Association between transfusion with human herpesvirus 8 antibody-positive blood and subsequent mortality.

BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda and transmissible by blood. We evaluated mortality following transfusion of HHV-8 antibody-positive blood. METHODS: In a hospital-based, observational, prospective cohort study with a 6-month follow-up, we examined the effect of HHV-8 antibody-positive blood on transfusion recipients surviving at least 7 days. RESULTS: Of 1092 recipients, 471 (43.1%) were transfused with HHV-8 antibody-positive blood. Median age was 1.8 years (range, 0.1-78); 111 (10.2%) died during follow-up. After adjusting for confounders (increasing age, human immunodeficiency virus infection, illness other than malaria, receipt of multiple transfusions), recipients of HHV-8 antibody-positive blood stored ≤4 days ("short-stored") were more likely to die than recipients of HHV-8 antibody-negative blood (adjusted hazards ratio [AHR], 1.92; 95% confidence interval [CI], 1.21-3.05; P = .01). The AHR of the effect of each additional short-stored HHV-8 antibody-positive transfusion was 1.79 (95% CI, 1.33-2.41; P = .001). CONCLUSIONS: Transfusion with short-stored HHV-8 antibody-positive blood was associated with an increased risk of death. Further research is warranted to determine if a causal pathway exists and to verify the observed association between acute HHV-8 infection and premature mortality.

Transmission of human herpesvirus 8 by blood transfusion.

BACKGROUND: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic. METHODS: We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood. RESULTS: Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%; P=0.005), a result consistent with the transmission of the virus by transfusion. Blood units stored for up to 4 days were more often associated with seroconversion than those stored for more than 4 days (excess risk, 4.2%; P<0.05). CONCLUSIONS: This study provides strong evidence that HHV-8 is transmitted by blood transfusion. The risk may be diminished as the period of blood storage increases.

Quantitation of human herpesvirus 8 (HHV-8) antibody in patients transfused with HHV-8-seropositive blood.

BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda where seroprevalence is approximately 40%. In a previous study, Ugandan patients receiving blood transfusions had multiple serum specimens collected for 6 months after transfusion to monitor for HHV-8 infection. It was observed that several HHV-8-seronegative patients were unexpectedly HHV-8 seropositive after blood transfusion. STUDY DESIGN AND METHODS: This study measured HHV-8 antibody in serially collected serum specimens from 542 patients who received transfusions and evaluated the risk of HHV-8 infection as a function of HHV-8 antibody levels in the donors. RESULTS: HHV-8 antibody was observed in 52% of patients transfused with HHV-8-seropositive blood in amounts that corresponded with their donor's antibody titer and waned within 40 days. Higher levels of passive HHV-8 antibody in patients who received transfusions appeared to be associated with a lower risk of HHV-8 infection. CONCLUSION: The source of transient antibody in patients who received transfusions was determined to be the transfused blood. Donors with higher HHV-8 antibody titers may have been less likely to have infectious virus in the blood.

The effect of HIV on morbidity and mortality in children with severe malarial anaemia.

BACKGROUND: Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed. METHODS: Children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children. Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders. FINDINGS: Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30-6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91-7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54-9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41-9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 - 6.07, P = 0.02) post-transfusion than HIV-uninfected children. CONCLUSION: HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.