Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma

Whitby, Denise; Boshoff, Chris; Hatzioannou, T.; Weiss, Robin A.; Schulz, Thomas F.; Howard, Mark; Brink, Nicola S.; Tedder, Richard S.; Tenant‐Flowers, Melinda; Copas, Andrew; Suggett, F; Aldam, D.; Denton, A; Miller, R F; Weller, I. V. D.

doi:10.1016/s0140-6736(95)91619-9

Cited by 798 publications

(499 citation statements)

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“…Thus, the virus has been found in all types of KS, and infection with the virus seems to precede development of the disease (Chang et al, 1994;Moore and Chang, 1995;Whitby et al, 1995). In addition, recent serological studies have indicated that KS incidence correlates with the seroprevalence of human herpesvirus-8 Simpson et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

High incidence of classical Kaposi's sarcoma in Iceland and the Faroe Islands

Hjalgrim

Tulinius²,

Dalberg³

et al. 1998

Br J Cancer

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Summary We have examined the incidence of non-AIDS-related Kaposi's sarcoma in Iceland and the Faroe Islands . In Iceland, 19 cases, nine in men and ten in women, were identified, and in the Faroe Islands four cases in men and three cases in women were found. This corresponded to surprisingly high incidence rates. In men, world standardized rates (per 100 000 person-years) were 0.4 and 0.6 in Iceland and the Faroe Islands, respectively, and for women, the figures were 0.3 (Iceland) and 0.5 (the Faroe Islands). These are among the highest rates ever reported. No explanation for the high rates of Kaposi's sarcoma in these two North Atlantic communities could be identified.Keywords: Kaposi's sarcoma; Iceland, Faroe Islands; epidemiology From an increasing number of epidemiological studies it has become evident that the incidence of classical Kaposi's sarcoma (KS) differs considerably between Caucasian populations. Accordingly, within Europe alone, reported annual rates per 100 000 persons have varied from 2.43 and 0.77 in Sardinian men and women, respectively, in the period 1977-91, to 0.014 in both men and women in the UK in the period (Grulich et al, 1992;Cottoni et al, 1996).The pronounced geographical gradient in incidence of classical KS in Europe, with high rates observed in the Mediterranean area and low rates in northern areas, is in accordance with other studies suggesting a disproportionately high number of persons of southEuropean descent among patients with classical KS even in nonMediterranean countries (DiGiovanna and Safai, 1981;Grulich et al, 1992;Kaldor et al, 1994;Hjalgrim et al, 1996a). However, in a recent study of classical KS in four Nordic countries (Sweden, Norway, Finland and Denmark) before the AIDS epidemic, we reported that highly significant variation in incidence amounting to eightfold in women and 13-fold in men may also exist between four ethnically very similar, neighbouring populations (Hjalgrim et al, 1996b). As this variation could not be attributed to any known risk factor for classical KS, including proportion of immigrants from high-risk areas, transplantations, diagnostic or registrational procedures, it may suggest the existence of an environmental factor of significance for the development of KS (Hjalgrim et al, 1996b).Intrigued by the variation in KS incidence between these four countries, we ascertained the incidence of classical KS in two other geographically distinct Nordic populations, Iceland and the MATERIAL AND METHODS Case-ascertainment proceduresThe Icelandic Cancer Registry has registered KS separately since its establishment in 1955. For the purpose of the present study, all reports of KS in the registry in the period until 1979 were identified, and the original histological specimens were reviewed by one of us (SH) to confirm the diagnosis. The limitation of the study period was applied to avoid misclassification of cases of AIDSrelated KS, because AIDS diagnoses are not recorded by the registry. Although attempts have been made to initiate continuous canc...

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Section: Discussionmentioning

confidence: 99%

High incidence of classical Kaposi's sarcoma in Iceland and the Faroe Islands

Hjalgrim

Tulinius²,

Dalberg³

et al. 1998

Br J Cancer

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“…The levels of antibodies to KSHV are higher in regions of Africa where endemic KS is more common (detailed references in ref 68) and high KSHV antibody levels in Africa strongly correlate with increased virus shedding in saliva [49,69]. Taken together with the observation that increased KSHV load in peripheral blood is associated with KS development [63], it is therefore possible that environmental or genetic factors promoting the lytic replication of KS serve as additional co-factors which are required for the development of KS. The clinical observation that KS can develop in areas of traumatized skin (Koebner phenomenon) [70], together with in vitro findings that inflammatory cytokines may increase KSHV replication [71], provide circumstantial evidence that inflammation triggered by trauma or perhaps other infectious agents could represent one possible co-factor.…”

Section: Epidemiological Evidence Of a Causative Associationmentioning

confidence: 80%

“…In the case of KS, (i) the regular detection of KSHV genomes in all clinical variants of KS (classic, endemic, transplant, AIDS-associated) (detailed references in refs 9 and 58), (ii) the presence of KSHV in the endothelial and spindle cells, the neoplastic component of KS lesions [59][60][61][62] (see Figure 2 for an example), combined with (iii) epidemiological prospective cohort studies showing that, among HIV-infected gay men, the detection of KSHV DNA in peripheral blood [63,64] and the seroconversion to KSHV [54,55,65,66] are strongly predictive of the future development of KS, provide conclusive evidence for the essential role of KSHV in the pathogenesis of KS. At the same time, KSHV only very rarely leads to the development of 'classic' KS in immunocompetent individuals (population-based incidence rates for classic KS in regions of southern Italy with a KSHV seroprevalence of 20-30% among blood donors are only in the range of 1-3/100 000); classic KS is markedly more common in elderly males than in females, in spite of similar seroprevalence rates for men and women [40,41] (further references in refs 9, 43, and 58); and endemic KS (the clinically more aggressive variant of HIV-negative KS seen mainly in Africa) is found in east/central Africa in spite of similarly high seroprevalence rates in other parts of subSaharan Africa [67].…”

Section: Epidemiological Evidence Of a Causative Associationmentioning

confidence: 99%

The pleiotropic effects of Kaposi's sarcoma herpesvirus

Schulz

2005

The Journal of Pathology

156

143

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Kaposi's sarcoma herpesvirus (KSHV), or human herpesvirus 8 (HHV8), is an essential factor in the pathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Case reports suggest an occasional involvement in bone marrow hypoplasia and haemophagocytic syndrome, but other disease associations are unconfirmed or controversial. KSHV-associated disease is of particular importance in immunosuppressed individuals, in particular in patients with HIV infection and transplant recipients. KSHV establishes a latent infection in the majority of infected cells in KS, MCD, and PEL, but lytic replication occurs in a small fraction of infected cells. Viral proteins expressed during both the latent and the lytic phase of the viral life cycle contribute to the pathogenesis of KSHV-associated diseases.

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“…Several studies have examined this by detecting viral DNA and seroconversion prior to KS development. In HIV-1-positive patients followed before and after onset of KS, it was observed that patients with KSHV viral DNA at study entry or any time prior to KS were significantly more likely to develop KS than those who were negative for viral DNA prior to KS (Moore et al, 1996c;Whitby et al, 1995). Similarly, in HIV-1-infected patients, those that developed KS were significantly more likely to be KSHV seropositive prior to the onset of KS than those that never developed KS (Gao et al, 1996a;Melbye et al, 1998).…”

Section: A Viral Etiology In Ksmentioning

confidence: 97%