An Evaluation of Dried Blood Spots and Oral Swabs as Alternative Specimens for the Diagnosis of Dengue and Screening for Past Dengue Virus Exposure

Non-invasive specimens for dengue diagnosis may be preferable where venous blood is difficult to collect and/or process, such as community-based or remote settings or when sampling from young children. We evaluated the performance of oral swabs and dried blood spots (DBS), compared with plasma, in diagnosing acute dengue and screening for past dengue virus (DENV) exposure. DENV-specific immunoglobulin (Ig) M, IgG, and NS1 antigen were detected both in oral swabs and DBS from acute patients. Oral swabs were less sensitive (IgM: 68.7%, IgG: 91.9%, NS1: 64.7%), but retained good specificity (100%, 92.3%, 95.8%, respectively) compared with plasma. DBS displayed high sensitivity (IgM: 100%, IgG: 96%, NS1: 100%) and specificity (IgM: 75%, IgG: 93%). DENV RNA was amplified from DBS (sensitivity 95.6%) but not from oral swabs. DENV-IgG (indicative of past flavivirus exposure) were detected with moderate sensitivity (61.1%) but poor specificity (50%) in oral swabs from healthy volunteers. Dried blood spots allow sensitive and specific diagnosis of acute dengue by serological, molecular, and antigen detection methods. Oral swabs may be an adequate alternative where blood cannot be collected.

[1]  T. V. Tuan,et al.  Validation of an internally controlled one-step real-time multiplex RT-PCR assay for the detection and quantitation of dengue virus RNA in plasma. , 2011, Journal of virological methods.

[2]  Michael I. Jordan,et al.  Dried blood spots for HIV-1 drug resistance and viral load testing: A review of current knowledge and WHO efforts for global HIV drug resistance surveillance. , 2010, AIDS reviews.

[3]  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.

[4]  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.

[5]  Cameron P. Simmons,et al.  Diagnostic Accuracy of NS1 ELISA and Lateral Flow Rapid Tests for Dengue Sensitivity, Specificity and Relationship to Viraemia and Antibody Responses , 2009, PLoS neglected tropical diseases.

[6]  E. Harris,et al.  Evaluation of immunological markers in serum, filter-paper blood spots, and saliva for dengue diagnosis and epidemiological studies. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[7]  J. Meynard,et al.  Dengue-3 outbreak in Paraguay: investigations using capillary blood samples on filter paper. , 2008, The American journal of tropical medicine and hygiene.

[8]  Teun Bousema,et al.  Dried blood spots as a source of anti-malarial antibodies for epidemiological studies , 2008, Malaria Journal.

[9]  M. Woolhouse,et al.  Reconstructing historical changes in the force of infection of dengue fever in Singapore: implications for surveillance and control. , 2008, Bulletin of the World Health Organization.

[10]  Measles and rubella laboratory network: 2007 meeting on use of alternative sampling techniques for surveillance. , 2008, Releve epidemiologique hebdomadaire.

[11]  M. Matlani,et al.  Immunodiagnosis of Dengue Virus Infection Using Saliva , 2007, Current Microbiology.

[12]  J. Meynard,et al.  Use of Capillary Blood Samples as a New Approach for Diagnosis of Dengue Virus Infection , 2007, Journal of Clinical Microbiology.

[13]  H. Oyen,et al.  Oral fluid as a medium for the detection of hepatitis B surface antigen , 2005, Journal of medical virology.

[14]  J. Groen,et al.  Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam , 2005, Tropical medicine & international health : TM & IH.

[15]  M. Guzmán,et al.  PCR detection of dengue virus using dried whole blood spotted on filter paper. , 2005, Journal of virological methods.

[16]  B. Sharp,et al.  Antifolate antimalarial resistance in southeast Africa: a population-based analysis , 2003, The Lancet.

[17]  M. Guzmán,et al.  Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva , 2003, Clinical Diagnostic Laboratory Immunology.

[18]  M. Cardosa,et al.  Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses. , 2002, BMC Microbiology.

[19]  K. Mayer,et al.  Dried blood spots (DBS): a valuable tool for HIV surveillance in developing/tropical countries , 2002, International journal of STD & AIDS.

[20]  A. Vyse,et al.  A comparison of oral fluid collection devices for use in the surveillance of virus diseases in children. , 2001, Public health.

[21]  D. Nokes,et al.  Has oral fluid the potential to replace serum for the evaluation of population immunity levels? A study of measles, rubella and hepatitis B in rural Ethiopia. , 2001, Bulletin of the World Health Organization.

[22]  R. Nogueira,et al.  Diagnosis of dengue infection by detecting specific immunoglobulin M antibodies in saliva samples. , 1999, Journal of virological methods.

[23]  A. Nisalak,et al.  Detection of Specific Antibodies in Saliva during Dengue Infection , 1998, Journal of Clinical Microbiology.

[24]  E. L. Miller,et al.  Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991-3 , 1994, BMJ.