Prevalence and Associated Risk Factors of HTLV-1 and Co-infections of Blood-Borne Viruses in Birjand, Iran's Eastern Border.

BACKGROUND: Blood-borne viruses (BBVs) are one of the most important public health concerns. South Khorasan has a long border with Afghanistan and concern has risen there about blood-borne oncogenic viral infections. The aim of the present study was to evaluate the prevalence and associated risk factors of human T-lymphotropic virus 1 (HTLV-1) and co-infections of BBVs in Birjand, Iran's eastern border. METHODS: In this cross-sectional study, 3441 subjects were tested for sero-prevalence of HTLV-1 by ELISA. The data on demographic features, HTLV-1-related risk factors and other characteristics of the population were analyzed by Pearson chi-square and logistic regression tests. Finally, the co-infection of BBVs was evaluated in the study. RESULTS: The prevalence of HTLV-1 was 0.3% (95% CI: 0.12-0.48). Notably, the sero-prevalence of HIV, hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV) in our previous studies was reported at 0%, 0.2%, 1.2% and 1.6%, respectively. The results indicated that the occurrence of HTLV-1 infection was associated only with the history of hospitalization (odds ratio [OR]: 0.27, 95% CI: 0.07-0.97, with P = 0.04). The co-infection of HBV with HCV was the most common (2.35%), while a co-infection rate of 1.17% was found for both HBV/HTLV-1 and HBV/HDV. CONCLUSION: Although a higher prevalence of the viruses was expected, it was close to the overall Iranian population. With respect to close relationship with an HTLV-1 endemic area (Mashhad and Neyshabour), the prevalence is very low; however, more attention is needed. Our findings reinforce the importance of increasing knowledge about BBV-related health risk behaviors to prevent the emergence of new cases, especially in low-risk populations.

The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.

BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4⁺CD25⁺ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4⁺CD25⁺ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

Anti-HHV-8/KSHV antibodies in infected individuals inhibit infection in vitro.

OBJECTIVE: To detect human herpesvirus (HHV)-8/Kaposi's sarcoma-associated herpesvirus (KSHV) neutralizing antibodies (nAb). DESIGN: Antibodies capable of inhibiting HHV-8 infection were measured by infecting transformed dermal microvascular endothelial cells (tDMVEC) with HHV-8 that had been pre-incubated with serum from HHV-8-seropositive or -seronegative subjects. The level of infection was quantified 48 h later. METHODS: HHV-8 was prepared from JSC-1 primary effusion lymphoma cells; the titre of enveloped virions was determined by electron microscopy. Virus was incubated with serum samples for 60 min before inoculating tDMVEC. The level of infection was quantified by indirect immunofluorescence assay, staining for HHV-8 latency-associated nuclear antigen (LANA)-1. Inhibition of infection was determined by comparing the level of infection obtained with HHV-8-seropositive subject serum with the level obtained by incubation with seronegative serum. RESULTS: Up to 61% of cells were infected with HHV-8 in the absence of human serum; this level was not affected by pre-incubating the virus with HHV-8-seronegative serum. At dilutions of 1:10 and 1:50, HHV-8-seropositive sera significantly inhibited infection compared to seronegative controls (P = 0.036 for both serum dilutions, Mann-Whitney). The endpoint of inhibition was 1:100, when the serum of one of five subjects inhibited virus infection. At 1:500 dilution, there was no difference in the level of infection after virus incubation with seropositive or seronegative sera (P = 0.578). Depletion of antibody from serum with protein A reversed the inhibitory effect, confirming it was antibody-mediated. CONCLUSIONS: This study is the first to identify HHV-8 antibodies in infected subjects that reduce in vitro infectivity of the virus.