|Year : 2013 | Volume
| Issue : 4 | Page : 145-148
Association of ABO Rh blood group with dengue fever and dengue hemorrhagic fever: A case-control study
Vitthal Khode1, Goutam Kabbin2, Komal Ruikar1
1 Department of Physiology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences, Sattur, Dharwad, Karnataka, India
2 Department of Paediatrics, Shri Dharmasthala Manjunatheshwara College of Medical Sciences, Sattur, Dharwad, Karnataka, India
|Date of Web Publication||26-Feb-2014|
Department of Physiology, Shri Dharmasthala Manjunatheshwara College of Medical Sciences, Sattur, Dharwad - 574 240, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Data on frequency distribution of ABO Rh blood group in pediatric dengue patients are not available. Dengue disease an emerging arthropod borne infection of public health concern belongs to Flaviviridae. The studies defining the relationship between blood groups and dengue disease and its severity are limited. Blood group antigens are generally known to act as receptors for various etiological agents. Hence, we hypothesized there will be an association between blood group and dengue disease and its severity and conducted this case-control study.
Study Design: Hospital-based case-control study.
Materials and Methods: Study was conducted in department of pediatrics, 244 pediatric subjects (age group 1 - 13 years) were enrolled divided into cases who were admitted cases of dengue (119, 65 males, 64 females) and controls who were attending outpatient department for various other ailments. (125, 67 males, 58 females) and demographic data (age, gender, blood group, and dengue infection status) were collected from them. The risk of acquiring dengue disease and severity and its association with factors such as blood group, gender were analyzed statistically.
Results: The data of this study showed a possible association between blood groups of the study population with dengue infection. We observed that dengue infections were higher in individuals with O positive blood group 42.8% when compared with controls 32%. (P = 0.043) But blood groups were not associated with severity of infection. These data present further evidence for the association of the blood groups, gender to susceptibility to dengue infection. Further studies are needed to confirm these findings.
Conclusion: Dengue disease is more common with blood group O. But severity of the disease is not associated with any blood groups.
Keywords: ABO blood groups, dengue fever, dengue hemorrhagic fever
|How to cite this article:|
Khode V, Kabbin G, Ruikar K. Association of ABO Rh blood group with dengue fever and dengue hemorrhagic fever: A case-control study. J Appl Hematol 2013;4:145-8
|How to cite this URL:|
Khode V, Kabbin G, Ruikar K. Association of ABO Rh blood group with dengue fever and dengue hemorrhagic fever: A case-control study. J Appl Hematol [serial online] 2013 [cited 2019 May 22];4:145-8. Available from: http://www.jahjournal.org/text.asp?2013/4/4/145/127899
| Introduction|| |
Infection with dengue virus is a serious emerging health threat and has commanded considerable medical and public-health concern worldwide.  Today, dengue disease is considered to be, in terms of morbidity and mortality, the most important arthropod-borne human viral disease.  Globally, it has been estimated that 50-100 million new dengue-virus infections occur annually. Among these, there are 200,000-500,000 cases of potentially life-threatening dengue hemorrhagic fever (DHF)/dengue-shock syndrome (DSS), characterized by thrombocytopenia and increased vascular permeability.  The death rate associated with the more severe form of DHF/DSS (DHF grades 3 [DHF3] or 4 [DHF4]) is 5%, mainly in children <15 years of age. 
The dengue viruses are mosquito-borne viruses of the Flaviviridae family. Four genetically related but distinct serotypes, designated "DENV-1," "- 2," "- 3," and "- 4," circulate worldwide.  Infection with any serotype can be either asymptomatic or lead to 1 of the 4 clinical scenarios of increasing severity: Undifferentiated fever, dengue fever (DF), DHF, and DSS.  Infection with one serotype leads to lifelong immunity to that serotype but to only partial and temporary immunity to the others; circulation of more than one serotype increases the risk of secondary infections and of DHF and DSS. 
The risk factors for dengue disease are complex and poorly understood. Secondary infections, which occur commonly in areas where dengue disease is endemic, have proven to be one of the main risk factors for severe dengue disease; , and this has led to the antibody dependent enhancement theory.  In addition, other probable risk factors for dengue disease are the infecting virus's strain/serotype, the age of the patient, and the genetic background of the patient;  however, none of these factors alone accounts for the risk of dengue virus infections. The important role that host genetics plays in determining the susceptibility to infectious pathogens in humans has long been known. Although predisposition to dengue disease determined by human leukocyte antigen (HLA) haplotype has been proposed by several researchers, no clear, specific polymorphisms have been unequivocally described for severe forms of dengue disease.  The ABO blood group system is part of the innate immune system  and it has been shown that individuals with different ABO blood groups differ in their susceptibility or resistance to viral and bacterial infections and diseases. , A relationship between blood groups and disease was first hypothesized by Kaipainen and Vuorinen  during 1960, and the gene involved in ABO blood groups was discovered in 1990.  However, not much study has been done in the world and in India to show the relationship between dengue disease, its severity and ABO blood group. Hence, we hypothesized there could be association between distribution of ABO Rh blood groups and dengue fever and its severity studied them in pediatric group of patients and compared with age- and sex-matched controls.
| Materials and Methods|| |
The study was carried over one year (June 2011 to June 2012), 244 pediatric subjects with age group of 1-13 years participated in the study and categorized into two groups. Group 1 had admitted patients of dengue disease and dengue hemorrhagic fever in our institution and Group 2 had age- and sex-matched controls who were attending pediatric outpatient department (OPD) of our institution for various ailments. Serum samples were collected from children with acute febrile illnesses who were enrolled in a study that has been described elsewhere.  The severity of DHF grading and diagnostic criteria followed World Health Organization guidelines. Acute dengue virus infections were confirmed serologically by enzyme-linked immunosorbent assay for immunoglobulin (Ig) M/IgG.  Standard hemagglutination assays were used to type the blood groups.  The protocol was approved by the human subjects research review board and the institutional review board. Written, informed consent was obtained from the parent or guardian of each child. All patients with confirmed dengue-virus infections and controls were included in these analyses.
All the continuous data presented as mean ± standard deviation and categorical data as percentiles. Data were analyzed using package SPSS 16 (2007). We compared age in dengue disease and controls and DF and DHF using independent t test. P < 0.05 was considered to be significant. We compared ABO and Rh blood-group frequencies in dengue disease and controls, as well as in DF and DHF. The Chi-square test for ABO and Rh blood groups (2 * 2 contingency tables) was used. P < 0.05 was considered to be significant.
| Results|| |
There was no significant difference in the age in group 1 (7.56 ± 5.5 years) and group 2 (7.86 ± 4.6 years) P = 0.657. The frequencies of each blood group in the dengue disease and control population are presented in [Table 1] and blood group distribution in controls were consistent with those in the general Indian population.  There was no significant difference age and sex among DF (7.86 ± 5.8 years) and DHF (6.44 ± 4.3 years) P = 0.260. The distribution of each blood group among patients with DF was similar to that among patients with DHF [Table 2]. In dengue-virus infections, all four blood groups and Rh had similar susceptibility to severe disease that is; no association between blood group and disease severity was seen. In contrast, among patients with dengue-virus infection and control, significant difference was observed. We observed that dengue infections were higher in individuals with O positive blood group (42.8%) when compared with controls (32%).
|Table 1: ABO and Rh blood group distribution in dengue disease and controls|
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|Table 2: ABO and Rh blood group distribution in dengue fever and dengue hemorrhagic fever|
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| Discussion|| |
The results of the present study suggest that blood group O may be a risk factor predisposing for dengue disease. No blood groups are associated with severity of dengue infection.
Among innate factors, a predisposition for an individual to be susceptible or resistant to phenotypes of infectious diseases and their clinical manifestations resides in host genetic factors.  Two genetic factors HLA and ABO blood groups have, to some extent, been demonstrated to play an important role in resistance or susceptibility to infectious diseases.  In ABO blood-group antigens, individuals who lack an antigen have natural antibodies with the ability to agglutinate cells carrying that antigen.  The antigens are carbohydrate in nature; the immundominant sugar in the case of the A determinant is N-Acetyl-D-galactosamine, and that in the case of the B determinant is d-galactose. Galactosyltransferases are involved in the synthesis of these carbohydrates.  The antibody that recognizes these carbohydrates is primarily natural IgM. Interestingly, several dengue viral proteins have been shown to be glycosylated,  and antibodies, particularly IgM, produced in patients with dengue-virus infection have been shown to cross-react with host cells.  Two earlier studies found no association between blood group and disease severity in patients with dengue-virus infection. , In a study where it was documented, ABO blood group is associated with severity of infection, ABO blood group distribution was O: 40.1%, A: 20.5%, B: 32.3%, AB: 7.1% compared with our study O: 42.8%, A: 21%, B: 32.7%, AB: 3.3%.  It has been documented that blood group AB is associated with severity of dengue infection. Since AB blood group has both the antigens antibodies produced by dengue infection cross react and, hence, AB blood group has more susceptibility to DHF. Our study suggests that there is association of dengue disease with blood group O, but blood groups are not associated with severity of infection. Therefore, whether the combination of ABO blood group and the level of natural IgM antibody circulating in individuals have an effect on dengue disease has to be elucidated.
DHF/DSS has been documented in infants during their first dengue-virus infection.  Presumably the enhancement of dengue disease in infants is due to preexistent dengue antibody that is passively acquired, via cord blood, from mothers immune to dengue-virus infection.  Since infants contain preexistent dengue antibodies, we excluded infants from our study. Factors contributing to DHF in children are unknown; perhaps individual genetic background may play a critical role. , Additionally, a correlation between HLA and dengue disease has been reported; but no specific polymorphisms have been found to be unequivocally associated with disease severity.  It, therefore, is of interest to see whether there is any correlation between a polymorphism in the galactosyltransferase gene and dengue-disease severity. Unfortunately, in the present study we found that, for blood group AB, more severe dengue disease was not associated. Blood group AB's association with DHF versus its association with DF was not significantly different from that in the other blood groups. The controls were selected from the pediatric OPD with various other ailments and, therefore, they differ from general population which could have been confounding factor. But their blood group distribution was consistent with Indian population. One of the strength of our study was that it was a case-control study. Previous articles studied blood group distribution only in dengue patients. Because of the limitations of the sample size in the present study, further studies will be necessary to determine whether dengue severity and ABO are independent variables and whether some blood subgroups are associated with a particularly high risk of dengue-virus infection.
| References|| |
|1.||World Health Organization. Dengue. Geneva: World Health Organization; 2004. |
|2.||Halstead SB. Epidemiology of dengue and dengue haemorrhagic fever. In: Gubler DJ, Kuno G, editors. Dengue and dengue haemorrhagic fever. Wallingford: CAB International; 1997. p. 23-44. |
|3.||Guzman MG. Global voices of science. Deciphering dengue: The Cuban experience. Science 2005;309:1495-7. |
|4.||Stephenson JR. The problem with dengue. Trans R Soc Trop Med Hyg 2005;99:643-6. |
|5.||Greenwell P. Blood group antigens: Molecules seeking a function? Glycoconj J 1997;14:159-73. |
|6.||Skripal IG. ABO system of blood groups in people and their resistance to certain infectious diseases (prognosis). Mikrobiol Z 1996;58:102-8. |
|7.||Kaipainen WJ, Vuorinen YV. ABO blood groups in pernicious anaemia and pernicious tapeworm anaemia. Ann Med Exp Biol Fenn 1960;38:212-3. |
|8.||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;176:313-21. |
|9.||Das PK, Nair SC, Harris VK, Rose D, Mammen JJ, Bose YN, et al. Distribution of ABO and Rh-D blood groups among blood donors in a tertiary care centre in South India. Trop Doct 2001;31:47-8. |
|10.||Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 1990;44:649-88. |
|11.||Lei HY, Yeh TM, Liu HS, Lin YS, Chen SH, Liu CC. Immunopathogenesis of dengue virus infection. J Biomed Sci 2001;8:377-88. |
|12.||Halstead S, Thirayodhin P, Olsson RA. Inquiry into hereditary factors in the pathogenesis of dengue haemorrhagic fever: A preliminary note. Bull World Health Organ 1966;35:56-7. |
|13.||Kalayanarooj S, Kanaphun P, Pansatienkul B, Nimmannitya S. The relationship between blood groups and dengue hemorrhagic fever. In: Kalayanarooj S, editor. Studies/collaborative studies on dengue infections/dengue hemorrhagic fever. Bangkok: Desire; 2003. p. 161-7. |
|14.||Kalayanarooj S, Gibbons RV, Vaughn D, Green S, Nisalak A, Jarman RG, et al. Blood Group AB is associated with increased risk for severe dengue disease in secondary infections. J Infect Dis 2007;195:1014-7. |
[Table 1], [Table 2]
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