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Human Herpesvirus—8 in Peruvian Blood Donors: A Population with Hyperendemic Disease?

  1. Salim Mohanna1,
  2. Jose-Andres Portillo1,
  3. Gabriela Carriquiry1,
  4. Julio Vidal2,
  5. Juan Carlos Ferrufino3,
  6. Juvenal Sanchez4,
  7. Francisco Bravo1, and
  8. Eduardo Gotuzzo1
  1. 1Human Herpesvirus 8 and Classic Kaposi Sarcoma Working Group, Instituto de Medicina Tropical “Alexander von Humboldt,” Universidad Peruana Cayetano Heredia, Lima, Peru
  2. 2Blood Bank, Lima, Peru
  3. 3Department of Pathology, Hospital Nacional Cayetano Heredia, Lima, Peru
  4. 4Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
  1. Reprints or correspondence: Dr. Salim Mohanna, Ave. Del Parque Norte 775, Corpac-San Isidro, Lima, Peru (salim.mohanna{at}yahoo.com).
 
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Abstract

Serum samples from 128 blood donors were tested for antibodies specific for human herpesvirus—8 by an immunofluorescence assay that detects antibodies against mainly lytic antigens. An overall seroprevalence of 56.25% was found (male donors, 54.68%; female donors, 57.11%). These findings indicate that human herpesvirus—8 infection is hyperendemic in Peruvian blood donors.

Human herpesvirus (HHV)–8, also known as Kaposi sarcoma (KS) herpesvirus, was discovered in 1994 [1]. This virus is now considered to be the etiological agent of all clinico-epidemiological forms of KS, primary effusion lymphoma, and multicentric Castleman disease [2]. The spread of the virus among the human population varies widely, depending on geographic region: low HHV-8 seroprevalence rates (0%–5%) were found in northern Europe, Asia, and North America; intermediate HHV-8 seroprevalence rates (5%–35%) were reported in the Mediterranean, Eastern European, and Caribbean countries; and high HHV-8 seroprevalence rates (>50%) were detected in Central and southern Africa [2, 3].

Several seroprevalence studies performed to date in South America have focused on the groups who have increased risk of acquiring HHV-8 infection, instead of the general population or localized populations where classic KS has been described [4]. Important contributions have been made by studies involving Amerindians in Brazil, Ecuador, and French Guiana, where results have demonstrated high HHV-8 seroprevalence rates [5– 7]. In contrast, studies involving blood donors from Chile, Brazil, and Argentina have demonstrated low HHV-8 seroprevalence rates [8– 10]. In Peru, a recent retrospective study reported an overall incidence of classic KS of 2.54 cases per 10,000 patients in a national cancer center [11]. Nevertheless, the seroprevalence of HHV-8 antibodies in the general population, blood donors, or risk groups has not yet been established. The aim of the present study was to determine the seroprevalence of antibodies, IgG class, against HHV-8 lytic antigens in blood donors.

Materials and methods. Serum samples from blood donors from Hospital Nacional Cayetano Heredia (Lima, Peru) were collected during a campaign in Huaral, Peru, in May 2006. All volunteers passed the standard donor medical and behavioral screening examination. Informed consent was obtained from all volunteers, and the study was conducted in accordance with the ethical committee of Universidad Peruana Cayetano Heredia.

All volunteers included in the study were mestizos (of mixed Quechua and white ethnicity) from the city of Huaral, which is located 40 min by automobile (75 km) north of Lima. Its population is dedicated predominantly to agriculture and is classified as being at a medium or low socioeconomic level.

Serum samples in Peruvian blood banks are routinely tested for HIV-1 and HIV-2, hepatitis B virus, hepatitis C virus, human T-lymphotropic virus—1 and human T-lymphotropic virus—2, syphilis, and Chagas disease. All samples were initially stored at -20°C then tested at a 1 : 40 dilution, according to manufacturer's instructions, for antibodies specific for HHV-8 by an immunofluorescence assay (HHV-8 IFA [Advanced Biotechnologies]) that detects antibodies against mainly lytic antigens, as described elsewhere [7, 12].

Rates were compared using the χ2 test and Fisher's exact test, when necessary. Significance was defined as P < .05. The data were analyzed using SPSS software, version 9.0 (SPSS).

Results. A total of 128 serum samples were obtained from 64 men and 64 women. The mean patient age was 31.6 years (range, 18–55 years). Detectable antibodies against lytic HHV-8 antigens were found in 72 serum samples (seroprevalence, 56.25%), with clear immunofluorescent reactivity on the cells. Men and women had very similar seroprevalence rates (54.68% and 57.11%, respectively).

As is shown in table 1, HHV-8 seroprevalence was high among persons 18–24 years old (64.86%) and was decreased among persons 25–29 years old (34.61%). Seroprevalence showed its highest peak among persons 30–34 years old (68.75%) and plateaued among persons ≥35 years old (range, 50%–64.7%). No significant differences were found among age groups or sexes.

Table 1
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Table 1

Prevalence of human herpesvirus (HHV)–8 antibodies, according to age and sex.

Only 6 (8.33%) of 72 serum samples that were positive for HHV-8 were reactive to other infectious agents (5 had results positive for hepatitis B virus [i.e., were reactive to anti-hepatitis B core antigen] and 1 had results positive for syphilis); only 5 (8.92%) of 56 serum samples negative for HHV-8 were positive for hepatitis B virus (were reactive to anti-hepatitis B core antigen).

Discussion. Since the discovery of HHV-8 in 1994 [1], many epidemiologic studies have clearly demonstrated that the seroprevalence of HHV-8 in the general population varies substantially according to geographic region. This seroprevalence parallels the incidence of KS, with a few notable exceptions in certain populations [2, 4]. The present study is the first in Peru aimed at assessing the seroprevalence of HHV-8 in blood donors. The overall seroprevalence rate that we observed (56.25%) is comparable with rates observed in Africa and in some Amerindian populations in South America, where seropositivity rates averaged>50% [3]. We have reported, in a recent study [11], an overall incidence of classic KS in mestizo patients of 2.54 cases per 10,000 patients during 1946–2004 at the national cancer center in Peru [11]. This classic KS incidence and the cumulative weight of>200 well-documented cases [4, 11, 13–16] in our country correlates with the high seroprevalence observed in the present study. Several biases, such as underdiagnosis or underreporting of classic KS, especially in areas with medium-low and low socioeconomic conditions, and the fact that only cases confirmed by histological testing were included in the previous study, may have led to an underestimation of the incidence of classic KS [11].

Different studies have suggested that HHV-8 transmission may differ between those countries where the virus is endemic and those where infection is sporadic. In countries where infection is highly endemic, HHV-8 seroprevalence is very low in children <2 years of age and increases soon after that age [2, 17, 18]. The data suggest that HHV-8 is mainly transmitted among family members and close contacts via a horizontal, nonsexual route; transmission during pregnancy and through breastfeeding has a minimal role in propagating the virus [2, 18, 19]. Some other studies have suggested that sexual transmission occurs in populations in which the disease is endemic, as well [2, 20]. In countries in which the diseases is not endemic, heterosexual transmission is probably not frequent [21]. In contrast, sexual transmission is more common among men who have sex with men [17]. Many studies have demonstrated that saliva is the principal reservoir for HHV-8, whereas viral load of HHV-8 is consistently lower in peripheral blood, secretions from genital sites, and semen [2, 17, 22, 23].

On the basis of our high HHV-8 prevalence, data suggest a horizontal route of transmission. Nonsexual transmission, mainly through saliva and close interpersonal contact (especially between mother and child and among siblings)—including contact of nonintact skin or mucous membranes with blood containing secretions or saliva—could have an important role in transmission, as mentioned by other studies [12]. We observed 2 peaks in seroprevalence, at the 18–24 and 30–34-year-old age groups; in this context, it is most likely that transmission through sexual activity (or the salivary exchange associated with it) also plays a role during adolescence and adulthood, when people are most sexually active. Our results revealed no statistically significant differences between the sexes; this could be explained by the hyperendemicity of the virus. Some authors have reported an increase in HHV-8 seroprevalence in populations>40 years of age, which postulates a less-efficient immunity in elderly people that could either reactivate silent HHV-8 infection or facilitate a new HHV-8 infection. Our results revealed a plateau among persons ≥35 years old. This may be associated with our study lacking the power to demonstrate these differences, which will probably require an increased sample size to analyze. All subjects included in the study belong to medium or low socioeconomic levels. These variables (poor education and low socioeconomic status) have been linked to higher rates of HHV-8 seroprevalence [2, 7, 21]. HIV infection is very unlikely to have influenced HHV-8 seroprevalence in our blood donors, because none of them were HIV seropositive.

To our knowledge, few studies have dealt with the epidemiology of HHV-8 infection in the general population of South America. Table 2 summarizes those studies and the serologic assays that were used. In general, latent-antigen—based assays are less sensitive than lytic-antigen—based assays (80%–90% vs.>95%), and the appearance of lytic antibodies precedes that of latent antibodies [18, 28]. It is worth noting that no case of KS has been reported among Amerindians in Brazil, Ecuador, or French Guiana, despite the high seroprevalence of HHV-8 and the relatively good medical surveillance in that area. In contrast, KS has been reported in Peruvian Amerindians and mestizos. This difference could be explained by the small sizes of those Amerindian populations and by the generally low incidence of KS that is observed even in areas of high endemicity, but it also might indicate the presence of unidentified cofactors for KS in the region or some genetic predisposition [2, 4, 21]. An important issue that has major public health implications is whether blood transfusion can transmit HHV-8. Transmission by blood is a possibility that must be considered in countries of high endemicity.

Table 2
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Table 2

Human herpesvirus (HHV)–8 seroprevalence studies in the general population of South America.

In conclusion, the results presented herein indicate that HHV-8 infection is hyperendemic in blood donors from Huaral, Peru. Our data suggest a horizontal route of transmission (sexual and nonsexual). It will be important for future investigations to assess whether blood donors in other regions of Peru exhibit comparable or elevated rates of HHV-8 infection. Identification of these populations may prove helpful in improving the safety of the Peruvian blood supply, because of the oncogenic properties of the virus in some circumstances. Peru is a country with a wide spectrum of population characteristics, including differences in culture, geography, and socioeconomic level. Further local studies are planned to focus on the epidemiological features of HHV-8 infection in different groups (e.g., in Quechuas, Aymaras, and Amazonic Amerindians).

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Acknowledgments

We thank the nurses, technicians, and medical team of the blood banks from Hospital Nacional Cayetano Heredia, Lima, and Hospital of Huaral, Huaral, Peru, who participated actively in the field work. We also thank all of the members of the Human Herpesvirus 8 and Classic Kaposi Sarcoma Working Group, Instituto de Medicina Tropical “Alexander von Humboldt,” Lima, Peru, for their continuous active support.

Financial support. Facultad de Medicina “Alberto Hurtado,” Universidad Peruana Cayetano Heredia, Lima, Peru (SIDISI: 50596).

Potential conflicts of interest. All authors: no conflicts.

  • Received October 2, 2006.
  • Accepted October 23, 2006.
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  1. Clin Infect Dis. (2007) 44 (4): 558-561. doi: 10.1086/511044
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