Human Herpesvirus 8 Antibodies Research Articles

Prevalence of human herpesvirus 8 infection in systemic lupus erythematosus

BackgroundFor decades, scientists have tried to understand the environmental factors involved in the development of systemic lupus erythematosus (SLE), in which viral infections was included. Previous studies have identified Epstein-Barr virus (EBV) to incite SLE. Human herpesvirus 8 (HHV-8), another member of the gammaherpesvirus family, shares a lot in common with EBV. The characteristics of HHV-8 make it a well-suited candidate to trigger SLE.ResultsIn the present study, serum samples from patients (n = 108) with diagnosed SLE and matched controls (n = 122) were collected, and the prevalence of HHV-8 was compared by a virus-specific nested PCR and a whole virus enzyme-linked immunoassay (EIA). There was significant difference in the prevalence of HHV-8 DNA between SLE patients and healthy controls (11 of 107 vs 1 of 122, p = 0.001); significant difference was also found in the detection of HHV-8 antibodies (19 of 107 vs 2 of 122, p < 0.001).We also detected the antibodies to Epstein-Barr virus viral capsid antigen (EBV-VCA) and Epstein-Barr nuclear antigen-1 (EBNA-1). Both patients and controls showed high seroprevalence with no significant difference (106 of 107 vs 119 of 122, p = 0.625).ConclusionOur finding indicated that there might be an association between HHV-8 and the development of SLE.

Human Herpesvirus 6 Infection in Hemodialysis and Peritoneal Dialysis Patients

Human herpesvirus 6 (HHV-6) infection occurs worldwide and can be reactivated from latency during periods of immunosuppression, especially after organ transplantation. No previous study has evaluated the influence of dialysis type on HHV-6 infection. The aim of the present study was to determine the prevalence of HHV-6 antibodies in hemodialysis (HD) and peritoneal dialysis (PD) patients. We studied 36 PD patients, 35 HD patients, and 20 healthy subjects, all with no history of organ transplantation. After systematic inquiries and a physical examination, blood was drawn for determination of biochemical parameters, cytomegalovirus immunoglobulin M (IgM) and immunoglobulin G (IgG), hepatitis B surface antigen, and the hepatitis C and human immunodeficiency virus antibodies. Titers of HHV-6 IgM and IgG antibodies were determined by ELISA. Titers for HHV-6 IgM antibody were positive in 9 HD patients (25.7%), 8 PD patients (22.2%), and 2 control subjects (10.0%, p > 0.05). More HD patients (20.0%) than PD patients (5.6%, p = 0.07) or control subjects (0.0%, p = 0.03) were positive for HHV-6 IgG antibody. In HD patients, HHV-6 IgG seropositivity and duration of dialysis were positively correlated (R = 0.33, p = 0.05). Infection with HHV-6 is not rare in PD and HD patients. In addition, HHV-6 IgG seropositivity was significantly higher in HD patients than in control subjects and approached significance when compared with seropositivity in PD patients. Moreover, in HD patients, HHV-6 IgG seropositivity correlated with duration on HD. These preliminary findings provide insight into the pre-transplantation period for patients and may aid our understanding of how to best protect patients against HHV-6 after transplantation.

Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran

Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8) infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%), renal transplant recipients (25%) and HIV (45.7%) patients compared to blood donors (2%). Kaposi's sarcoma (KS) is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

Comparison of Prevalence of Kaposi's Sarcoma in HHV8+ and HHV8- HIV Infected Patients in South-South Nigeria

This study was carried out to see if there are any differences between the prevalence of Kaposi’s sarcoma in HIVinfected patients with antibody to Human Herpes Virus 8 (HHV8) or not.Methods: The sera of 180 subjects were evaluated for HIV and HHV8 using double ELISA (Genscreen UltraHIV Ag-Ab ELISA and JN HIV 1/2 ELISA Kit) for HIV screening and advanced Biotechnology IncorporatedELISA for HHV8 IgG antibody detection respectively. Those HIV infected patients that had skin lesionssuspected to be Kaposi’s sarcoma were biopsied for histological diagnosis.Results: A total of 180 subjects were recorded for this study. The ratio of male: female was 1:1.02. In all, 100subjects tested positive to HIV screening and 87 (87%) patients tested positive to HHV8 antibody. Of the 87patients that were positive to HHV8 antibodies 32 (36.7%) were histologically confirmed to have Kaposi’ssarcoma.Conclusion: We found a high rate of prevalence of Kaposi’s sarcoma KS among HIV infected patients withHHV8 antibodies.

Human Herpesvirus 8 Infection in Children and Adults in a Population-based Study in Rural Uganda

Human herpesvirus 8 (HHV-8) infection is endemic in sub-Saharan Africa. We examined sociodemographic, behavioral, and biological factors associated with HHV-8 infection in children and adults to determine HHV-8 seroprevalence and potential routes of transmission. Participants were 1383 children and 1477 adults from a population-based sample in a rural community in Uganda. Serum samples were tested for HHV-8 antibodies with use of an enzyme immunoassay against K8.1. HHV-8 seroprevalence increased from 16% among children aged 1.5-2 years to 32% among children aged 10-13 years (P <.001) and from 37% among participants aged 14-19 years to 49% among adults aged ≥ 50 years (P <.05). HHV-8 seropositivity in children was independently associated with residing with a seropositive parent (P < .001) and residing with ≥ 1 other seropositive child aged <14 years (P < .001). History of sharing food and/or sauce plates was marginally associated with HHV-8 infection in children (P = .05). Among 1404 participants aged ≥ 15 years , there was no association between correlates of sexual behavior (eg, number of lifetime sex partners and HIV infection) and HHV-8 seropositivity (P > .10). Our data suggest that HHV-8 is acquired primarily through horizontal transmission in childhood from intrafamilial contacts and that transmission continues into adulthood potentially through nonsexual routes.

Do fewer cases of Kaposi’s sarcoma in HIV-infected patients reflect a decrease in HHV8 seroprevalence?

Infection with human herpes virus 8 (HHV8) is associated with development of Kaposi's sarcoma (KS); therefore also known as KS-associated herpes virus. KS is closely associated with human immunodeficiency virus (HIV) infection, and consequently HHV8 seroprevalence is higher in HIV-infected compared to HIV-negative patients. Currently, KS is rarely seen in clinical practice, which might be a consequence of an optimized anti-HIV treatment leading to an improved immunological status, or alternatively of a decrease in HHV8 prevalence. To determine the prevalence of HHV8 antibodies in HIV-positive compared to HIV-negative patients from the University Hospital Frankfurt/Main, Germany, and to compare our results with previously published data to illustrate trends in the spread of infection. Hundred serum samples each of HIV-positive and HIV-negative patients were analyzed for HHV8 antibodies by using an IgG immunofluorescence test. The overall HHV8 seroprevalence was 16% with no statistically significant gender-specific differences; however, the distribution between the HIV-infected patients and the HIV-negative control group was significantly different (30 and 2%, respectively). The highest rate of seroprevalence in HIV-infected patients was detected at the age of 40-49 (42%) and the lowest rate at the age of 20-29 years (16.6%). In comparison with formerly conducted studies, our data clearly showed an increase in the HHV8 seroprevalence in HIV-infected patients, both in men and women. Therefore, we conclude that the low rate of clinical KS is associated with an improved immunological status due to an optimized anti-HIV therapy.

Human Herpesvirus 8 Infections and AIDS-Associated Kaposi Sarcoma in Zaria, Northern Nigeria

Studies on human herpesvirus 8 (HHV8) infection in patients with AIDS-associated Kaposi sarcoma (AIDS-KS), from Nigeria are lacking. We examined the seroprevalence of HHV8 infection in patients with AIDS-KS presenting to Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria, and also described their clinical presentation. A total of 20 (11 males and 9 females) histologically confirmed adults with AIDS-KS were recruited consecutively in 2007. The clinical types of lesions, associated diseases, and the AIDS clinical trial group staging of AIDS-KS were noted. Anti-lytic HHV8 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Kaposi sarcoma skin lesions were diverse but mostly nodules (19 cases) and papules (16). Majority (18 cases) had poor risk AIDS-KS, with 10 (50%) patients having concomitant opportunistic infections and 3 (15%) patients having generalized skin lesions. Females had a more severe disease. Seventeen patients (85%) were HHV8-seropositive. AIDS-KS is associated with high HHV8 infection and presents with a variety of skin manifestations that are often aggressive, advanced, and worse in females.

Detection of HHV-8 (human herpesvirus-8) genomes in induced peripheral blood mononuclear cells (PBMCs) from US blood donors

Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma and can be detected and induced in peripheral blood mononuclear cells (PBMCs) from infected individuals. The prevalence of viral genomes in induced/cultured PBMCs from healthy blood donors has not been systematically studied. PBMCs from 164 donors were purified and stored as two equal aliquots in liquid nitrogen. One aliquot was used for CD19+ B-cell purification with a fraction reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in culture media containing n-butyrate and tetradecanoyl phorbol acetate. DNA was extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs harvested at days 2 and 4 of culture. A sensitive real-time PCR with a DNA equivalent of 3×10(5) cells per reaction was run in duplicate for all samples along with a quantitative HHV-8 DNA standard ranging from 1.6 to 200 copies. For all 164 donors, HHV-8 genomes were not detected in the DNA equivalent of 3-6×10(5) of PBMCs and induced/cultured PBMCs with a real-time PCR assay (95% CI: 0-3.5/164). HHV-8 DNA was not detected from DNA equivalent of 1.5 (0.5-5.6)×10(5) CD19+ B cells from 139/164 donors. HHV-8 antibodies were detected in 7 of the 164 donors (4.3%). HHV-8 genomes were not detected from PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level of detectable HHV-8 genomes in blood donors seems to be extremely low, if they exist.

Patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with Kaposi's sarcoma in Mozambique

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV-8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV-8 seen at public health centers and 24 patients with Kaposi's sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV-8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV-8 were detected mostly in persons co-infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV-8 had elevated titers of HHV-8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV-8.

Seroprevalence of human herpesvirus 8 infection in individuals from health care centers in Mozambique: Potential for endemic and epidemic Kaposi's sarcoma

Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its prevalence in Mozambique is unknown. The seroprevalence of HHV-8 in a cohort of individuals seen at public health centers in Northern (n = 208), Central (n = 226), or Southern (n = 318) Mozambique was examined. All individuals were interviewed to obtain socioeconomic, demographic and clinical data and were tested for serum anti-HHV-8 antibodies using an immunofluorescence assay. The overall frequency of HHV-8 antibodies was 21.4% and, in spite of the diversity of epidemiological characteristics of the tested individuals, did not differ significantly among regions: 18.7%, 24.3% and 21.4% in the North, Center, and South, respectively (chi(2), 2.37; P = 0.305). The variables that were associated significantly with the presence of HHV-8 antibodies were gender, age, level of education, number of siblings and HIV serostatus, but these differed across the regions. In the North, although tested individuals lived under poor socioeconomic conditions, no association between HHV-8 infection and household variables was detected, with the exception of the number of siblings (P = 0.042). In the Central region, HHV-8 infection was associated with gender (P = 0.010), the number of household members (P = 0.031), and the place of attendance (P = 0.021). In the South, HHV-8 infection was associated with the number of siblings (P = 0.023) and HIV status (P = 0.002). The overall prevalence of HHV-8 seropositivity increased with age. These results demonstrate that Mozambique is another country in Africa with endemic HHV-8 infection, and, because of the AIDS epidemic, continued access to antiretroviral treatment is necessary to avert an outbreak of AIDS-Kaposi's sarcoma.

Human herpesvirus 8 genomes and seroprevalence in United States blood donors

Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that causes Kaposi's sarcoma. The prevalence of HHV-8 genomes in US blood donors has not been systemically studied. A sensitive and quantitative real-time polymerase chain reaction (PCR) assay was used to detect HHV-8 DNA from purified CD19+ B lymphocytes from randomly selected US whole blood donors. Cellular target for the GAPDH gene was used to quantify cell-equivalent DNA. HHV-8 PCR was run in duplicate for each donor specimen along with an HHV-8 genomic copy standard. HHV-8 antibodies were detected by an indirect immunofluorescence assay. Specimens were obtained from 962 blood donors. DNA from more than 3 x 10(5) B-cell equivalents were obtained from 684 donors. No HHV-8 DNA was detected from any of the blood donor specimens. For the 684 donors, HHV-8 genomes were not detected in the DNA equivalent of 3 x 10(5) to 6 x 10(5) CD19+ B cells with real-time PCR, which has a detection limit of eight copies (95% confidence interval, 0-3/684). Negative results from the remaining 220 donors were potentially confounded by insufficient input DNA into the PCR procedures. Antibodies to HHV-8 were detected in 7.3% (70/962) of the donors. HHV-8 genomes were not detected from 40 of 70 HHV-8-seropositive donor B-cell DNA samples. The results indicate that the prevalence of detectable HHV-8 genomes in healthy blood donors is very low.

HHV‐6 IgG4 isotype response following measles infection

Human herpesvirus 6 (HHV-6) is widespread in the human population by infecting most individuals in early childhood. After primary infection, HHV-6 establishes a latent infection by remaining in circulating mononuclear cells of healthy individuals. The HHV-6 antibody titer increases after primary infection with measles virus. The present study was undertaken to determine the specific antiviral IgG1, IgG2, IgG3, and IgG4 subclass response patterns to HHV-6 in HHV-6-seropositive individuals with natural measles virus infection, measles vaccination, and rubella virus infection. The purpose of this study was to examine HHV-6-specific IgG isotype response in patients with acute virus coinfection. Serum samples were obtained from individuals who were seropositive for HHV-6 after natural primary infection with measles virus during an outbreak, measles vaccination, or rubella virus infection, and from healthy individuals. Sera were examined by indirect immunofluorescence assays for detection of HHV-6-specific IgG1, IgG2, IgG3, and IgG4 antibodies. A high percentage (69%) of those infected with measles virus had an HHV-6 IgG1 and IgG4 response (P < 0.001, chi(2) test), whereas persons vaccinated against measles, those infected with rubella, and healthy individuals showed an HHV-6 IgG1 response. These results demonstrate that natural measles virus infection induces an HHV-6 IgG isotype response, which suggests a shift in immune activity from a Th1 to a Th2 response. J. Med. Virol. 82:396-399, 2010. (c) 2010 Wiley-Liss, Inc.

Quantitation of human herpesvirus 8 (HHV‐8) antibody in patients transfused with HHV‐8–seropositive blood

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. 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. 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. 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.

Reactivation of human herpesvirus 6 (HHV-6) infection in patients with connective tissue diseases

Background Little is known about the involvement of human herpesviruses 6 and 7 (HHV-6 and HHV-7) in autoimmune connective tissue diseases (ACTD). Objective To determine the prevalence of active infection with HHV-6 and HHV-7 in patients with ACTD. Study design The presence and quantity of HHV-6 DNA was determined by quantitative real-time PCR in a cross-sectional study of serum, peripheral blood mononuclear cells, and tissues obtained from 58 ACTD patients and 38 healthy subjects (HS). Specific anti-HHV-6 antibody titer was also measured. Results HHV-6 serum viremia occurred in a significantly higher proportion of ACTD patients compared to HS [26/58 (44.8%) vs. 1/38 (2.6%), p = 0.001] with the highest reactivation frequency [7/10 (70%)] observed in patients with scleroderma. Moreover, HHV-6 in serum was associated with ACTD activity (22/38 vs. 4/20, p < 0.05). Higher titers of HHV-6 antibodies were found in ACTD patients than in HS, although HHV-6 seroprevalence among patients with ACTD and HS was similar. HHV-7 viremia was not detected in any patients or HS controls. Conclusion The frequent reactivation of HHV-6 in scleroderma and other ACTD, especially when active, suggests that HHV-6 may play a role in the pathogenesis of these diseases.

Lack of Evidence for Frequent Heterosexual Transmission of Human Herpesvirus 8 in Zimbabwe

There is conflicting evidence about the contribution of heterosexual transmission to the spread of human herpesvirus 8 (HHV-8) in southern Africa. This study evaluated the hypothesis that HHV-8 infection is associated with risk factors for human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections among Zimbabwean men. HHV-8 seroprevalence was determined for 2750 participants in the Zimbabwe AIDS Prevention Project cohort of male factory workers in Harare, Zimbabwe. Potential associations of HHV-8 antibody detection with risk factors for HIV-1 infection were examined by univariate analysis. Variables with P < .1 in the univariate analysis were included in a multivariate logistic regression model. HHV-8 seroprevalence was also determined among 297 heterosexual couples. Prevalence of HHV-8, HIV-1, and HHV-8 and HIV-1 coinfection was 28.5% (95% confidence interval [CI], 26.8%-30.2%), 19.5% (95% CI, 18.0%-20.9%), and 6.5% (95% CI, 5.6%-7.5%), respectively. Detection of HHV-8 antibodies was independently associated with older age and HIV-1 infection but not with number of recent sex partners, marital status, education, condom use, prior sexually transmitted infections, payment for sex, chronic hepatitis B infection, or incident HIV-1 infection. HHV-8 seroprevalence was 31.7% (95% CI, 26.3-37.0) among wives in the couples tested, but HHV-8 infection of wives was not associated with HHV-8 infection of husbands (odds ratio, 1.08; 95% CI, 0.62-1.88; P = .8). HHV-8 and HIV-1 infection did not have common sexual risk factors among urban Zimbabwean men. Sexual transmission does not explain the high prevalence of HHV-8 in this population.

A comparative study of the frequency of antibody and titers against human herpesvirus 8 latent and lytic antigens in “at‐risk” individuals and among patients with Kaposi's sarcoma

Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi's sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross- sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS-KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using "in house" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher's exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different "at-risk" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS.

Detection of human herpesvirus‐6 in cerebrospinal fluid of patients with encephalitis

Virus infections are the most common causes of encephalitis, a syndrome characterized by acute inflammation of the brain. More than 150 different viruses have been implicated in the pathogenesis of encephalitis; however, because of limitations with diagnostic testing, causative factors of more than half of the cases remain unknown. To investigate whether human herpesvirus-6 (HHV-6) is a causative agent of encephalitis, we examined for evidence of virus infection by determining the presence of viral sequence using polymerase chain reaction and assessed HHV-6 antibody reactivity in the cerebrospinal fluid of encephalitis patients with unknown cause. In a cohort study, we compared virus-specific antibody levels in cerebrospinal fluid samples of patients with encephalitis, relapsing-remitting multiple sclerosis, and other neurological diseases. Our results demonstrated increased levels of HHV-6 IgG, as well as IgM levels, in a subset of encephalitis patients compared with other neurological diseases. Moreover, cell-free viral DNA that is indicative of active infection was detected in 40% (14/35) of encephalitis patients, whereas no amplifiable viral sequence was found in either relapsing-remitting MS or other neurological diseases patients. In addition, a significant correlation between polymerase chain reaction detection and anti-HHV-6 antibody response was also demonstrated. Collectively, these results suggested HHV-6 as a possible pathogen in a subset of encephalitis cases.

Recombinant ORF66 and ORFK12 antigens for the detection of human herpesvirus 8 antibodies in HIV-positive and -negative patients

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), is not routinely isolated in cell cultures, and thus detection of HHV-8-specific antibodies is usually performed. In this study, we performed recombinant antigens ORF66- and ORFK12-based Western blot strip assays and ELISA, and surveyed the seroprevalence of HHV-8 antibodies in HIV-positive and -negative patients. In serum samples from patients with positive plasma HHV-8 DNA, the sensitivity of the Western blot strip assay was 100% for the anti-ORF66 antibodies and 83.3% for the anti-ORFK12 antibodies. In addition, ORF66-based ELISA showed higher levels of specificity (87.3%) and sensitivity (84.8%) than ORFK12-based ELISA. Moreover, the area under the receiver-operating characteristics curves (AUROC) was 0.76 for ORF66-based ELISA and 0.66 for ORFK12-based ELISA. The seroprevalence of HHV-8 antibodies to ORF66 and/or ORFK12 in the HIV-infected patients (55%, 97/176) was significantly higher than in the DM patients (45%, 135/301) (P = 0.03) and the HIV-/DM-negative group (11%, 11/100) (P < 0.01). In the HIV-infected patients, the seropositivity of the HHV-8-specific antibody was 30% to both antigens, 19% to ORFK12 and 5.7% to ORF66. Importantly, HHV-8 seropositivity in the HIV-infected patients was significantly associated with the transmission method of intravenous injection and high levels of HIV RNA loading (P < 0.01), but not with gender, CD4 cell numbers or AIDS symptoms. This study assessed the sensitivity and specificity of ORF66 and ORFK12 for the detection of HHV-8 antibodies, providing novel antigens for the diagnosis of HHV-8 infection and epidemiology of HHV-8 seroprevalence.

Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial

Kaposi sarcoma (KS), a malignancy of dermal endothelial cells that is caused by human herpesvirus 8 (HHV8) infection, is sensitive to perturbations of immunity. Nicotine might be effective against KS because of its immunologic and vascular effects and because smoking is associated with a low risk of KS. We conducted a masked, randomized phase 2 clinical trial of transdermal nicotine and placebo patches to assess the safety and efficacy of nicotine against classic KS (cKS). Three cKS lesions, predominantly nodules, in each of 24 non-smoking patients were randomly assigned to 15 weeks continuous treatment with nicotine patch (escalated to 7 mg), identical masked placebo patch or no patch. Changes in lesion area and elevation from baseline through six follow-up visits, by direct measurement and by two independent readers using digital photographs of the lesions, were compared using non-parametric and regression methods. Changes in longitudinal levels of HHV8 antibodies and DNA in blood cells were similarly assessed. There were no systemic or serious adverse events, and compliance was good. One patient resumed smoking and discontinued patches, and two patients withdrew at week 12 for unrelated indications. Six (29%) of the remaining 21 suspended use of patches to relieve local skin irritation; four of these six completed the trial at reduced dose. Treatment assignment was not associated with significant or consistent changes in cKS lesion area or elevation, HHV8 viral load or antibodies. Transdermal nicotine and placebo patches caused no serious toxicities but had no demonstrable effect on nodular cKS lesions or HHV8 levels.

Ketosis-Prone Type 2 Diabetes Mellitus and &lt;emph type="ital"&gt;Human Herpesvirus 8&lt;/emph&gt; Infection in Sub-Saharan Africans

An atypical form of type 2 diabetes mellitus (DM-2) is revealed by ketosis (ketosis-prone type 2 diabetes mellitus), frequently occurring in individuals who are black and of African origin, and characterized by an acute onset requiring transient insulin therapy. Its sudden onset suggests precipitating factors. To investigate the putative role of human herpesvirus 8 (HHV-8) in the pathogenesis of ketosis-prone DM-2. A cross-sectional study in which antibodies were searched against latent and lytic HHV-8 antigens using immunofluorescence. The presence of HHV-8 in genomic DNA was investigated in 22 of the participants at clinical onset of diabetes. We also tested whether HHV-8 was able to infect human pancreatic beta cells in culture in vitro. The study was conducted at Saint-Louis University Hospital, Paris, France, from January 2004 to July 2005. All participants were black and of African origin: 187 were consecutive diabetic patients of whom 81 had ketosis-prone DM-2 and 106 had nonketotic DM-2, and 90 individuals were nondiabetic control participants who were matched for age and sex. Seroprevalence of HHV-8 and percentage of patients with HHV-8 viremia at onset in ketosis-prone DM-2. HHV-8 antibodies were found in 71 patients (87.7%) with ketosis-prone DM-2 vs 16 patients (15.1%) with nonketotic DM-2 (odds ratio, 39.9; 95% confidence interval, 17.1-93.4; P < .001) and 36 of the control participants (40.0%) (odds ratio, 10.7; 95% confidence interval, 4.9-23.4; P < .001). HHV-8 in genomic DNA was present in 6 of 13 patients with ketosis-prone DM-2 tested at acute onset and in 0 of 9 patients with nonketotic DM-2. HHV-8 proteins were present in human islet cells that were cultured for 4 days in the presence of HHV-8. In this preliminary cross-sectional study, the presence of HHV-8 antibodies was associated with ketosis-prone DM-2 in patients of sub-Saharan African origin. Longitudinal studies are required to understand the clinical significance of these findings.