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1.  Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda 
Background:
Determinants of Kaposi sarcoma–associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key.
Methods:
Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother–child pairs in Entebbe, Uganda.
Results:
Seroprevalence increased with increasing age of the child (P = 0.0003) and was higher among those with KSHV seropositive mothers than in those without (12% vs 9%; odds ratio: 1.4, 95% confidence interval: 1.1 to 2.0). It was also higher among children with HIV infection (29% vs 10%; odds ratio: 3.1, 95% confidence interval: 1.2 to 8.3) or malaria parasitemia (30% vs 10%; odds ratio: 4.1, 95% confidence interval: 2.4 to 7.0) than in children without. These associations were not explained by socioeconomic status.
Conclusions:
The finding that KSHV serostatus is associated with malaria parasitemia in children is novel. In a country endemic for KSHV, malaria may be a cofactor for KSHV infection or reactivation among children.
doi:10.1097/QAI.0b013e31828a7056
PMCID: PMC3707567  PMID: 23403859
Kaposi sarcoma-associated herpesvirus; Sub-Saharan Africa; children; HIV; Kaposi sarcoma
2.  Long-Lived Memory B-Cell Responses following BCG Vaccination 
PLoS ONE  2012;7(12):e51381.
The role of T-cells in immunity against Mycobacterium tuberculosis (M. tuberculosis) infection has been extensively studied, however, that of B-cells still remains comparatively unexplored. In this study, we determined the presence and frequencies of mycobacteria-specific memory B-cells (MBCs) in peripheral blood from clinically healthy, Bacillus Calmette Guerin (BCG) vaccinated (n = 79) and unvaccinated (n = 14) donors. Purified protein derivative (PPD)-specific MBCs were present in most donors (both vaccinated and unvaccinated) but their frequencies were significantly higher in vaccinated than in unvaccinated donors. MBCs specific for other mycobacterial antigens [antigen-85A (Ag85A), antigen-85B (Ag85B), 6 kDalton early secretory antigenic target (ESAT-6) and the 10 kDalton-culture filtrate protein (CFP-10)] were less prevalent than those recognising PPD. Furthermore, PPD-specific MBCs were detected in BCG vaccinated donors without ESAT-6 and CFP-10 specific responses. Together, these results indicate that BCG vaccination induces long-lived MBC responses. Similar patterns of response were seen when we examined mycobacteria-specific antibody and T-cell responses in these donors. Our data show for the first time that BCG vaccination elicits long-lived mycobacteria-specific MBC responses in healthy individuals, suggesting a more substantial role of B-cells in the response to BCG and other mycobacterial infections than previously thought.
doi:10.1371/journal.pone.0051381
PMCID: PMC3519837  PMID: 23240017
3.  Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing 
PLoS ONE  2012;7(10):e47340.
Background
Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population.
Methodology/Principal Findings
We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens.
Conclusions/Significance
We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of children as TB-infected or TB-uninfected difficult. Existing tools for the diagnosis of TB infection are unsatisfactory in determining infection among children in this setting.
doi:10.1371/journal.pone.0047340
PMCID: PMC3471887  PMID: 23077594
4.  Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV) in Ugandan women 
Background
Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda.
Results
Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education.
Conclusions
Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.
doi:10.1186/1750-9378-6-15
PMCID: PMC3197512  PMID: 21962023

Results 1-4 (4)