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1.  Estimating the Incidence of Acute Infectious Intestinal Disease in the Community in the UK: A Retrospective Telephone Survey 
PLoS ONE  2016;11(1):e0146171.
Objectives
To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design.
Design/Setting
A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days.
Participants
14,813 individuals for all of whom we had a legible recording of their agreement to participate
Outcomes
Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause.
Results
The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135–2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377–778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time.
Conclusions
The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates.
doi:10.1371/journal.pone.0146171
PMCID: PMC4725772  PMID: 26807916
2.  Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis 
Background: The Ebola virus disease outbreak that started in Western Africa in 2013 was unprecedented because it spread within densely populated urban environments and affected many thousands of people. As a result, previous advice and guidelines need to be critically reviewed, especially with regard to transmission risks in different contexts.
Methods: Scientific and grey literature were searched for articles about any African filovirus. Articles were screened for information about transmission (prevalence or odds ratios especially). Data were extracted from eligible articles and summarized narratively with partial meta-analysis. Study quality was also evaluated.
Results: A total of 31 reports were selected from 6552 found in the initial search. Eight papers gave numerical odds for contracting filovirus illness; 23 further articles provided supporting anecdotal observations about how transmission probably occurred for individuals. Many forms of contact (conversation, sharing a meal, sharing a bed, direct or indirect touching) were unlikely to result in disease transmission during incubation or early illness. Among household contacts who reported directly touching a case, the attack rate was 32% [95% confidence interval (CI) 26–38%]. Risk of disease transmission between household members without direct contact was low (1%; 95% CI 0–5%). Caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease, probably due to a high degree of direct physical contact with case or cadaver.
Conclusions: Transmission of filovirus is unlikely except through close contact, especially during the most severe stages of acute illness. More data are needed about the context, intimacy and timing of contact required to raise the odds of disease transmission. Risk factors specific to urban settings may need to be determined.
doi:10.1093/ije/dyv307
PMCID: PMC4795563  PMID: 26589246
Ebola virus disease; Marburg virus; risk factors; bodily fluids; systematic review
3.  Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports 
BMJ Open  2015;5(10):e008846.
Objectives
To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people.
Design
Diagnostic accuracy study.
Participants
Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis).
Reference standard for hydration status
Directly measured serum/plasma osmolality: current dehydration (serum osmolality >300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg).
Index tests
39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality.
Results
Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86×(Na++ K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status.
Conclusions
Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults.
Trial registration numbers:
DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012.
doi:10.1136/bmjopen-2015-008846
PMCID: PMC4636668  PMID: 26490100
GERIATRIC MEDICINE; PREVENTIVE MEDICINE; NUTRITION & DIETETICS
4.  Parametric Functional Maps of Visual Inputs to the Tectum 
Neuron  2012;76(2):317-324.
SUMMARY
How features of the visual scene are encoded in the population activity of retinal ganglion cells (RGCs) targeting specific regions of the brain is not well understood. To address this, we have used a genetically encoded reporter of presynaptic function (SyGCaMP3) to record visually evoked activity in the population of RGC axons innervating the zebrafish tectum. Using unbiased voxel-wise analysis of SyGCaMP3 signals, we identify three subtypes of direction-selective and two subtypes of orientation-selective retinal input. Composite parametric functional maps generated across many larvae show laminar segregation of direction- and orientation-selective responses and unexpected retinotopic biases in the distribution of functional subtypes. These findings provide a systematic description of the form, organization, and dimensionality of visual inputs to the brain and will serve as a platform for understanding emergent properties in tectal circuits associated with visually driven behavior.
doi:10.1016/j.neuron.2012.08.040
PMCID: PMC4516722  PMID: 23083735
5.  Cryptosporidium Pathogenicity and Virulence 
Clinical Microbiology Reviews  2013;26(1):115-134.
Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.
doi:10.1128/CMR.00076-12
PMCID: PMC3553671  PMID: 23297262
6.  Needs assessment to strengthen capacity in water and sanitation research in Africa: experiences of the African SNOWS consortium 
Background
Despite its contribution to global disease burden, diarrhoeal disease is still a relatively neglected area for research funding, especially in low-income country settings. The SNOWS consortium (Scientists Networked for Outcomes from Water and Sanitation) is funded by the Wellcome Trust under an initiative to build the necessary research skills in Africa. This paper focuses on the research training needs of the consortium as identified during the first three years of the project.
Methods
We reviewed the reports of two needs assessments. The first was a detailed needs assessment led by one northern partner, with follow-up visits which included reciprocal representation from the African universities. The second assessment, led by another northern partner, focused primarily on training needs. The reports from both needs assessments were read and stated needs were extracted and summarised.
Results
Key common issues identified in both assessments were supervisory skills, applications for external research funding, research management, and writing for publication in the peer-reviewed scientific literature. The bureaucratisation of university processes and inconsistencies through administration processes also caused problems. The lack of specialist laboratory equipment presented difficulties, particularly of inaccessibility through a lack of skilled staff for operation and maintenance, and of a budget provision for repairs and running costs. The lack of taught PhD modules and of research training methods also caused problems. Institutionally, there were often no mechanisms for identifying funding opportunities. On the other hand, grantees were often unable to understand or comply with the funders’ financial and reporting requirements and were not supported by their institution. Skills in staff recruitment, retention, and performance were poor, as were performance in proposal and paper writing. The requirements for ethical clearance were often not known and governance issues not understood, particularly those required by funders.
Conclusions
SNOWS believes that working with African universities to develop networks that support African-led research driven by the local context is an effective approach to develop and retain research skills needed to change policy and practice in water, sanitation, and hygiene in Africa.
Electronic supplementary material
The online version of this article (doi:10.1186/1478-4505-12-68) contains supplementary material, which is available to authorized users.
doi:10.1186/1478-4505-12-68
PMCID: PMC4274706  PMID: 25510403
Research; Water; Sanitation; Training; Water
7.  The Causes and Circumstances of Drinking Water Incidents Impact Consumer Behaviour: Comparison of a Routine versus a Natural Disaster Incident 
When public health is endangered, the general public can only protect themselves if timely messages are received and understood. Previous research has shown that the cause of threats to public health can affect risk perception and behaviours. This study compares compliance to public health advice and consumer behaviour during two “Boil Water” notices issued in the UK due to a routine incident versus a natural disaster incident. A postal questionnaire was sent to 1000 randomly selected households issued a routine “Boil Water” notice. Findings were then compared to a previous study that explored drinking water behaviour during a “Boil Water” notice issued after serious floods. Consumers affected by the routine incident showed a significant preference for official water company information, whereas consumers affected by the natural disaster preferred local information sources. Confusion over which notice was in place was found for both incidents. Non-compliance was significantly higher for the natural disaster (48.3%) than the routine incident (35.4%). For the routine incident, compliance with advice on drinking as well as preparing/cooking food and brushing teeth was positively associated with receiving advice from the local radio, while the opposite was true for those receiving advice from the water company/leaflet through the post; we suggest this may largely be due to confusion over needing boiled tap water for brushing teeth. No associations were found for demographic factors. We conclude that information dissemination plans should be tailored to the circumstances under which the advice is issued. Water companies should seek to educate the general public about water notices and which actions are safe and unsafe during which notice, as well as construct and disseminate clearer advice on brushing teeth and preparing/cooking food.
doi:10.3390/ijerph111111915
PMCID: PMC4245651  PMID: 25411725
public health communication; compliance; routine incident; human error; natural disaster; drinking water
8.  A Systematic Review and Meta-Analysis of the Association between Self-Reported Diarrheal Disease and Distance from Home to Water Source 
The aim of this study was to identify whether there was a relationship between the distance that people have to carry water home and ill health. We conducted a systematic review for papers that reported on the association between diarrheal risk and distance. Six papers were identified for inclusion in the meta-analysis. These were all observational studies, and only two reported effect sizes that adjusted for possible confounding. Multiple different types of water sources supplied the study communities. The combined odds ratio (OR) showed a significant increase in illness risk in people living farther away from their water source (OR = 1.45; 95% confidence interval [CI] = 1.04–1.68). There is a need for better designed studies to further elucidate the health impacts on having to carry water home.
doi:10.4269/ajtmh.2010.10-0215
PMCID: PMC2929055  PMID: 20810824
9.  Climate change and the emergence of vector-borne diseases in Europe: case study of dengue fever 
BMC Public Health  2014;14:781.
Background
Dengue fever is the most prevalent mosquito-borne viral disease worldwide. Dengue transmission is critically dependent on climatic factors and there is much concern as to whether climate change would spread the disease to areas currently unaffected. The occurrence of autochthonous infections in Croatia and France in 2010 has raised concerns about a potential re-emergence of dengue in Europe. The objective of this study is to estimate dengue risk in Europe under climate change scenarios.
Methods
We used a Generalized Additive Model (GAM) to estimate dengue fever risk as a function of climatic variables (maximum temperature, minimum temperature, precipitation, humidity) and socioeconomic factors (population density, urbanisation, GDP per capita and population size), under contemporary conditions (1985–2007) in Mexico. We then used our model estimates to project dengue incidence under baseline conditions (1961–1990) and three climate change scenarios: short-term 2011–2040, medium-term 2041–2070 and long-term 2071–2100 across Europe. The model was used to calculate average number of yearly dengue cases at a spatial resolution of 10 × 10 km grid covering all land surface of the currently 27 EU member states. To our knowledge, this is the first attempt to model dengue fever risk in Europe in terms of disease occurrence rather than mosquito presence.
Results
The results were presented using Geographical Information System (GIS) and allowed identification of areas at high risk. Dengue fever hot spots were clustered around the coastal areas of the Mediterranean and Adriatic seas and the Po Valley in northern Italy.
Conclusions
This risk assessment study is likely to be a valuable tool assisting effective and targeted adaptation responses to reduce the likely increased burden of dengue fever in a warmer world.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-781) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-781
PMCID: PMC4143568  PMID: 25149418
Dengue fever; Climate change; Europe; Disease risk
10.  Impact of the Provision of Safe Drinking Water on School Absence Rates in Cambodia: A Quasi-Experimental Study 
PLoS ONE  2014;9(3):e91847.
Background
Education is one of the most important drivers behind helping people in developing countries lift themselves out of poverty. However, even when schooling is available absenteeism rates can be high. Recently interest has focussed on whether or not WASH interventions can help reduce absenteeism in developing countries. However, none has focused exclusively on the role of drinking water provision. We report a study of the association between absenteeism and provision of treated water in containers into schools.
Methods and Findings
We undertook a quasi-experimental longitudinal study of absenteeism rates in 8 schools, 4 of which received one 20 L container of treated drinking water per day. The water had been treated by filtration and ultraviolet disinfection. Weekly absenteeism rates were compared across all schools using negative binomial model in generalized estimating equations. There was a strong association with provision of free water and reduced absenteeism (Incidence rate ratio = 0.39 (95% Confidence Intervals 0.27–0.56)). However there was also a strong association with season (wet versus dry) and a significant interaction between receiving free water and season. In one of the intervention schools it was discovered that the water supplier was not fulfilling his contract and was not delivering sufficient water each week. In this school we showed a significant association between the number of water containers delivered each week and absenteeism (IRR = 0.98 95%CI 0.96–1.00).
Conclusion
There appears to be a strong association between providing free safe drinking water and reduced absenteeism, though only in the dry season. The mechanism for this association is not clear but may in part be due to improved hydration leading to improved school experience for the children.
doi:10.1371/journal.pone.0091847
PMCID: PMC3954794  PMID: 24632573
11.  Emergent Properties of the Optic Tectum Revealed by Population Analysis of Direction and Orientation Selectivity 
The Journal of Neuroscience  2013;33(35):13940-13945.
How local circuits within the brain process visual information has classically been addressed at the single neuron level. Such reductionist approaches, however, struggle to capture the full scope of functional properties associated with even “simple” brain nuclei. Using population functional calcium imaging, we aim to describe how local circuits within the zebrafish optic tectum process visual information. Specifically, how are previously identified direction-selective (DS) and orientation-selective (OS) retinal ganglion cell (RGC) inputs (Nikolaou et al., 2012) represented in tectal cells? First, we identify an emergent population of DS tectal cell with a direction preference not explicitly present in any one of the RGC inputs. Second, this is associated with a striking shift from a tiled and triangular representation of directional space (RGC inputs) into an overlapping cardinal representation by tectal cell populations. Third, and in contrast, we find that orientation space is represented similarly in both the RGC input and tectal cell populations illustrating feature-dependent differences in how tectal circuits process their inputs. Finally, we identify OS and two populations of DS cells at the superficial border of the tectal neuropil, one of which is an emergent population. This study, together with our previous one (Nikolaou et al., 2012), demonstrate that direction-selectivity is established in both the retina and tectum.
doi:10.1523/JNEUROSCI.1493-13.2013
PMCID: PMC3756745  PMID: 23986231
12.  A Systems-Based Dissection of Retinal Inputs to the Zebrafish Tectum Reveals Different Rules for Different Functional Classes during Development 
The Journal of Neuroscience  2013;33(35):13946-13956.
We have examined the form, diversity, and organization of three functional classes of retinal inputs to the zebrafish optic tectum during development. Our systems-based approach was to analyze data from populations of retinal ganglion cells labeled with a presynaptic targeted calcium indicator, synaptophysin GCaMP3 (SyGCaMP3). Collectively, our findings provide an insight as to the degree of visual encoding during retino-tectal development and how it dynamically evolves from a nascent and noisy presynaptic neural-scape to an increasingly complex and refined representation. We report five key features: (1) direction-selective inputs are developmentally invariant; (2) orientation-selective inputs exhibit highly dynamic properties over the same period, with changes in their functional characteristics and spatial organization; (3) inputs defined as anisotropic are an early dominant functional class, with heterogeneous response profiles, which progressively diminish in incidence and spatial extent; (4) dark rearing selectively affects the orientation-selective responses: both functional characteristics and relative spatial distributions; and (5) orientation-selective inputs exhibit four subtypes, two more than previously identified in any species. Our approach was to label RGC axon terminals with an indicator of activity and quantitatively characterize coherent response properties to different visual stimuli. Its application in the zebrafish, given its small size and the accessibility of the tectum, has enabled a quick yet robust assessment of multiple functional populations of responses.
doi:10.1523/JNEUROSCI.1866-13.2013
PMCID: PMC3756746  PMID: 23986232
13.  Water source and diarrhoeal disease risk in children under 5 years old in Cambodia: a prospective diary based study 
BMC Public Health  2013;13:1145.
Background
Despite claims that the Millennium Development Goals (MDG) targets on access to safe drinking water have been met, many 100 s of millions of people still have no access. The challenge remains how to provide these people and especially young children with safe drinking water.
Method
We report a longitudinal study designed to assess the effectiveness of an intervention based on provided treated drinking water in containers on self-reported diarrhoea in children. The intervention was “1001 fontaines pour demain” (1001 F) is a non-governmental not for profit organization (created in 2004 and based in Caluire, France) that helps local entrepreneurs treat package, and sell safe drinking water. Cases and controls were chosen at village and household level by propensity score matching Participants were visited twice a month over six months and asked to complete a diarrhoea health diary.
Results
In total 4275 follow-up visits were completed on 376 participants from 309 homes. Diarrhoea was reported in 20.4% of children on each visit, equating to an incidence rate estimate of 5.32 episodes per child per year (95% confidence interval = 4.97 to 5.69). Compared to those drinking 1001 F water, children drinking surface water were 33% (95% CI -1 to 17%), those drinking protected ground water were 62% (95% CI 19 to 120%) and those drinking other bottled water 57% (95% CI 15 to 114%) more likely to report diarrhoea. Children drinking harvested rainwater had similar rates of diarrhoea to Children drinking 1001 F water.
Conclusion
Our study suggests that 1001 F water provides a safer alternative to groundwater or surface water. Furthermore, our study raises serious concerns about the validity of assuming protected groundwater to be safe water for the purposes of assessing the MDG targets. By contrast our study provides addition evidence of the relative safety of rainwater harvesting.
doi:10.1186/1471-2458-13-1145
PMCID: PMC4029329  PMID: 24321624
Water; Diarrhoea; Latrines; Cambodia; Child health; Bottled water; Disinfection
14.  The Effects of Weather and Climate Change on Dengue 
Background
There is much uncertainty about the future impact of climate change on vector-borne diseases. Such uncertainty reflects the difficulties in modelling the complex interactions between disease, climatic and socioeconomic determinants. We used a comprehensive panel dataset from Mexico covering 23 years of province-specific dengue reports across nine climatic regions to estimate the impact of weather on dengue, accounting for the effects of non-climatic factors.
Methods and Findings
Using a Generalized Additive Model, we estimated statistically significant effects of weather and access to piped water on dengue. The effects of weather were highly nonlinear. Minimum temperature (Tmin) had almost no effect on dengue incidence below 5°C, but Tmin values above 18°C showed a rapidly increasing effect. Maximum temperature above 20°C also showed an increasing effect on dengue incidence with a peak around 32°C, after which the effect declined. There is also an increasing effect of precipitation as it rose to about 550 mm, beyond which such effect declines. Rising access to piped water was related to increasing dengue incidence. We used our model estimations to project the potential impact of climate change on dengue incidence under three emission scenarios by 2030, 2050, and 2080. An increase of up to 40% in dengue incidence by 2080 was estimated under climate change while holding the other driving factors constant.
Conclusions
Our results indicate that weather significantly influences dengue incidence in Mexico and that such relationships are highly nonlinear. These findings highlight the importance of using flexible model specifications when analysing weather–health interactions. Climate change may contribute to an increase in dengue incidence. Rising access to piped water may aggravate dengue incidence if it leads to increased domestic water storage. Climate change may therefore influence the success or failure of future efforts against dengue.
Author Summary
Relationships between weather and mosquito-borne diseases are nonlinear in nature. This means that the number of disease cases does not vary equally with changes in the climate system. Identifying adequately the form of the relationship between disease outcomes and their drivers in an empirical fashion can be tedious and imprecise. Here, we use a statistical modelling approach that estimates the form of the relationships between dengue and weather in an automated way. We use this approach to analyse a comprehensive dataset covering 23 years of dengue reports from Mexico. Our model incorporates the effects of some non-climatic factors that are key for disease occurrence. We then use our estimations to project the potential impact of climate change on dengue incidence under three different scenarios for three different time periods. The estimated effects of weather on dengue were highly nonlinear. These results highlight the importance of using flexible modelling approaches for the analysis of disease-weather relationships with a nonlinear behaviour. Rising access to water supply was related to increases in dengue incidence. This situation may be related to increased water storage induced by unreliable water supply. Dengue incidence may increase to about 40% by 2080 due to climate change. This increase in dengue incidence may be aggravated by a rising access to piped water if it leads to domestic water storage, although any adaptation measures to rising dengue may also affect the risk. Our results contribute to a better overall understanding of the epidemiology of dengue.
doi:10.1371/journal.pntd.0002503
PMCID: PMC3828158  PMID: 24244765
15.  Mediational Effects of Self-Efficacy Dimensions in the Relationship between Knowledge of Dengue and Dengue Preventive Behaviour with Respect to Control of Dengue Outbreaks: A Structural Equation Model of a Cross-Sectional Survey 
Background
Dengue fever is endemic in Malaysia, with frequent major outbreaks in urban areas. The major control strategy relies on health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites close to people's homes. However, such campaigns have not always been 100% effective. The concept of self-efficacy is an area of increasing research interest in understanding how health promotion can be most effective. This paper reports on a study of the impact of self-efficacy on dengue knowledge and dengue preventive behaviour.
Methods and Findings
We recruited 280 adults from 27 post-outbreak villages in the state of Terengganu, east coast of Malaysia. Measures of health promotion and educational intervention activities and types of communication during outbreak, level of dengue knowledge, level and strength of self-efficacy and dengue preventive behaviour were obtained via face-to-face interviews and questionnaires. A structural equation model was tested and fitted the data well (χ2 = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963). Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. Level and strength of self-efficacy fully mediated the relationship between knowledge of dengue and dengue preventive behaviours. Strength of self-efficacy acted as partial mediator in the relationship between knowledge of dengue and dengue preventive behaviours.
Conclusions
To control and prevent dengue outbreaks by behavioural measures, health promotion and educational interventions during outbreaks should now focus on those approaches that are most likely to increase the level and strength of self-efficacy.
Author Summary
Dengue fever is one of the most rapidly increasing vector-borne diseases of humans in the tropics. There is currently no treatment and no vaccine, so control of the disease depends on controlling the mosquito vector. Unfortunately health promotional campaigns aimed at encouraging people to reduce mosquito breeding sites have not always been 100% effective. Self-efficacy is an area of increasing research interest and can be thought of as people's confidence in their ability to engage in health behaviours. We report a study of the impact of self-efficacy on dengue preventive behaviour. We conducted face to face interviews in villages in the state of Terengganu, Malaysia that had been affected by dengue outbreaks. A structural equation model was tested and fitted the data well. Mass media, local contact and direct information-giving sessions significantly predicted level of knowledge of dengue. However, self-efficacy fully mediated the relationship between knowledge of dengue and engagement in dengue preventive behaviours. We conclude that educational components of community dengue control programmes should focus on interventions.
doi:10.1371/journal.pntd.0002401
PMCID: PMC3784466  PMID: 24086777
16.  Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks 
PLoS ONE  2013;8(8):e72279.
Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases.
doi:10.1371/journal.pone.0072279
PMCID: PMC3743774  PMID: 23967294
17.  Sporadic Cryptosporidiosis Case-Control Study with Genotyping 
Emerging Infectious Diseases  2004;10(7):1241-1249.
Risk factors for Cryptosporidiosis in United Kingdom.
We report a case-control study of sporadic cryptosporidiosis with genotyping of isolates from case-patients. A postal questionnaire was completed by 427 patients and 427 controls. We obtained genotyping data on isolates from 191 patients; 115 were Cryptosporidium hominis, and 76 were C. parvum. When all cryptosporidiosis cases were analyzed, three variables were strongly associated with illness: travel outside the United Kingdom, contact with another person with diarrhea, and touching cattle. Eating ice cream and eating raw vegetables were both strongly negatively associated with illness. Helping a child <5 years of age to use the toilet and the number of glasses of tap water drunk at home each day were also independently positively associated with risk. Eating tomatoes was negatively associated. For C. hominis infections, the strongly significant risk factors were travel abroad and changing diapers of children <5 years of age. For C. parvum, eating raw vegetables and eating tomatoes were strongly negatively associated with illness; touching farm animals was associated with illness.
doi:10.3201/eid1007.030582
PMCID: PMC3323324  PMID: 15324544
Cryptosporidiosis; Cryptosporidium parvum; Cryptosporidium hominis; case-control study; risk factors
18.  Foot and Mouth Disease and Cryptosporidiosis: Possible Interaction between Two Emerging Infectious Diseases 
Emerging Infectious Diseases  2003;9(1):109-112.
During 2001, a large outbreak of foot and mouth disease occurred in the United Kingdom, during which approximately 2,030 confirmed cases of the disease were reported, >6 million animals were slaughtered, and strict restrictions on access to the countryside were imposed. We report a dramatic decline in the reported incidence of human cryptosporidiosis in northwest England during weeks 13–38 in 2001, compared with the previous 11 years. This decline coincided with the period of foot and mouth restrictions. No similar reduction occurred in the other 26 weeks of the year. We also noted a substantial decline in the proportion of human infections caused by the bovine strain (genotype 2) of Cryptosporidium parvum during weeks 13–38 that year but not during the other weeks.
doi:10.3201/eid0901.020265
PMCID: PMC2873749  PMID: 12533291
cryptosporidiosis; Cryptosporidium parvum; foot and mouth disease; incidence; zoonosis; dispatch
19.  Cryptosporidium Oocysts in a Water Supply Associated with a Cryptosporidiosis Outbreak 
Emerging Infectious Diseases  2002;8(6):619-624.
An outbreak of cryptosporidiosis occurred in and around Clitheroe, Lancashire, in northwest England, during March 2000. Fifty-eight cases of diarrhea with Cryptosporidium identified in stool specimens were reported. Cryptosporidium oocysts were identified in samples from the water treatment works as well as domestic taps. Descriptive epidemiology suggested that drinking unboiled tap water in a single water zone was the common factor linking cases. Environmental investigation suggested that contamination with animal feces was the likely source of the outbreak. This outbreak was unusual in that hydrodynamic modeling was used to give a good estimate of the peak oocyst count at the time of the contamination incident. The oocysts’ persistence in the water distribution system after switching to another water source was also unusual. This persistence may have been due to oocysts being entrapped within biofilm. Despite the continued presence of oocysts, epidemiologic evidence suggested that no one became ill after the water source was changed.
doi:10.3201/eid0806.010271
PMCID: PMC3369585  PMID: 12023920
Cryptosporidium Oocysts in a Water Supply Associated with a Cryptosporidiosis Outbreak; Cryptosporidium; outbreak; oocysts; water; zoonosis; biofilm
20.  A new heterogeneous family of telomerically encoded Cryptosporidium proteins 
Evolutionary applications  2013;6(2):207-217.
Cryptosporidiosis is predominantly caused by two closely related species of protozoan parasites the zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis which diverge phenotypically in respect to host range and virulence. Using comparative genomics we identified two genes displaying overt heterogeneity between species. Although initial work suggested both were species specific, Cops-1 for C. parvum and Chos-1 for C. hominis, subsequent study identified an abridged ortholog of Cops-1 in C. hominis. Cops-1 and Chos-1 showed limited, but significant, similarity to each other and share common features: (i) telomeric location: Cops-1 is the last gene on chromosome 2, whilst Chos-1 is the first gene on chromosome 5, (ii) encode circa 50-kDa secreted proteins with isoelectric points above 10, (iii) are serine rich, and (iv) contain internal nucleotide repeats. Importantly, Cops-1 sequence contains specific SNPs with good discriminatory power useful epidemiologically. C. parvum-infected patient sera recognized a 50-kDa protein in antigen preparations of C. parvum but not C. hominis, consistent with Cops-1 being antigenic for patients. Interestingly, anti-Cops-1 monoclonal antibody (9E1) stained oocyst content and sporozoite surface of C. parvum only. This study provides a new example of protozoan telomeres as rapidly evolving contingency loci encoding putative virulence factors.
doi:10.1111/j.1752-4571.2012.00277.x
PMCID: PMC3586618  PMID: 23467513
bioinfomatics/phyloinfomatics; biomedicine; genomics/proteomics; host parasite interactions; microbial biology; molecular evolution; parasitology; virulence
21.  A new heterogeneous family of telomerically encoded Cryptosporidium proteins 
Evolutionary Applications  2012;6(2):207-217.
Cryptosporidiosis is predominantly caused by two closely related species of protozoan parasites the zoonotic Cryptosporidium parvum and anthroponotic Cryptosporidium hominis which diverge phenotypically in respect to host range and virulence. Using comparative genomics we identified two genes displaying overt heterogeneity between species. Although initial work suggested both were species specific, Cops-1 for C. parvum and Chos-1 for C. hominis, subsequent study identified an abridged ortholog of Cops-1 in C. hominis. Cops-1 and Chos-1 showed limited, but significant, similarity to each other and share common features: (i) telomeric location: Cops-1 is the last gene on chromosome 2, whilst Chos-1 is the first gene on chromosome 5, (ii) encode circa 50-kDa secreted proteins with isoelectric points above 10, (iii) are serine rich, and (iv) contain internal nucleotide repeats. Importantly, Cops-1 sequence contains specific SNPs with good discriminatory power useful epidemiologically. C. parvum-infected patient sera recognized a 50-kDa protein in antigen preparations of C. parvum but not C. hominis, consistent with Cops-1 being antigenic for patients. Interestingly, anti-Cops-1 monoclonal antibody (9E1) stained oocyst content and sporozoite surface of C. parvum only. This study provides a new example of protozoan telomeres as rapidly evolving contingency loci encoding putative virulence factors.
doi:10.1111/j.1752-4571.2012.00277.x
PMCID: PMC3586618  PMID: 23467513
bioinfomatics/phyloinfomatics; biomedicine; genomics/proteomics; host parasite interactions; microbial biology; molecular evolution; parasitology; virulence
22.  Does Village Water Supply Affect Children’s Length of Stay in a Therapeutic Feeding Program in Niger? Lessons from a Médecins Sans Frontières Program 
PLoS ONE  2012;7(12):e50982.
Objective
With an increasing move towards outpatient therapeutic feeding for moderately and severely malnourished children, the home environment has become an increasingly important factor in achieving good program outcomes. Infections, including those water-borne, may significantly delay weight gain in a therapeutic feeding program. This study examined the relationship between adequacy of water supply and children’s length of stay in a therapeutic feeding program in Niger.
Methods
The length of stay in a therapeutic feeding program of Médecins Sans Frontières in Niger was registered for 1518 children from 20 villages in the region. In parallel, the quality and quantity of the water source in each village were documented, and the association between adequacy of the water supply and length of stay in the program was assessed through Generalized Estimating Equation analysis.
Results
36% of the children presented with a secondary infection, 69% of which were water-related. When stratified by the adequacy of the quantity and/or quality of the water supply in their village of origin, non-adequacy of the water supply was clearly associated with a higher prevalence of secondary water-related infections and with much longer lengths of stay of malnourished children in the therapeutic feeding program.
Conclusion
This study suggests that therapeutic feeding programs using an outpatient model should routinely evaluate the water supply in their target children’s villages if they are to provide optimal care.
doi:10.1371/journal.pone.0050982
PMCID: PMC3517616  PMID: 23236416
23.  Climate Change and Food Security: Health Impacts in Developed Countries 
Environmental Health Perspectives  2012;120(11):1520-1526.
Background: Anthropogenic climate change will affect global food production, with uncertain consequences for human health in developed countries.
Objectives: We investigated the potential impact of climate change on food security (nutrition and food safety) and the implications for human health in developed countries.
Methods: Expert input and structured literature searches were conducted and synthesized to produce overall assessments of the likely impacts of climate change on global food production and recommendations for future research and policy changes.
Results: Increasing food prices may lower the nutritional quality of dietary intakes, exacerbate obesity, and amplify health inequalities. Altered conditions for food production may result in emerging pathogens, new crop and livestock species, and altered use of pesticides and veterinary medicines, and affect the main transfer mechanisms through which contaminants move from the environment into food. All these have implications for food safety and the nutritional content of food. Climate change mitigation may increase consumption of foods whose production reduces greenhouse gas emissions. Impacts may include reduced red meat consumption (with positive effects on saturated fat, but negative impacts on zinc and iron intake) and reduced winter fruit and vegetable consumption. Developed countries have complex structures in place that may be used to adapt to the food safety consequences of climate change, although their effectiveness will vary between countries, and the ability to respond to nutritional challenges is less certain.
Conclusions: Climate change will have notable impacts upon nutrition and food safety in developed countries, but further research is necessary to accurately quantify these impacts. Uncertainty about future impacts, coupled with evidence that climate change may lead to more variable food quality, emphasizes the need to maintain and strengthen existing structures and policies to regulate food production, monitor food quality and safety, and respond to nutritional and safety issues that arise.
doi:10.1289/ehp.1104424
PMCID: PMC3556605  PMID: 23124134
adaptation; climate change; food safety; food security; nutrition; regulation
24.  Contaminated Small Drinking Water Supplies and Risk of Infectious Intestinal Disease: A Prospective Cohort Study 
PLoS ONE  2012;7(8):e42762.
Background
This study sought to identify whether elevated risk of infectious intestinal disease (IID) exists in contaminated small water supply consumers compared with consumers drinking from small supplies complying with current standards and whether this effect is modified by age.
Methodology and Principal Findings
A prospective cohort study of 611 individuals receiving small supplies in England was conducted. Water supplies received sanitary inspection and examination for indicator bacteria and participants maintained a daily record of IID. Regression modeling with generalized estimating equations that included interaction terms between age and indicators of fecal pollution was performed. Crude IID prevalence was 9·3 days with symptoms/1000 person days (95%CI: 8·4, 10·1) and incidence was 3·2 episodes/1000 person days (95%CI, 2·7, 3·7) or 1·2 episodes per person year. Although there was no overall association between IID risk and indicator presence, there was strong interaction between age and indicator presence. In children under ten, relative risk (RR) of IID in those drinking from enterococci contaminated supplies was 4.8 (95%CI: 1.5, 15.3) for incidence and 8.9 (95%CI: 2.8, 27.5) for prevalence. In those aged 10 to 59, IID risk was lower but not statistically significant.
Conclusions
Contaminated small water supplies pose a substantial risk of IID to young children who live in homes reliant on these supplies. By contrast older children and adults do not appear to be at increased risk. Health care professionals with responsibility for children living in homes provided by very small water supplies should make parents aware of the risk.
doi:10.1371/journal.pone.0042762
PMCID: PMC3427350  PMID: 22936989
25.  The Value of Educational Messages Embedded in a Community-Based Approach to Combat Dengue Fever: A Systematic Review and Meta Regression Analysis 
Background
The effects of various dengue control measures have been investigated in previous studies. The aim of this review was to investigate the relative effectiveness (RE) of different educational messages embedded in a community-based approach on the incidence of Aedes aegypti larvae using entomological measures as outcomes.
Methods and Findings
A systematic electronic search using Medline, Embase, Web of Science and the Cochrane Library was carried out to March 2010. Previous systematic reviews were also assessed. Data concerning interventions, outcomes, effect size and study design were extracted. Basic meta-analyses were done for pooled effect size, heterogeneity and publication bias using Comprehensive Meta-analysis. Further analysis of heterogeneitity was done by multi-level modelling using MLwiN. 21 publications with 22 separate studies were included in this review. Meta-analysis of these 22 pooled studies showed an RE of 0.25 (95% CI 0.17–0.37), but with substantial heterogeneity (Cochran's Q = 1254, df = 21, p = <0.001,). Further analysis of this heterogeneity showed that over 60% of between study variance could be explained by just two variables; whether or not studies used historic or contemporary controls and time from intervention to assessment. When analyses were restricted to those studies using contemporary control, there was a polynomial relationship between effectiveness and time to assessment. Whether or not chemicals or other control measures were used did not appear have any effect on intervention effectiveness.
Conclusion
The results suggest that such measures do appear to be effective at reducing entomological indices. However, those studies that use historical controls almost certainly overestimate the value of interventions. There is evidence that interventions are most effective some 18 to 24 months after the intervention but then subsequently decline.
Author Summary
Dengue fever is a mosquito-borne viral infection that is widespread in the tropics. Each year there are an estimated 50 million infections worldwide. Preventing infection relies on controlling the mosquitoes that spread disease. Unfortunately it is still not clear what does and does not work in the control of the mosquito vector. There have been several systematic reviews into control of dengue fever but still no consensus has been reached. This lack of consensus reflects the substantial heterogeneity in published effectiveness of studies of dengue control interventions. Prior systematic reviews have not adequately addressed this heterogeneity. We used multi-level modelling meta regression to investigate what variables modify the effectiveness of studies of educational messages embedded in a community-based approach. Most of the between study variation was explained by two variables, study design and time from intervention to assessment. In particular, studies using historic controls substantially overestimated the effectiveness of the intervention compared to those studies using contemporary controls. When the analysis was restricted to just those studies using contemporary controls, effectiveness was highest about 12 to 24 months after intervention but then declined.
doi:10.1371/journal.pntd.0001278
PMCID: PMC3160295  PMID: 21886848

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