University of Groningen

Dengue in VenezuelaVelasco, Zoraida

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.

Document VersionPublisher's PDF, also known as Version of record

Publication date:2014

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):Velasco, Z. (2014). Dengue in Venezuela: A study on viral transmission, risk factors and clinical diseasepresentation [S.l.]: [S.n.]

CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.

Download date: 13-06-2018

8Summarizing Discussion

176

CHAPTER 8

Dengue has become the most important mosquito-borne viral disease and a major international public health concern1. Despite control measures, epidemics of increasing magnitude regularly occur in Venezuela against a background of an established endemic situation2,3. Concomitantly, the number of severe dengue cases has risen over time2. An early diagnosis and proper treatment of dengue cases can reduce the risk of development of severe disease4-6. Furthermore, in Venezuela, patients with dengue infection tend to seek medical help at a relatively late stage after fever onset7.

In this thesis, three neighbourhoods of high dengue incidence in Maracay, Venezuela were studied through a prospective community-based cohort study (Chapters 2, 4, 5 and 7). Dengue seroprevalence was estimated in the study population and risk factors for dengue infection were identified (Chapter 4). Areas of high dengue transmission were recognized at block and household level through spatial analysis (Chapter 5). This information can be used by the health authorities in order to direct personnel effort and control measures in an effective way and, thus reduce dengue transmission. In addition, a health center-based observational cohort study was established in three primary health centers in the same study area (Chapter 3). The aim of this study was to identify clinical, haematological and biochemical parameters that discriminate dengue from other febrile illnesses (OFI) at the early stage of the disease (Chapter 6). We proposed a decision-tree algorithm that distinguishes dengue from OFI during the first 3 days of the illness. This decision-tree algorithm may aid the physician in the early identification of dengue patients and thus reduce case mortality due to misdiagnosis and overburdening of health centres. Early diagnosis is also influenced by health-seeking behaviour (HSB) and access to care (Chapter 7). We studied the intended patterns of HSB at community level. We showed that intended pathways to seek care for suspected dengue differed from fever.

Summary of the Design of the Two Different Cohort Studies

In order to achieve the aims of this thesis, two cohort studies were established in three neighbourhoods of high dengue incidence in Maracay, Venezuela. The studies were: a) a prospective community-based cohort study and b) an observational health center-based cohort study. The set-up of the prospective community-based cohort study is described and explained in detail in Chapter 2. We enrolled 2014 individuals aged 5-30 years belonging to Caña de Azúcar, Candelaria and Cooperativa neighbourhoods through house-to house visits. Similar to other cohort studies8, individuals recruited into the study signed a written informed consent and agreed to attend the designated health center in case of any symptoms. However, we decided to recruit individuals aged 5-30 years since this age group reported the highest dengue incidence in this area.

177

Summarizing Discussion

During the recruitment process, a baseline cross-sectional study was performed. Data were collected in two structured questionnaires. Socio-demographic, epidemiologic and clinical history data were collected in an individual questionnaire. On the other hand, socio-economic and environmental risk factors were collected in a household questionnaire. At the same time, the geolocation of the households was recorded with a hand-held Global Positioning System (GPS, Garmin, Ltd). Blood samples were drawn to perform a total blood count and to determine dengue seroprevalence. The data collected were analyzed and presented in Chapters 4 and 5. To accomplish this study, health-related personnel were trained in the standardised operation procedures of the baseline study, bioethics and good clinical practices of research. A detailed description of the training process is presented in Chapter 2. The strategies used to inform the communities about this study and seek cooperation are also described in this chapter. The prospective community-based cohort study was followed for four years. Annual surveys were performed. Structured questionnaires were applied for different purposes and blood samples were collected in order to estimate dengue incidence in each annual survey. To better estimate the annual dengue incidence a weekly active surveillance of febrile individuals was carried out. The steps to follow in case of finding a febrile participant have also been explained in detail in Chapter 2.

The set-up of the observational health center-based cohort study is described and explained in detail in Chapter 3. The primary HCs chosen for this study covered the population of the neighbourhoods mentioned above. In case of severe dengue, patients were transferred and hospitalized at the main tertiary Central Hospital of Maracay. Patients of all ages, presenting at the HC within a maximum of 4 days (96 h) of fever, with symptoms suggesting dengue infection according to WHO 2009 criteria5 or without any signs of a localised infection were invited to participate in the study. Patients that agreed to participate were asked to sign an informed consent form, in case of adults (≥ 18 years old) and children guardians and, an assent form in case of children from 8 to 17 years old. Demographic, epidemiological, background clinical history, clinical findings, laboratory tests, complementary tests and treatment received data were collected in a follow-up questionnaire and were the basis for the analysis presented in Chapter 6. The patient was asked to return daily for monitoring and evaluation until 48 h afebrile and at 21-30 days after fever onset for a follow-up visit. The procedures that the study nurse and medical doctor needed to follow in case of a suspected dengue patient are presented in a flow-chart and described in Chapter 3. This chapter also includes a detail explanation of the different topics contained in the informed consent form. Study nurses were trained in the identification of febrile patients, dengue criteria, study criteria, explanation of the study to the participants, the follow-up questionnaire and its documentation, the correct performance of the tourniquet test and blood sampling.

178

The set-up of both studies described in Chapters 2 and 3 was approved by the regional health authorities and two bioethics committees. Results obtained in the context of the cohort studies during the course of the study are discussed in the sections below.

Risk Factors for Past and Recent Dengue Infection in Venezuela

Although previous studies have described certain risk factors for dengue transmission3,9,10, a detailed evaluation was necessary in order to identify possible control targets that can inform health authorities and ameliorate future dengue epidemics. A prospective community-based cohort study was set up in three neighbourhoods of high dengue incidence in Maracay, Venezuela (Chapter 2) to estimate dengue prevalence and identify risk factors for dengue transmission. The set-up of this study was performed in 2010 when the biggest dengue epidemic occurred. Amongst 2014 individuals recruited into the study, we found that 77.4% had anti-DENV antibodies (Chapter 4) while 10% were recently infected. A previous study performed in the same city during the 2001 epidemic found a lower prevalence (51%) in schoolchildren 5-13 years old11 compared to our study where 59% of children from the same age group were seropositive. This finding indicates an increase in transmission intensity over time. We found that poverty-related socio-economic factors and factors/constraints related to intradomiciliary potential mosquito breeding sites were associated with a greater risk of acquiring a dengue infection. We therefore propose that the combination of increasingly crowded living conditions, growing population density, precarious homes and water storage due to enduring problems in public services in Maracay, are the most likely factors that determine the permanent dengue transmission and the failure of vector control programs. Unplanned urbanization and population growth are some of the major determinants that have been associated with the spread and persistence of dengue in the last decades1,2,12. In Aragua state, the population density grew from 209.5 individuals/km2 in the year 2001 to 235.6 individuals/km2 in 2011. Concomitantly, the proportion of “ranchos” or shacks had enlarged from 8% to 9.6%13. Deficits in public services such as frequent and prolonged interruptions in water supply and electricity, and irregular and insufficient garbage collection are the consequence of the unplanned urbanization and population growth. These shortcomings have been associated to higher dengue incidence and severe cases in Maracay, including our study areas3. Although present for many years, these inadequacies have become more pronounced in recent years. Our results also suggest that the study population have been mainly infected by DENV at home. Therefore, dengue control measures and surveillance by health authorities should be directed to residential areas.

CHAPTER 8

179

Spatial Analysis of Dengue Transmission

Control of dengue and of its mosquito vector has proven challenging in settings of uncontrolled urban growth and unreliable water supply. Despite control measures, transmission of dengue in Venezuela has become perennial with three large epidemics in the past decade14. Previous studies in Venezuela using reported epidemiological data show that the neighbourhoods chosen for the prospective community-based cohort study (Chapter 2) are more prone to maintain higher dengue transmission and for longer periods than other areas10. The ability to identify high-risk areas of dengue transmission can be used to target surveillance and control measures to those locations in a cost-effective manner. Using mapping technology and spatial analysis of epidemiological and seroprevalence data we attempted to draw risk-maps at a fine scale to identify clusters (“hot spots”) of dengue transmission within the studied neighbourhoods (chapter 5). We found significant clusters of recent dengue infection, but not for past infection, at block and household levels. The homogeneous distribution of past dengue infection in the studied areas could be explained by the high proportion (77%) of participants infected by dengue virus in the past (Chapter 4). On the other hand, the presence of hot spots at block and household levels for recent dengue prevalence indicates a heterogeneous distribution in recent dengue transmission. This transmission occurred in a range of 50-80 m suggesting that dengue infection is highly focal. We speculate that the majority of mosquitoe breeding sites are localized inside and outside of the households belonging to these small spatial areas. Thereby, the female mosquito flies short distances for oviposition15,16. The majority of hot spots were found in the Caña de Azúcar neighbourhood. Furthermore, the only cluster that indicates the most probable grouping of cases (Kulldorff cluster) was found in this neighbourhood. This result is in concordance with the study presented in Chapter 4 where living in Caña de Azúcar was found to be a risk factor for dengue infection17.

A Decision-Tree Algorithm Differentiating Dengue from Other Febrile Illness

At the beginning of the disease, the patient presents with non-specific symptoms that can be easily confused with other diseases18-21. To date, there are not accepted guidelines for the early recognition of dengue infection22. In Chapter 6, we aimed to identify clinical parameters and accessible haematological and biochemical tests that, at an early stage, could differentiate dengue from OFI. For this purpose, as indicated above, an observational health center-based cohort study was established in three

Summarizing Discussion

180

primary health centers (Chapter 3). We constructed a diagnostic algorithm using WBC counts, rash, mean corpuscular haemoglobin (MCH) levels and haemorrhagic manifestations in sequential order that distinguished dengue from OFI with a sensitivity of 88% and specificity of 63%. The majority of the published decision-tree algorithms have been designed to discriminate dengue from severe dengue7,23. Only one study that differentiates dengue from OFI at the early stage of the disease has been published. This study, conducted in Asia, uses mainly haematological parameters with different cut-offs compared to our study24. Among our decision tree, a novel parameter is included, MCH (≤ 29 pg). A decrease of MCH values has been associated to iron deficiency in the body25. We speculate that the decrease of MCH values during the first 3 days of the illness is due to the increased levels of Interleukine-6 (IL-6) in dengue patients26. IL-6 stimulates the production of the hormone hepcidin27, which in turn inhibits the release of iron into the plasma from macrophages and duodenum enterocytes28. We also present clinical and haematological parameters associated to dengue after day 3 of the disease. We found that body temperature <39°C, the presence of rash, haemorrhagic manifestations, platelet count (˂150 x 103 platelet/uL) and WBC count (˂4000 cells/uL) were positively and independently associated with dengue cases. Those parameters have been previously associated to dengue and severe dengue29-32. Finally, a lower cholesterol and a higher albumin were the two biochemical parameters independently associated with dengue infection during the first 3 days of the disease. Few studies have compared biochemical parameters between dengue and OFI patients. Inconsistent associations and/or patterns have been reported for albumin levels33-35. Although, none of these studies have compared cholesterol levels between patients with dengue and OFI, a decrease of cholesterol levels has been associated with severe dengue36.

Health-Seeking Behaviour in Case of Suspected Dengue

Early diagnosis and adequate supportive care are of great importance in the management of dengue so as to avoid the development of severe disease. Thus, an early treatment intervention can reduce the case-fatality rate from 20% to 1% or less5,6. In Venezuela, patients with a suspected dengue infection tend to seek medical help beyond the third day after the onset of fever7. Delay in care-seeking is found to be significantly associated with severe dengue37. We aimed to understand intended patterns of health-seeking behaviour (HSB) in individuals living in areas with a high dengue incidence in order to improve early attendance to health centres. A subsample of 105 individuals belonging to the prospective community-based cohort study (Chapter 2) was interviewed during the annual survey from September 2013 to February 2014.

CHAPTER 8

181

Structured questionnaires were applied to these individuals in order to compare HSB intentions of adults and of parent/guardians with respect to their children in the case of fever and/or suspected dengue. In Chapter 7 we found that intended pathways to care differed for suspected dengue infection compared to fever, as well as for children and adults in case of suspected dengue. In case of fever, the majority of the people would treat at home before paying a visit to a doctor while, in case of suspected dengue, most individuals reported that they would seek medical care as their first action. We also found that parents/guardians would take children earlier to the health facility than adults would seek medical care. These findings suggests that dengue is in general perceived as more severe than fever in agreement with other studies38,39. We also suspect that dengue infections will mostly be first treated at home, since a dengue infection is likely to present with fever as a main symptom40,41. We found that the appearance of a new symptom or a perceived increase in severity of the condition were the main reasons that would make the participants visit a doctor. Primary health centres were the first choice to visit for nearly all participants. Although we found an improvement of the general knowledge of dengue in Venezuela42, this improvement was related to dengue transmission and not related to the symptoms of the disease. This can be partially explained by the fact that dengue fever is a complicated disease with a great variation in expression of symptoms as shown in Chapter 6. Moreover, dengue campaigns in the Venezuelan media mainly focus on eradicating the dengue vector. Recognition of dengue symptoms plays an important role in self-diagnosis and thereby health-seeking. A timely care-seeking may be achieved when people will be able to properly self-diagnose dengue or when a tool that diagnoses dengue at home will be designed.

Perspectives

In this thesis, we identified risk factors for dengue infection in three neighbourhoods in Maracay city, the capital of Aragua state, Venezuela, which is an area of high dengue incidence. We also identified geographic clusters of high dengue transmission at block and household level. Is the presence of hot spots of dengue transmission related to certain risk factors for dengue infection? In this regard, it will be interesting to explore the persistence of hot spots over time. If the clusters of high dengue transmission at block and/or household level persist over time, the resources for dengue surveillance and mosquito control can be efficiently used in the target areas and reduce dengue incidence in a more permanent way.

Despite a quite good knowledge on dengue in our study population in general, we observed the presence of mosquito breeding sites inside and outside of the participants’ households. This paradoxical behaviour might be better understood if a study concerning

Summarizing Discussion

182

the relationship between knowledge on dengue, risk perception and practices were performed. Understanding human behaviour in relation with mosquito breeding sites in an endemic area is essential to detect and eliminate weaknesses in mosquitoe control campaigns.

We propose a decision-tree algorithm that differentiates dengue from OFI at the early stage of the disease. This decision-tree has to be validated in a large and different population. In addition, the decision-tree could be improved by the integration with biochemical parameters. We found a novel parameter that discriminates dengue from OFI during the first 3 days of the illness in our study population. Are MCH levels ˂ 29 pg also present in dengue patients from other countries of the Americas and Asia? Are these levels of MCH also an early indicator of severe dengue? These questions remain unclear. Currently, chikungunya virus has been spreading in the Caribbean and the Americas. Indeed, recently, autochthonous chikungunya cases have been reported in Venezuela by the health authorities. Signs and symptoms of chikungunya are very similar to those of dengue. A study that differentiates both diseases at the early stage of the illness will be very helpful for physicians and the general population.

In this thesis, we demonstrate that people intend to seek medical help early in case of dengue. The early attendance to primary HC depends on dengue signs and recognition of symptoms. Knowledge on dengue clinical presentation can be improved in the Venezuelan population. Alternatively, a tool or device that early diagnoses dengue at home could be designed.

Dengue control is a challenge that requires major efforts on the part of both the public health system and the community. Although knowledge on dengue has improved over time, several important issues remain.

References1. Gubler DJ. Dengue, urbanization and

globalization: The unholy trinity of the 21(st) century. Trop Med Health. 2011;39(4 Suppl):3-11.

2. San Martin JL, Brathwaite O, Zambrano B, Solorzano JO, Bouckenooghe A, Dayan GH, et al. The epidemiology of dengue in the Americas over the last three decades: A worrisome reality. Am J Trop Med Hyg. 2010;82(1):128-135.

3. Barrera R, Delgado N, Jiménez M, Valero S. Eco-epidemiological factors associated with hyperendemic dengue haemorrhagic fever in Maracay city, Venezuela. Dengue Bulletin. 2002;26:84-94.

4. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: A continuing global threat. Nat Rev Microbiol. 2010;8(12 Suppl):S7-16.

5. World Health Organization. Dengue, guidelines for diagnosis, treatment and control. World Health Organization. Geneva; 2009.

6. Stephenson JR. The problem with dengue. Trans R Soc Trop Med Hyg. 2005;99(9):643-646.

7. Brasier AR, Ju H, Garcia J, Spratt HM, Victor SS, Forshey BM, et al. A three-component biomarker panel for prediction of dengue hemorrhagic fever. Am J Trop Med Hyg. 2012;86(2):341-348.

CHAPTER 8

183

8. Kuan G, Gordon A, Aviles W, Ortega O, Hammond SN, Elizondo D. The Nicaraguan pediatric dengue cohort study: Study design, methods, use of information technology, and extension to other infectious diseases. Am J Epidemiol. 2009;170(1):120-129.

9. Barrera R, Navarro J, Mora J, Dominguez D, Gonzalez J. Public service deficiencies and Aedes aegypti breeding sites in Venezuela. Bull Pan Am Health Organ. 1995;29(3):193-205.

10. Barrera R, Delgado N, Jiménez M, Villalobos I, Romero I. Stratification of a city with hyperendemic dengue hemorrhagic fever. Rev Panam Salud Publica. 2000;8:225-233.

11. Comach G, Blair PJ, Sierra G, Guzman D, Soler M, de Quintana MC, et al. Dengue virus infections in a cohort of schoolchildren from Maracay, Venezuela: A 2-year prospective study. Vector Borne Zoonotic Dis. 2009;9(1):87-92.

12. San Martin JL, Brathwaite-Dick O. Integrated strategy for dengue prevention and control in the region of the Americas. Rev Panam Salud Publica. 2007;21(1):55-63.

13. INE. Instituto nacional de estadística. Available at: http://www.ine.gov.ve/,. Accessed June 25.

14. Boletines Epidemiológicos (2002-2012). Ministerio del poder popular para la salud. Available at: http://www.mpps.gob.ve/index.php?option=com_phocadownload&view=section&id=4:boletin-epidemiologico. Updated 2013. Accessed March 15.

15. Harrington LC, Scott TW, Lerdthusnee K, Coleman RC, Costero A, Clark GG, et al. Dispersal of the dengue vector Aedes aegypti within and between rural communities. Am J Trop Med Hyg. 2005;72(2):209-220.

16. Scott TW, Amerasinghe PH, Morrison AC, Lorenz LH, Clark GG, Strickman D,et al. Longitudinal studies of Aedes aegypti (diptera: Culicidae)

in Thailand and Puerto Rico: Blood feeding frequency. J Med Entomol. 2000;37(1):89-101.

17. Velasco-Salas ZI, Sierra GM, Guzman DM, Zambrano J, Vivas D, Comach G, Wilschut JC, Tami A. Dengue seroprevalence and risk factors for past and recent viral transmission in venezuela: A comprehensive community-based study. Am J Trop Med Hyg. 2014;91(5):1039-1048 doi: 10.4269/ajtmh.14-0127.

18. Ellis RD, Fukuda MM, McDaniel P, Welch K, Nisalak A, Murray CK, et al. Causes of fever in adults on the Thai-Myanmar Border. Am J Trop Med Hyg. 2006;74:108-113.

19. Caglioti C, Lalle E, Castilletti C, Carletti F, Capobianchi MR, Bordi L. Chikungunya virus infection: An overview. New Microbiol. 2013;36(3):211-227.

20. Halstead SB. Epidemiology of dengue and dengue hemorrhagic fever. In: Gubler DJ, Kuno G, eds. Dengue and dengue hemorrhagic fever. Wallingford, Oxon, UK; 1997:23-44.

21. World Health Organization (WHO). Dengue control. Available at: http://www.who.int/denguecontrol/arbo-viral/other_arboviral_chikungunya/en/ Accessed March 2014.

22. Ho TS, Wang SM, Lin YS, Liu CC. Clinical and laboratory predictive markers for acute dengue infection. J Biomed Sci. 2013;20:75 doi:10.1186/1423-0127-20-75.

23. Potts JA, Thomas SJ, Srikiatkhachorn A, Supradish PO, Li W, Nisalak A. Classification of dengue illness based on readily available laboratory data. Am J Trop Med Hyg. 2010;83(4):781-788.

24. Tanner L, Schreiber M, Low JG, Ong A, Tolfvenstam T, Lai YL, et al. Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness. PLoS Negl Trop Dis. 2008;2(3):e196.

Summarizing Discussion

184

25. National Institute of Health (NIH). Anemia. Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/anemia/. Accessed on July 2014., .

26. Pinto LM, Oliveira SA, Braga EL, Nogueira RM, Kubelka CF. Increased pro-inflammatory cytokines (tnf-alpha and il-6) and antiinflammatory compounds (Stnfrp55 and Stnfrp75) in Brazilian patients during exanthematic dengue fever. Mem Inst Oswaldo Cruz. 1999;94(3):387-394.

27. Fuqua BK, Vulpe CD, Anderson GJ. Intestinal iron absorption. J Trace Elem Med Biol. 2012;26(2-3):115-119.

28. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-2093.

29. Deparis X, Murgue B, Roche C, Cassar O, Chungue E. Changing clinical and biological manifestations of dengue during the dengue-2 epidemic in French Polynesia in 1996/97-description and analysis in a prospective study. Trop Med Int Health. 1998;3(11):859-865.

30. Biswas HH, Ortega O, Gordon A, Standish K, Balmaseda A, Kuan G, et al. Early clinical features of dengue virus infection in Nicaraguan children: A longitudinal analysis. PLoS Negl Trop Dis. 2012;6(3):e1562.

31. Yoon IK, Srikiatkhachorn A, Hermann L, Buddhari D, Scott TW, Jarman RG, et al. Characteristics of mild dengue virus infection in Thai children. Am J Trop Med Hyg. 2013;89(6):1081-1087.

32. Diaz FA, Martinez RA, Villar LA. Clinical criteria to diagnose dengue in its early stages. Biomedica: revista del Instituto Nacional de Salud. 2006;26:22-30.

33. Chadwick D, Arch B, Wilder-Smith A, Paton N. Distinguishing dengue fever from other infections on the basis of simple clinical and laboratory features: Application of logistic regression analysis. J Clin Virol. 2006;35:147-153.

34. Villar-Centeno LA, Lozano-Parra A, Salgado-Garcia D, Herran OF. Biochemical alterations as prediction markers for the severity of illness in dengue fever patients. Biomedica. 2013;33 Suppl 1:63-69.

35. Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Suntayakorn S, Kunentrasai N, et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis. 1997;176(2):313-321.

36. van Gorp EC, Suharti C, Mairuhu AT, Dolmans WM, van Der Ven J, Demacker PNM, et al. Changes in the plasma lipid profile as a potential predictor of clinical outcome in dengue hemorrhagic fever. Clin Infect Dis. 2002;34(8):1150-1153.

37. Vicente CR, Lauar JC, Santos BS, Cobe VM, Cerutti Jr C. Factors related to severe dengue during an epidemic in Vitoria, state of Espirito Santo, Brazil, 2011. Rev Soc Bras Med Trop. 2013;46(5):629-632.

38. Ferraz FO, Bomfim MR, Totola AH, Ávila TV, Cisalpino D, Pessanha JEM, et al. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. J Clin Virol. 2013;58(1):41-46.

39. Vong S, Khieu V, Glass O, Ly S, Duong V, Huy R, et al. Dengue incidence in urban and rural Cambodia: Results from population-based active fever surveillance, 2006-2008. PLoS Negl Trop Dis. 2010;4(11):e903.

40. Suarez MR, Olarte SM, Ana MF, Gonzalez UC. Is what I have just a cold or is it dengue? addressing the gap between the politics of dengue control and daily life in Villavicencio-Colombia. Soc Sci Med. 2005;61(2):495-502.

41. Khun S, Manderson L. Health seeking and access to care for children with suspected dengue in Cambodia: An ethnographic study. BMC Public Health. 2007;7:262.

CHAPTER 8

185

42. Brightmer MI, Fantato MG. Human and environmental factors in the increasing incidence of dengue fever: A case study from Venezuela. Geo Journal. 1998;44(2):103-109.

Summarizing Discussion