JBM  Vol.7 No.6 , June 2019
The Seropositivity Rate of Human Herpesvirus Type 6 among Infants in Diyala Province, Iraq
Abstract: Background: Human herpesvirus type 6 (HHV-6) has been shown to infect almost all children by 4 years of age. Primary infection causes an undifferentiated febrile illness, with approximately 30% of children exhibiting the classic clinical manifestations of roseola infantum. Objectives: The current study was carried out to explore the anti-HHV-6 IgG positivity rate as a marker of past infection among apparently healthy infants and to figure out the effect of certain infant and family characteristics on the infectivity rate. Materials and methods: This is a cross sectional study conducted in Diyala province during the period from August 2017-July 2018. A total of 180 apparently healthy infants were included, their ages ranged between 6 - 24 months. They consist of 100 males with mean age ± SD 15.05 ± 6.42 months and 80 females with mean age ± SD 15.56 ± 6.66 months. Human privacy was respected by obtaining parental consent. Venous blood samples were collected aseptically from each participant. Sera were separated and tested for the anti-HHV6 IgG (Sunlong Biotech, China) by Enzyme Linked Immunosorbant assay (ELISA) technique. Statistical analysis was done using SPSS version 23 and P value < 0.05 was considered significant. Results: The overall anti-HHV6 IgG positivity rate among apparently healthy infants was 43.9%. The highest positivity rate was among the age group 19 - 24 months compared to other age groups, and the positivity rate was insignificantly higher among males compared to females (44.0% vs. 43.8%, P = 0.973). Furthermore, the positivity rate was insignificantly higher among infants on mixed feeding compared to other feeding categories (55.3%, P = 0.083). The results also recognized that infants who had negative history of hospitalization had higher but insignificant positivity rate compared to their counterpart (46.8% vs. 26.9%, P = 0.065). Interestingly, a significantly higher anti-HHV6 IgG positivity rate was found among infants whom their families had current history of positive case (62.2%) compared to families with negative history (35.8%) or those with past history of positive case (50.0%, P = 0.006). Conclusion: About one half of apparently healthy infants aged up to two years of Diyala population have anti-HHV6 IgG antibodies and the presence of intrafamilial primary HHV-6 positive case is markedly associated with increased rate of anti-HHV6 IgG among siblings.
Cite this paper: Hasan, A. , Mehdi, S. and Noor, A. (2019) The Seropositivity Rate of Human Herpesvirus Type 6 among Infants in Diyala Province, Iraq. Journal of Biosciences and Medicines, 7, 129-137. doi: 10.4236/jbm.2019.76008.

[1]   Salahuddin, S.Z., Ablashi, D.V., Markham, P.D., Josephs, S.F., Sturzenegger, S., Kaplan, M., Halligan, G., Biberfeld, P., Wong-Staal, F. and Kramarsky, B. (1986) Isolation of a New Virus, HBLV, in Patients with Lymphoproliferative Disorders. Science, 234, 596-601.

[2]   Ablashi, D.V., Salahuddin, S.Z., Josephs, S.F., Imam, F., Lusso, P. and Gallo, R.C. (1987) HBLV (or HHV-6) in Human Cell Lines. Nature, 329, 207.

[3]   Frenkel, N., Schirmer, E.C., Wyatt, L.S., Katsafanas, G., Roffman, E., Danovich, R.M. and June, C.H. (1990) Isolation of a New Herpesvirus from Human CD4+ T Cells. Proceedings of the National Academy of Sciences of the United States of America, 87, 748-752.

[4]   Flamand, L., Komaroff, A.L., Arbuckle, J.H., Medveczky, P.G. and Ablashi, D.V. (2010) Human Herpesvirus-6—Basic Biology, Diagnostic Testing, and Antiviral Efficacy. Journal of Medical Virology, 82, 1560-1568.

[5]   Stone, R.C., Micali, G.A. and Schwartz, R.A. (2014) Roseola Infantum and Its Causal Human Herpesviruses. International Journal of Dermatology, 53, 397-403.

[6]   Ward, K.N. (2005) The Natural History and Laboratory Diagnosis of Human Herpesviruses-6 and -7 Infections in the Immunocompetent. Journal of Clinical Virology, 32, 183-193.

[7]   Becerra, A., Gibson, L., Stern, L.J. and Calvo-Calle, J.M. (2014) Immune Response to HHV-6 and Implications for Immunotherapy. Current Opinion in Virology, 9, 154-161.

[8]   Rhoads, M.P., Magaret, A.S. and Zerr, D.M. (2007) Family Saliva Sharing Behaviors and Age of Human Herpesvirus-6B Infection. Journal of Infection, 54, 623-626.

[9]   Hall, C.B., Caserta, M.T., Schnabel, K.C., McDermott, M.P., Lofthus, G.K., Carnahan, J.A., Gilbert, L.M. and Dewhurst, S. (2006) Characteristics and Acquisition of Human Herpesvirus (HHV) 7 Infections in Relation to Infection with HHV-6. The Journal of Infectious Diseases, 193, 1063-1069.

[10]   Pantry, S.N. and Medveczky, P.G. (2017) Latency, Integration, and Reactivation of Human Herpesvirus-6. Viruses, 9, pii: E194.

[11]   Zerr, D.M., Meier, A.S., Selke, S.S., Frenkel, L.M., Huang, M.L., Wald, A., Rhoads, M.P., Nguy, L., Bornemann, R., Morrow, R.A. and Corey, L. (2005) A Population-Based Study of Primary Human Herpesvirus 6 Infection. The New England Journal of Medicine, 352, 768-776.

[12]   Tesini, B.L., Epstein, L.G. and Caserta, M.T. (2014) Clinical Impact of Primary Infection with Roseoloviruses. Current Opinion in Virology, 9, 91-96.

[13]   Agut, H., Bonnafous, P. and Gautheret-Dejean, A. (2015) Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections. Clinical Microbiology Reviews, 28, 313-335.

[14]   Arnez, M., Avsie-Zupanc, T., Ursic, T. and Petrovec, M. (2016) Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia. Case Reports in Pediatrics, 2016, Article ID: 2483183.

[15]   Caserta, M.T., Hall, C.B., Schnabel, K., Lofthus, G., Marino, A., Shelley, L., Yoo, C., Carnahan, J., Anderson, L. and Wang, H. (2010) Diagnostic Assays for Active Infection with Human Herpesvirus 6 (HHV-6). Journal of Clinical Virology, 48, 55-57.

[16]   Farshadmoghadam, H., Pourakbari, B., Mahmoudi, S., Sadeghi, R.H. and Mamishi, S. (2014) Human Herpesvirus 6 Infection in Febrile Children: Frequency in an Iranian Referral Hospital. British Journal of Biomedical Science, 71, 108-110.

[17]   Caserta, M.T., McDermott, M.P., Dewhurst, S., Schnabel, K., Carnahan, J.A., Gilbert, L., Lathan, G., Lofthus, G.K. and Hall, C.B. (2004) Human Herpesvirus 6 (HHV6) DNA Persistence and Reactivation in Healthy Children. The Journal of Pediatrics, 145, 478-484.

[18]   Dockrell, D.H. (2003) Human Herpesvirus 6: Molecular Biology and Clinical Features. Journal of Medical Microbiology, 52, 5-18.

[19]   Bhattarakosol, P., Pancharoen, C., Mekmullica, J. and Bhattarakosol, P. (2001) Seroprevalence of Anti-Human Herpes Virus-6 IgG Antibody in Children of Bangkok, Thailand. The Southeast Asian Journal of Tropical Medicine and Public Health, 32, 143-147.

[20]   Cermelli, C., Moroni, A., Pietrosemoli, P., Pecorari, M. and Portolani, M. (1992) IgG Antibodies to Human Herpesvirus-6 (HHV-6) in Italian People. Microbiologica, 15, 57-63.

[21]   Politou, M., Koutras, D., Kaparos, G., Valsami, S., Pittaras, T., Logothetis, E., Panayiotakopoulos, G. and Kouskouni, E. (2014) Seroprevalence of HHV-6 and HHV-8 among Blood Donors in Greece. Virology Journal, 11, 153.

[22]   Cuende, J.I., Ruiz, J., Civeira, M.P. and Prieto, J. (1994) High Prevalence of HHV-6 DNA in Peripheral Blood Mononuclear Cells of Healthy Individuals Detected by Nested-PCR. Journal of Medical Virology, 43, 115-118.

[23]   Ongradi, J., Csiszar, A., Marodi, C.L., Solyom, J., Horvath, A. and Menezes, J. (1999) Presence of Antibodies to Human Herpesvirus Type 6 and 7 in Hungarian Children. Orvosi Hetilap, 140, 935-940.

[24]   Agut, H., Bonnafous, P. and Gautheret-Dejean, A. (2017) Update on Infections with Human Herpesviruses 6A, 6B, and 7. Médecine et Maladies Infectieuses, 47, 83-91.

[25]   Suga, S., Yoshikawa, T., Kajita, Y., Ozaki, T. and Asano, Y. (1998) Prospective Study of Persistence and Excretion of Human Herpesvirus-6 in Patients with Exanthem Subitum and Their Parents. Pediatrics, 102, 900-904.

[26]   De Bolle, L., Naesens, L. and De Clercq, E. (2005) Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy. Clinical Microbiology Reviews, 18, 217-245.

[27]   Ward, K.N., Couto Parada, X., Passas, J. and Thiruchelvam, A.D. (2002) Evaluation of the Specificity and Sensitivity of Indirect Immunofluorescence Tests for IgG to Human Herpesviruses-6 and -7. Journal of Virological Methods, 106, 107-113.

[28]   Biganzoli, P., Ferreyra, L., Sicilia, P., Carabajal, C., Frattari, S., Littvik, A., Nates, S. and Pavan, J. (2010) IgG Subclasses and DNA Detection of HHV-6 and HHV-7 in Healthy Individuals. Journal of Medical Virology, 82, 1679-1683.

[29]   Davidkin, I., Valle, M., Peltola, H., Hovi, T., Paunio, M., Roivainen, M., Linnavuori, K., Jokinen, S. and Leinikki, P. (1998) Etiology of Measles- and Rubella-Like Illnesses in Measles, Mumps, and Rubella-Vaccinated Children. The Journal of Infectious Diseases, 178, 1567-1570.

[30]   Helwig, H. and Cremer, H. (2011) Exanthema Subitum—3 Day Fever—HHV 6 Infection—Roseola Infantum—6th Disease. Kinderkranken-schwester, 30, 164-165.

[31]   Ward, K.N., Gray, J.J., Fotheringham, M.W. and Sheldon, M.J. (1993) IgG Antibodies to Human Herpesvirus-6 in Young Children: Changes in Avidity of Antibody Correlate with Time after Infection. Journal of Medical Virology, 39, 131-138.

[32]   Asano, Y., Yoshikawa, T., Suga, S., Yazak, T., Ozaki, T., Saito, Y., Hatano, Y. and Takahashi, M. (1990) Enzyme-Linked Immunosorbent Assay for Detection of IgG Antibody to Human Herpes-virus 6. Journal of Medical Virology, 32, 119-123.

[33]   Pereira, C.M., Gasparetto, P., Correa, M.E., Costa, F.F., de Almeida, O.P. and Barjas-Castro, M.L. (2004) Human Herpesvirus 6 in Oral Fluids from Healthy Individuals. Archives of Oral Biology, 49, 1043-1046.

[34]   Lanphear, B.P., Hall, C.B., Black, J. and Auinger, P. (1998) Risk Factors for the Early Acquisition of Human Herpesvirus 6 and Human Herpesvirus 7 Infections in Children. The Pediatric Infectious Disease Journal, 17, 792-795.

[35]   Vianna, R.A., de Oliveira, S.A., Camacho, L.A., Knowles, W., Brown, D., Pereira, A.C., Velarde, L.G. and Siqueira, M.M. (2008) Role of Human Herpesvirus 6 Infection in Young Brazilian Children with Rash Illnesses. The Pediatric Infectious Disease Journal, 27, 533-537.