Racial differences in seroprevalence of HAV and HEV in blood donors in the Western Cape, South Africa: a clue to the predominant HEV genotype?

Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. This infection causes major water-borne outbreaks in low- and middle-income countries, whilst in industrialised countries this infection is zoonotic. These differences in epidemiology are related to different HEV genotypes. HEV genotype 3 is a zoonotic infection, whilst genotype 2 causes large outbreaks. This study determined the seroprevalence of HEV in blood donors from the Western Cape. Anti-hepatitis A virus (anti-HAV) antibody was detected in 184/300 (61%) donors. Antibody to HEV (anti-HEV) was detected in 78 of 300 donors (26%). It was highest in mixed race donors (62/100), followed by white donors (23/100) and lowest in black donors (19/100) P = 0.019. Since it is thought that genotypes 1 and 2 predominate both viruses would be acquired by the oro-faecal route, it is surprising that HEV seroprevalence does not mirror that of HAV. We postulate that this may reflect differences in socio-economic status and consumption of dietary meat. So the marked divergence between HEV and HAV seroprevalence may be the result of different routes of transmission. Further data are needed to explore the risk factors associated with HEV infection.

The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention.

BACKGROUND AND OBJECTIVES: Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. MATERIALS AND METHODS: 'Strategies To Reduce Iron Deficiency' (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. RESULTS: Iron deficient erythropoiesis was present in 52·7% of males and 74·6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0·002), but not more common in those receiving iron than placebo (P = 0·68). CONCLUSION: The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo.

Reduction of the risk of transfusion-transmitted viral infection by nucleic acid amplification testing in the Western Cape of South Africa: a 5-year review.

BACKGROUND AND OBJECTIVES: In October 2005, individual donation nucleic acid amplification testing (ID-NAT) for HIV, HBV and HCV was introduced in the Western Cape Province of South Africa. After 5 years, the impact on HIV, HBV and HCV transmission risk was assessed. MATERIALS AND METHODS: A total of 649745 donations were tested by ID-NAT using the Ultrio assay on the Tigris instrument (Novartis Diagnostics) and for anti-HIV, HBsAg and anti-HCV (Abbott Prism). Initial reactive samples were repeated in duplicate. Discrepant repeat reactive samples were subjected to confirmatory assays. ID-NAT nonrepeat reactive donations were further screened for occult HBV infection (OBI) by anti-HBc assay. RESULTS: ID-NAT yielded 6 HIV-RNA-positive donations in the anti-HIV-negative window period (WP) but only 2 were p24 Ag nonreactive (1:325000). Mathematical modelling estimated a similar HIV transmission risk for lapsed and repeat donations, in the order of 3 per million. The WP risk for HBV was 13 per million. Eight acute (1:81000) and 13 chronic OBI yield cases (1:50000) were interdicted. There were significantly more anti-HBc-positive donors in the Ultrio initial reactive/nonrepeat reactive group (12%) than in an Ultrio nonreactive control group (6%). CONCLUSION: ID-NAT in the Western Cape Province of South Africa has contributed significantly to enhancing blood safety, particularly for HBV transmission risk and to a lesser extent for HIV. Anti-HBc testing of NAT nonrepeat reactive donations seems useful in identifying a subgroup of donors with OBI who may be at risk of transmitting HBV.

L-Asparagine synthetase in serum as a marker for neoplasia.

L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect.

Babesiosis in a renal transplant recipient acquired through blood transfusion.

BACKGROUND: The success of organ-replacement therapies has resulted in a population of chronically immunosuppressed but active people who experience increased vulnerability to tick-borne zoonoses. Several of these infections may be life threatening. Human babesiosis is an emerging zoonosis that is transmitted by the same tick that transmits Lyme disease and human granulocytic ehrlichiosis. METHODS: We briefly review these zoonoses and present a case of a renal transplant recipient who survived infection by Babesia microti contracted through blood transfusion. RESULTS: A recipient of a living-related renal transplant developed acute postoperative hemolytic anemia. The etiology of this anemia was diagnosed by peripheral red blood cell smear as Babesia microti. The patient was managed by a reduction in transplant immunosuppressive therapy and administration of clindamycin and quinine antimicrobials. CONCLUSIONS: Transplant patients may contract babesiosis after tick exposure and/or via blood transfusion. The diagnosis of babesiosis may be confused with malaria and should be included in the differential diagnosis of posttransplant hemolytic-uremic syndrome in organ transplant patients.

Concanavalin A induces patching/capping of the platelet membrane glycoprotein IIb/IIIa complex.

Two recent reports have shown platelet patching/capping by concanavalin A (Con A). In these studies, Con A receptors were shown to mobilize from pseudopodia and lamellipodia to the central cell parts during platelet attachment and spreading. The molecular mechanism underlying Con A receptor capping was not examined in either study. Con a binds maximally to human platelet membrane glycoproteins IIb and IIIa. In order to test whether Con A-induced capping caused the capping of this membrane glycoprotein complex, we treated normal human platelets with unlabeled Con A. After fixation, platelets were further treated with mouse monoclonal antibodies against the membrane glycoprotein IIb/IIIa complex and stained with fluorescein isothiocyanate (FITC) tagged anti-mouse IgG. An average of 16% platelets manifested capping with one monoclonal antibody preparation (N = 2) and 12% with a second preparation (N = 2). Control studies showed that only 18% of normal human fresh platelets exhibit capping with FITC-Con A (N = 17). If platelets were first incubated with unlabeled Con A, followed by staining with FITC-labeled anti-Con A antibody, an average of 15% platelets manifested caps (N = 17). Capping was inhibited by methyl-alpha-D-mannopyranoside (a known inhibitor of Con A), at cold temperature and by pre-treatment of platelets with colchicine. Our studies confirm the earlier findings on Con A induced capping. Also, our findings suggest that the molecular mechanism for Con A receptor capping involves patching and capping of the platelet membrane glycoprotein IIb/IIIa complex. It is possible that glycoprotein IIb/IIIa redistribution might be intimately involved during platelet attachment and spreading.

Effect of methods of platelet resuspension on stored platelets.

Platelets are prepared from whole blood by differential centrifugation. Following their isolation as a platelet button, platelets are allowed to rest for a short period in the residual plasma before resuspension. In this study, the feasibility of resuspending platelets without this rest period is studied. A total of 35 platelet concentrates (PC) were prepared from blood collected in CPDA-1 and resuspended by one of the following four methods: (1) no resting period, PC placed on a rotator immediately after preparation, (2) a 1.5 hour rest period and gentle shaking prior to rotation, (3) no rest period and immediate gentle shaking prior to rotation, and (4) a 1.5 hour resting phase and no shaking prior to rotation. Following the previous processing, all platelet concentrates were stored for 72 hours on an elliptical platelet rotator at 20 to 24 degrees C to provide continuous agitation. A number of in vitro tests were used as indicators of platelet viability during storage. These included platelet morphology, pO2, pCO2, pH, osmotic recovery, number of platelets in the concentrate, and platelet volume distribution. Our findings demonstrate that platelets are of similar quality after storage in all of the four groups described. Our studies suggest that the resting phase is unnecessary for platelet preparation. The elimination of the resting phase would allow platelet concentrates to be available sooner and improve cost-effectiveness of platelet preparation.

Trends in hepatitis B surface antigen (HBsAg) prevalence in volunteer blood donors in Connecticut, 1973-1983.

A total of 1,573,769 blood donations from volunteer blood donors from Connecticut were tested for Hepatitis B Surface Antigen (HBsAg) from 1973 to 1983. The prevalence of HBsAg decreased over this 10 year period among first time as well as repeat donors. This decrease was much more pronounced in the first three years of the study (1973 to 1975) in repeat donors. Thereafter, prevalence was stable. In first-time donors, the largest decrease also occurred in the first three years. In contrast to repeat donors, however, marked fluctuations in the prevalence were noted in first time donors. As has been the case in previous studies, HBsAg prevalence in first-time donors was significantly higher than that observed in repeat donors. Our study encompasses the longest period of observation in comparison to previous reports on HBsAg prevalence among blood donors. While it has been previously established that a decrease in prevalence over time does occur among repeat donors, stabilization of prevalence after an initial reduction found in our study has not been previously documented. This may indicate an irreducible minimum prevalence rate in the repeat donor population. In addition, our study for the first time convincingly demonstrates a reduction in prevalence in first-time donors which may reflect better communications at the donor recruitment and nursing level.

Characteristics and natural history of alloimmunization following HLA-matched leukocyte transfusion in Hunter's syndrome.

The characteristics and natural history of alloimmunization to HLA were studied in five patients with Hunter's syndrome receiving long term transfusions of leukocytes collected from human leukocyte antigen (HLA) matched donors. Patients were not given any other blood component transfusions. All patients became alloimmunized at an average interval of eight months following an average of 15 transfusions. All patients developed HLA alloantibodies to transfused cross-reactive HLA antigens. Antibodies to transfused incompatible HLA antigens also developed in all patients. Multispecific HLA antibodies in which specificity determination could not be made were also seen in four patients. In a small number of patients in this study, despite matching for the private HLA specificities, HLA alloimmunization was not prevented. In fact, broad alloimmunization was seen uniformly in our patients.

HLA alloimmunization with leukocyte concentrates from HLA-matched and HLA-non-matched donors in patients with Hunter's syndrome.

The incidence and characteristics of HLA alloimmunization following transfusions of leukocyte concentrates as a source of enzyme replacement were determined in male patients with Hunter's syndrome. Five patients were given leukocyte concentrates from HLA matched donors (Group I) and another five patients received leukocyte concentrates from non-HLA matched donors (Group II). No other blood products were transfused in either group. Immune response pattern of HLA alloimmunization measured as the proportion of screening cells manifesting cytotoxicity with patient's sera obtained during the follow-up period was similar in both groups. HLA alloimmunization is seen with transfused leukocyte concentrates from either HLA-matched or non-HLA-matched donors in patients with Hunter's syndrome. There appears to be a trend for an earlier onset of HLA alloimmunization with fewer transfusions when leukocyte concentrates from non-HLA-matched donors are transfused as compared to leukocyte concentrates from HLA-matched donors. Once HLA alloimmunization occurs, immune response patterns appear similar with either leukocyte product.