Review of the distribution of Kaposi's sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi's sarcoma (original) (raw)

Kaposi's sarcoma associated herpesvirus in a rural Ugandan cohort: 1992-2008

The Journal of infectious diseases, 2017

The prevalence and titres of antibodies against Kaposi's sarcoma associated herpesvirus (KSHV) in rural Africa are not completely understood, nor are their trends over time in populations in which HIV is also endemic. We examined prevalence, titres, temporal trends and determinants of anti KSHV antibodies in each of three time periods (1990-91, 1999-2000 and 2007-2008) within a long-standing, rural population-based cohort in southwestern Uganda. For each period, we measured antibodies to the K8.1 and ORF73 KSHV antigens in ~ 3000 people of all ages (1:1 sex ratio). In all periods, KSHV prevalence increased rapidly through childhood to ~ 90% by age 15 years, plateauing at ~ 95% thereafter. Similarly, antibody titres, particularly against the lytic antigen K8.1, were amongst the highest seen and increased significantly with age, suggesting sustained viral replication in this population. Male sex was also independently associated with higher prevalence, whereas HIV co-infection was...

Kaposi sarcoma-associated herpesvirus (KSHV) seroprevalence in population-based samples of African children: evidence for at least 2 patterns of KSHV …

Journal of Infectious …, 2009

Background. Kaposi sarcoma-associated herpesvirus (KSHV) infection is endemic among adult populations in Africa. A prevailing view is that childhood transmission is primarily responsible for the high seroprevalence of KSHV among adults that is observed throughout the continent. However, few studies have directly examined children, particularly in locations where KS is not commonly endemic. Methods. Participants were children aged 1.5-8.9 years, including 427 children from a population-based sample in South Africa, 422 from a population-based sample in Uganda, and 567 from a clinic-based sample in Uganda. All serum specimens were tested by the same laboratory for KSHV antibodies with use of 2 enzyme immunoassays (against K8.1 and ORF65) and 1 immunofl orescence assay. Results. KSHV seroprevalence was 7.5%-9.0% among South African children and was not associated with age. In contrast, in the Ugandan population-based sample, KSHV seroprevalence increased from 10% among 2year-old children to 30.6% among 8-year-old children (). In the Ugandan clinic-based sample, sero-P ! .001 trend prevalence increased from 9.3% among 2-year-old children to 36.4% among 8-year-old children (). P ! .001 trend Conclusion. Two distinct relationships between age and KSHV infection among children imply that KSHV transmission among children is not uniform throughout Africa and is therefore not always responsible for the high seroprevalence observed in adults. There are at least 2 patterns of KSHV transmission in Africa. Since its identificatio in 1994 [1], Kaposi sarcomaassociated herpesvirus (KSHV), or human herpesvirus 8, has been established as the etiologic agent of KS [2-6]. Consistent with its etiologic role, KSHV seroprevalence has generally, where studied, paralleled that of

The sero-epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in adults with cancer in Uganda

International Journal of Cancer, 2002

The association between the prevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV-8]) and sociodemographic, sexual, reproductive and lifestyle factors was investigated in a study of adults presenting with cancer at hospitals in Kampala, Uganda. Patients were interviewed and tested for antibodies against KSHV (using an indirect immunofluorescent assay). Data are presented for 607 patients who were not infected with the human immunodeficiency virus-1 (HIV) and who did not have Kaposi's sarcoma (these included people with cancers of the uterine cervix [140], breast [58], liver [41], oesophagus [36], lymphoma [47], other cancers [285] and benign tumours [63]). The prevalence of anti-KSHV antibodies was 50% overall (302/607) and did not differ significantly by cancer site (p ‫؍‬ 0.4) or sex (p ‫؍‬ 0.2), but increased linearly with age from 35% in those under 25 years to 55% in those 45 years and over (2 trend [1 df] ‫؍‬ 9.1; p < 0.001). After adjusting for age and sex, anti-KSHV antibodies were more common in tribal groups other than the Baganda tribe (54% vs. 45% among Baganda; p ‫؍‬ 0.02), but there was no significant (p > 0.05) variation in seroprevalence by district of birth, region of residence prior to becoming ill or various measures of wealth. The prevalence of anti-KSHV antibodies decreased with increasing number of older siblings, although this may be due to chance (p ‫؍‬ 0.05) and was higher among people who had ever been married (p ‫؍‬ 0.03). There was no significant association (p > 0.05) between the presence of antibodies against KSHV and other sexual and reproductive factors. Among the 302 patients with anti-KSHV antibodies, the proportion with high titres increased linearly with increasing age (p ‫؍‬ 0.03) and was higher among those reporting having had a blood transfusion (p ‫؍‬ 0.03). In conclusion, in this population in Uganda, where KSHV is relatively common, the prevalence of anti-KSHV antibodies increased with age but showed little association with nearly 50 other factors studied.

Risk factors for Kaposi's sarcoma: A case-control study of HIV-seronegative people in Uganda

International Journal of Cancer, 2003

As part of a larger investigation of cancer in Uganda, we conducted a case-control study of Kaposi's sarcoma in human immunodeficiency virus-1 (HIV)-seronegative adults presenting at hospitals in Kampala. Cases comprised 117 HIV-seronegative patients with Kaposi's sarcoma and controls comprised 1,282 HIV-seronegative patients with a provisional diagnosis of cancer other than Kaposi's sarcoma. Study participants were interviewed about social and lifestyle factors, tested for HIV and, if there was sufficient sera, for antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 [HHV8]), using an immunofluorescent assay. Independent effects of these factors were identified using unconditional logistic regression, after adjusting for age group (<30, 30 -44, 45؉) and sex. Antibody status for KSHV was available for 68% (80) of cases and for 45% (607) of controls. Among cases, 78% (91) were male and 57% (66) were over the age of 35. Cases were more likely than controls to be from tribal groups other than the Baganda (p ‫؍‬ 0.05), to have higher household incomes (p ‫؍‬ 0.003), to have left their home region at younger ages (p < 0.001), to own goats or pigs (p ‫؍‬ 0.02) and to rarely or never use shoes (p < 0.001). Similar results were obtained when analyses were restricted to cases and controls with anti-KSHV antibodies. The seroprevalence of KSHV was 79% (63/80) in those with Kaposi's sarcoma as compared to 50% (302/607) in those without ( 2 heterogeneity (1 df) ‫؍‬ 21.0; p < 0.001) and the risk of the tumour increased with increasing anti-KSHV antibody titres ( 2 trend (1 df) ‫؍‬ 29.7; p < 0.001). The risk of Kaposi's sarcoma is clearly linked to antibody status for KSHV, but it would seem that in Uganda other factors are also important in the development of the tumour.

Comparison of Kaposi sarcoma risk in HIV-positive adults across five continents: a multiregional multicohort study

Clinical Infectious Diseases

Background. We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods. We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results. We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by ≥95% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa.

Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

Clinical Infectious Diseases, 2017

Background. We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods. We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs). Results. We included 208 140 patients from 57 countries. Over a period of 1 066 572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100 000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were <50 cells/µL, the KS risk was halved in South Africa (aHR, 0.53; 95% CI, .17-1.63) but reduced by ≥95% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts are essential to further reducing KS incidence worldwide, but additional measures might be needed, especially in Southern Africa.