Risk assessment of vector-borne diseases for public health governance.

OBJECTIVES: In the context of public health, risk governance (or risk analysis) is a framework for the assessment and subsequent management and/or control of the danger posed by an identified disease threat. Generic frameworks in which to carry out risk assessment have been developed by various agencies. These include monitoring, data collection, statistical analysis and dissemination. Due to the inherent complexity of disease systems, however, the generic approach must be modified for individual, disease-specific risk assessment frameworks. STUDY DESIGN: The analysis was based on the review of the current risk assessments of vector-borne diseases adopted by the main Public Health organisations (OIE, WHO, ECDC, FAO, CDC etc…). METHODS: Literature, legislation and statistical assessment of the risk analysis frameworks. RESULTS: This review outlines the need for the development of a general public health risk assessment method for vector-borne diseases, in order to guarantee that sufficient information is gathered to apply robust models of risk assessment. Stochastic (especially spatial) methods, often in Bayesian frameworks are now gaining prominence in standard risk assessment procedures because of their ability to assess accurately model uncertainties. CONCLUSIONS: Risk assessment needs to be addressed quantitatively wherever possible, and submitted with its quality assessment in order to enable successful public health measures to be adopted. In terms of current practice, often a series of different models and analyses are applied to the same problem, with results and outcomes that are difficult to compare because of the unknown model and data uncertainties. Therefore, the risk assessment areas in need of further research are identified in this article.

Predictive modelling of adult emergence in a polyphagous Eucolaspis (Chrysomelidae: Eumolpinae) leaf beetle.

Eucolaspis sp. "Hawke's Bay" (Chrysomelidae: Eumolpinae) is a pest that inflicts huge economic loss in many organic apple (Malus domestica Borkh.) orchards in New Zealand. The timing of control methods for this pest has been shown to be crucial for success. To aid in planning control programs, we studied threshold temperature and degree-days required for the development of Eucolaspis sp. "Hawke's Bay" pupae and modeled adult emergence in the field. Pupal development was observed at three constant temperatures. Pupae required 237.0 +/- 21.67 degree-days above lower threshold temperature of 4.7 degrees C +/- 0.89 degrees C to develop into adults. The emergence of adults was modeled with these thermal values and the model was tested for accuracy with field data. The model performed well with a precision of +/- 4 d. The proposed phenology model has wide applicability in monitoring and planning pest control measures.

Collection of Culicoides (Diptera: Ceratopogonidae) using CO2 and enantiomers of 1-octen-3-ol in the United Kingdom.

The host kairomones carbon dioxide (CO2) and 1-octen-3-ol elicit a host seeking response in a wide range of haematophagous Diptera. This study investigates the response of Culicoides biting midges (Diptera: Ceratopogonidae) to these cues using field-based experiments at two sites in the United Kingdom with very different species complements. Traps used for surveillance (miniature CDC model 512) and control (Mosquito Magnet Pro) were modified to release ratios of (R)- and (S)-1-octen-3-ol enantiomers in combination with CO2 and, in the case of the latter trap type, a thermal cue. Abundance and species diversity were then compared between these treatments and against collections made using a trap with a CO2 lure only, in a Latin square design. In both habitats, results demonstrated that semiochemical lures containing a high proportion of the (R)-enantiomer consistently attracted a greater abundance of host-seeking Culicoides females than any other treatment. Culicoides collected using an optimal stimulus of 500 ml/min CO2 combined with 4.1 mg/h (R)-1-octen-3-ol were then compared with those collected on sheep through the use of a drop trap. While preliminary in nature, this trial indicated Culicoides species complements are similar between collections made using the drop trap in comparison to the semiochemical-baited CDC trap, and that there are advantages in using (R)-1-octen-3-ol.

The global spread of malaria in a future, warmer world.

The frequent warnings that global climate change will allow falciparum malaria to spread into northern latitudes, including Europe and large parts of the United States, are based on biological transmission models driven principally by temperature. These models were assessed for their value in predicting present, and therefore future, malaria distribution. In an alternative statistical approach, the recorded present-day global distribution of falciparum malaria was used to establish the current multivariate climatic constraints. These results were applied to future climate scenarios to predict future distributions, which showed remarkably few changes, even under the most extreme scenarios.

Invasion of bluetongue and other orbivirus infections into Europe: the role of biological and climatic processes.

The invasion of multiple strains of the midge-borne bluetongue virus into southern Europe since the late 1990s provides a rare example of a clear impact of climate change on a vector-borne disease. However, the subsequent dramatic continent-wide spread and burden of this disease has depended largely on altered biotic interactions with vector and host communities in newly invaded areas. Transmission by Palearctic vectors has facilitated the establishment of the disease in cooler and wetter areas of both northern and southern Europe. This paper discusses the important biological and climatic processes involved in these invasions, and the lessons that must be drawn for effective risk management of bluetongue and other midge-borne viruses in Europe.

Malaria early warning in Kenya.

Kenya displays large spatiotemporal diversity in its climate and ecology. It follows that malaria transmission will reflect this environmental heterogeneity in both space and time. In this article, we discuss how such heterogeneity, and its epidemiological consequences, should be considered in the development of early warning systems for malaria epidemics.

Satellites, space, time and the African trypanosomiases.

The human and animal trypanosomiases of Africa provide unique challenges to epidemiologists because of the spatial and temporal scales over which variation in transmission takes place. This chapter describes how our descriptions of the different components of transmission, from the parasites to the affected hosts, eventually developed to include geographical dimensions. It then briefly mentions two key analytical techniques used in the application of multi-temporal remotely sensed imagery to the interpretation of field data; temporal Fourier analysis for data reduction, and a variety of discriminant analytical techniques to describe the distribution and abundance of vectors and diseases. Satellite data may be used both for biological, process-based models and for statistical descriptions of vector populations and disease transmission. Examples are given of models for the tsetse Glossina morsitans in the Yankari Game Reserve, Nigeria, and in The Gambia. In both sites the satellite derived index of Land Surface Temperature (LST) is the best correlate of monthly mortality rates and is used to drive tsetse population models. The Gambia model is then supplemented with a disease transmission component; the mean infection rates of the vectors and of local cattle are satisfactorily described by the model, as are the seasonal variations of infection in the cattle. High and low spatial resolution satellite data have been used in a number of statistical studies of land cover types and tsetse habitats. In addition multi-temporal data may be related to both the incidence and prevalence of trypanosomiasis. Analysis of past and recent animal and human trypanosomiasis data from south-east Uganda supports the suggestion of the importance of cattle as a reservoir of the human disease in this area; mean infection prevalences in both human and animal hosts rise and fall in a similar fashion over the same range of increasing vegetation index values. Monthly sleeping sickness case data from the districts and counties of south-east Uganda are analysed and often show significant correlations with local LST. Case numbers increase with LST in areas that are relatively cooler than average for this part of Uganda, but decrease with LST in areas that are on average warmer. This indicates different seasonal cycles of risk across the region, and may be related to the differing vectorial roles of the two local tsetse, G. fuscipes and G. pallidipes. Finally, the increasing pace of change, and the likelihood of new or reemerging vector-borne diseases, highlight the need for accurate and timely information on habitat changes and the impacts these will have on disease transmission. The next generation of satellites will have significantly more spectral and spatial resolution than the current satellites, and will enable us to refine both statistical and biological predictions of trypanosomiasis and other vector-borne diseases within disease early warning systems.

Forecasting disease risk for increased epidemic preparedness in public health.

Emerging infectious diseases pose a growing threat to human populations. Many of the world's epidemic diseases (particularly those transmitted by intermediate hosts) are known to be highly sensitive to long-term changes in climate and short-term fluctuations in the weather. The application of environmental data to the study of disease offers the capability to demonstrate vector-environment relationships and potentially forecast the risk of disease outbreaks or epidemics. Accurate disease forecasting models would markedly improve epidemic prevention and control capabilities. This chapter examines the potential for epidemic forecasting and discusses the issues associated with the development of global networks for surveillance and prediction. Existing global systems for epidemic preparedness focus on disease surveillance using either expert knowledge or statistical modelling of disease activity and thresholds to identify times and areas of risk. Predictive health information systems would use monitored environmental variables, linked to a disease system, to be observed and provide prior information of outbreaks. The components and varieties of forecasting systems are discussed with selected examples, along with issues relating to further development.

Fragile transmission cycles of tick-borne encephalitis virus may be disrupted by predicted climate change.

Repeated predictions that vector-borne disease prevalence will increase with global warming are usually based on univariate models. To accommodate the full range of constraints, the present-day distribution of tick-borne encephalitis virus (TBEv) was matched statistically to current climatic variables, to provide a multivariate description of present-day areas of disease risk. This was then applied to outputs of a general circulation model that predicts how climatic variables may change in the future, and future distributions of TBEv were predicted for them. The expected summer rise in temperature and decrease in moisture appears to drive the distribution of TBEv into higher-latitude and higher-altitude regions progressively through the 2020s, 2050s and 2080s. The final toe-hold in the 2080s may be confined to a small part of Scandinavia, including new foci in southern Finland. The reason for this apparent contraction of the range of TBEv is that its transmission cycles depend on a particular pattern of tick seasonal dynamics, which may be disrupted by climate change. The observed marked increase in incidence of tick-borne encephalitis in most parts of Europe since 1993 may be due to non-biological causes, such as political and sociological changes.

A galactose-specific lectin from the red marine alga Ptilota filicina.

A lectin from the red marine alga Ptilota filicina (PFL) was isolated by affinity chromatography on cross-linked guar gum. PFL agglutinated native and papain-treated human erythrocytes with preference for type O erythrocytes. The lectin was inhibited by galactose and its derivatives. The most potent inhibitors were p-Nitrophenyl-N-acetyl-alpha- and beta-D-galactosaminide. Porcine stomach mucin, bovine submaxillary gland mucin and asialo bovine mucin were also inhibitory. The M(r) of PFL, determined by gel filtration, was 56,900. SDS-PAGE gave one band with a subunit M(r) of 19,320, indicating the native protein to be a trimer of apparently identical subunits. PFL was shown to be rich in acidic and hydroxyl amino acids but low in basic amino acids. The ten N-terminal amino acids were Asx-Thr-Lys-Thr-Leu-Leu-Ala-.

Predicting malaria seasons in Kenya using multitemporal meteorological satellite sensor data.

This article describes research that predicts the seasonality of malaria in Kenya using remotely sensed images from satellite sensors. The predictions were made using relationships established between long-term data on paediatric severe malaria admissions and simultaneously collected data from the Advanced Very High Resolution Radiometer (AVHRR) on the National Oceanic and Atmospheric Administrations (NOAA) polar-orbiting meteorological satellites and the High Resolution Radiometer (HRR) on the European Organization for the Exploitation of Meteorological Satellites' (EUMETSAT) geostationary Meteosat satellites. The remotely sensed data were processed to provide surrogate information on land surface temperature, reflectance in the middle infra-red, rainfall, and the normalized difference vegetation index (NDVI). These variables were then subjected to temporal Fourier processing and the fitted Fourier data were compared with the mean percentage of total annual malaria admissions recorded in each month. The NDVI in the preceding month correlated most significantly and consistently with malaria presentations across the 3 sites (mean adjusted r2 = 0.71, range 0.61-0.79). Regression analyses showed that an NDVI threshold of 0.35-0.40 was required for more than 5% of the annual malaria cases to be presented in a given month. These thresholds were then extrapolated spatially with the temporal Fourier-processed NDVI data to define the number of months, in which malaria admissions could be expected across Kenya in an average year, at an 8 x 8 km resolution. The resulting maps were compared with the only existing map (Butler's) of malaria transmission periods for Kenya, compiled from expert opinion. Conclusions are drawn on the appropriateness of remote sensing techniques for compiling national strategies for malaria intervention.

Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and review.

This paper presents the results of an extensive search of the formal and informal literature on annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa from 1980 onwards. It first describes how the annual EIR data were collated, summarized, geo-referenced and staged for public access on the internet. Problems of data standardization, reporting accuracy and the subsequent publishing of information on the internet follow. The review was conducted primarily to investigate the spatial heterogeneity of malaria exposure in Africa and supports the idea of highly heterogeneous risk at the continental, regional and country levels. The implications for malaria control of the significant spatial (and seasonal) variation in exposure to infected mosquito bites are discussed.

Trypanosomiasis 'risk' or 'challenge': a review.

Definitions of the term 'challenge' as applied to the African trypanosomiases are reviewed. Data from one West and one East African site show simple linear relationships between the incidence of trypanosomiasis in both humans and animals, and either the amount of man-tsetse contact, or the Apparent Density of flies. Data from a number of East African sites are analysed and show a linear relationship between the mean Berenil Index of cattle and the logarithm of the challenge, where challenge is the simple product of Apparent Density and mean fly infection rate. Apparent Density is a more variable element of total challenge than is infection rate. The results of field studies are analysed to show that Berenil has a short prophylactic effect, lasting for about 22 days in cattle. When allowance is made for this effect there is a direct, apparently linear relationship between the daily probability of infection of cattle and total challenge, the latter varying over almost three orders of magnitude. Variations in tsetse fly density account for about 50% of the variability of Apparent Density. Hence the latter is a crude estimate of the former. Seasonal and density-related changes in the availability of flies to human catchers could account for the inadequacies of the fly-round technique in assessing fly density and/or challenge. Evidence at present available suggests that trypanotolerant cattle are more likely to be an economic alternative to drug-treated zebu at higher rather than lower challenge levels. Whether either type of animal could profitably be raised in areas of the highest challenge and without some form of tsetse control remains an open question.

Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of 'normal' infants and adults, and patients with various neuropsychiatric and neurologic disorders.

Levels of thyrotropin-releasing hormone (TRH) - and cyclo(His-Pro) (CHP)-like immunoreactivities and the activity of enzyme Pyroglutamate aminopeptidase (PAPase) were measured in cerebrospinal fluid (CSF) of over 100 normal adults (NA) and infants, and adult patients with various neurologic and neuropsychiatric disorders (NNDA). Levels of TRH and CHP in CSF of over 70% of the NA group were below 50 and 500 pg/ml respectively. The TRH- and CHP-like immunoreactivities in the remainder of the 30% of NA specimens exhibiting higher peptide concentrations were enzymatically and chromatographically characterized and were found to behave like authentic peptides. The levels of both of these peptides were significantly elevated in the CSF of most of the NNDA patients. An elevation in the CSF level of CHP was significantly correlated with the level of TRH, but not PAPase. Results from this study suggest that CSF elevation of TRH level may be due to a nonspecific response to stress that may be associated with hospitalization, myelogram procedure, and/or the neurologic and neuropsychiatric diseases for which the patients were admitted.

Lectins for drug delivery within the oral cavity--investigation of lectin binding to oral mucosa.

The aim of this study was to identify receptors present on the buccal mucosa in order to select appropriate lectins that will allow the retention of a dosage form within the oral cavity. Studies using human buccal cells, the avidin-biotin-complex/diaminobenzidine method for identifying lectin binding and a microdensitometer to allow a semi-quantitative analysis of stain intensity, showed a wide diversity of lectin receptors. Kinetic studies of lectin binding to buccal cells revealed significant binding after 20 s, particularly for lectins from Pisum sativum and Arachis hypogaea. A significant reduction in lectin binding was observed after exposing buccal cells to a series of lectin solutions pre-treated with a large excess of secretor or non-secretor saliva. However when bound to the buccal cells, there was little displacement of lectins on exposure to either saliva types. Further studies on rat oral tissue suggested that the lectins appeared to bind to varying degrees on whole oral epithelial surfaces although differences in binding between this and the human buccal cell model were evident. It was concluded that a wide range of possible target receptors for lectins are present on rat oral epithelium and human buccal cells. Lectin binding to these receptors can be affected by the exposure time and the presence of saliva.

Prediction of bluetongue vector distribution in Europe and north Africa using satellite imagery.

Bluetongue is an infectious, non-contagious arboviral disease thought to infect all known ruminant species. Since 1998, an unprecedented epizootic of the disease has occurred in the Mediterranean region, resulting in the deaths of over 800,000 sheep to date. Bluetongue virus (BTV) is transmitted by biting midges of which one species, Culicoides imicola, is the major vector in the old world. C. imicola was trapped for 2 years at 87 sites across Portugal and models were developed for predicting the presence and abundance of the midge at these sites. Discriminant analysis was used to identify the best models from 40 temporally Fourier-processed 1 km spatial resolution remotely-sensed variables. The best models correctly predicted presence and absence at 83 of the 87 sites, and abundance at 76 sites. The models were then used to predict C. imicola presence and abundance elsewhere across Europe and north Africa. C. imicola was predicted to be present and in high abundance at the majority of areas affected in the recent bluetongue epizootic, including the Balearics, Sardinia, Corsica, Sicily, areas of mainland Italy, large areas of Greece, western Turkey and northern Algeria and Tunisia.

Lectins in drug delivery: a study of the acute local irritancy of the lectins from Solanum tuberosum and Helix pomatia.

Lectins are proteins or glycoproteins of non-immune origin capable of binding to one or more specific sugar residues. The potential for using lectins as a means of 'anchoring' a drug delivery system to the mucosal surfaces of the eye has been investigated in previous work, with the lectins from Solanum tuberosum and Helix pomatia showing particular promise. In this study the acute local dermal irritancy of these lectins, in terms of their potential to cause inflammation and tissue necrosis, was investigated. After an initial study in terminally anaesthetised animals (to ensure no gross toxicity was evident), five male New Zealand white rabbits from the same litter were briefly anaesthetised and Evans blue injected intravenously as a marker of inflammation. Sterile lectin solutions in normal saline at a range of concentrations from 50 to 500 microg ml(-1) were prepared and 50-microl volumes injected intradermally at 18 sites across a shaved area of each rabbit's back. The rabbits were then allowed to regain consciousness. There was no evidence of tissue necrosis, oedema or Evans blue infiltration with any of the lectin solutions administered. The rabbits did not display any signs of discomfort such as scratching or continued grooming throughout the experiment. Histological examination of the injection sites revealed little sign of any inflammation, such as heterophil migration, oedema or tissue damage. It was concluded that these lectins demonstrate minimal acute irritancy, and will, therefore, be taken forward for formulation and in vivo studies.

Tsetse flies and their control.

The authors use a quantitative modelling framework to describe and explore the features of the biology of tsetse flies (Glossina spp.) which are important in determining the rate of transmission of the African trypanosomiases between hosts. Examples are presented of the contribution of previous research on tsetse to quantified epidemiological and epizootiological understanding, and areas of current ignorance are identified for future study. Spatial and temporal variations in risk are important (but rarely-studied) determinants of the impact of trypanosomiasis on humans, domestic animals and agricultural activities. Recent grid-based sampling surveys to Togo provide valuable data sets on tsetse, cattle and trypanosomiasis throughout the country. A combination of ground-based meterological and remotely-sensed satellite data, within linear discriminant analytical models, enables description of the observed distributions of the five species of tsetse occurring in Togo, with accuracies of between 72% (Glossina palpalis and G. tachinoides) and 98% (G. fusca). Abundance classes of the two most widespread species, G. palpalis and G. tachinoides, are described with accuracies of between 47% and 83%. This is especially remarkable given the relatively small differences between the average values of the predictor variables in areas of differing fly abundance. Similar analyses could be used to predict the occurrence and abundance of flies in other areas, which have not been surveyed to date, in order to plan tsetse control campaigns or explore development options. Finally, some recent tsetse control campaigns are briefly reviewed. The shift of emphasis from fly eradication to fly control is associated with a devolution of responsibility for control activities from central government to local areas, communities or even individuals. The future role of central governments will remain crucial, however, in determining the areas in which different control options are practised, in facilitating control by local communities and in protecting controlled areas from re-invasion by flies from other areas.

Predicting the risk of bluetongue through time: climate models of temporal patterns of outbreaks in Israel.

Determining the temporal relationship between climate and epidemics of Culicoides-borne viral disease may allow control and surveillance measures to be implemented earlier and more efficiently. In Israel, outbreaks of bluetongue (BT) have occurred almost annually since at least 1950, with severe episodes occurring periodically. In this paper, the authors model a twenty-year time-series of BT outbreaks in relation to climate. Satellite-derived correlates of low temperatures and high moisture levels increased the number of outbreaks per year. This is the first study to find a temporal relationship between the risk of Culicoides-borne disease and satellite-derived climate variables. Climatic conditions in the year preceding a BT episode, between October and December, coincident with the seasonal peak of vector abundance and outbreak numbers, appeared to be more importantthan spring or early summer conditions in the same year as the episode. Since Israel is an arid country, higher-than-average moisture levels during this period may increase the availability of breeding sites and refuges for adult Culicoides imicola vectors, while cooler-than-average temperatures will increase fecundity, offspring size and survival through adulthood in winter, which, in turn, increases the size of the initial vector population the following year. The proportion of variance in the annual BT outbreak time-series resulting from climate factors was relatively low, at around 20%. This was possibly due to temporal variation in other factors, such as viral incursions from surrounding countries and levels of herd immunity. Alternatively, since most BT virus (BTV) circulation in this region occurs silently, in resistant breeds of local sheep, the level of transmission is poorly correlated with outbreak notification so that strong relationships between BTV circulation and climate, if they exist, are obscured.