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

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

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)–associated Kaposi’s sarcoma in both adults and children. Our findings of 8 A, 1 B, 14 C, and 2 E subtypes showed high HHV-8 diversity in these patients and association between E genotype and KS development. The figures make no assumptions about incidence rates which may increase due to the further introduction of tobacco and a more westernized lifestyle. Overall HHV-8 seroprevalence was 60%, increasing with age. There are also (primarily retrospective) data suggesting a beneficial effect of HAART on KS, but some evidence for KS as a manifestation of immune reconstitution inflammatory syndrome. The epidemiology of HHV8 and KS in Iran needs further evaluation. Human herpesvirus-8 (HHV-8) or Kaposi’s sarcoma associated herpesvirus (KSHV) is a Gammaherpesvirus, first identified in a tumor biopsy from an AIDS-related Kaposi’s sarcoma (KS) [1].

The KSHV+ group gained a similar number of cells at 6- (difference of 10 cells/mm3, 95% CI: −11–31), 12- (3 cells/mm3, 95% CI: −19–25) and 18-months (24 cells/mm3, 95% CI: −13–61) compared to the KSHV− group. Human Herpesvirus-8 (HHV-8) infection is associated with three human malignancies: Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD) [1]. AIDS KS samples were primarily A1, A4, and C3 variants. HHV-8 is considered to be the etiological agent of all forms of Kaposi’s sarcoma [2], and has been consistently associated with two types of lymphoproliferative disease, namely body cavity-based lymphoma [17] as well as multicentric Castelman’s disease [16,18]. Seroepidemiological surveys have shown that HHV-8 infection is not ubiquitous [19]. HBV infection is associated with HHV8 infection but not with HCV infection. Several studies have been performed in some Middle Eastern countries.

In Israel seropositivity of HHV-8 has been ranging from 8.4% to 22% in healthy individuals [24,25]. HHV-8 infection was determined by nested PCR to obtain a 220-bp (variable region [VR] 1-inner fragment) and a 240-300-bp (VR2-inner) fragment of the ORF-K1 (13). Few studies have been performed on the HHV-8 distribution and incidence of Kaposi’s sarcoma in Iran. PMID 7992043. A systematic review of the published articles from January 1980 to December 2010 was conducted to assess the seroprevalence of HHV-8 and the incidence of KS in Iran. Similarly, 75 percent of Kaposi’s sarcoma (associated with human herpesvirus 8, or HHV-8), the most common cancer in East African adults, can be treated for less than $720 a case. Data from the National Cancer Registry of Iran have reported that KS is the rarest cancer among Iranians [27].

The inclusion criteria were not restricted by study size, population race or publication language, date or type. In the USA, Chinese-Americans comprise the majority of NPC patients, together with workers exposed to fumes, smoke and chemicals, implying a role for chemical carcinogenesis. However, routes of HHV-8 transmission and factors associated with increased risk of HHV-8 acquisition have yet to be delineated. Using electricity 20 years ago was protective. There were no published reports about AIDS-KS in Iran. Figure 2. The regions with the highest incidence are Africa, where KS represents 3% to 9% of all cancer cases [31], Mediterranean and Eastern European areas, with specific geographic foci in Italy, Greece, and Israel [4,5].

Only wells that contained cells with punctate nuclear fluorescence were scored as a positive result for HHV-8 antibody. Frozen whole blood specimens were retrieved from a repository of blood samples obtained from voluntary first time blood donors who tested positive for HHV-8 antibodies using a whole cell ELISA. The rate of chronic kidney disease and renal transplantations has increased during the last two decades in Iran [34-36]. About 1.14-6% (mean = 2.8%) of Iranian renal transplant recipients develop cancer lesions, mostly skin cancers (Table ) [37-43]. These findings are consistent with other report in Middle Eastern countries. The prevalence of all malignancies in renal transplant recipients was 1.9% in Pakistan [44], 4% in Turkey [45], 6.8% in Saudi Arabia [46], 4.8% in Kuwait [47], 5.9% in Iraq [48], and 1.7% in Jordan [49]. In South Africa, our design allowed for a comparison between urban and rural settings, but we found no differences.

Seroprevalence of Human herpesvirus 8 (HHV-8) and incidence of Kaposi's sarcoma in Iran
At the same time, HHV-8 seroprevalence appears to be lower than that of other herpesviruses that are mainly transmitted through saliva, such as HHV-6, EBV, and CMV. The findings in the current study also highlight the limitations of using a cross-sectional sero-epidemiological study to demonstrate HHV8 transmission. In other countries of this region, the figures were 0.55% in Jordan [49], 3.2% in Turkey [56] and 4.9% in Saudi Arabia [46]. The incidence of KS was 0.7% [56], 1.7% [57] and 3.9% [58] among renal transplant recipients in Taiwan, Greece and South Africa, respectively. Therefore, the incidence of KS following kidney transplantation varies significantly in different geographic areas [59], and this is supporting the theory of ethnic or environmental factors in its pathogenesis. An altered version of APRF-wt, APRF-mut., containing changes within the core STAT binding sequences was used in competition assays with the APRF-wt probe. The KS incidence among Iranian transplants recipients had a peak during the first 2 years post transplantation.

The time interval between transplantation and onset of KS was relatively early compared to other skin tumors. The sensitivity (LOD and LOQ) of the HHV-8 ORF26 assay was 10-fold greater than the HHV-8 ORF73 qPCR assay but the CV was much higher (CV = 0.7740) with LOD of 5.61×102 ± 5.46×102 copies/μL TE Buffer (Cq = 35.51 ± 1.54) and LOQ of 3.01×102 ± 2.43×102 copies/μL TE Buffer (Cq = 36.78 ± 2.02) (Table 3). The mean-age of Iranian renal transplants developing KS is below 50 years, which is lower than that of patients with classic Kaposi’s sarcoma (50-79 years). This finding is consistent with data reported by other studies on renal transplant patients from different regions of the world [30,32,45,60,61]. About 90% percent of transplant recipients affected by KS present cutaneous or mucosal lesions or both types. This is in contrast to the appreciable amount of seropositivity found among virginal and monogamous women. The TKS samples were all collected at the National Cheng Kung University Hospital, Taiwan, Republic of China (64).

In agreement with these worldwide studies, 80% of Iranian transplant recipients with KS developed cutaneous lesions. Visceral involvement was observed in 20% of patients (Table ) [37,38,40,53,54]. Most cases of post-transplantation KS develop as a result of viral reactivation, since more than 80 percent of transplant recipients with KS are seropositive for HHV-8 before transplantation [34,64]. Renal recipient patients who were seropositive for HHV-8 before transplantation, have a risk to develop KS of 23% to 28% that is significantly higher compared to risk of 0.7% in patients who are seronegative before receiving a kidney transplant [32-34,65]. Few serological survey on HHV-8 infection have been performed in Iran [55,66]. Classic KS is three times more frequent in males than in females [31]. Culture supernatants were collected at different time points and analyzed for p24 release.

ORF-K1 of KSHV from tissue samples of 28 KS patients was amplified and sequenced. All sera were tested for the presence of antibodies against HHV-8 lytic antigens by HHV-8 IgG EIA and by HHV-8 IgG IFA commercial kits (Biotrin, Ireland) as for manufacturer’s instructions and each sample defined as “positive” if tested positive to both assays. Since it is not easily visible at these other sites it may often be missed. The specificity of EIA and IFA was 93% and 94%, respectively. Among the 256 healthy Iranian blood donors (242 males and 14 females with mean age of 38 years, range 18-60 years) only 5 (2%, CI 95% = 0.003-0.03), including 4 males and one female, were positive for HHV-8 antibodies. No increases over time were observed in Nigeria and South Africa (Parkin et al. ) labeled with 32P as a probe as described previously (41) with the modification that the gel was dried before denaturation and neutralization.

To this end, we used an expression vector containing the human CD2 promoter, which primarily targets gene expression to hematopoietic cells ( A). tirucalli and other Euphorbiaceae, need to be further elucidated. Overall, there was a statistically significant higher risk of HHV-8 seropositivity in haemodialysis (OR = 10.24, 95% CI: 3.5 – 32.1) and HIV (OR = 42.27, 95%CI: 12.7 – 150) patients compared to blood donors, although several variables between the three enrolled groups cannot be excluded. Low prevalence of HHV-8 in blood donors may indicate that virus is not widespread in this population; however, this study is not sufficient to determine the extrapolation of the true prevalence of HHV-8 in Iranian healthy population. Blood donors in above mentioned study were only from Tehran and it may be representative of the prevalence of HHV-8 in Tehran rather than Iran. The frequency of different K1 types variants observed in the 65 Zimbabweans in our study and in 48 Ugandan patients from previous studies (Cook et al. Bars show the seroprevalence …

It is better that future study populations be general population rather than blood donors to estimate more relevant prevalence of HHV-8 infection. In another study by Ahmadpoor et al., 100 serum from Iranian renal transplant recipients (60 male, 40 female) were analyzed for antibodies against the latent nuclear antigen of HHV-8 [66] and 25% tested seropositive for HHV-8 (Table ). The mean age was 41.1 years (range, 17-74 years) and there was a statistically significant difference in HHV-8 seropositivity among recipients older than 55 years (P = 0.02). Seropositivity to KSHV was significantly different amongst the municipal regions, ranging from 35.4% in Tshwane to 49.0% in the West Rand (P4df = 0.0015) (Table ). There were no significant differences in HHV-8 seropositivity regarding sex. Venous blood was collected from all study participants at every visit, and plasma was separated and stored. The risk of HHV8 infection in transplanted patients is significantly higher (OR = 16.73, 95% CI: 5.8 – 51.8) compared to blood donors, although different HHV8 detection methods were used (Table ).

Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P, editors. Different rates of HHV-8 infection have been reported in various populations in the world. 18. In India a prevalence of 3.7% and 2.3% has been reported in healthy individuals and HIV positive patients, respectively [68]. In one study from Saudi Arabia the seroprevalence of HHV-8 in healthy Saudi national’s people was reported to be 1.7% [26]. In Europe, the prevalence of HHV-8 was found to be lowest in Spain or Greece (6%-8%) and highest in Italy (20.4%) [71-75]. Only ESS values of > 250 were accepted.

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