality standards. Second, recent scientific developments on state-of-the-art design and analysis of surveys need to be translated into field applications and legislation. Finally, knowledge about the risk assessment process among MO&SS planners and managers should be promoted in order to assure high-quality data.     

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale,Multicentre Study

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.     

The Impact of the February 2012 Cold Spell on Health in Italy Using Surveillance Data

In February 2012 Italy was hit by an exceptional cold spell with extremely low temperatures and heavy snowfall. The aim of this work is to estimate the impact of the cold spell on health in the Italian cities using data from the rapid surveillance systems. In Italy, a national mortality surveillance system has been operational since 2004 in 34 cities for the rapid monitoring of daily mortality. Data from this system were used to evaluate the impact of the February 2012 cold spell on mortality shortly after the occurrence of the event. Furthermore, a cause-specific analysis was conducted in Roma using the Regional Mortality Registry and the emergency visits (ER) surveillance system. Cold spell episodes were defined as days when mean temperatures were below the 10^th percentile of February distribution for more than three days. To estimate the impact of the cold spell, excess mortality was calculated as the difference between observed and daily expected values. An overall 1578 (+25%) excess deaths among the 75+ age group was recorded in the 14 cities that registered a cold spell in February 2012. A statistically significant excess in mortality was observed in several cities ranging from +22% in Bologna to +58% in Torino. Cause-specific analysis conducted in Roma showed a statistically significant excess in mortality among the 75+ age group for respiratory disease (+64%), COPD (+57%), cardiovascular disease +20% ischemic heart disease (14%) and other heart disease (+33%). Similar results were observed for ER visits. Surveillance systems need to become are a key component of prevention plans as they can help improve public health response and are a valid data source to rapidly quantify the impact on health. Cold-related mortality is still an important issue and should not be underestimated by public health Authorities.     

Panel discussion

Risk assessment is part of the risk analysis process as it is used in veterinary medicine to estimate risks related to international trade and food safety. Data from monitoring and surveillance systems (MO&;SS) are used throughout the risk assessment process for hazard identification, release assessment, exposure assessment and consequence assessment. As the quality of risk assessments depends to a large extent on the availability and quality of input data, there is a close relationship between MO&;SS and risk assessment. In order to improve the quality of risk assessments, MO&;SS should be designed according to minimum quality standards. Second, recent scientific developments on state-of-the-art design and analysis of surveys need to be translated into field applications and legislation. Finally, knowledge about the risk assessment process among MO&;SS planners and managers should be promoted in order to assure high-quality data.

     

Evaluation of Local Media Surveillance for Improved Disease Recognition and Monitoring in Global Hotspot Regions

Digital disease detection tools are technologically sophisticated, but dependent on digital information, which for many areas suffering from high disease burdens is simply not an option. In areas where news is often reported in local media with no digital counterpart, integration of local news information with digital surveillance systems, such as HealthMap (Boston Children’s Hospital), is critical. Little research has been published in regards to the specific contribution of local health-related articles to digital surveillance systems. In response, the USAID PREDICT project implemented a local media surveillance (LMS) pilot study in partner countries to monitor disease events reported in print media. This research assessed the potential of LMS to enhance digital surveillance reach in five low- and middle-income countries. Over 16 weeks, select surveillance system attributes of LMS, such as simplicity, flexibility, acceptability, timeliness, and stability were evaluated to identify strengths and weaknesses in the surveillance method. Findings revealed that LMS filled gaps in digital surveillance network coverage by contributing valuable localized information on disease events to the global HealthMap database. A total of 87 health events were reported through the LMS pilot in the 16-week monitoring period, including 71 unique reports not found by the HealthMap digital detection tool. Furthermore, HealthMap identified an additional 236 health events outside of LMS. It was also observed that belief in the importance of the project and proper source selection from the participants was crucial to the success of this method. The timely identification of disease outbreaks near points of emergence and the recognition of risk factors associated with disease occurrence continue to be important components of any comprehensive surveillance system for monitoring disease activity across populations. The LMS method, with its minimal resource commitment, could be one tool used to address the information gaps seen in global ‘hot spot’ regions.     

T346Hunter: A Novel Web-Based Tool for the Prediction of Type III,Type IV and Type VI Secretion Systems in Bacterial Genomes

T346Hunter (Type Three, Four and Six secretion system Hunter) is a web-based tool for the identification and localisation of type III, type IV and type VI secretion systems (T3SS, T4SS and T6SS, respectively) clusters in bacterial genomes. Non-flagellar T3SS (NF-T3SS) and T6SS are complex molecular machines that deliver effector proteins from bacterial cells into the environment or into other eukaryotic or prokaryotic cells, with significant implications for pathogenesis of the strains encoding them. Meanwhile, T4SS is a more functionally diverse system, which is involved in not only effector translocation but also conjugation and DNA uptake/release. Development of control strategies against bacterial-mediated diseases requires genomic identification of the virulence arsenal of pathogenic bacteria, with T3SS, T4SS and T6SS being major determinants in this regard. Therefore, computational methods for systematic identification of these specialised machines are of particular interest. With the aim of facilitating this task, T346Hunter provides a user-friendly web-based tool for the prediction of T3SS, T4SS and T6SS clusters in newly sequenced bacterial genomes. After inspection of the available scientific literature, we constructed a database of hidden Markov model (HMM) protein profiles and sequences representing the various components of T3SS, T4SS and T6SS. T346Hunter performs searches of such a database against user-supplied bacterial sequences and localises enriched regions in any of these three types of secretion systems. Moreover, through the T346Hunter server, users can visualise the predicted clusters obtained for approximately 1700 bacterial chromosomes and plasmids. T346Hunter offers great help to researchers in advancing their understanding of the biological mechanisms in which these sophisticated molecular machines are involved. T346Hunter is freely available at http://bacterial-virulence-factors.cbgp.upm.es/T346Hunter.     

Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation

Diabetes mellitus and fine particulate matter from diesel exhaust (DEP) are both important contributors to the development of cardiovascular disease (CVD). Diabetes mellitus is a progressive disease with a high mortality rate in patients suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in the air are attributed to the development of various CVDs, presumably since fine DEP (<2.5 μm in diameter) can be inhaled and gain access to the circulatory system. However, mechanisms defining how DEP affects diabetic or control cardiomyocyte function remain poorly understood. The purpose of the present study was to evaluate cardiomyocyte function and reactive oxygen species (ROS) generation in isolated rat ventricular myocytes exposed overnight to fine DEP (0.1 μg/ml), and/or high glucose (HG, 25.5 mM). Our hypothesis was that DEP exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley rats cultured overnight and sarcomeric contractile properties were evaluated, including: peak shortening normalized to baseline (PS), time-to-90% shortening (TPS(90)), time-to-90% relengthening (TR(90)) and maximal velocities of shortening/relengthening (±dL/dt), using an IonOptix field-stimulator system. ROS generation was determined using hydroethidine/ethidium confocal microscopy. We found that DEP exposure significantly increased TR(90), decreased PS and ±dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG. Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and 0.5 mM N-Acetyl-L-cysteine) completely restored contractile function in DEP, HG and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells with NADPH oxidase inhibition. Our results suggest that DEP exacerbates myocardial dysfunction in isolated cardiomyocytes exposed to HG-containing media, which is potentially mediated by various ROS generation pathways.     

Yellow fever in Africa: public health impact and prospects for control in the 21st century

In the last two decades, yellow fever re-emerged with vehemence to constitute a major public health problem in Africa. The disease has brought untold hardship and indescribable misery among different populations in Africa. It is one of Africa's stumbling blocks to economic and social development. Despite landmark achievements made in the understanding of the epidemiology of yellow fever disease and the availability of a safe and efficacious vaccine, yellow fever remains a major public health problem in both Africa and America where the disease affects annually an estimated 200,000 persons causing an estimated 30,000 deaths. Africa contributes more than 90% of global yellow fever morbidity and mortality. Apart from the severity in morbidity and mortality, which are grossly under reported, successive outbreaks of yellow fever and control measures have disrupted existing health care delivery services, overstretched scarce internal resources, fatigued donor assistance and resulted in gross wastage of vaccines. Recent epidemics of yellow fever in Africa have affected predominantly children under the age of fifteen years. Yellow fever disease can be easily controlled. Two examples from Africa suffice to illustrate this point. Between 1939 and 1952, yellow fever virtually disappeared in parts of Africa, where a systematic mass vaccination programme was in place. More recently, following the 1978-1979 yellow fever epidemic in the Gambia, a mass yellow fever vaccination programme was carried out, with a 97% coverage of the population over 6 months of age. Subsequently, yellow fever vaccination was added to the EPI Programme. The Gambia has since then maintained a coverage of over 80%, without a reported case of yellow fever, despite being surrounded by Senegal which experienced yellow fever outbreaks in 1995 and 1996. The resurgence of yellow fever in Africa and failure to control the disease has resulted from a combination of several factors, including: 1) collapse of health care delivery systems; 2) lack of appreciation of the full impact of yellow fever disease on the social and economic development of the affected communities; 3) insufficient political commitment to yellow fever control by governments of endemic countries; 4) poor or inadequate disease surveillance; 5) inappropriate disease control measures, and 6) preventable poverty coupled with misplaced priorities in resource allocation. Yellow fever can be controlled in Africa within the next 10 years, if African governments seize the initiative for yellow fever control by declaring an uncompromising resolve to control the disease, the governments back up their resolve with an unrelenting commitment and unwavering political will through adequate budgetary allocations for yellow fever control activities, and international organisations, such as WHO, UNICEF, GAVI, etc., provide support and technical leadership and guidance to yellow fever at risk countries. Over a ten-year period, of stage-by-stage mass yellow fever vaccination campaigns, integrated with successful routine immunisation, Africa can bring yellow fever under control. Subsequently, for yellow fever to cease being a public health problem, Africa must maintain at least an annual 80% yellow fever vaccine coverage of children under the age of 1 year, and sustain a reliable disease surveillance system with a responsive disease control programme. This can be achieved at an affordable annual expenditure of less than US$1.00 per person per year, with a reordering of priorities.     

Mathematical models and lymphatic filariasis control: monitoring and evaluating interventions

Monitoring and evaluation are crucially important to the scientific management of any mass parasite control programme. Monitoring enables the effectiveness of implemented actions to be assessed and necessary adaptations to be identified; it also determines when management objectives are achieved. Parasite transmission models can provide a scientific template for informing the optimal design of such monitoring programmes. Here, we illustrate the usefulness of using a model-based approach for monitoring and evaluating anti-parasite interventions and discuss issues that need addressing. We focus on the use of such an approach for the control and/or elimination of the vector-borne parasitic disease, lymphatic filariasis.     

A tool box for operational mosquito larval control: preliminary results and early lessons from the Urban Malaria Control Programme in Dar es Salaam, Tanzania

Background

As the population of Africa rapidly urbanizes, large populations could be protected from malaria by controlling aquatic stages of mosquitoes if cost-effective and scalable implementation systems can be designed.

Methods

A recently initiated Urban Malaria Control Programme in Dar es Salaam delegates responsibility for routine mosquito control and surveillance to modestly-paid community members, known as Community-Owned Resource Persons (CORPs). New vector surveillance, larviciding and management systems were designed and evaluated in 15 city wards to allow timely collection, interpretation and reaction to entomologic monitoring data using practical procedures that rely on minimal technology. After one year of baseline data collection, operational larviciding with Bacillus thuringiensis var. israelensis commenced in March 2006 in three selected wards.

Results

The procedures and staff management systems described greatly improved standards of larval surveillance relative to that reported at the outset of this programme. In the first year of the programme, over 65,000 potential Anopheles habitats were surveyed by 90 CORPs on a weekly basis. Reaction times to vector surveillance at observations were one day, week and month at ward, municipal and city levels, respectively. One year of community-based larviciding reduced transmission by the primary malaria vector, Anopheles gambiae s.l., by 31% (95% C.I. = 21.6–37.6%; p = 0.04).

Conclusion

This novel management, monitoring and evaluation system for implementing routine larviciding of malaria vectors in African cities has shown considerable potential for sustained, rapidly responsive, data-driven and affordable application. Nevertheless, the true programmatic value of larviciding in urban Africa can only be established through longer-term programmes which are stably financed and allow the operational teams and management infrastructures to mature by learning from experience.     

Monitoring for the Management of Disease Risk in Animal Translocation Programmes

Monitoring is best viewed as a component of some larger programme focused on science or conservation. The value of monitoring is determined by the extent to which it informs the parent process. Animal translocation programmes are typically designed to augment or establish viable animal populations without changing the local community in any detrimental way. Such programmes seek to minimize disease risk to local wild animals, to translocated animals, and in some cases to humans. Disease monitoring can inform translocation decisions by (1) providing information for state-dependent decisions, (2) assessing progress towards programme objectives, and (3) permitting learning in order to make better decisions in the future. Here we discuss specific decisions that can be informed by both pre-release and post-release disease monitoring programmes. We specify state variables and vital rates needed to inform these decisions. We then discuss monitoring data and analytic methods that can be used to estimate these state variables and vital rates. Our discussion is necessarily general, but hopefully provides a basis for tailoring disease monitoring approaches to specific translocation programmes.     

Environmental DNA/RNA for pathogen and parasite detection,surveillance, and ecology

Detection of pathogens, parasites, and other symbionts in environmental samples via eDNA/eRNA (collectively eNA) is an increasingly important source of information about their occurrence and activity. There is great potential for using such detections as a proxy for infection of host organisms in connected habitats, for pathogen monitoring and surveillance, and for early warning systems for disease. However, many factors require consideration, and appropriate methods developed and verified, in order that eNA detections can be reliably interpreted and adopted for surveillance and assessment of disease risk, and potentially inclusion in international standards, such as the World Organisation for Animal Health guidelines. Disease manifestation results from host–symbiont–environment interactions between hosts, demanding a multifactorial approach to interpretation of eNA signals.     

Measuring Progress on the Control of Porcine Reproductive and Respiratory Syndrome (PRRS) at a Regional Level: The Minnesota N212 Regional Control Project (Rcp) as a Working Example

Due to the highly transmissible nature of porcine reproductive and respiratory syndrome (PRRS), implementation of regional programs to control the disease may be critical. Because PRRS is not reported in the US, numerous voluntary regional control projects (RCPs) have been established. However, the effect of RCPs on PRRS control has not been assessed yet. This study aims to quantify the extent to which RCPs contribute to PRRS control by proposing a methodological framework to evaluate the progress of RCPs. Information collected between July 2012 and June 2015 from the Minnesota Voluntary Regional PRRS Elimination Project (RCP-N212) was used. Demography of premises (e.g. composition of farms with sows = SS and without sows = NSS) was assessed by a repeated analysis of variance. By using general linear mixed-effects models, active participation of farms enrolled in the RCP-N212, defined as the decision to share (or not to share) PRRS status, was evaluated and used as a predictor, along with other variables, to assess the PRRS trend over time. Additionally, spatial and temporal patterns of farmers’ participation and the disease dynamics were investigated. The number of farms enrolled in RCP-N212 and its geographical coverage increased, but the proportion of SS and NSS did not vary significantly over time. A significant increasing (p<0.001) trend in farmers’ decision to share PRRS status was observed, but with NSS producers less willing to report and a large variability between counties. The incidence of PRRS significantly (p<0.001) decreased, showing a negative correlation between degree of participation and occurrence of PRRS (p<0.001) and a positive correlation with farm density at the county level (p = 0.02). Despite a noted decrease in PRRS, significant spatio-temporal patterns of incidence of the disease over 3-weeks and 3-kms during the entire study period were identified. This study established a systematic approach to quantify the effect of RCPs on PRRS control. Despite an increase in number of farms enrolled in the RCP-N212, active participation is not ensured. By evaluating the effect of participation on the occurrence of PRRS, the value of sharing information among producers may be demonstrated, in turn justifying the existence of RCPs.     

Combining livestock and wildlife surveillance data to assess the likelihood of freedom from bovine tuberculosis in New Zealand

Bovine tuberculosis (Tb) has historically occurred in livestock throughout most of New Zealand, and also in wildlife over about 40% of the country. Using a test-and-cull strategy to eliminate Tb from livestock, intensive control of the major wildlife host (brushtail possums), and surveillance of key spillover hosts (wild ferrets, pigs and deer), the Animal Health Board has reduced the number of infected cattle herds by over 90% since 1994. Many formerly infected areas appear to now be free of the disease, so a key question is whether the disease control programme can be stopped in those places. We have developed a Bayesian framework for combining spatially explicit data derived from livestock testing and surveys of Tb prevalence in key wildlife hosts, and using those data to updating or refine an estimate of the probability of Tb freedom from wildlife provided by a priori prediction derived from a model of how Tb levels in possum are likely to have been affected by the duration and intensity of control. This paper outlines the conceptual framework, and some preliminary “case-study” steps toward implementation.     

Long-term monitoring and the conservation of tropical wetlands: high ideals and harsh realities

Long-term monitoring of wetlands is an essential element of management for wise use. Indeed, the Ramsar Convention requires regular monitoring in order to detect changes in ecological character at listed sites. However, there are few examples of successful long-term monitoring in tropical wetlands. Monitoring schemes run into three kinds of difficulties: conceptual, logistical and political. To be effective, monitoring schemes must be carefully planned and designed. In practice, the questions to be addressed are rarely made explicit. Strictly defined, monitoring should assess deviations from a pre-set level so that appropriate corrective action can be taken. This assumes that good baseline information exists, and that we have sufficient knowledge of the system to set sensible signal levels. Neither is usually the case in tropical wetlands. This means that carefully focused surveillance (a time-series of systematic observations) is an essential first step. Providing resources and co-ordination for surveillance or monitoring is challenging over the long term, especially if the variables being measured require expensive analyses and highly trained staff. I suggest that surveillance or monitoring programmes should focus on likely threats, and ecological or economic concerns, should be as simple, robust and inexpensive as possible, should be sustained and consistent, and should involve local people and volunteers. If it is to be effective, monitoring must have a clear linkage to wetland management. Ideally, it should form part of each country's wetland policy. I suggest some variables that could be incorporated in sustainable long-term monitoring programmes. Two examples of successful surveillance work at Kenyan wetlands illustrate that the challenges involved in long-term programmes can, at least in part, be overcome.     

Prediction of Dengue Outbreaks Based on Disease Surveillance and Meteorological Data

Research is needed to create early warnings of dengue outbreaks to inform stakeholders and control the disease. This analysis composes of a comparative set of prediction models including only meteorological variables; only lag variables of disease surveillance; as well as combinations of meteorological and lag disease surveillance variables. Generalized linear regression models were used to fit relationships between the predictor variables and the dengue surveillance data as outcome variable on the basis of data from 2001 to 2010. Data from 2011 to 2013 were used for external validation purposed of prediction accuracy of the model. Model fit were evaluated based on prediction performance in terms of detecting epidemics, and for number of predicted cases according to RMSE and SRMSE, as well as AIC. An optimal combination of meteorology and autoregressive lag terms of dengue counts in the past were identified best in predicting dengue incidence and the occurrence of dengue epidemics. Past data on disease surveillance, as predictor alone, visually gave reasonably accurate results for outbreak periods, but not for non-outbreaks periods. A combination of surveillance and meteorological data including lag patterns up to a few years in the past showed most predictive of dengue incidence and occurrence in Yogyakarta, Indonesia. The external validation showed poorer results than the internal validation, but still showed skill in detecting outbreaks up to two months ahead. Prior studies support the fact that past meteorology and surveillance data can be predictive of dengue. However, to a less extent has prior research shown how the longer-term past disease incidence data, up to years, can play a role in predicting outbreaks in the coming years, possibly indicating cross-immunity status of the population.     

The generation of diesel exhaust particle aerosols from a bulk source in an aerodynamic size range similar to atmospheric particles

The influence of diesel exhaust particles (DEP) on the lungs and heart is currently a topic of great interest in inhalation toxicology. Epidemiological data and animal studies have implicated airborne particulate matter and DEP in increased morbidity and mortality due to a number of cardiopulmonary diseases including asthma, chronic obstructive pulmonary disorder, and lung cancer. The pathogeneses of these diseases are being studied using animal models and cell culture techniques. Real-time exposures to freshly combusted diesel fuel are complex and require significant infrastructure including engine operations, dilution air, and monitoring and control of gases. A method of generating DEP aerosols from a bulk source in an aerodynamic size range similar to atmospheric DEP would be a desirable and useful alternative. Metered dose inhaler technology was adopted to generate aerosols from suspensions of DEP in the propellant hydrofluoroalkane 134a. Inertial impaction data indicated that the particle size distributions of the generated aerosols were trimodal, with count median aerodynamic diameters less than 100 nm. Scanning electron microscopy of deposited particles showed tightly aggregated particles, as would be expected from an evaporative process. Chemical analysis indicated that there were no major changes in the mass proportion of 2 specific aromatic hydrocarbons (benzo[a]pyrene and benzo[k]fluoranthene) in the particles resulting from the aerosolization process.