|Year : 2015 | Volume
| Issue : 4 | Page : 162-167
Seroprevalence of transfusion transmissible viral markers in sickle cell disease patients and healthy controls in Ile-Ife, South-Western Nigeria: A case–control study
Rahman A Bolarinwa1, John C Aneke2, Samuel A Olowookere3, Lateef Salawu1
1 Department of Haematology, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538, Ile-Ife, Nigeria
2 Department of Haematology, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538, Ile-Ife; Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra, Nigeria
3 Department of Family Medicine, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538, Ile-Ife, Nigeria
|Date of Web Publication||16-Dec-2015|
John C Aneke
Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, PMB 5025, Nnewi, Anambra
Source of Support: None, Conflict of Interest: None
Background: The risk of acquiring transfusion transmissible viral infections is said to be higher in patients requiring regular blood transfusions such as those with sickle cell disease (SCD). Aim: We determined the seroprevalence of blood transfusion viral markers among our patients with SCD. Subjects and Methods: This a case–control analytical study consisting of 82 confirmed SCD patients on routine follow-up at our facility in steady state and 90 age-matched controls. Demographic and transfusion history were recorded while 5 ml of blood was drawn for hematocrit levels, and serum tested for transfusion transmissible viral markers for hepatitis B, (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [HBsAb], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B core antibody [HBcAb]), hepatitis C virus (HCV) and human immunodeficiency viruses (HIVs) using the rapid test kits. Ethical approval for the study was obtained from the Institutional Review Board and each participant gave informed consent. Data were analyzed using descriptive and inferential statistics. Results: The seroprevalence of HBsAg, HBsAb, and HBeAg in cases was 2 (2.4%), 7 (8.5%), and 0 (0.0%), respectively, whereas it was 7 (8.5%), 11 (13.4%), 6 (7.3%), and 2 (2.4%) for HBeAb, HBcAb, HCV, and HIV antibodies. Compared to the controls, cases had higher prevalence rate of HBeAb (P = 0.005). No significant difference was observed in those with or without low hematocrit (≤18%) or those that received blood transfusion and those that did not (P > 0.05). Conclusion: We conclude that blood transfusion did not significantly increase the seroprevalence of markers of transfusion transmissible viral infection in SCD patients.
Keywords: Blood transfusion viral markers, seroprevalence, sickle cell disease
|How to cite this article:|
Bolarinwa RA, Aneke JC, Olowookere SA, Salawu L. Seroprevalence of transfusion transmissible viral markers in sickle cell disease patients and healthy controls in Ile-Ife, South-Western Nigeria: A case–control study. J Appl Hematol 2015;6:162-7
|How to cite this URL:|
Bolarinwa RA, Aneke JC, Olowookere SA, Salawu L. Seroprevalence of transfusion transmissible viral markers in sickle cell disease patients and healthy controls in Ile-Ife, South-Western Nigeria: A case–control study. J Appl Hematol [serial online] 2015 [cited 2017 Aug 19];6:162-7. Available from: http://www.jahjournal.org/text.asp?2015/6/4/162/171985
| Introduction|| |
Sickle cell disease (SCD) is an autosomal recessive disorder in which the sickle hemoglobin is present in association with other abnormal hemoglobins. It is characterized by recurrent acute events known as crises and chronic anemia, in which the homozygous hemoglobin S phenotype (HbSS) state could lead to significant end organ dysfunction., Sickle red cells assume an abnormal, rigid shape under conditions of reduced oxygen tension and equally adhere to the endothelial walls (in addition with platelets and white cells), leading to vascular occlusion and endothelial dysfunction.,
Viral hepatitis caused by hepatitis B and C viruses (HBVs, HCVs) is of major public health concern worldwide whereas human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pandemic poses a major threat to public health and development with immense socioeconomic burden worldwide., HBVs and HCVs and HIV share common routes of transmission such as blood transfusion, injury with contaminated sharps, and sexual contacts., Viral hepatitis and HIV/AIDS are endemic in tropical Africa including Nigeria.,,
While SCD patients are prone to recurrent crises, end organ dysfunction, and chronic anemia, blood transfusion support may actually be lifesaving in those with severe anemia. The transfusion requirements of SCD patients, therefore, place them at high risk of infections with transfusion transmissible viruses, particularly in climes where pretransfusion screening is inadequate. The morbidity of SCD is significantly increased following infection with these viruses with worsened clinical severity, coupled with accelerated development of end-organ dysfunction such as liver cirrhosis.,
In Nigeria, the burden of transfusion transmissible infections (TTIs) is high among blood donors and even in the general population. Studies have reported prevalence rates of 7.9%, 7.3%, and 5.0% for HBV, HCV, and HIV, respectively, among blood donors and 12.0%, 3.0%, and 3.0% in the general population.,,, It is, therefore, important that blood given to SCD patients is routinely screened for these TTIs, especially those on regular blood transfusion. This is even made more imperative by the observation that a larger proportion of the blood donor pool in Nigeria is commercial (paid) donors. The reason for this may be attributable to a number of factors, ranging from poor awareness on voluntary blood donation to poverty and illiteracy, particularly among the rural populations of the country.
According to the National Blood Transfusion Service, Nigeria utilizes up to 1.5 million units of blood annually and current legislation mandates that all potential blood donors are screened for HCV hepatitis B surface antigen (HBsAg), HIV, and syphilis, using a combination of rapid qualitative immunochromatographic test kits, enzyme-linked immunosorbent assays, and p24 antigen assay (for HIV).
The objective of this work, therefore, was to determine the seroprevalence of blood transfusion transmissible viral markers in a cohort of patients with SCD who regularly attend outpatient follow-up clinic in our facility.
| Subjects and Methods|| |
This is a case–control study carried out at the Hematology Department of our hospital from August 2011 to March 2012. Subjects included 82 confirmed (by cellulose acetate hemoglobin electrophoresis, in alkaline ph) SCD patients (67 HbSS and 15 double heterozygous S + C [HbSC] hemoglobin phenotypes), who regularly attend hematology out-patient clinic in our facility, and 90 age-matched healthy hemoglobin AA controls. Subjects were recruited in steady state conditions, defined as no manifest crises in last 1 month and no blood transfusion in 3 months preceding recruitment. Ethical approval was obtained from the Hospital's Health and Research Ethics Committee. Each participant gave written informed consent. Bio-data of participants were recorded in a proforma form, whereas transfusion history was obtained and recorded similarly as “transfused” or “never transfused.” Following standard protocols, 5 ml of venous blood was collected, packed cell volume (PCV) was determined immediately after sample collection by the microhematocrit method, whereas the remaining sample was left on the bench to clot for approximately 20 min. Serum was thereafter extracted from the clotted sample by centrifugation at 5000 rpm for 5 min and pipetted into clean plain tubes for viral screening. Testing for HBV markers including the B surface antigen and antibody (HBsAg and hepatitis B surface antibody [HBsAb]), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) was carried out using the LumiQuick ® HBV multiple panel rapid test kits (LumiQuick Diagnostics, CA, USA) whereas HCV and HIV antibodies were tested using rapid HCV test kit (Acumen Labs and diagnostic Centre, Bengaluru, Karnataka, India) and Determine test kit (Alere Medical Co., Ltd., 357, Chiba, 270-2214 Japan), respectively. The instructions of the manufacturers were followed for the test runs and each test strip had in-built procedural control.
Test results were presented as frequencies, percentages, and means (±standard deviation). Subjects were further stratified into those with or without severe anemia (PCV ≤18% and >18%, respectively) and those transfused and never transfused. The Chi-square statistic was used to compare transfusion transmissible viral screening test results with variables such as age, sex, hemoglobin type, and blood transfusion history. Level of statistical significance was set at P < 0.05.
| Results|| |
The mean age of cases was 26.01 ± 7.05 years, whereas that of controls was 24.78 ± 4.83 years. The mean PCV in cases was 24.20 ± 5.12 L/L, whereas it was 34.61 ± 8.34 L/L in controls. The cases included 44 males (53.7%) and 38 females (46.3%); 67 (53.7%) and 15 (18.3%) had HbSS and HbSC hemoglobin phenotypes, respectively [Table 1]. Nine (11.0%) of these had PCV ≤18%, whereas 73 (89.0%) had PCV >18% [Table 1]. Correspondingly, 40 (48.8%) cases did not receive any blood transfusion, whereas 42 (51.2%) had received one or more blood transfusions [Table 1].
|Table 1: The profile of SCD cases and healthy controls at enrolment into the study|
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The prevalence rates of HBsAg, HBsAb, and HBeAg in cases were 2 (2.4%), 7 (8.5%), and 0 (0.0%), whereas it were 2 (2.2%), 14 (15.6%), and 0 (0.0%) in controls, respectively [Table 2]. Correspondingly, the prevalence rates of HBeAb, hepatitis B core, and HCV antibodies in cases were 7 (8.5%), 11 (13.4%), and 6 (7.3%), whereas it were 0 (0.0%), 8 (8.9%), and 4 (4.4%) in controls, respectively [Table 2]. HIV antibodies had a prevalence of 2 (2.4%) in cases and 0 (0.0%) in controls [Table 2]. There was a significant difference in the prevalence rate of HBeAb in cases and controls [P = 0.005, [Table 2]. There were no significant differences in the prevalence rates of other transfusion transmissible viral markers in cases and controls [P > 0.05, [Table 2].
|Table 2: Comparison of seroprevalence of viral markers in patients and controls|
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Among the cases, 40 (48.8%) did not receive any previous blood transfusion, whereas 42 (51.2%) had been transfused at least once at the time of recruitment. There were no significant differences in the seroprevalence of all markers of transfusion transmissible viral infections among cases that received blood transfusion and those that did not [P > 0.05, [Table 3].
|Table 3: Seroprevalence of viral markers in cases by transfusion history|
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Among cases and healthy controls above 25 years of age, females tended to have higher positivity for transfusion transmissible viral markers, these differences were however not significantly different (P > 0.05).
| Discussion|| |
The prevalence of viral infections, particularly those that are transfusion transmissible has been reported to be higher in patients who have chronic anemia and require regular blood transfusions. SCD, either in the homozygous or the double heterozygous state, is characterized by chronic anemia, end organ dysfunction, a number of acute events known as crises, and a defect in immune surveillance. The subnormal immune surveillance thus could predispose these patients to a wide range of infectious agents, including viruses.
Ségbéna et al. reported a prevalence of 20.2%, 6.5%, and 5.04% for HBV, HCV, and HIV infections, respectively, in a cohort of patients with sickle cell anemia (SCA) in Togo. The study concluded that SCA patients are particularly prone to infection with a number of these viruses due to frequent hospitalizations and attendant blood transfusions. In this study, the prevalence of HIV (2.4%) was lower, whereas the HCV was comparable (7.3%) with earlier reports in blood donors and patients with SCA subjects., HBV infection has a particularly high prevalence in Nigeria and indeed the whole of sub-Saharan Africa. It has been attributed with the highest risk of residual transmission among the transfusion transmitted diseases. Okocha et al. reiterated this observation in a study involving 96 SCA patients in Benin, Nigeria; however, the prevalence of HBsAg was much higher than we reported 29.2% versus 2.4%, respectively. Interestingly, this study noted that the overall risk of HBV infection in SCA patients was not clearly increased by blood transfusion. This conclusion is in agreement with the findings in this study, in which the prevalence of viral markers was not significantly different in cases that had received blood transfusion and those who did not [Table 3]. The lower prevalence of HBV among SCD patients in this study compared to an earlier study in Nigeria by Okocha et al. (with a comparable study sample size) may indeed represent regional differences in rates of viral transmission in the country; while our patients are from South-Western region of the country, the study subjects in the earlier study were recruited from Mid-Western Nigeria. Until recently, SCD patients in Nigeria were not routinely vaccinated against HBV; however, it is currently available for patients, being a component of the National Programme on Immunization. The finding of nonsignificant association between blood transfusion and seroprevalence of blood transfusion viral markers in this study is in contrast with a number of reports which had consistently linked high blood transfusion rates with increased predisposition to acquiring transfusion transmissible viral infections.,, This difference may be related to the transfusion rate; all the patients evaluated in this study had cumulative red cell transfusions of <10 units, and none was on hyper-transfusion regimen suggesting a low transfusion rate in our cohort.
Following acute hepatitis B infection, the surface antigen and the core antibody commonly become detectable in the serum; both may remain in the serum even after viral clearance. It is therefore for the above reason that both markers have been used as evidence of previous exposure to the virus. The prevalence of the antigen and core antibody in this study was 2.4% and 13.4%, respectively; these were not significantly different from the controls [Table 2]. Detection of antibody to the surface antigen (HBsAb) is generally assumed to depict immunity to HBV infection. The prevalence of HBsAb in cases in this study was 8.5%; this was also not significantly different from the controls [Table 2].
In this study, the seroprevalence of HBeAb in the cases was significantly higher than in controls [8.5% vs. 0.0%, P = 0.005, [Table 2], while the corresponding antigen (HBeAg) had 0.0% prevalence in cases and controls [Table 2]. The presence of the HBeAg in the serum generally depicts active HBV replication within hepatocytes, with attendant high risk of viral transmission, including maternal to child transmission (MTCT). Correspondingly, the presence of the HBeAb in the serum (with HBsAg negativity) has been recognized to coincide with clinical remission in chronic HBV infection and equally offers some protection against HBV MTCT.
Previously, the HBeAg was assumed to be a surrogate marker for the presence of the HBV DNA, and cases that were negative to the former were thought to have achieved viral clearance, however this notion has been challenged following the discovery of cases of HBeAg-negative (HBeAb-positive) chronic HBV infection, with very active disease. In fact, Hadziyannis and Vassilopoulos had emphasized that patients who are positive for HBsAg and HBeAb but negative for HBeAg required further evaluation (HBV DNA, and serum transaminases) to differentiate them from those with (inactive) HBsAg carrier state. In this study, the high prevalence of HBeAb (8.5%) in cases when considered with the low prevalence of HBsAg (2.4%) may well mean that these group of patients have cleared the virus and are in remission. Despite this possibility, further evaluation of these cohorts for HBV viral activity is necessary.
Previous studies noted significant variations in the seroprevalence of sexually transmitted viral infections, particularly HBV across age groups and attributed this difference to an added influence of horizontal mode of transmission particularly in the 10–20 year age group, as well as increasing sexual exposure (sexual transmission) in the 21–30 year age groups., Although more cases and controls aged ≥25 years tested positive to markers of viral infection than those <25 years in this study, the differences were not statistically different (P > 0.05). While the reason for this discrepancy was not apparent from this study, it is likely that increased sexual activity around this period could be responsible.
Sánchez et al. had earlier noted that the seroprevalence of viral infections was significantly higher in male compared to female subjects in Lima, Peru. The authors attributed this to the increased tendency for high risk sexual behaviors (including the likelihood for more sexual partners) in male subjects compared to females, which could predispose them to acquiring sexually transmitted viral infections. More recently, however, Okocha et al. and Matee et al. in studies among SCA subjects and blood donors, respectively, failed to show any significant difference in the seroprevalence of transfusion transmissible viral infections across gender groups., Our report agrees with these recent observations; no significant differences were observed in the seroprevalence of markers of transfusion transmissible viral infection in males and females in both cases and controls.
| Conclusion|| |
Blood transfusion did not significantly increase the seroprevalence of markers of transfusion transmissible viral infection in our SCD patients; this may be related to the low transfusion rate observed in patients, coupled with the universal pretransfusion screening protocols applied in our center. The high levels of HBeAb and low HBsAg in this cohort could represent inactive HBV carrier state.
Limitations of the Study
The study is limited by the nonavailability of biochemical indices of hepatic damage (particularly transaminases) and HBV viral load which could help to adequately delineate cases of chronic (active) HBV infection that will benefit from further evaluation and treatment. This will need to be further explored and evaluated in follow-up studies.
Financial Support and Sponsorship
Conflicts of Interest
There are no conflicts of interest
| References|| |
Lal A, Vichinsky EP. Sickle cell disease. In: Hoffbrand AV, Catovsky D, Tuddenhan EG, editors. Postgraduate Hematology. 5th
ed. Oxford: Blackwell Publishing; 2005. p. 104.
Al Adnani MS, Al Kasab FM, Al Alusi FA. Hepatitis B surface antigenemia in sickle cell disease. Lancet 1992;2:1286.
Okpala I. The intriguing contribution of white blood cells to sickle cell disease – A red cell disorder. Blood Rev 2004;18:65-73.
Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000;64:51-68.
Mayosi BM, Lawn JE, van Niekerk A, Bradshaw D, Abdool Karim SS, Coovadia HM; Lancet South Africa team. Health in South Africa: Changes and challenges since 2009. Lancet 2012;380:2029-43.
Ishak KG. Pathologic features of chronic hepatitis. A review and update. Am J Clin Pathol 2000;113:40-55.
Ghendon Y. Perinatal transmission of hepatitis B virus in high-incidence countries. J Virol Methods 1987;17:69-79.
Francis TI. Epidemiology of viral hepatitis in the tropics. Bull N
Y Acad Med 1977;51:501-7.
Prince AM. Prevalence of serum-hepatitis-related antigen (SH) in different geographic regions. Am J Trop Med Hyg 1970;19:872-9.
Wallis JP, Wells AW, Matthews JN, Chapman CE. Long-term survival after blood transfusion: A population based study in the North of England. Transfusion 2004;44:1025-32.
Nsiah K, Dzogbefia VP, Osei-Akoto A, Ansong D. The prevalence of seropositivity to hepatitis B surface antigen and the corresponding hemato-biochemical features in sickle cell patients in Ghana. J Hematol Malig 2012;2:13-8.
Chamberland ME, Alter HJ, Busch MP, Nemo G, Ricketts M. Emerging infectious disease issues in blood safety. Emerg Infect Dis 2001;7 3 Suppl: 552-3.
Kassim OD, Oyekale TO, Aneke JC, Durosinmi MA. Prevalence of seropositive blood donors for Hepatitis B, C and HIV viruses at the federal medical centre, Ido-Ekiti, Nigeria. Ann Trop Pathol 2012;3:47-55.
Aminu M, Okachi EE, Abubakar SM, Yahaya A. Prevalence of hepatitis B virus surface antigen among healthy asymptomatic students in a Nigerian University. Ann Afr Med 2013;12:55-6.
Ejele OA, Nwauche CA, Erhabor O. Seropositivity of hepatitis C virus in Niger Delta of Nigeria. Niger Postgrad Med J 2006;13:3-6.
Mahy M, Nzima M, Ogungbemi MK, Ogbang DA, Morka MC, Stover J. Redefining the HIV epidemic in Nigeria: From national to state level. AIDS 2014;28 Suppl 4:S461-7.
Buseri FI, Muhibi MA, Jeremiah ZA. Sero-epidemiology of transfusion-transmissible infectious diseases among blood donors in Osogbo, South-West Nigeria. Blood Transfus 2009;7:293-9.
The Nigerian National Blood Transfusion Policy. National Blood Transfusion Service, Federal Ministry of Health, Abuja; May, 2006. p. 1.
Akinola NO, Stevens SM, Franklin IM, Nash GB, Stuart J. Subclinical ischaemic episodes during the steady state of sickle cell anaemia. J Clin Pathol 1992;45:902-6.
Sassi F, Bardi R, Neji T, Ayed K, Ben Dridi MF. Immunological study in sickle cell disease patients: Importance of the complement system. Tunis Med 2003;81:195-9.
Ségbéna AY, Prince-David M, Kagoné TS, Dagnra AY. Human immunodeficiency virus, hepatitis C virus and hepatitis B viruses in patients with sickle-cell disease in Togo. Transfus Clin Biol 2005;12:423-6.
Mutimer DJ, Olomu A, Skidmore S, Olomu N, Ratcliffe D, Rodgers B, et al.
Viral hepatitis in Nigeria – Sickle-cell disease and commercial blood donors. QJM 1994;87:407-11.
Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med 1996;334:1685-90.
Okocha EC, Ejele OA, Ibeh CC, Aneke JC. Prevalence of hepatitis B surface antigen (HBsAg) seropositivity in sickle cell anemia patients in Benin city, Mid-Western Nigeria. Ann Trop Pathol 2013;4:83-7.
Ocak S, Kaya H, Cetin M, Gali E, Ozturk M. Seroprevalence of hepatitis B and hepatitis C in patients with thalassemia and sickle cell anemia in a long-term follow-up. Arch Med Res 2006;37:895-8.
Namasopo SO, Ndugwa C, Tumwine JK. Hepatitis C and blood transfusion among children attending the Sickle Cell Clinic at Mulago Hospital, Uganda. Afr Health Sci 2013;13:255-60.
Almeida Neto C, Strauss E, Sabino EC, Sucupira MC, Chamone DA. Significance of isolated hepatitis B core antibody in blood donors from São Paulo. Rev Inst Med Trop Sao Paulo 2001;43:203-8.
Schillie S, Walker T, Veselsky S, Crowley S, Dusek C, Lazaroff J, et al.
Outcomes of infants born to women infected with hepatitis B. Pediatrics 2015;135:e1141-7.
Lu LL, Chen BX, Wang J, Wang D, Ji Y, Yi HG, et al.
Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women. Int J Infect Dis 2014;28:41-4.
Hadziyannis SJ. Hepatitis B e antigen negative chronic hepatitis B: From clinical recognition to pathogenesis and treatment. Viral Hepat Rev 1995;1:7-36.
Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2001;34(4 Pt 1):617-24.
Halim NK, Offor E, Ajayi OI. Hepatitis B surface antigen (HBsAg) epidemiological and seroprevalence studies. Afr J Med Pract 1998;5:239-44.
Sánchez J, Gotuzzo E, Escamilla J, Carrillo C, Phillips IA, Barrios C, et al.
Gender differences in sexual practices and sexually transmitted infections among adults in Lima, Peru. Am J Public Health 1996;86:1098-107.
Matee MI, Magesa PM, Lyamuya EF. Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses and syphilis infections among blood donors at the Muhimbili National Hospital in Dar es Salaam, Tanzania. BMC Public Health 2006;6:21.
[Table 1], [Table 2], [Table 3]