X. Deng

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

BACKGROUND: Blood and plasma donor screening for hepatitis B virus (HBV) DNA, HBV surface antigen (HBsAg), and antibodies to surface (anti-HBs) and core (anti-HBc) antigens allows identification of individuals who acquired HBV despite previous HBV vaccination. METHODS: Of 14 HBV acute infection donor panels (HBV-DNA-positive/anti-HBc-negative), 6 donors were previously vaccinated (anti-HBs+). We investigated the differences in viral kinetics and immune responses in vaccinated and nonvaccinated individuals. Serial specimens were characterized for HBV DNA and serological markers and 39 cytokines. RESULTS: The rate of viral load increase was blunted, and virus was cleared more rapidly in vaccinated individuals (P = .004). In unvaccinated individuals, induced protein 10 (IP-10), interleukin 10 (IL-10), macrophage inflammatory protein 1β (MIP-1β), and soluble interleukin 2Rα (sIL-2Rα) levels were commonly elevated at the time of peak viremia. In contrast, vaccinated individuals had earlier peaks in IL-10 and IP-10 responses that occurred at much lower viral loads and coincided with anamnestic anti-hepatitis B surface (HBs) responses and clearance of viremia. CONCLUSION: There is earlier engagement of innate and adaptive immunity in infected subjects with previous vaccination, possibly explaining suppressed viremia in vaccine breakthrough infections. Although breakthrough infections occur in partially protected vaccine recipients, vaccination likely contributes to early control of replication, limiting immune activation and preventing development of clinically significant acute and chronic HBV infection.

BACKGROUND: An association between GB virus C (GBV-C) and improved outcomes of human immunodeficiency virus (HIV) infection has been reported in HIV-positive individuals with active GBV-C coinfection. This study provides insights into the immune mechanisms underlying the protective role of GBV-C in HIV-infected patients. METHODS: The concentrations of 64 cytokines and chemokines were measured in plasma samples obtained from the Viral Activation Transfusion Study cohort before transfusion and longitudinally from 30 patients positive for both HIV and GBV-C (hereafter, "cases") and 30 patients positive for HIV and negative for GBV-C (hereafter, "controls"). RESULTS: Cases had lower HIV viral loads and higher CD4 T-cell counts than controls after acquisition of GBV-C infection. Most of the modulated cytokines and chemokines were reduced after GBV-C detection, including many proinflammatory cytokines, suggesting an overall antiinflammatory effect of GBV-C in HIV-positive subjects. Most pathways and functions of the measured cytokines were downregulated in cases, except cell death pathways, which were upregulated in various cell subsets in the 3 months after GBV-C detection. CONCLUSIONS: GBV-C has a protective effect, in part through a competition mechanism leading to decreased inflammation and improved HIV disease outcome in cases. Further studies are necessary to establish whether GBV-C may have deleterious effects on the host at the cellular level, including depleting the cells that are the targets of HIV.