Early Age at Time of Primary Epstein–Barr Virus Infection Results in Poorly Controlled Viral Infection in Infants From Western Kenya: Clues to the Etiology of Endemic Burkitt Lymphoma

Piriou, Erwan; Asito, Amolo S.; Sumba, Peter Odada; Fiore, Nancy; Middeldorp, Jaap M.; Moormann, Ann M.; Ploutz‐Snyder, Robert; Rochford, Rosemary

doi:10.1093/infdis/jir872

Cited by 150 publications

(218 citation statements)

References 29 publications

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“…Surprisingly, it remained about the same. Recent evidence suggests that infection with EBV at an early age increases the risk of developing EBV-related cancer (Piriou et al, 2012). Despite the burden of EBV-associated cancers, vaccine development is still in progress (Balfour, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical manifestations of EBV infections vary according to age, ranging from silent infections in infants to infectious mononucleosis in adolescents and adults. In addition, many serological and molecular studies have provided evidence that EBV is associated with various types of malignancies such as lymphoma, nasopharyngeal carcinoma (NPC), Hodgkin disease and gastric carcinoma (Cohen et al, 2008;Hjalgrim et al, 2000;Mitarnun et al, 2004;Piriou et al, 2012;Tiwawech et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Seroprevalence of Anti-EBV IgG among Various Age Groups from Khon Kaen Province, Thailand

Suntornlohanakul¹,

Wanlapakorn²,

Vongpunsawad³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Epstein-Barr virus (EBV) is an extremely common herpesvirus that may cause asymptomatic infection or various diseases, including infectious mononucleosis, certain lymphoproliferative diseases and several types of neoplasms. Vaccine development is an important strategy to reduce the burden of EBV-associated diseases and the timing of vaccinations should be before primary infection occurs. In the past, more than 90% of Thai children were infected with EBV in early childhood. Now, due to the improved healthcare system in Thailand, we aim to determine current prevalence of EBV infection among people in different age groups. A total of 538 sera were collected from residents of Khon Kaen province in northeastern Thailand for detecting anti-EBV IgG. Sera of infants under 2-years-old were also tested for anti-EBV IgM and EBV-DNA. The prevalence of anti-EBV IgG was 47.1% (95% CI: 23.3-70.8) in infants aged 0-6 months, 34.9% (95% CI: 23.1-46.7) in those aged 6-24 months, 87.9% (95% CI: 79.5-96.3) in children aged 3-5 years and then maintained at above 95% through adulthood. These seropositivity rates among Thai children remain similar to those found in a previous study conducted 20 years ago. Thai children are still exposed to EBV from an early age. Therefore, a prophylactic vaccine should be given within the first two years of life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Seroprevalence of Anti-EBV IgG among Various Age Groups from Khon Kaen Province, Thailand

Suntornlohanakul¹,

Wanlapakorn²,

Vongpunsawad³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Both infection with Epstein-Barr virus (EBV) and repeated episodes of Plasmodium falciparum malaria are known risk factors for eBL (2), but the mechanism(s) by which these two agents interact to promote the emergence of malignant B cell clones has not been elucidated. Recently, we found that infants from a region of malaria endemicity of western Kenya were infected with EBV by 6 months of age (3). Living in regions of malaria endemicity was a predictor of this early age of primary infection.…”

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confidence: 90%

“…Clinically, elevated levels of anti-VCA and anti-EBNA1 immunoglobulin G (IgG) antibodies have been used as evidence of past infection (9), while the presence of IgG antibodies to the EBV early antigens (EAd and Zta) generally reflects recent or reactivated infections (10,11). Although EBV-specific antibody patterns reflect the dynamics of EBV activity in adults, few studies have addressed this issue in infants and children (3,(12)(13)(14)(15) or in newborns (16,17). More importantly, no comparison to maternal antibody levels has been made and there has been no analysis of how maternal malaria infections impact transplacental transfer of EBV-specific antibodies.…”

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confidence: 99%

Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy

Ogolla

Daud

Asito

et al. 2015

Clin Vaccine Immunol

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h Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV-and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P ‫؍‬ 0.0234 and P ‫؍‬ 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. E ndemic Burkitt's lymphoma (eBL) is a distinct form of nonHodgkin's lymphoma and is the most common pediatric malignancy in regions of malaria endemicity of sub-Saharan Africa (1). Both infection with Epstein-Barr virus (EBV) and repeated episodes of Plasmodium falciparum malaria are known risk factors for eBL (2), but the mechanism(s) by which these two agents interact to promote the emergence of malignant B cell clones has not been elucidated. Recently, we found that infants from a region of malaria endemicity of western Kenya were infected with EBV by 6 months of age (3). Living in regions of malaria endemicity was a predictor of this early age of primary infection. This aberrant primary EBV infection may set the stage for lymphoma development, as previously hypothesized (4-6).The lytic and latent phases of the EBV life cycle induce distinct antibodies in response to specific lytic and latent antigens. Anti-EBV nuclear antigen-1 (EBNA1) antibodies are produced against EBNA1, the only antigen expressed in latently infected memory B cells and in eBL tumors (7). Anti-viral capsid antigen (anti-VCA), anti-early antigen (ant...

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“…Burkitt lymphoma is more common among infants who have primary EBV infection at very early ages and the accompanying high EBV viremia [8] . Many studies have shown that EBV seroprevalence increases with age [7,[9][10][11] .…”

Section: Resultsmentioning

confidence: 99%

Seroprevalence and Risk Factors for Epstein-Barr Virus Infection in Adults

Altintaş¹,

Erol²,

Engin³

et al. 2018

mjima

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Introduction: Epstein-Barr virus (EBV), also known as human herpesvirus 4, is the causative agent of infectious mononucleosis. Infection with EBV is associated with multiple malignancies. The aim of this study was to determine the seroprevalence and risk factors for seropositivity. Materials and Methods: This study was conducted in Haydarpaşa Numune Training and Research Hospital in İstanbul between August 2012 and October 2012. Epstein-Barr virus viral capsid antigen IgG antibody was measured using ELISA in 500 cases. Age, gender, occupation, education level, family income, the area and type of residence, and chronic illness of the participants were also evaluated. Differences between risk groups were statistically analyzed. Results: The mean age of the 500 study participants was 47.7±19.1 (15-87) years and 289 (57.8%) were male. Mean EBV seropositivity was 96.4%, and 91% of the cases became seropositive for EBV by 15 years of age. No significant associations with age, gender, occupation, education level, family income, area and type of residence, and chronic illness were detected. Conclusion: Epstein-Barr virus seropositivity rates were very high and about 91% of the cases become seropositive for EBV by 15 years of age. There was no significant relationship between risk factors and seroprevalence of EBV.

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Early Age at Time of Primary Epstein–Barr Virus Infection Results in Poorly Controlled Viral Infection in Infants From Western Kenya: Clues to the Etiology of Endemic Burkitt Lymphoma

Abstract: Children from a region at high risk for eBL were infected very early in life with EBV, resulting in higher viral loads throughout infancy.

Cited by 150 publications

References 29 publications

Seroprevalence of Anti-EBV IgG among Various Age Groups from Khon Kaen Province, Thailand

Seroprevalence of Anti-EBV IgG among Various Age Groups from Khon Kaen Province, Thailand

Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy

Seroprevalence and Risk Factors for Epstein-Barr Virus Infection in Adults

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