Human herpesvirus-8 and other viral infections, Papua New Guinea.
ABSTRACT We studied residents of remote villages and the capital (Port Moresby) of Papua New Guinea to determine the distribution of human herpesvirus-8 (HHV-8) infection. Our data suggest that HHV-8 has been endemic on the island for a long time and that the epidemiologic pattern of HHV-8 is more similar to that of herpes simplex virus-2 than hepatitis C virus.
Article: Kaposi's sarcoma: breeding ground of herpesviridae - A tour de force over viral evolution (review).[show abstract] [hide abstract]
ABSTRACT: After reviewing the molecular biological basis of prominent theories for the integration of viruses into the earliest forms of living matter, an account is given on the immunoevasive strategies viruses have had to acquire in order to secure their existence against the most sophisticated anti-viral defensive mechanisms evolving in their hosts. Herpes-viridae and Kaposi's sarcoma illustrate the complexity of host-virus relationship. In following the evolutionary steps of simians and hominoids to Homo, it becomes evident that: a) Epstein-Barr virus evolved in Africa and its ancestral viruses are present in cercopithecines and hominoids; b) human herpes-virus-8-related viruses are present in macaques, in S. American primates and in Homo but such isolates from the great apes are missing. Thus interspecies transfer occurred from lower monkeys to Homo but when and at what geographical location? The human retrolentiviruses also jumped species barriers: this occurred recently in Africa, from great apes (chimpanzee and bonobo) to Homo sapiens (except when HIV-2 was transferred to mankind from sooty mangabeys). The matter is further complicated by the long coevolutionary cooperative interactions between herpes- and retrolentiviruses. Of pathological entities suspected to be etiologically affected by such complex viral cooperation, the origin of Reed-Sternberg cells of Hodgkin's disease is singled out for critical analysis. In this article the senior author summarizes his own 52 years of studentship in virology.International Journal of Oncology 05/1999; 14(4):615-46. · 2.40 Impact Factor
Nature 09/2000; 407(6801):151-152. · 36.28 Impact Factor
Article: A chimpanzee rhadinovirus sequence related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8: increased detection after HIV-1 infection in the absence of disease.[show abstract] [hide abstract]
ABSTRACT: To look for a virus related to Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) in chimpanzees and to investigate phylogenetic and biological similarities to KSHV. Peripheral blood mononuclear cell (PBMC) DNA samples from chimpanzees (Pan troglodytes troglodytes) were screened with newly designed consensus oligonucleotide primers for the DNA polymerase gene of KSHV-related gamma2-herpesviruses (rhadinoviruses). Samples from HIV-1-infected and -uninfected chimpanzees were screened with virus-specific primers. Antibodies to KSHV structural and latent antigens were measured by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Western blot. We identified 972 base pairs (bp) of a new viral DNA polymerase sequence with 81.6% (nucleotides) and 93.2% (protein) identity to that of KSHV/HHV8. It was detected in 15/37 (41%) animals experimentally infected with HIV-1, but only in one out of 30 uninfected animals (P<0.001). Antibodies were found by immunofluorescence to structural, but not latent, KSHV antigens in nearly all HIV-1-infected and uninfected animals. Like man and two other Old World primate species, chimpanzees harbour a virus closely related to KSHV/HHV8, termed Pan troglodytes rhadinovirus-1 (PtRV-1). Like KSHV, PtRV-1 is more easily detected by polymerase chain reaction (PCR) in the PBMC of HIV-1-infected than of HIV-1-uninfected individuals, suggesting increased viral load. Despite the close phylogenetic relationship and biological similarities between KSHV and PtRV-1, Kaposi's sarcoma (KS) has not been reported in HIV-1-infected chimpanzees. PtRV-1 may lack some of the pathogenic determinants of KSHV, or humans and chimpanzees may differ in how they control the infection with their respective rhadinoviruses.AIDS 12/2000; 14(17):F129-35. · 6.24 Impact Factor
Vol. 7, No. 5, September-October 2001
Emerging Infectious Diseases
Human Herpesvirus-8 and Other Viral Infections,
Papua New Guinea
Giovanni Rezza,* Robert T. Danaya,† Theresa M. Wagner,* Loredana Sarmati,‡
Ifor L. Owen,§ Paolo Monini,* Massimo Andreoni,‡ Barbara Suligoi,*
Barbara E nsoli,* and E doardo Pozio*
*Istituto Superiore di Sanità, Rome, Italy; †Port Moresby General Hospital, Port Moresby, Papua New
Guinea; ‡Tor Vergata University, Rome, Italy; and §National Veterinary Laboratory, Department of
Agriculture and Livestock, Boroko, Papua New Guinea
We studied residents of remote villages and the capital (Port Moresby) of
Papua New Guinea to determine the distribution of human herpesvirus-8
(HHV-8) infection. Our data suggest that HHV-8 has been endemic on the
island for a long time and that the epidemiologic pattern of HHV-8 is more
similar to that of herpes simplex virus-2 than hepatitis C virus.
The distribution of human herpesvirus-8 (HHV-8) infec-
tion and its main clinical consequence, Kaposi sarcoma (KS),
appears to vary greatly by geographic area; however, its glo-
bal distribution has not been determined (1). HHV-8-related
viruses have been found not only in lower African and Asian
simians and South American primates (2) but also in great
apes, such as chimpanzees (3,4). Although the precise time of
divergence from related viruses of nonprimates is not
known, evidence indicates that interspecies transmission to
humans occurred on an evolutionary time scale of tens of
thousands of years. HHV-8 seroprevalence studies of remote
populations from different areas of the world may contribute
to understanding the geographic origin and spread of the
Paralleling the distribution of KS, HHV-8 rates are high
in central Africa and low in the United States and Europe,
except for Mediterranean countries, which have intermedi-
ate rates (1). Little information is available about the distri-
bution of HHV-8 infection and KS in indigenous populations
of Australasia. HHV-8 seroprevalence appears to be low in
countries of Southeast Asia, such as Malaysia (5), where KS
is considered very rare. In Papua New Guinea, little infor-
mation is available about KS, although cases have been
reported among children, suggesting that it does occur,
although it is probably relatively uncommon (6).
To verify whether HHV-8 infection is endemic in Papua
New Guinea and to determine seroprevalence rates, we stud-
ied sera from Melanesian residents of remote villages in
Western Province, Papua New Guinea. In Port Moresby, the
capital, Melanesian residents were studied as a reference
population group. Serologic tests for other viruses were also
done to characterize the study population and explore
modalities of transmission of HHV-8 infection by comparing
the patterns of these infections with that of HHV-8.
The Melanesian study participants live in six remote vil-
lages (total population 524) in a flat, rural area called the
Bensbach in southwestern Papua New Guinea. Participants
from these villages were recruited for a study on trichinello-
sis, a parasitic infection recently reported in this area; at
least 5 mL of venous blood had been collected from each par-
ticipant in 1999, and these specimens were separated and
treated as described elsewhere (7). Participants from Port
Moresby were teachers and students at a local high school.
For serologic testing for antibodies to HHV-8 and other
viruses, serum samples were stored at –20°C in the laborato-
ries of Tor Vergata University, Rome, Italy. As described
(8,9), antibodies to lytic and latent antigens of HHV-8 were
detected by using two immunofluorescence assays based on
the BCBL-1 cell line. Samples reactive at >1:20 dilution were
Antibodies to herpes simplex 2 (HSV-2) were detected by
an immunoglobulin (Ig) G-based type-specific enzyme-linked
immunosorbent assay (ELISA; Gull Laboratories, Inc., Salt
Lake City, UT). An ELISA was also used to detect antibodies
to the Epstein-Barr virus (EBV) gp125 viral capsid antigen
(Gull Laboratories, Inc.). Antibodies against hepatitis C
virus (HCV) were detected by a third-generation enzyme
immunoabsorbent assay (Innotest HCV Ab III, Innogenetics,
Seroprevalence ratios for each of the four viruses were
calculated to assess differences stratified by age group, sex,
and geographic area. These associations were evaluated by
the chi-square test and the Cochran-Armitage test for trend.
The viral correlates of HHV-8 infection were evaluated by
estimating crude and adjusted prevalence ratios and their
associated p-values by univariate and multivariate log-bino-
mial linear regression analysis (GENMOD procedure in
SAS, version 6.12). The relationship between antilytic and
antilatent antibodies was assessed by calculating the propor-
tion of antilatent positive persons by level of antilytic titer.
Sera from 150 participants, 56 from the villages and 94
from Port Moresby, were studied. Fifty-one (34%) were
female; the proportion of females was the same among vil-
lage (19 [34%] of 56) and urban (32 [34%] of 94) residents.
Address for correspondence: Giovanni Rezza, L aboratory of E pide-
miology and Biostatistics, Istituto Superiore di Sanità, Viale Regina
E lena, 299, 00161, Rome, Italy; fax: 0039–06-49387210; e-mail:
Emerging Infectious Diseases
Vol. 7, No. 5, September-October 2001
Median age was 22.5 years; residents of the remote area
were older (median 35 years, range 15 to 85) than those
recruited in the town (median 18 years, range 16 to 49
Seroprevalence data for HHV-8 and the other viruses
were stratified by age, sex, and area of residence (Table 1).
HHV-8 and HSV-2 seroprevalence tended to increase with
age. These increases, while different for each virus, were
similar for urban and rural residents (for HHV-8, from 18.1%
for those <25 years of age to 40.0% for those >35 in the city
and from 18.2% to 41.4% in the villages; and for HSV-2, from
1.4% to 33.3% in the city and from 18.2% to 39.3% in the vil-
lages). Overall, age was significantly associated with infec-
tion with both HHV-8 (test for trend p=0.01) and HSV-2 (test
for trend p=0.001). No significant difference was observed
between women and men, although HHV-8 prevalence was
slightly higher in women. HHV-8 infection was more com-
mon in rural dwellers and HCV in the capital, but the differ-
ences were not statistically significant. Rural participants
were four times more likely to be infected with HSV-2 than
those in the city (p=0.001), but this disparity was attribut-
able to the differing age distribution of the two groups. No
difference was seen in prevalence of EBV.
The analysis of serologic correlates of HHV-8 infection
showed a significant association with HSV-2 infection (Table
2). However, after data were adjusted for age and other vari-
ables, the prevalence ratio of HHV-8 infection was no longer
different from 1 for HSV-2-positive vs. -negative partici-
Of the 37 HHV-8 antilytic-positive participants, 16 had a
titer of 1:20, 10 of 1:80, 9 of 1:160, and 2 of 1:320. Ten of
these 37 also had antilatent antibodies. The proportion of
antilatent positivity changed according to the antilytic titer:
none of the 16 participants with an antilytic titer of 1:20 had
antilatent antibodies, but 2 (20%), 7 (77.7%), and 1 (50%) of
those with antilytic titers of 1:80, 1:160, and 1:320, respec-
tively, were also antilatent-positive. One antilytic-negative
participant also had antilatent antibodies, with a titer of
1:160. Because the 16 residents with an antilytic titer of 1:20
did not have antilatent antibodies and could be considered
false-positives, we repeated the analysis considering these
participants as seronegative and obtained similar results
(data not shown).
This study shows a relatively high prevalence of HHV-8
infection in Papua New Guinea; the prevalence does not
appear to differ substantially between the capital and
remote villages, suggesting that the infection has been
endemic for a long time in this region and, as reported for
other herpesvirus infections (10), can persist in small, iso-
lated population groups. This similarity between remote
rural communities and an urban center does not fully sup-
port the conclusions of a study on Amerindians of diverse
tribes, which suggested that the limited genetic pool in iso-
lated groups may permit more frequent transmission of a
virus with a low prevalence than in heterogeneous popula-
Other viral infections, such as HSV-2, EBV, and HCV,
were prevalent both in villages and the capital. In particular,
HSV-2 was more common in remote villages, but the differ-
ence was largely explained by age. EBV prevalence was as
high as expected on the basis of previous studies (12). The
prevalence of HCV antibodies was higher in Port Moresby
than in the villages; however, the difference was not statisti-
cally significant. A similar prevalence (4.1%) was found in
residents of villages in another part of Western Province
The potential association between HHV-8 and HSV-2
was nonsignificant after the data were adjusted for age.
Although seroprevalence of both infections tended to
increase with age, the presence of HSV-2-negative and HHV-
Table 1. Seroprevalence of human herpesvirus-8 and other infections, stratified by geographic area, age, and sex
E pstein-Barr virusHepatitis C virus Herpes simplex virus
Urban RuralUrbanRural UrbanRural UrbanRural
aHHV-8 = human herpesvirus-8.
bChi-square p-value <0.05, comparing age groups in rural and urban strata with reference group: <25 years.
cChi-square p-value <0.05, comparing rural with urban.
Vol. 7, No. 5, September-October 2001
Emerging Infectious Diseases
8-positive young adults suggests that HHV-8 infection is not
necessarily sexually transmitted. In particular, salivary
spread, as for EBV, may not be ruled out, as suggested by
studies conducted in isolated tribes of the New World, show-
ing high prevalence rates in children (11,14).
Some limitations and possible biases of our study should
be mentioned. First, to what extent residents of isolated vil-
lages had contacts with others is difficult to quantify.
Although government contact with the area was made early
in the 20th century, infrastructure and services remain poor,
making access difficult. There are no direct connections with
this area, which during the rainy season can be reached only
by canoe and then on foot, after a 1-hour flight from Port
Moresby. To our knowledge, only one person had worked out-
side the area before retiring to his village of origin. Second,
the differing age distribution between study participants
recruited in urban and rural areas may represent a possible
bias; however, the statistical analysis accounted for these
differences. Finally, HHV-8 prevalence might have been
overestimated if low antilytic titers were false-positive
results; however, the specificity of our assay is supported by
the high risk for KS among HIV-infected persons with low
antilytic titers (9).
In conclusion, HHV-8 infection appears to be common in
remote population groups of Papua New Guinea as well as in
Port Moresby, suggesting that the infection has been
endemic for a long time among the indigenous population of
the country. The detection of a high prevalence of HHV-8
emphasizes the need for clinical monitoring of the study pop-
ulation. The identification of the main modes of transmission
for HHV-8 and other infections may help in instituting public
health measures to control the infection.
We thank A. Pisau for assistance in the field and G. Williamson
for facilitating access to lines of communication. We also thank Drs.
M. Mecgrath and D. Ganem for providing the BCBL -1 cell line.
This study was funded in part by the Programma Ricerche
AIDS (Progetto E pidemiologia e Modelli Assistenziali, Azione Con-
certata HHV-8), Istituto Superiore di Sanità. F unds for airfares in
Papua New Guinea were supplied by the North Australia Quaran-
Dr. Rezza is a medical epidemiologist and director of the AIDS
and STD Unit, L aboratory of E pidemiology and Biostatistics, Isti-
tuto Superiore di Sanità (Italian National Institute of Health). His
research focuses on HIV, HHV-8, and other potentially oncogenic
sexually transmitted viruses.
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Table 2. Serologic correlates of human herpesvirus-8 infection,
Papua New Guinea
HCV - 35/137
E BV - 1/8
E BV +35/141
1.98 0.47 1.710.54
2.16 0.01 1.640.15
aHHV-8 = human herpesvirus-8; HCV = hepatitis C virus; E BV = E pstein-
Barr virus; HSV2 = herpes simplexvirus-2.
bPrevalence ratio, crude and adjusted for age, sex, and urban residence.