The Risk of Malaria in Travelers to India

Background.  Several countries have reported a decline in malaria cases imported by travelers returning from India.
Methods.  We collected data on imported malaria for the period 1992 to 2005 from nine countries. Traveler statistics denominator data were obtained from the Indian Ministry of   Tourism.
Results.  The malaria case numbers declined from 93 cases per 100,000 travelers in 1992 to 19 cases per 100,000 travelers in 2005. The proportion of Plasmodium falciparum decreased steadily throughout the years. The proportion of Plasmodium vivax accounts for more than 80% of all cases of malaria in travelers to India. Deaths due to malaria were rare; only the UK and the United States reported deaths, a total of 16, between 1992 and 2005. The high-risk areas for malaria in India can be clearly identified using endemic malaria data. High-risk states are Chhattisgarh, Orissa, Jharkhand, West Bengal, Goa (mainly P vivax ), and the states east of Bangladesh.
Conclusions.  The decreasing incidence of malaria in travelers to India and the high proportion of P vivax support the current change in guidelines in some European countries advocating the use of the standby emergency self-treatment strategy or bite precautions plus awareness of risk instead of chemoprophylaxis. Otherwise in high-risk states, chemoprophylaxis should still be considered particularly in high-transmission seasons.     

Japanese Encephalitis: Defining Risk Incidence for Travelers to Endemic Countries and Vaccine Prescribing From the UK and Switzerland

Background.  Large numbers of Western travelers visit countries endemic for Japanese encephalitis (JE). The risk of infection is unknown. This study attempts at estimating a risk incidence for visitors from two European countries with the available data.
Methods.  Using the total number of case reports between 1978 and 2008, the number of visits made by European tourists to endemic regions, and total doses of vaccines sold in the two study countries, the risk incidence of JE in travelers was estimated. The proportion of vaccinated visitors to endemic regions was retrieved from the data of two travel clinics (in London and Basel) and related to vaccine prescribing in UK and Swiss travelers.
Results.  In 2004, an estimated 0.16% to 0.3% of UK and Swiss travelers were vaccinated against JE, with no surveillance reports of JE cases. Between 116,000 and 152,000 European travelers would receive vaccination. More than 99% travel to endemic countries without vaccination. Only 40 cases of JE infection have been reported in travelers for the past 30 years. The risk incidence is thus 1.3 per year in 7.1 million visits of the 17 million European travelers who are at a potential risk of JE infection.
Conclusions.  This study and the analysis of the existing literature support the recommendation that all travelers should be informed about the risk of JE infection but also suggest that there is no evidence for justifying a general recommendation for JE vaccination in travelers to endemic areas.     

Hepatitis A Risk in Travelers

Background.  Traveling to highly endemic areas for hepatitis A is increasing while the immunization level in travelers has been shown to be low in the countries studied.
Methods.  In this population-based study, we have estimated the incidence rate of travel-related hepatitis A during 1997 to 2005 by use of the Swedish notification system of communicable diseases and an ongoing national database on travel patterns. We have also acquired airport-based immunization data from 2007.
Results.  During the study period, 636 cases of travel-related hepatitis A were notified. Traveling to East Africa was associated with the highest incidence rate (14.1 cases/100,000 person months), followed by the Middle East (5.8/100,000 person months), and India with neighboring countries (5.6/100,000 person months). Visiting Friends and Relatives (VFR) travelers represented 83, 91, and 70% of the cases to these three regions. By age-group, the highest incidence was found in children 0 to 14 years (3.1/100,000 travelers) where 88% of the cases were VFR travelers. Incidence rate in unprotected travelers to East Asia, North Africa, and the Middle East was 2, 12, and 18 cases/100,000 person months, respectively. In 2007, 79% of the travelers were immunized against hepatitis A.
Conclusions.  We conclude that travelers, and especially children, who are VFR in endemic areas constitute a high-risk group for acquiring hepatitis A infection, while the risk for unprotected tourists to East Asia is low.     

Risk Factors for Typhoid Fever in Travelers

Background: The incidence of typhoid fever in the developing world remains high and has been estimated at 540 cases per 100,000 of the population per year. International travelers to such areas are at risk of infection, especially if they travel under low hygienic standards.
Methods: In order to identify the risk factors leading to infection in travelers and expatriates, travel histories, anamnestic and clinical features of 31 patients with typhoid fever, who presented to a German travel clinic, were investigated.
Results: Compared to the total patient population of the outpatient clinic during the period of investigation (n = 17,029 patients), patients who presented with typhoid fever were older (39 years versus 31 years, p < .001) and traveled longer (58 days versus 19 days, p < .001). While only 19.2% of the total patient population had traveled to the Indian subcontinent prior to referral, 35.4% of the patients with typhoid fever had acquired the infection there (p < .001). Similar results were obtained for South East Asia and Indonesia: twenty percent of the total patient population traveled there in contrast with 32.2% of patients with typhoid fever (p < .001). Latin America was visited by 16.3% of all patients, but only 6.4% of patients with typhoid (p < .001).     

Pretravel Advice Neglects Rabies Risk for Travelers to Tropical Countries

BACKGROUND: While the risk of acquiring rabies in Europe is low, there have been a number of reports on cases of human rabies "imported" from abroad in recent years. Few studies have been conducted concerning pretravel advice for international travelers about the risk of rabies. METHODS: One-hundred and fifty German and 150 Swiss general practitioners (GPs) who give pretravel advice were interviewed to assess their awareness of the risk of rabies for travelers, and of the relevant preventive measures, using a pretested telephone interview followed by a written questionnaire with a multiple choice list. GPs were asked specifically about pretravel health advice for journeys to Thailand and Kenya. RESULTS: During the telephone interview a majority (76%) of the 300 GPs recommended "nothing" as a preventive measure against rabies for travelers. One or two important preventive measures were mentioned by only a few GPs. No major differences were detected between the German and the Swiss groups concerning their recommendations for rabies prevention. The 119 German and 121 Swiss GPs who returned the completed questionnaire said they would recommend the three important preventive measures in the future significantly more often than they had recommended them to their clients in the past. CONCLUSIONS: The risk of rabies in travelers to tropical countries appears to be neglected in pretravel advice provided by Swiss and German GPs. The recommendations on travel advice published in the Swiss Bulletin of the Federal Office of Public Health (BFOPH) and in the "Deutsches Arzteblatt" should be extended to "other specific health risks." In Switzerland this has now been done.     

Risk of Cholera Among Western and Japanese Travelers

Background : There has been concern about an increased risk of cholera in travelers to Latin America since the spread of the pandemic to this part of the world. Additionally, before this study the continuous high incidence of imported cholera to Japan had so far not been analyzed.
Methods : A retrospective analysis of cases notified in 1991 to national surveillance centers in industrialized countries and to the World Health Organization was carried out. Denominator data were obtained by the World Tourism Organization.
Results : The reported rate of imported cholera in European and North American travelers visiting endemic areas remains in the range of 0,2 per 100,000, as was observed 10 years ago. This rate is, however, is manyfold higher in Japanese travelers, with a highest value of 13,0 per 100,000 reported in those returning from Indonesia, usually Bali. No secondary outbreaks were observed in those countries to which cholera was imported.
Conclusions : It is assumed that the higher rates in Japanese travelers are mainly due to more intensive surveillance. On Bali and elsewhere, further studies are needed to determine both the role of V. cholerae as a cause of traveler's diarrhea in tourists and to re-evaluate the need for cholera vaccination at specific high-risk destinations.     

心脏研究中的数学模型概述

概述用于心脏研究的数学模型,通过对这些数学模型的分析比较,展望了数学模型在心脏研究中的应用与发展。     

Health Problems of Corporate Travelers: Risk Factors and Management

Background: Numerous studies have been done regarding health problems experienced by tourists in developing countries; however, little data exist about these health risks and illnesses experienced by corporate travelers.
Methods: The authors examined by electronic survey the health risks encountered, compliance with pretravel health recommendations, and illnesses and injuries experienced by employees of the Coca-Cola Company who travel internationally.
Results: Two hundred twenty-six travelers responded. Although most travelers ate meals at their hotels and chose foods that were cooked and still hot, over half also ate foods that remained at room temperature for prolonged periods and/or ate from cold salad bars. Almost half drank untreated tap water. Thirty-five percent of travelers developed diarrhea and 29% reported respiratory illnesses, with 12% seeking medical attention for their problems. Forty-three percent of those traveling to malarious regions admitted to noncompliance with antimalarial recommendations. Health kits provided were used by only 51% of travelers.
Conclusions: Although many corporate travelers followed pretravel health recommendations, some did not. Injuries, fever, and illnesses such as diarrhea and respiratory infections occurred. Strategies to improve access to the travel clinic and the acquisition of health information and travel health kits are being implemented. The health risks and behaviors of corporate travelers, including the potential impact of psychosocial stressors, need greater attention.     

Quantitative Risk Analysis of Particulate Matter in the Air: Interspecies Extrapolation with Bioassay and Mathematical Models

We analyzed the health risk of particulate matters in the air to humans using bioassay data and a mathematical model. We designed an original dosimetry model to estimate the particle concentration in human respiratory organs, and the concentration of the inhaled particles at the target organ was used for interspecies extrapolation from rat to human. Our model is based on the conventional dosimetry model and deposition model in the previous literature, but clearance parameters have been newly introduced for the simulation of long-term exposure. Lung cancer was set as the risk endpoint in our risk study, and the dose-response relationship at the target organ (lung) was quantitatively analyzed by the benchmark dose (BMD) method. For interspecies extrapolation based on target organ concentration, we assumed benchmark concentration (BMC) related to 1% excess cancer in rats and humans, and the human equivalent concentration (HEC) was searched by back-estimation using our model. The obtained HEC was 948 to 1098 mg/m³, and the unit risk to humans was 9.11 to 10.5 × 10^?9 per 1 μ g/m³ of particulate matter. The estimated cancer risk for Japanese people in general was estimated as approximately 9–10 persons per 100,000,000 when the particle concentration in the air is 10 μg/m³.     

Mathematical Modeling of Circadian Cortisol Concentrations Using Indirect Response Models: Comparison of Several Methods

Six mathematical functions to describe the chronobiology of cortisol concentrations were assessed. Mean data from a dose-proportionality study of inhaled fluticasone propionate were fitted with an indirect response model using various biorhythmic functions (single cosine, dual ramps, dual zero-order, dual cosines, and Fourier series with 2 and n-harmonics) for production rate. Data with known parameters and random variation were also generated and fitted using the ADAPT II program. Fitted parameters, model estimation criteria, and runs tests were compared. Models with preassigned functions: the dual ramps, the dual zero-order and the dual cosines provide maximum and minimum times for cortisol release rate, were suitable for describing asymmetric circadian patterns and yielding IC₅₀ values. Fourier analysis differs from the other methods in that it uses the placebo data to recover equations for cortisol secretion rate rather than by postulation. Nonlinear regression for Fourier analysis, instead of the L ² -norm method, was useful to characterize the baseline cortisol data but was restricted to a maximum of two harmonics. Apart from the single cosine function, which predicts symmetrical cortisol concentrations, all methods were satisfactory in describing the baseline and suppressed cortisol concentrations. On the other hand, Fourier series with L ² -norm produced the best unbiased estimate for baseline patterns. The Fourier method is flexible, accurate, and can be extended to other drug-induced changes in normal periodic rhythms.     

Using Bayesian Space-Time Models to Understand the Substance Use Environment and Risk for Being Referred to Child Protective Services

Parental substance misuse has often been cited as a cause of children being referred for investigation of child abuse and neglect. Research on how the substance use environment might affect this relationship is still in its infancy with primarily only cross-sectional studies finding a positive relationship of alcohol outlet density at the level of neighborhoods and alcohol prices at level of states and maltreatment. A longitudinal study shows that increasing female drug-related arrests are related to increasing rates of maltreatment in rural and urban counties. The current study incorporates three aspects of the substance use environment in a panel study of 58 California counties over 4 years (n = 232) to study this relationship for referrals to child protective services (CPS) for child abuse and neglect. We use conditionally autoregressive (CAR) Bayesian models to model the spatial and temporal structure in the data. We find that use of welfare benefits, the number of outliers per population, and the number of drug-related arrests per population are positively related to referrals while unemployment and admissions to publicly funded alcohol and drug user treatment programs are negatively correlated to referrals. Significant spatial structure and space-time relationships are also found. The findings indicate that supply of alcohol and drugs (as measured by number of alcohol outlets and arrests for drug use and sales) may increase risk for being referred to CPS, but treatment for substance use does not increase the risk for referral.     

Knowledge, Attitudes and Practices of Business Travelers Regarding Malaria Risk and Prevention

Background This study aimed to determine the knowledge, attitudes and practices of Swiss business travelers with regard to malaria.
Methods Questionnaires printed in three languages were distributed by employers, travel agencies and tropical medicine specialists to business travelers with destinations in malaria endemic countries.
Results In total, 401 questionnaires were evaluated. Thirty-three percent visited high-risk areas, 27% visited low-risk areas, and 40% visited only malaria-free areas within endemic countries. Among the investigated business travelers, 6% had experienced malaria infection, and 29% had previously had blood smears tested for malaria at least once. Almost all business travelers, 95%, knew that mosquitoes are the main vectors of malaria. The infection risk between dusk and dawn was known to 71%, and the incubation time to 36%. Apart from fever (99%) and headache (63%), other malaria symptoms were known to only 13% to 36% of the travelers. If signs of illness such as fever and headache occurred, 63% would react adequately and seek medical advice within 24 h. Only 16% of the travelers to African high-risk areas followed the recommended behavior concerning antimosquito and antimalarial strategies; 31% of those on trips to low-risk areas used an adequate protective strategy. Of the business travelers using chemoprophylaxis during travel, just 50% continued intake posttravel, as requested, after leaving the endemic area.
Conclusions Business travelers are well informed regarding the mode of transmission and the risk of malaria at specific destinations but tend to comply poorly with anti-mosquito and chemoprophylactic strategies. The knowledge, attitudes and practices of business travelers with regard to malaria prevention need to be improved.     

The Effect of Collinearity on Parameter Estimates in Nonlinear Mixed Effect Models

Purpose. To demonstrate how correlations among predictor variables in a population pharmacokinetic model affect the ability to discern which covariates should enter into the structural pharmacokinetic model. Methods. Monte Carlo simulation was used to generate multiple-dose concentration-time data similar to that seen in a Phase III clinical trial. The drugs' pharmacokinetics were dependent on two covariates. Five data sets were simulated with increasing correlation between the two covariates. All data sets were analyzed using NONMEM both with and without inclusion of the covariates in the structural pharmacokinetic model. Summary measures for ill-conditioning and sensitivity analysis were used to examine how increasing correlation among covariates affects the accuracy and precision of the parameter estimates. Results. When covariates were included in the structural pharmacokinetic model and the correlation between covariates increased, the standard error of the parameter estimates increased and the value of parameter estimates themselves became increasingly biased. When the correlation between predictor variables was 0.75, the standard errors of the parameter estimates were too large to declare statistical significance. Conclusions. Correlations among predictor variables greater than 0.5 when entered into the model simultaneously should be a warning to researchers because the (1) the accuracy of the parameter estimates themselves may be biased and (2) the precision of the estimates may be inflated due to ill-conditioning.     

Variability of Safe Dose Estimates When Using Complicated Models of the Carcinogenic Process: A Case Study: Methylene Chloride

Advances in understanding carcinogenesis have led to the developmentof mathematical models that have biologically interpretableparameters. These models utilize more of the available scientificdata than the empirical models routinely employed for quantifyingcarcinogenic risk. They also require consideration of sourcesof uncertainty in risk estimates that were previously ignored,such as animal-to-animal variability of physiological and pharmacologicalconstants. A numerical technique is proposed for studying theconsequences of incorporating the intrapopulation variabilityof biologically interpretable parameters into the risk assessmentprocess. To demonstrate the technique, the variability of safedose estimates for exposure to methylene chloride is considered.The results suggest that intrapopulation variability of themodel parameters can increase the variability of safe dose estimatesan appreciable amount.