The company malaria keeps: how co-infection with Epstein–Barr virus leads to endemic Burkitt lymphoma

Co-infection with Plasmodium falciparum (Pf-) malaria and Epstein-Barr virus (EBV) are implicated in the etiology of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in equatorial Africa. Although the causal association between EBV and eBL has been established, Pf-malaria’s role is not as clearly defined. This review focuses on how malaria may disrupt EBV persistence and immunity

Longevity of Genotype-Specific Immune Responses to Plasmodium falciparum Merozoite Surface Protein 1 in Kenyan Children from Regions of Different Malaria Transmission Intensity

Naturally acquired immunity to Plasmodium falciparum presents a changing landscape as malaria control programs and vaccine initiatives are implemented. Determining which immunologic indicators remain surrogates of past infection, as opposed to mediators of protection, led us to compare stability of immune responses across regions with divergent malaria transmission intensities. A repeat cross-sectional study of Kenyan children from a malaria-holoendemic area and an epidemic-prone area was used to examine longitudinal antibody and interferon-gamma (IFN-gamma) responses to the 3D7 and FVO variants of merozoite surface protein 1 (MSP1). Antibodies to MSP1 were common in both study populations and did not significantly wane over a 21-month time period. IFN-gamma responses were less frequent and rapidly disappeared in children after a prolonged period of no malaria transmission. Antibody and IFN-gamma responses rarely correlated with each other; however, MSP1-specific IFN-gamma response correlated with lack of concurrent P. falciparum parasitemia of the same genotype, though only statistically significantly in the malaria-holoendemic region (odds ratio = 0.31, 95% confidence interval = 0.12-0.84). This study affirms that antimalarial antibodies are informative for evaluation of history of malaria exposure within individuals, whereas cell-mediated immunity, though short lived under natural exposure conditions, might provide an assessment of recent infection and protection from parasitemia

Recurrent Plasmodium falciparum Malaria Infections in Kenyan Children Diminish T-Cell Immunity to Epstein Barr Virus Lytic but Not Latent Antigens

Plasmodium falciparum malaria (Pf-malaria) and Epstein Barr Virus (EBV) infections coexist in children at risk for endemic Burkitt's lymphoma (eBL); yet studies have only glimpsed the cumulative effect of Pf-malaria on EBV-specific immunity. Using pooled EBV lytic and latent CD8+ T-cell epitope-peptides, IFN-γ ELISPOT responses were surveyed three times among children (10 months to 15 years) in Kenya from 2002–2004. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated in association with Pf-malaria exposure, defined at the district-level (Kisumu: holoendemic; Nandi: hypoendemic) and the individual-level. We observed a 46% decrease in positive EBV lytic antigen IFN-γ responses among 5–9 year olds residing in Kisumu compared to Nandi (PR: 0.54; 95% CI: 0.30–0.99). Individual-level analysis in Kisumu revealed further impairment of EBV lytic antigen responses among 5–9 year olds consistently infected with Pf-malaria compared to those never infected. There were no observed district- or individual-level differences between Pf-malaria exposure and EBV latent antigen IFN-γ response. The gradual decrease of EBV lytic antigen but not latent antigen IFN-γ responses after primary infection suggests a specific loss in immunological control over the lytic cycle in children residing in malaria holoendemic areas, further refining our understanding of eBL etiology

Real-World Experience with Oritavancin Therapy in Invasive Gram-Positive Infections

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Prevalence of EBV-specific CD8+ T-cell IFNγ response by age group and residence.

<p>Prevalence of positive EBV lytic (A) and latent (B) antigen CD8+ T-cell IFNγ response by age group and site of residence, Kenya 2002–2004. Age group was classified as a time-varying factor. For both graphs, the number of observations for children in each age group in Kisumu was: 33 (0–4 years), 87 (5–9 years) and 78 (≥10 years). The number of observations for children in each age group in Nandi was: 54 (0–4 years), 125 (5–9 years) and 70 (≥10 years). <i>P</i> values for differences between areas of residence by age group are indicated.</p

Summary of participants in the Kisumu/Nandi cohort, Kenya 2002–2004^a.

<p><i>n</i>, number; %, percentage.</p>a<p>Data in the table are weighted according to the 149 children who participated in all surveys and had interpretable Epstein-Barr virus (EBV) specific CD8+ T-cell IFN-γ response.</p

Prevalence Ratios for EBV Lytic Antigen CD8+ T-cell IFN-γ Response.

<p><i>Pf</i>-malaria, <i>Plasmodium falciparum</i> malaria; EBV, Epstein-Barr virus; PR, prevalence ratio; CI, confidence interval; Ref, referent group.</p>a<p>Adjusted for sex and survey period. Unstratified estimates for constant <i>Pf</i>-malaria infections compared to never infected in Kisumu (<i>P</i> = 0.72) and Nandi (<i>P</i> = 0.97) were not significant. Specific details on the number and prevalence of positive responses for each age group are included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031753#pone-0031753-t002" target="_blank">Table 2</a>.</p>b<p>Adjusted for sex and age group. Unstratified estimates for constant <i>Pf</i>-malaria infections compared to never infected was not significant in Kisumu (<i>P</i> = 0.65) but significant in Nandi (<i>P</i> = 0.03). The number of children in Kisumu for each survey period was 66 and the number of children in Nandi was 83.</p

Change in prevalence of EBV-specific CD8+ T-cell IFNγ responses with age.

<p>Changes in prevalence of positive EBV lytic (A and C) and latent (B and D) antigen CD8+ T-cell IFNγ response from 2002–2004. Age group at each survey period is based on age at baseline. In Kisumu: 16 (0–4 years), 33 (5–9 years) and 17 (≥10 years). In Nandi: 30 (0–4 years), 35 (5–9 years) and 18 (≥10 years). Solid black line: 0–4 year olds; hash-mark green line: 5–9 year olds; and dotted blue line: ≥10 year old children.</p

EBV-specific CD8+ T-cell IFN-γ Response by Residence and Age Group^a.

<p><i>n</i>, number; %, percentage; EBV, Epstein-Barr Virus; PHA, Phytohemagglutinin.</p>a<p>Data in the table are weighted according to the 149 children who participated in all surveys and had interpretable Epstein-Barr Virus (EBV) specific CD8+ T-cell IFN-γ response.</p>b<p>Phytohemagglutinin (PHA) was used as a positive control.</p>c<p>Median EBV-specific CD8+ T-cell IFN-γ responses were calculated among children with positive responses and is expressed as spot forming units (SFU) per 1×10⁶ peripheral blood mononuclear cells (PBMC).</p