Andreoni M, Sarmati L, Nicastri E, El Sawaf G, El Zalabani M, Uccella I, Bugarini R, Parisi SG, Rezza G. Primary Human Herpesvirus 8 Infection in Immunocompetent Children. JAMA. 2002;287(10):1295-1300. doi:10.1001/jama.287.10.1295
Author Affiliations: Department of Public Health, University of Tor Vergata (Drs Andreoni, Sarmati, Uccella, and Parisi), Istituto Nazionale per le Malattie Infettive, IRCCS Lazzaro Spallanzani (Dr Nicastri), AIDS and STD Unit, Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità (Drs Bugarini and Rezza), Rome, Italy; and Medical Research Institute, Alexandria University, Alexandria, Egypt (Drs El Sawaf and El Zalabani).
Context Human herpesvirus 8 (HHV-8) infection causes Kaposi sarcoma and lymphoproliferative
disorders in immunosuppressed adults. Its manifestations in immunocompetent
hosts are unknown.
Objectives To determine whether HHV-8 primary infection is symptomatic in immunocompetent
children and to identify the epidemiological and virological correlates of
Design and Setting Prospective cohort study conducted in the pediatric emergency department
of a hospital in Alexandria, Egypt, between December 1, 1999, and April 30,
Patients Eighty-six children aged 1 to 4 years who were evaluated for a febrile
syndrome of undetermined origin.
Main Outcome Measures Serological assay and polymerase chain reaction of blood and saliva
samples for HHV-8. Information on potential risk factors for HHV-8 infection
was also collected.
Results Thirty-six children (41.9%) were seropositive; HHV-8 DNA sequences were
detected in 14 (38.9%) of these 36 children (detected in saliva in 11 of 14).
Significant associations were found between HHV-8 infection and close contact
with at least 2 other children in the community (36 of 63 vs 6 of 23 for <2
children; adjusted odds ratio [OR], 3.50; 95% confidence interval [CI], 1.11-12.22)
and admission to the emergency department in December or January (28 of 47
vs 14 of 39 for February-April; adjusted OR, 3.15; 95% CI, 1.23-8.58). Six
children had suspected primary HHV-8 infection; all but 1 had a febrile cutaneous
craniocaudal maculopapular rash, which was more common among these children
(5 of 6 vs 10 of 75; P<.001). For 3 of these 6
children, a second blood sample was obtained after the convalescence phase,
and all 3 seroconverted for HHV-8.
Conclusions Primary infection with HHV-8 may be associated with a febrile maculopapular
skin rash among immunocompetent children. The finding of HHV-8 DNA sequences
in saliva supports the hypothesis that transmission through saliva is the
main mode of transmission in the pediatric age group.
Human herpesvirus 8 (HHV-8) has recently been implicated in the development
of Kaposi sarcoma, primary effusion B-cell lymphoma, and multicentric Castleman
disease of the plasma-cell type.1- 3
Its consistent detection in tissue lesions of Kaposi sarcoma and the results
of epidemiological studies4- 7
confirm that HHV-8 is the cause of this neoplasm.
In countries with a low prevalence of HHV-8 infection, such as the United
States, the infection appears to be restricted to sexually active homosexual
men, and its prevalence appears to be low among children.8
In high-prevalence areas, such as many African countries, the infection is
also widespread among children.5,9
However, the risk factors for acquiring HHV-8 infection are still uncertain,
although saliva exchange is likely to play a major role.10
It is unknown whether primary HHV-8 infection causes specific clinical
manifestations in immunocompetent hosts, partly because HHV-8 seroconversion
has usually been documented retrospectively5,11
and among immunosuppressed adults. Although the development of Kaposi sarcoma
and lymphoproliferative disorders is a late event strictly corresponding to
immunosuppression related to HIV (human immunodeficiency virus) infection,
the use of immunosuppressive drugs for organ transplantation, and aging, to
the best of our knowledge, only 3 cases of symptomatic primary disease have
been reported. The first was an HIV-infected patient who had developed transient
angiolymphoid hyperplasia characterized by transient fever, arthralgia, cervical
adenopathy, and splenomegaly during primary HHV-8 infection.12
The other 2 cases were patients who had each received a kidney from the same
HHV-8–seropositive cadaveric donor: HHV-8 seroconversion and viremia
occurred with disseminated Kaposi sarcoma in one patient and with bone marrow
failure with plasmocytosis in the other.13
The objectives of this study were to determine whether primary HHV-8
infection can cause specific clinical manifestations in immunocompetent children
and to identify the epidemiological and virological correlates of HHV-8 infection.