Association of Household Food- and Drink-Sharing Practices With Human Herpesvirus 8 Seroconversion in a Cohort of Zambian Children.

Background: Human herpesvirus 8 (HHV-8) infection occurs in early childhood and is associated with human immunodeficiency virus type 1 (HIV-1) infection and risk for Kaposi sarcoma, but behaviors associated with HHV-8 transmission are not well described. Methods: We enrolled and followed a prospective cohort of 270 children and their household members to investigate risk factors for HHV-8 transmission in Lusaka, Zambia. Results: We report an incidence of 30.07 seroconversions per 100 child-years. Independent risk factors for HHV-8 incident infection included having a child who shared utensils with a primary caregiver (hazards ratio [HR], 2.33; 95% confidence interval [CI], 1.49-7.14), having an increasing number of HHV-8-infected household members (HR, 1.27; 95% CI, 1.09-2.79), and having ≥5 siblings/children in the household (HR, 2.24; 95% CI, 1.03-4.88). Playing with >5 children a day was protective against infection (HR, 0.54; 95% CI, .33-0.89), as was increasing child age (HR, 0.96; 95% CI, .93-.99). Conclusions: This is the first study to find a temporal association between limited child feeding behaviors and risk for HHV-8 infection. Child food- and drink-sharing behaviors should be included in efforts to minimize HHV-8 transmission, and households with a large number of siblings should receive additional counseling as childhood infections occur in the home context.

Risk factors for early childhood infection of human herpesvirus-8 in Zambian children: the role of early childhood feeding practices.

BACKGROUND: Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva. METHODS: To understand the horizontal transmission of HHV-8 within households to children, we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV type I (HIV-1) and health and behavioral questionnaires were completed. Multilevel logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children. RESULTS: Risk factors for HHV-8 infection included increasing number of HHV-8-positive household members [OR = 2.5; 95% confidence interval (CI), 1.9-3.3; P < 0.01] and having a primary caregiver who tested the temperature of food with their tongue before feeding the child (OR = 2.4; 95% CI, 1.93-3.30; P = 0.01). Breastfeeding was protective against infection with HHV-8 for children (OR = 0.3; 95% CI, 0.16-0.72; P < 0.01). CONCLUSIONS: These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection, with specific feeding behaviors likely playing a role in transmission. IMPACT: Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods.

The Zambia Children's KS-HHV8 Study: rationale, study design, and study methods.

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)-associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia.

Primary gamma-herpesviral infection in Zambian children.

BACKGROUND: HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8. METHODS: This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range of clinical manifestations were collected. Logistic regression was used to test for significant associations between the collected variables and HHV-8 or EBV serostatus at 12 months of age. RESULTS: We observed a significantly higher seroprevalence for EBV (58.9%) as compared to HHV-8 (13.4%). HIV-1 infected children had at a significantly higher risk of being infected with HHV-8 (Odds ratio [OR] 3.69, 95% confidence interval [CI] 1.64 - 8.32). HIV-1 infection of the mothers was a significant risk factor for increased acquisition of EBV but not HHV-8 by children (OR 1.86, 05% CI 1.20 - 2.87). Self reported rash was marginally associated with primary infection for HHV-8 and EBV. CONCLUSIONS: These results suggest that there is no correlation between EBV and HHV-8 infections. Infection by one does not increase the susceptibility for the second virus. Primary HHV-8 and EBV infection in early childhood may clinically present as rash but remains largely asymptomatic and may remain undetected in this population. HIV infection in the mother or child are important risk factors that contribute to EBV or HHV-8 infection.

Early childhood infection by human herpesvirus 8 in Zambia and the role of human immunodeficiency virus type 1 coinfection in a highly endemic area.

Kaposi's sarcoma occurs at high incidence among Zambian adults and children, but there is a paucity of data on human herpesvirus 8 (HHV-8) incidence and routes of infection, especially in children. Between 1998 and 2004, the authors conducted a prospective study of viral transmission in a cohort of 684 children in Lusaka, Zambia, to estimate the annual incidence of HHV-8 from birth through 48 months of age. Maternal and pediatric human immunodeficiency virus type 1 (HIV-1) infection status was also determined. The results, based on 1,532 child-years of follow-up, showed that HHV-8 seroconversion occurs early in life. The incidence rate of HHV-8 seroconversion was 13.8 infections per 100 child-years by 48 months of age. HIV-1-infected children were at substantially higher risk for HHV-8 seroconversion (adjusted hazard ratio = 4.60, 95% confidence interval: 2.93, 7.22). Maternal HIV-1 and HHV-8 infection status were not independently associated with risk of HHV-8 seroconversion in the child. HHV-8 antibody titers in children followed at all consecutive time points revealed sero-reversion of HHV-8 antibodies, with undetectable titers in some children at one or more time points after seroconversion. These results demonstrate that cross-sectional serologic screening probably underestimates true HHV-8 seroprevalence in young Zambian children because of fluctuations in detectable antibody titers.

Development of an immunofluorescence assay using recombinant proteins expressed in insect cells to screen and confirm presence of human herpesvirus 8-specific antibodies.

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma (KS)-associated herpesvirus, has been linked to all forms of KS. The results of most current serological assays for the detection of HHV-8-specific antibodies have low levels of concordance among themselves. To establish a sensitive and specific testing strategy that can be used to screen for HHV-8-specific antibodies, three HHV-8 proteins, ORF65, ORF73, and K8.1A, were expressed by using baculoviral vectors in insect cells and incorporated into a monoclonal antibody-enhanced immunofluorescence assay (mIFA) termed the Sf9 three-antigen mIFA. The results obtained by this mIFA were compared to those obtained by a standard mIFA with an HHV-8-infected B-cell line (BC3 mIFA). Test sera were obtained from patients diagnosed with KS, human immunodeficiency virus type 1-infected patients at high risk for HHV-8 infection, and healthy controls from a local blood bank. The combined use of both assays had a sensitivity of 94% and a specificity of 96%. The performance of these two assays when they were used together indicates that they may be useful for the reliable detection of HHV-8-specific immunoglobulin G antibodies in a population.