ABSTRACT
Beta- thalassemia syndromes are the most common causes of chronic haemolytic anemia in Egypt. The disease appears early in life as a Variable degree of anaemia associated with splenomegaly, stunted growth, bone changes and mongoloid facies. Patients are usually treated with regular blood transfusion which leads to iron overload and therefore chelation therapy is very important to avoid iron overload and its complications. The patients may have immunological abnormalities mostly due to iron overload, repeated exposure to allogenic antigens and immunosuppressive viruses in blood transfusions, desferrioxamine chelation therapy and splenectomy. Infection has been reported to be one of the main causes of morbidity and mortality in beta-thalassemia. It is described as the second most common cause of death in these patients with a prevalence of 12-13%. Besides the well-known risks of blood-borne infections associated with multiple transfusions, a less familiar clinical problem is the increased susceptibility of these patients to infections, due to the coexistent immune deficiency. One of these infections may be parvovirus B19. Parvovirus B19 is a single-stranded DNA virus. The virus is classified as a member of the erythrovirus genus because replication occurs only in human erythrocyte precursors. This work was designed to study some transfusion related viral infections in thalassemic children attending the hematology unit of Pediatrics department of Assiut University and to discuss the possible predisposing and underlying factors. The study was carried out in the period between September 2004 and October 2005 in the departments of clinical pathology and pediatrics, Assiut university hospital, Egypt It included 50 individuals, 35 transfusion-dependant children with beta-thalassemia major, aged 2 to 15 years and 15 apparently healthy children as a control group. Patients recruited in the study had thorough history taking and complete clinical examination. In addition, the following laboratory investigations were performed for all cases and controls: complete blood picture including reticulocytic count and calculation of the reticulocytic index; liver functions, [iron status [including serum iron, TIBC and ferritin]; human parvovirus B19 IgG; Hepatitis C virus antigen by PCR and antibodies [HCV-Abs] by ELISA, hepatitis B virus surface antigen [HBsAg], and human immunodeficiency virus types 1 and 2 antibodies by ELISA. Thalassemic patients had significantly lower Hb, RBCs and TIBC and significantly higher reticulocytic count, reticulocytic index, serum iron, serum ferritin, serum bilirubin, AST and ALT than the controls. The studied patients had 83% positivity for Parvovirus lgG antibodies, 97% for Hepatitis C IgG antibodies, 80% for Hepatitis C antigen by PCR. Patients had significantly lower CD4 T lympocytes, higher CD8 T lymphocytes than the controls. CD4/CD8 ratio was also inverted in the patients. Parvovirus positive cases had significantly lower Hb, RBCs, reticulocytic count and index and significantly higher AST and ALT than parvovirus negative cases. Serum ferritin, parvovirus IgG, and CD8 T lymphocytes correlated positively with the number of blood transfusions. Parvovirus lgG correlated positively with AST and ALT and negatively with reticulocytic count. Infectious complications constitute an important part of the clinical spectrum of beta-thalassemia, being associated with significant morbidity and mortality. The recently recognized immune defects in these patients involve multiple components of the immune system and have been attributed to specific features of the disease, as well as to the therapeutic modalities applied. Iron overload, a primary complication of both thalassemia itself and transfusion therapy, is thought to be the main precipitating mechanism, due to the important immunoregulatory properties of iron and its binding proteins. Iron excess may derange the immune balance in favor of the growth of infectious organisms. Other factors include multiple transfusions, associated with constant allo-antigenic stimulation, as well as with transmission of immunosuppressive viruses including the parvovirus B19. Infection with this virus in thalassemic patients can lead to persistent anemia indicated by reticulocytpenia and decreased reticulocytic index. Surveillance for infections in patients with beta-thalassemia is crucial, while additional studies are required to establish more clearly the clinical significance of the suspected precipitating mechanisms, hence providing new methods for the further amelioration of the survival rate and quality of life. Blood or blood products intended for use in high-risk groups such as immunocompromised individuals and patients with underlying hematological problems should be screened for B19. New inactivation methods for blood or blood products should be implemented to reduce the transmission of the parvovirus B19 via blood transfusion. Screening of blood donors for B19 can be an alternative to viral inactivation. Regular chelation therapy is a must to prevent the effects of the iron overload on the immune response. lntroduction of parvovirus B19 vaccines particularly for the immunocompromised patients may be helpful in the near future