Dengue Incidence in Urban and Rural Cambodia: Results from Population-Based Active Fever Surveillance, 2006–2008

Background Dengue vaccines are now in late-stage development, and evaluation and robust estimates of dengue disease burden are needed to facilitate further development and introduction. In Cambodia, the national dengue case-definition only allows reporting of children less than 16 years of age, and little is known about dengue burden in rural areas and among older persons. To estimate the true burden of dengue in the largest province of Cambodia, Kampong Cham, we conducted community-based active dengue fever surveillance among the 0-to-19–year age group in rural villages and urban areas during 2006–2008. Methods and Findings Active surveillance for febrile illness was conducted in 32 villages and 10 urban areas by mothers trained to use digital thermometers combined with weekly home visits to identify persons with fever. An investigation team visited families with febrile persons to obtain informed consent for participation in the follow-up study, which included collection of personal data and blood specimens. Dengue-related febrile illness was defined using molecular and serological testing of paired acute and convalescent blood samples. Over the three years of surveillance, 6,121 fever episodes were identified with 736 laboratory-confirmed dengue virus (DENV) infections for incidences of 13.4–57.8/1,000 person-seasons. Average incidence was highest among children less than 7 years of age (41.1/1,000 person-seasons) and lowest among the 16-to-19–year age group (11.3/1,000 person-seasons). The distribution of dengue was highly focal, with incidence rates in villages and urban areas ranging from 1.5–211.5/1,000 person-seasons (median 36.5). During a DENV-3 outbreak in 2007, rural areas were affected more than urban areas (incidence 71 vs. 17/1,000 person-seasons, p<0.001). Conclusion The large-scale active surveillance study for dengue fever in Cambodia found a higher disease incidence than reported to the national surveillance system, particularly in preschool children and that disease incidence was high in both rural and urban areas. It also confirmed the previously observed focal nature of dengue virus transmission.

[1]  H. Margolis,et al.  Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study , 2009, BMC public health.

[2]  J. Hombach Guidelines for clinical trials of dengue vaccine in endemic areas. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[3]  P. Buchy,et al.  National dengue surveillance in Cambodia 1980-2008: epidemiological and virological trends and the impact of vector control. , 2010, Bulletin of the World Health Organization.

[4]  Akira Igarashi,et al.  Comparison of clinical features and hematologic abnormalities between dengue fever and dengue hemorrhagic fever among children in the Philippines. , 2005, The American journal of tropical medicine and hygiene.

[5]  A. Krattiger,et al.  The introduction of new vaccines into developing countries. IV: Global Access Strategies. , 2007, Vaccine.

[6]  S. Yoksan,et al.  Laboratory assays and field dengue vaccine evaluation at Ratchaburi province, Thailand: a preliminary result. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[7]  Willem Takken,et al.  Ecological aspects for application of genetically modified mosquitoes , 2003 .

[8]  G. Kuno,et al.  Review of the factors modulating dengue transmission. , 1995, Epidemiologic reviews.

[9]  T. Scott,et al.  Comparison of two active surveillance programs for the detection of clinical dengue cases in Iquitos, Peru. , 2009, The American journal of tropical medicine and hygiene.

[10]  D. Gubler,et al.  Dengue/dengue hemorrhagic fever: the emergence of a global health problem. , 1995, Emerging infectious diseases.

[11]  Dr Ferdiye Taner,et al.  The enzyme-linked immunosorbent assay (ELISA). , 1976, Bulletin of the World Health Organization.

[12]  J. Lang,et al.  A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. , 2010, The Journal of infectious diseases.

[13]  A. Nisalak,et al.  Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. , 2000, The Journal of infectious diseases.

[14]  M. Guzmán,et al.  Dengue 3 Epidemic, Havana, 2001 , 2004, Emerging infectious diseases.

[15]  R. Lanciotti,et al.  Rapid detection and typing of dengue viruses from clinical samples by using reverse transcriptase-polymerase chain reaction , 1992, Journal of clinical microbiology.

[16]  A. Nisalak,et al.  A prospective study of dengue infections in Bangkok. , 1988, The American journal of tropical medicine and hygiene.

[17]  T. Scott,et al.  Aedes aegypti density and the risk of dengue-virus transmission , 2004 .

[18]  M. Guzmán,et al.  Dengue and dengue hemorrhagic fever in the Americas: lessons and challenges. , 2003, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[19]  R. Mahoney,et al.  The introduction of new vaccines into developing countries. , 1999, Vaccine.

[20]  Stefan Hoyer,et al.  Improved Molecular Detection of Dengue Virus Serotype 1 Variants , 2003, Journal of Clinical Microbiology.

[21]  P. Kittayapong,et al.  Distribution of dengue and Japanese encephalitis among children in rural and suburban Thai villages. , 2000, The American journal of tropical medicine and hygiene.

[22]  Donald S Burke,et al.  Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999. , 2003, The American journal of tropical medicine and hygiene.

[23]  A. Teeraratkul,et al.  Changing epidemiology of dengue hemorrhagic fever in Thailand , 1999, Epidemiology and Infection.

[24]  J. Clemens,et al.  Policymakers' views on dengue fever/dengue haemorrhagic fever and the need for dengue vaccines in four southeast Asian countries. , 2003, Vaccine.

[25]  E. C. Holmes,et al.  Cross-protective immunity can account for the alternating epidemic pattern of dengue virus serotypes circulating in Bangkok , 2006, Proceedings of the National Academy of Sciences.

[26]  Juan Carlos Albarracín Matute,et al.  Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in Nicaragua. , 2010, The Journal of infectious diseases.

[27]  Alan L Rothman,et al.  Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. , 2002, American journal of epidemiology.

[28]  S. Halstead,et al.  A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995-1996. , 1999, The American journal of tropical medicine and hygiene.

[29]  Rosanna W. Peeling,et al.  Evaluation of Commercially Available Anti–Dengue Virus Immunoglobulin M Tests , 2009, Emerging infectious diseases.

[30]  A. Nisalak,et al.  Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study , 2007, The Lancet.

[31]  E. Harris,et al.  The Nicaraguan Pediatric Dengue Cohort Study: Study Design, Methods, Use of Information Technology, and Extension to Other Infectious Diseases , 2009, American journal of epidemiology.

[32]  I. Kurane,et al.  Analysis of specific IgM responses in secondary dengue virus infections: levels and positive rates in comparison with primary infections. , 2004, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[33]  Charles H. Hoke,et al.  SEROTYPE-SPECIFIC DENGUE VIRUS CIRCULATION AND DENGUE DISEASE IN BANGKOK, THAILAND FROM 1973 TO 1999 , 2003 .

[34]  R. Rico-Hesse,et al.  Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. , 1997, Virology.

[35]  J. Lang,et al.  A prospective cohort study of dengue infection in schoolchildren in Long Xuyen, Viet Nam. , 2010, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[36]  Dana A. Focks,et al.  Epidemiology of Dengue Virus in Iquitos, Peru 1999 to 2005: Interepidemic and Epidemic Patterns of Transmission , 2010, PLoS neglected tropical diseases.

[37]  Richard G Jarman,et al.  Analysis of repeat hospital admissions for dengue to estimate the frequency of third or fourth dengue infections resulting in admissions and dengue hemorrhagic fever, and serotype sequences. , 2007, The American journal of tropical medicine and hygiene.

[38]  J. Lang Recent progress on sanofi pasteur's dengue vaccine candidate. , 2009, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[39]  Alan L Rothman,et al.  Spatial and Temporal Clustering of Dengue Virus Transmission in Thai Villages , 2008, PLoS medicine.

[40]  K. K. Datta,et al.  An outbreak of dengue fever in rural areas of northern India. , 2001, The Journal of communicable diseases.

[41]  P. Glaziou,et al.  Secondary dengue virus type 4 infections in Vietnam. , 2005, The Southeast Asian journal of tropical medicine and public health.

[42]  M. Guzmán,et al.  Dengue: an update. , 2002, The Lancet. Infectious diseases.

[43]  D. Gubler,et al.  Dengue Prevention and 35 Years of Vector Control in Singapore , 2006, Emerging infectious diseases.

[44]  E. Engvall,et al.  Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. , 1972, Journal of immunology.

[45]  Bachti Alisjahbana,et al.  Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia. , 2005, The American journal of tropical medicine and hygiene.

[46]  Cambodia,et al.  Cambodia Demographic and Health Survey 2010 , 2006 .

[47]  V. S. Nam,et al.  New strategy against Aedes aegypti in Vietnam , 2005, The Lancet.

[48]  A. Nisalak,et al.  Hospital-based Diagnosis of Hemorrhagic Fever, Encephalitis, and Hepatitis in Cambodian Children , 2002, Emerging infectious diseases.

[49]  S. Halstead,et al.  Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. , 1984, American journal of epidemiology.

[50]  D. Socheat,et al.  The Development and Testing of Water Storage Jar Covers in Cambodia , 2004 .

[51]  M. Guzmán,et al.  Reemergence of dengue in Cuba: a 1997 epidemic in Santiago de Cuba. , 1998, Emerging infectious diseases.

[52]  Derek A. T. Cummings,et al.  Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006 , 2010, PLoS neglected tropical diseases.