Yesim Tozan

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Yesim Tozan

Clinical Associate Professor of Global Health

Professional overview

Dr. Yesim Tozan’s research centers on health decision science and priority setting, and explores the costs and cost-effectiveness of health care interventions using decision analytic models and the issues of health care resource allocation in low- and middle-income countries. Her main focus has been infectious disease prevention and control with an emphasis on dengue and malaria. Dr. Tozan is currently leading a health economics work package in a European Union-funded research project on dengue surveillance and control with field sites in Sri Lanka and Thailand. She is also leading a prospective multi-center study on the cost of dengue illness in international travelers utilizing a network of travel clinics in Europe, the US, the Middle East and Australia. Most recently, she has been working on economic evaluation of artemisinin-based combination therapies for the treatment of uncomplicated childhood malaria using data from multi-site randomized clinical trials in Africa and Asia. Dr. Tozan was a task force associate for the UN Millennium Project’s Task Force on HIV/AIDS, Malaria, Tuberculosis and Access to Essential Medicines and was lead author of the malaria task force report entitled “Coming to grips with malaria in the new millennium.”

Education

BS, Environmental Engineering, Istanbul Technical University, Turkey
MS, Environmental Technology, Bogazici University, Turkey
MA, Public Affairs, Princeton University, Princeton, NJ
PhD, Public Affairs, Princeton University, Princeton, NJ

Areas of research and study

Cost Effectiveness
Cost-effective Health Programs and Policies
Economic Evaluation
Health Economics
Infectious Diseases
Prevention Interventions

Publications

Economic cost and quality of life of family caregivers of schizophrenic patients attending psychiatric hospitals in Ghana

Opoku-Boateng, Y.N., Kretchy, I.A., Aryeetey, G.C., Dwomoh, D., Decker, S., Agyemang, S.A., … Nonvignon, J.

Publication year

2017

Journal title

BMC Health Services Research

Volume

17
10.1186/s12913-017-2642-0
Abstract

Background: Low and middle income countries face many challenges in meeting their populations' mental health care needs. Though family caregiving is crucial to the management of severe mental health disabilities, such as schizophrenia, the economic costs borne by family caregivers often go unnoticed. In this study, we estimated the household economic costs of schizophrenia and quality of life of family caregivers in Ghana. Methods: We used a cost of illness analysis approach. Quality of life (QoL) was assessed using the abridged WHO Quality of Life (WHOQOL-BREF) tool. Cross-sectional data were collected from 442 caregivers of patients diagnosed with schizophrenia at least six months prior to the study and who received consultation in any of the three psychiatric hospitals in Ghana. Economic costs were categorized as direct costs (including medical and non-medical costs of seeking care), indirect costs (productivity losses to caregivers) and intangible costs (non-monetary costs such as stigma and pain). Direct costs included costs of medical supplies, consultations, and travel. Indirect costs were estimated as value of productive time lost (in hours) to primary caregivers. Intangible costs were assessed using the Zarit Burden Interview (ZBI). We employed multiple regression models to assess the covariates of costs, caregiver burden, and QoL. Results: Total monthly cost to caregivers was US$ 273.28, on average. Key drivers of direct costs were medications (50%) and transportation (27%). Direct costs per caregiver represented 31% of the reported monthly earnings. Mean caregiver burden (measured by the ZBI) was 16.95 on a scale of 0-48, with 49% of caregivers reporting high burden. Mean QoL of caregivers was 28.2 (range: 19.6-34.8) out of 100. Better educated caregivers reported lower indirect costs and better QoL. Caregivers with higher severity of depression, anxiety and stress reported higher caregiver burden and lower QoL. Males reported better QoL. Conclusions: These findings highlight the high household burden of caregiving for people living with schizophrenia in low income settings. Results underscore the need for policies and programs to support caregivers.

Household costs of hospitalized dengue illness in semi-rural Thailand

Tozan, Y., Ratanawong, P., Sewe, M.O., Wilder-Smith, A., & Kittayapong, P.

Publication year

2017

Journal title

PLoS Neglected Tropical Diseases

Volume

11
10.1371/journal.pntd.0005961
Abstract

Background: Dengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries, imposing a major economic burden on households, health systems, and governments. This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao province in eastern Thailand. Methods: We conducted a prospective cost-of-illness study of hospitalized pediatric and adult dengue patients at three public hospitals. We examined all hospitalized dengue cases regardless of disease severity. Patients or their legal guardians were interviewed using a standard questionnaire to determine household-level medical and non-medical expenditures and income losses during the illness episode. Results: Between March and September 2015, we recruited a total of 224 hospitalized patients (<5 years, 4%; 5–14 years, 20%, 15–24 years, 36%, 25–34 years, 15%; 35–44 years, 10%; 45+ years, 12%), who were clinically diagnosed with dengue. The total cost of a hospitalized dengue case was higher for adult patients than pediatric patients, and was US$153.6 and US$166.3 for pediatric DF and DHF patients, respectively, and US$171.2 and US$226.1 for adult DF and DHF patients, respectively. The financial burden on households increased with the severity of dengue illness. Conclusions: Although 74% of the households reported that the patient received free medical care, hospitalized dengue illness cost approximately 19–23% of the monthly household income. These results indicated that dengue imposed a substantial financial burden on households in Thailand where a great majority of the population was covered by the Universal Coverage Scheme for health care.

Mitigating Diseases Transmitted by Aedes Mosquitoes: A Cluster-Randomised Trial of Permethrin-Impregnated School Uniforms

Kittayapong, P., Olanratmanee, P., Maskhao, P., Byass, P., Logan, J., Tozan, Y., … Wilder-Smith, A.

Publication year

2017

Journal title

PLoS Neglected Tropical Diseases

Volume

11
10.1371/journal.pntd.0005197
Abstract

Background: Viral diseases transmitted via Aedes mosquitoes are on the rise, such as Zika, dengue, and chikungunya. Novel tools to mitigate Aedes mosquitoes-transmitted diseases are urgently needed. We tested whether commercially insecticide-impregnated school uniforms can reduce dengue incidence in school children. Methods: We designed a cluster-randomised controlled trial in Thailand. The primary endpoint was laboratory-confirmed dengue infections. Secondary endpoints were school absenteeism; and impregnated uniforms’ 1-hour knock-down and 24 hour mosquito mortality as measured by standardised WHOPES bioassay cone tests at baseline and after repeated washing. Furthermore, entomological assessments inside classrooms and in outside areas of schools were conducted. Results: We enrolled 1,811 pupils aged 6–17 from 5 intervention and 5 control schools. Paired serum samples were obtained from 1,655 pupils. In the control schools, 24/641 (3.7%) and in the intervention schools 33/1,014 (3.3%) students had evidence of new dengue infections during one school term (5 months). There was no significant difference in proportions of students having incident dengue infections between the intervention and control schools, with adjustment for clustering by school. WHOPES cone tests showed a 100% knock down and mortality of Aedes aegypti mosquitoes exposed to impregnated clothing at baseline and up to 4 washes, but this efficacy rapidly declined to below 20% after 20 washes, corresponding to a weekly reduction in knock-down and mosquito mortality by 4.7% and 4.4% respectively. Results of the entomological assessments showed that the mean number of Aedes aegypti mosquitoes caught inside the classrooms of the intervention schools was significantly reduced in the month following the introduction of the impregnated uniforms, compared to those collected in classrooms of the control schools (p = 0.04) Conclusions: Entomological assessments showed that the intervention had some impact on the number of Aedes mosquitoes inside treatment schools immediately after impregnation and before insecticidal activity declined. However, there was no serological evidence of protection against dengue infections over the five months school term, best explained by the rapid washing-out of permethrin after 4 washes. If rapid washing-out of permethrin could be overcome by novel technological approaches, insecticide-treated clothes might become a potentially cost-effective and scalable intervention to protect against diseases transmitted by Aedes mosquitoes such as dengue, Zika, and chikungunya. Trial Registration: ClinicalTrials.gov NCT01563640

Using remote sensing environmental data to forecast malaria incidence at a rural district hospital in Western Kenya

Sewe, M.O., Tozan, Y., Ahlm, C., & Rocklöv, J.

Publication year

2017

Journal title

Scientific Reports

Volume

7
10.1038/s41598-017-02560-z
Abstract

Malaria surveillance data provide opportunity to develop forecasting models. Seasonal variability in environmental factors correlate with malaria transmission, thus the identification of transmission patterns is useful in developing prediction models. However, with changing seasonal transmission patterns, either due to interventions or shifting weather seasons, traditional modelling approaches may not yield adequate predictive skill. Two statistical models,a general additive model (GAM) and GAMBOOST model with boosted regression were contrasted by assessing their predictive accuracy in forecasting malaria admissions at lead times of one to three months. Monthly admission data for children under five years with confirmed malaria at the Siaya district hospital in Western Kenya for the period 2003 to 2013 were used together with satellite derived data on rainfall, average temperature and evapotranspiration(ET). There was a total of 8,476 confirmed malaria admissions. The peak of malaria season changed and malaria admissions reduced overtime. The GAMBOOST model at 1-month lead time had the highest predictive skill during both the training and test periods and thus can be utilized in a malaria early warning system.

A spatial hierarchical analysis of the temporal influences of the el niño-southern oscillation and weather on dengue in Kalutara District, Sri Lanka

Liyanage, P., Tissera, H., Sewe, M., Quam, M., Amarasinghe, A., Palihawadana, P., … Rocklöv, J.

Publication year

2016

Journal title

International Journal of Environmental Research and Public Health

Volume

13
10.3390/ijerph13111087
Abstract

Dengue is the major public health burden in Sri Lanka. Kalutara is one of the highly affected districts. Understanding the drivers of dengue is vital in controlling and preventing the disease spread. This study focuses on quantifying the influence of weather variability on dengue incidence over 10 Medical Officer of Health (MOH) divisions of Kalutara district. Weekly weather variables and data on dengue notifications, measured at 10 MOH divisions in Kalutara from 2009 to 2013, were retrieved and analysed. Distributed lag non-linear model and hierarchical-analysis was used to estimate division specific and overall relationships between weather and dengue. We incorporated lag times up to 12 weeks and evaluated models based on the Akaike Information Criterion. Consistent exposure-response patterns between different geographical locations were observed for rainfall, showing increasing relative risk of dengue with increasing rainfall from 50 mm per week. The strongest association with dengue risk centred around 6 to 10 weeks following rainfalls of more than 300 mm per week. With increasing temperature, the overall relative risk of dengue increased steadily starting from a lag of 4 weeks. We found similarly a strong link between the Oceanic Niño Index to weather patterns in the district in Sri Lanka and to dengue at a longer latency time confirming these relationships. Part of the influences of rainfall and temperature can be seen as mediator in the causal pathway of the Ocean Niño Index, which may allow a longer lead time for early warning signals. Our findings describe a strong association between weather, El Niño-Southern Oscillation and dengue in Sri Lanka.

Characteristics of and factors associated with dengue vector breeding sites in the City of Colombo, Sri Lanka

Louis, V.R., Montenegro Quiñonez, C.A., Kusumawathie, P., Palihawadana, P., Janaki, S., Tozan, Y., … Tissera, H.A.

Publication year

2016

Journal title

Pathogens and Global Health

Volume

110

Page(s)

79-86
10.1080/20477724.2016.1175158
Abstract

Introduction: Dengue has emerged as a major public health problem in Sri Lanka. Vector control at community level is a frequent and widespread strategy for dengue control. The aim of the study was to assess Aedes mosquito breeding sites and the prevention practices of community members in a heavily urbanized part of Colombo. Methods: A cross-sectional entomological survey was conducted from April to June 2013 in 1469 premises located in a subdistrict of the City of Colombo. Types of breeding sites and, where found, their infestation with larvae or pupae were recorded. Furthermore, a questionnaire was administered to the occupants of these premises to record current practices of dengue vector control. Results: The surveyed premises consisted of 1341 residential premises and 110 non-residential premises (11 schools, 99 work or public sites), 5 open lands, and 13 non-specified. In these 1469 premises, 15447 potential breeding sites suitable to host larvae of pupae were found; of these sites18.0% contained water. Among the 2775 potential breeding sites that contained water, 452 (16.3%) were positive for larvae and/or pupae. Schools were associated with the proportionally highest number of breeding sites; 85 out of 133 (63.9%) breeding sites were positive for larvae and/or pupae in schools compared with 338 out of 2288 (14.8%) in residential premises. The odds ratio (OR) for schools and work or public sites for being infested with larvae and/or pupae was 2.77 (95% CI 1.58, 4.86), when compared to residential premises. Occupants of 80.8% of the residential premises, 54.5% of the schools and 67.7% of the work or public sites reported using preventive measures. The main prevention practices were coverage of containers and elimination of mosquito breeding places. Occupants of residential premises were much more likely to practice preventive measures than were those of non-residential premises (OR 2.23; 1.49, 3.36). Conclusion: Schools and working sites were associated with the highest numbers of breeding sites and lacked preventive measures for vector control. In addition to pursuing vector control measures at residential level, public health strategies should be expanded in schools and work places.

Costs of Dengue Control Activities and Hospitalizations in the Public Health Sector during an Epidemic Year in Urban Sri Lanka

Thalagala, N., Tissera, H., Palihawadana, P., Amarasinghe, A., Ambagahawita, A., Wilder-Smith, A., … Tozan, Y.

Publication year

2016

Journal title

PLoS Neglected Tropical Diseases

Volume

10
10.1371/journal.pntd.0004466
Abstract

Background: Reported as a public health problem since the 1960s in Sri Lanka, dengue has become a high priority disease for public health authorities. The Ministry of Health is responsible for controlling dengue and other disease outbreaks and associated health care. The involvement of large numbers of public health staff in dengue control activities year-round and the provision of free medical care to dengue patients at secondary care hospitals place a formidable financial burden on the public health sector. Methods: We estimated the public sector costs of dengue control activities and the direct costs of hospitalizations in Colombo, the most heavily urbanized district in Sri Lanka, during the epidemic year of 2012 from the Ministry of Health’s perspective. The financial costs borne by public health agencies and hospitals are collected using cost extraction tools designed specifically for the study and analysed retrospectively using a combination of activity-based and gross costing approaches. Results: The total cost of dengue control and reported hospitalizations was estimated at US$3.45 million (US$1.50 per capita) in Colombo district in 2012. Personnel costs accounted for the largest shares of the total costs of dengue control activities (79%) and hospitalizations (46%). The results indicated a per capita cost of US$0.42 for dengue control activities. The average costs per hospitalization ranged between US$216–609 for pediatric cases and between US$196–866 for adult cases according to disease severity and treatment setting. Conclusions: This analysis is a first attempt to assess the economic burden of dengue response in the public health sector in Sri Lanka. Country-specific evidence is needed for setting public health priorities and deciding about the deployment of existing or new technologies. Our results suggest that dengue poses a major economic burden on the public health sector in Sri Lanka.

Current issues in the economics of vaccination against dengue

Tozan, Y.

Publication year

2016

Journal title

Expert Review of Vaccines

Volume

15

Page(s)

519-528
10.1586/14760584.2016.1129278
Abstract

Dengue is a major public health concern in tropical and subtropical areas of the world. The prospects for dengue prevention have recently improved with the results of efficacy trials of a tetravalent dengue vaccine. Although partially effective, once licensed, its introduction can be a public health priority in heavily affected countries because of the perceived public health importance of dengue. This review explores the most immediate economic considerations of introducing a new dengue vaccine and evaluates the published economic analyses of dengue vaccination. Findings indicate that the current economic evidence base is of limited utility to support country-level decisions on dengue vaccine introduction. There are a handful of published cost-effectiveness studies and no country-specific costing studies to project the full resource requirements of dengue vaccine introduction. Country-level analytical expertise in economic analyses, another gap identified, needs to be strengthened to facilitate evidence-based decision-making on dengue vaccine introduction in endemic countries.

Internet-based media coverage on dengue in Sri Lanka between 2007 and 2015

Wilder-Smith, A., Cohn, E., Lloyd, D.C., Tozan, Y., & Brownstein, J.S.

Publication year

2016

Journal title

Global Health Action

Volume

9
10.3402/gha.v9.31620
Abstract

Background: Internet-based media coverage to explore the extent of awareness of a disease and perceived severity of an outbreak at a national level can be used for early outbreak detection. Dengue has emerged as a major public health problem in Sri Lanka since 2009. Objective: To compare Internet references to dengue in Sri Lana with references to other diseases (malaria and influenza) in Sri Lanka and to compare Internet references to dengue in Sri Lanka with notified cases of dengue in Sri Lanka. Design: We examined Internet-based news media articles on dengue queried from HealthMap for Sri Lanka, for the period January 2007 to November 2015. For comparative purposes, we compared hits on dengue with hits on influenza and malaria. Results: There were 565 hits on dengue between 2007 and 2015, with a rapid rise in 2009 and followed by a rising trend ever since. These hits were highly correlated with the national epidemiological trend of dengue. The volume of digital media coverage of dengue was much higher than of influenza and malaria. Conclusions: Dengue in Sri Lanka is receiving increasing media attention. Our findings underpin previous claims that digital media reports reflect national epidemiological trends, both in annual trends and interannual seasonal variation, thus acting as proxy biosurveillance to provide early warning and situation awareness of emerging infectious diseases.

Spatial variations in dengue transmission in schools in Thailand

Ratanawong, P., Kittayapong, P., Olanratmanee, P., Wilder-Smith, A., Byass, P., Tozan, Y., … Louis, V.R.

Publication year

2016

Journal title

PLoS One

Volume

11
10.1371/journal.pone.0161895
Abstract

Background: Dengue is an important neglected tropical disease, with more than half of the world's population living in dengue endemic areas. Good understanding of dengue transmission sites is a critical factor to implement effective vector control measures. Methods: A cohort of 1,811 students from 10 schools in rural, semi-rural and semi-urban Thailand participated in this study. Seroconversion data and location of participants' residences and schools were recorded to determine spatial patterns of dengue infections. Blood samples were taken to confirm dengue infections in participants at the beginning and the end of school term. Entomological factors included a survey of adult mosquito density using a portable vacuum aspirator during the school term and a follow up survey of breeding sites of Aedes vectors in schools after the school term. Clustering analyses were performed to detect spatial aggregation of dengue infections among participants. Results: A total of 57 dengue seroconversions were detected among the 1,655 participants who provided paired blood samples. Of the 57 confirmed dengue infections, 23 (40.0%) occurred in students from 6 (6.8%) of the 88 classrooms in 10 schools. Dengue infections did not show significant clustering by residential location in the study area. During the school term, a total of 66 Aedes aegypti mosquitoes were identified from the 278 mosquitoes caught in 50 classrooms of the 10 schools. In a follow-up survey of breeding sites, 484 out of 2,399 water containers surveyed (20.2%) were identified as active mosquito breeding sites. Discussion and Conclusion: Our findings suggest that dengue infections were clustered among schools and among classrooms within schools. The schools studied were found to contain a large number of different types of breeding sites. Aedes vector densities in schools were correlated with dengue infections and breeding sites in those schools. Given that only a small proportion of breeding sites in the schools were subjected to vector control measures (11%), this study emphasizes the urgent need to implement vector control strategies at schools, while maintaining efforts at the household level.

An economic evaluation of the posttreatment prophylactic effect of dihydroartemisinin-piperaquine versus artemether-lumefantrine for first-line treatment of plasmodium falciparum malaria across different transmission settings in Africa

Pfeil, J., Borrmann, S., Bassat, Q., Mulenga, M., Talisuna, A., & Tozan, Y.

Publication year

2015

Journal title

American Journal of Tropical Medicine and Hygiene

Volume

93

Page(s)

961-966
10.4269/ajtmh.15-0162
Abstract

Malaria disproportionately affects young children. Clinical trials inAfrican children showed that dihydroartemisinin-piperaquine (DP) is an effective antimalarial and has a longer posttreatment prophylactic (PTP) effect against reinfections than other artemisinin-based combination therapies, including artemether-lumefantrine (AL). Using a previously developed Markov model and individual patient data from a multicenter African drug efficacy trial, we assessed the economic value of the PTP effect of DP versus AL in pediatric malaria patients from health-care provider's perspective in lowto-moderate and moderate-to-high transmission settings under different drug co-payment scenarios. In low-to-moderate transmission settings, first-line treatment with DP was highly cost-effective with an incremental cost-effectiveness ratio of US5 (95% confidence interval [CI] = ?76 to 196) per disability-adjusted life year (DALY) averted. In moderate-to-high transmission settings, DP first-line treatment led to a mean cost saving of US1.09 (95% CI = ?0.88 to 3.85) and averted 0.05 (95% CI = ?0.08 to 0.22) DALYs per child per year. Our results suggested that DP might be superior to AL for first-line treatment of uncomplicated childhood malaria across a range of transmission settings in Africa.

Complexity and Dynamism from an Urban Health Perspective: a Rationale for a System Dynamics Approach

Tozan, Y., & Ompad, D.

Publication year

2015

Journal title

Journal of Urban Health

Volume

92

Page(s)

490-501
10.1007/s11524-015-9963-2
Abstract

In a variety of urban health frameworks, cities are conceptualized as complex and dynamic yet commonly used epidemiological methods have failed to address this complexity and dynamism head on due to their narrow problem definitions and linear analytical representations. Scholars from a variety of disciplines have also long conceptualized cities as systems, but few have modeled urban health issues as problems within a system. Systems thinking in general and system dynamics in particular are relatively new approaches in public health, but ones that hold immense promise as methodologies to model and analyze the complexity underlying urban processes to effectively inform policy actions in dynamic environments. This conceptual essay reviews the utility of applying the concepts, principles, and methods of systems thinking to the study of complex urban health phenomena as a complementary approach to standard epidemiological methods using specific examples and provides recommendations on how to better incorporate systems thinking methods in urban health research and practice.

Measuring population health: Costs of alternative survey approaches in the Nouna health and demographic surveillance system in rural Burkina Faso

Lietz, H., Lingani, M., Sié, A., Sauerborn, R., Souares, A., & Tozan, Y.

Publication year

2015

Journal title

Global Health Action

Volume

8
10.3402/gha.v8.28330
Abstract

Background: There are more than 40 Health and Demographic Surveillance System (HDSS) sites in 19 different countries. The running costs of HDSS sites are high. The financing of HDSS activities is of major importance, and adding external health surveys to the HDSS is challenging. To investigate the ways of improving data quality and collection efficiency in the Nouna HDSS in Burkina Faso, the stand-alone data collection activities of the HDSS and the Household Morbidity Survey (HMS) were integrated, and the paper-based questionnaires were consolidated into a single tablet-based questionnaire, the Comprehensive Disease Assessment (CDA). Objective: The aims of this study are to estimate and compare the implementation costs of the two different survey approaches for measuring population health. Design: All financial costs of stand-alone (HDSS and HMS) and integrated (CDA) surveys were estimated from the perspective of the implementing agency. Fixed and variable costs of survey implementation and key cost drivers were identified. The costs per household visit were calculated for both survey approaches. Results: While fixed costs of survey implementation were similar for the two survey approaches, there were considerable variations in variable costs, resulting in an estimated annual cost saving of about US$45,000 under the integrated survey approach. This was primarily because the costs of data management for the tablet-based CDA survey were considerably lower than for the paper-based stand-alone surveys. The cost per household visit from the integrated survey approach was US$21 compared with US$25 from the stand-alone surveys for collecting the same amount of information from 10,000 HDSS households. Conclusions: The CDA tablet-based survey method appears to be feasible and efficient for collecting health and demographic data in the Nouna HDSS in rural Burkina Faso. The possibility of using the tablet-based data collection platform to improve the quality of population health data requires further exploration.

Reviewing Dengue: Still a Neglected Tropical Disease?

Horstick, O., Tozan, Y., & Wilder-Smith, A.

Publication year

2015

Journal title

PLoS Neglected Tropical Diseases

Volume

9
10.1371/journal.pntd.0003632
Abstract

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

RTS, S/AS01 malaria vaccine and child mortality

Müller, O., Tozan, Y., & Becher, H.

Publication year

2015

Journal title

The Lancet

Volume

386

Page(s)

1736
10.1016/S0140-6736(15)00694-7

Dihydroartemisinin-piperaquine vs. artemether-lumefantrine for first-line treatment of uncomplicated malaria in African children: A cost-effectiveness analysis

Pfeil, J., Borrmann, S., & Tozan, Y.

Publication year

2014

Journal title

PLoS One

Volume

9
10.1371/journal.pone.0095681
Abstract

Background: Recent multi-centre trials showed that dihydroartemisinin- piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission. Methods: We developed a Markov model to assess the cost-effectiveness of DP versus AL for first-line treatment of uncomplicated malaria in young children from the provider perspective, taking into consideration the post-treatment prophylactic effects of the drugs as reported by a recent multi-centre trial in Africa and using the maximum manufacturer drug prices for artemisinin-based combination therapies set by the Global Fund in 2013. We estimated the price per course of treatment threshold above which DP would cease to be a cost-saving alternative to AL as a first-line antimalarial drug. Results: First-line treatment with DP compared to AL averted 0.03 DALYs (95% CI: 0.006-0.07) and 0.001 deaths (95% CI: 0.00-0.002) and saved $0.96 (95% CI: 0.33-2.46) per child over one year. The results of the threshold analysis showed that DP remained cost-saving over AL for any DP cost below $1.23 per course of treatment. Conclusions: DP is superior to AL from both the clinical and economic perspectives for treatment of uncomplicated P. falciparum malaria in young children. A paediatric dispersible formulation of DP is under development and should facilitate a targeted deployment of this antimalarial drug. The use of DP as first-line antimalarial drug in paediatric malaria patients in moderate to high transmission areas of Africa merits serious consideration by health policymakers.

Modeling tools for dengue risk mapping - a systematic review

Louis, V.R., Phalkey, R., Horstick, O., Ratanawong, P., Wilder-Smith, A., Tozan, Y., & Dambach, P.

Publication year

2014

Journal title

International Journal of Health Geographics

Volume

13
10.1186/1476-072X-13-50
Abstract

Introduction: The global spread and the increased frequency and magnitude of epidemic dengue in the last 50 years underscore the urgent need for effective tools for surveillance, prevention, and control. This review aims at providing a systematic overview of what predictors are critical and which spatial and spatio-temporal modeling approaches are useful in generating risk maps for dengue. Methods: A systematic search was undertaken, using the PubMed, Web of Science, WHOLIS, Centers for Disease Control and Prevention (CDC) and OvidSP databases for published citations, without language or time restrictions. A manual search of the titles and abstracts was carried out using predefined criteria, notably the inclusion of dengue cases. Data were extracted for pre-identified variables, including the type of predictors and the type of modeling approach used for risk mapping. Results: A wide variety of both predictors and modeling approaches was used to create dengue risk maps. No specific patterns could be identified in the combination of predictors or models across studies. The most important and commonly used predictors for the category of demographic and socio-economic variables were age, gender, education, housing conditions and level of income. Among environmental variables, precipitation and air temperature were often significant predictors. Remote sensing provided a source of varied land cover data that could act as a proxy for other predictor categories. Descriptive maps showing dengue case hotspots were useful for identifying high-risk areas. Predictive maps based on more complex methodology facilitated advanced data analysis and visualization, but their applicability in public health contexts remains to be established. Conclusions: The majority of available dengue risk maps was descriptive and based on retrospective data. Availability of resources, feasibility of acquisition, quality of data, alongside available technical expertise, determines the accuracy of dengue risk maps and their applicability to the field of public health. A large number of unknowns, including effective entomological predictors, genetic diversity of circulating viruses, population serological profile, and human mobility, continue to pose challenges and to limit the ability to produce accurate and effective risk maps, and fail to support the development of early warning systems.

Use of insecticide-treated school uniforms for prevention of dengue in schoolchildren: A cost-effectiveness analysis

Tozan, Y., Ratanawong, P., Louis, V.R., Kittayapong, P., & Wilder-Smith, A.

Publication year

2014

Journal title

PLoS One

Volume

9
10.1371/journal.pone.0108017
Abstract

Background: Dengue-related illness is a leading cause of hospitalization and death, particularly among children. Practical, acceptable and affordable measures are urgently needed to protect this age group. Schools where children spend most of their day is proposed as an ideal setting to implement preventive strategies against day-biting Aedes mosquitoes. The use of insecticide-treated school uniforms is a promising strategy currently under investigation.

Methods: Using a decision-analytic model, we evaluated the cost-effectiveness of the use of insecticide-treated school uniforms for prevention of dengue, compared with a ''do-nothing'' alternative, in schoolchildren from the societal perspective. We explored how the potential economic value of the intervention varied under various scenarios of intervention effectiveness and cost, as well as dengue infection risk in school-aged children, using data specific to Thailand.

Results: At an average dengue incidence rate of 5.8% per year in school-aged children, the intervention was cost-effective (ICER≤$16,440) in a variety of scenarios when the intervention cost per child was $5.3 or less and the intervention effectiveness was 50% or higher. In fact, the intervention was cost saving (ICER,0) in all scenarios in which the intervention cost per child was $2.9 or less per year and the intervention effectiveness was 50% or higher. The results suggested that this intervention would be of no interest to Thai policy makers when the intervention cost per child was $10.6 or higher per year regardless of intervention effectiveness (ICER>$16,440).

Conclusions: Our results present the potential economic value of the use of insecticide-treated uniforms for prevention of dengue in schoolchildren in a typical dengue endemic setting and highlight the urgent need for additional research on this intervention.

Dengue Research Funded by the European Commission-Scientific Strategies of Three European Dengue Research Consortia

Jaenisch, T., Sakuntabhai, A., Wilder-smith, A., Halstead, S.B., & Tozan, Y.

Publication year

2013

Journal title

PLoS Neglected Tropical Diseases

Volume

7

Page(s)

e2320
10.1371/journal.pntd.0002320

Evaluation of the Affordable Medicines Facility - Malaria

Tozan, Y., Jahn, A., & Müller, O.

Publication year

2013

Journal title

The Lancet

Volume

381

Page(s)

1095
10.1016/S0140-6736(13)60756-4

Moving towards universal coverage with malaria control interventions: Achievements and challenges in rural Burkina Faso

De Allegri, M., Louis, V.R., Tiendrébeogo, J., Souares, A., Yé, M., Tozan, Y., … Mueller, O.

Publication year

2013

Journal title

International Journal of Health Planning and Management

Volume

28

Page(s)

102-121
10.1002/hpm.2116
Abstract

This paper reports on a study, which assessed coverage with malaria control interventions in rural Burkina Faso, namely insecticide-treated mosquito nets (ITN) ownership, intermittent preventive treatment (IPTp) for pregnant women and artemisinin-based combination therapy (ACT) for under-five children. The study also addressed the distributional impact of such interventions, with specific reference to equity. The study used data from a representative household survey conducted on 1106 households in the Nouna Health District in 2010. Findings indicated that 59% of all households owned at least one ITN, 66% of all pregnant women received IPT at least once and 34% of under-five children reporting a malaria case were treated with ACT. Multivariate logistic regression revealed that higher socio-economic status, ownership of at least one radio and living in a village within a Health and Demographic Surveillance System were significantly positively associated with ITN, IPTp and ACT coverage. ITN coverage was higher among households in villages, which had previously hosted an ITN trial and/or the most favourable arm of a trial. Comparing current findings with previous estimates suggests that the country has made substantial progress towards scaling up malaria control interventions but that current coverage rates are still far from achieving the universal coverage targets set by the Roll Back Malaria Partnership. In addition, current coverage patterns reveal the existence of multiple inequities across groups, suggesting that current policies are inadequate to achieve equitable scaling up. Future planning of malaria control interventions ought to take into consideration current inadequacies and lead to programmes better designed to overcome them.

Dengue tools: Innovative tools and strategies for the surveillance and control of dengue

Wilder-Smith, A., Renhorn, K.E., Tissera, H., Bakar, S.A., Alphey, L., Kittayapong, P., … Gubler, D.

Publication year

2012

Journal title

Global Health Action

Volume

5
Abstract

Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of 'Comprehensive control of Dengue fever under changing climatic conditions'. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named 'DengueTools' to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change.The consortium comprises 12 work packages to address a set of research questions in three areas:Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring.Research area 2: Develop novel strategies to prevent dengue in children.Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change.In this paper, we report on the rationale and specific study objectives of 'DengueTools'. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589 Dengue Tools.

DengueTools: innovative tools and strategies for the surveillance and control of dengue

Wilder-smith, A., Renhorn, K., Tissera, H., Bakar, S.A., Alphey, L., Kittayapong, P., … Gubler, D.

Publication year

2012

Journal title

Global Health Action

Volume

5
10.3402/gha.v5i0.17273

Pre-referral rectal artesunate treatment of childhood malaria in the community: Training manual and for community health workers to assess danger signs, provide emergency pre-referral treatment and refer treated children to a health facility

Tozan, Y., & Gomez, M.

Publication year

2012

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: Study protocol for a randomised controlled trial in Thailand

Wilder-Smith, A., Byass, P., Olanratmanee, P., Maskhao, P., Sringernyuang, L., Logan, J.G., … Kittayapong, P.

Publication year

2012

Journal title

Trials

Volume

13
10.1186/1745-6215-13-212
Abstract

Background: There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence.Methods: A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons.Discussion: Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed.Trial registration: clinicaltrial.gov. Registration number: NCT01563640.

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