Publications by authors named "Whitby D"

This qualitative sub-study investigated household practices affecting orally shed infections using Kaposi's sarcoma-associated herpesvirus (KSHV) as a focus. Participants enrolled from 50 households in rural south-western Uganda were followed monthly up to three times. At enrolment, in-depth interviews were completed, and venous blood collected.

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Article Synopsis
  • The study investigates how HIV infection within a household affects the shedding of Kaposi’s sarcoma-associated herpesvirus (KSHV) among individuals.
  • Out of 469 enrolled individuals from 90 households, 44% were found to be KSHV shedders, with a notable link between the number of KSHV-positive household members and the likelihood of shedding.
  • Findings indicate that younger individuals (ages 10-19) are more likely to consistently shed KSHV and have higher viral loads, especially in households with people living with HIV.
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  • The Cancer Immunotherapy Trials Network 12 study showed that pembrolizumab is safe and effective for treating advanced Kaposi sarcoma (KS) in people with HIV on antiretroviral therapy.
  • In a phase I trial involving 32 participants, 62.1% had a positive response to pembrolizumab, with even higher rates (87.5%) for those who hadn't received previous KS treatments.
  • The treatment led to significant progression-free survival, with a median of 28.2 months, and immune-mediated adverse events were effectively managed according to established guidelines.
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  • The study analyzed how HIV infection in households affects the shedding of Kaposi's sarcoma-associated herpesvirus (KSHV) among participants, involving 469 individuals from 90 households sampled over three months.
  • Out of 340 KSHV seropositive individuals, 44% were found to be ever shedders, with a notable association between the number of KSHV-positive household members and the likelihood of shedding.
  • The findings revealed that younger individuals (ages 10-19) were more often consistent shedders, and both higher viral loads and shedding rates were linked to increased household members and the presence of individuals living with HIV.
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Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS).

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Kaposi sarcoma herpesvirus (KSHV)-associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated multicentric Castleman disease (MCD), and KS inflammatory cytokine syndrome (KICS). PEL, MCD, and KICS are associated with elevated circulating inflammatory cytokines. However, activation of the inflammasome, which generates interleukin-1β (IL-1β) and IL-18 via active caspase-1/4/5, has not been evaluated in patients with KSHV-associated diseases (KADs).

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SUMMARYWithin weeks of the first report of acquired immunodeficiency syndrome (AIDS) in 1981, it was observed that these patients often had Kaposi sarcoma (KS), a hitherto rarely seen skin tumor in the USA. It soon became apparent that AIDS was also associated with an increased incidence of high-grade lymphomas caused by Epstein-Barr virus (EBV). The association of AIDS with KS remained a mystery for more than a decade until Kaposi sarcoma-associated herpesvirus (KSHV) was discovered and found to be the cause of KS.

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Article Synopsis
  • KSHV is linked to about 1% of human tumors, including primary effusion lymphoma (PEL), often found with co-infection of EBV.
  • In research with humanized mice, it's shown that KSHV/EBV co-infection triggers immune responses, particularly the production of IgM antibodies and the growth of specific T cells.
  • The findings suggest that the K6 antigen from the lytic phase of KSHV could be a potential vaccine target to combat KSHV-related diseases, especially in areas like Sub-Saharan Africa where the virus is prevalent.
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Objective: Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples.

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Background: To determine the pattern of immune cell subsets across the life span in rural sub-Saharan Africa (SSA), and to set a reference standard for cell subsets amongst Africans, we characterised the major immune cell subsets in peripheral blood including T cells, B cells, monocytes, NK cells, neutrophils and eosinophils, in individuals aged 3 to 89 years from Uganda.

Methods: Immune phenotypes were measured using both conventional flow cytometry in 72 individuals, and full spectrum flow cytometry in 80 individuals. Epstein-Barr virus (EBV) IFN-γ T cell responses were quantified in 332 individuals using an ELISpot assay.

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Background: Epstein-Barr virus (EBV) infection is ubiquitous and in sub-Saharan Africa, occurs early in life. In a population-based rural African cohort, we leveraged historical samples from the General Population Cohort (GPC) in Uganda to examine the epidemiology of infection with EBV over time, in the era of HIV.

Methods: We used 9024 serum samples collected from the GPC in 1992, 2000, 2008, from 7576 participants across the age range (0-99 years of age) and tested for anti-EBV immunoglobulin G (IgG) antibodies to EAd, VCA, and EBNA-1 using a multiplex bead-based assay.

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Kaposi sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern United States. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for KS-associated herpesvirus (KSHV) IgG. Seroprevalence, seroconversion between time points, and demographic and clinical correlates were measured.

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Background: Previously, we showed that children with asymptomatic Plasmodium falciparum (Pf) malaria infection had higher Kaposi sarcoma-associated herpesvirus (KSHV) viral load, increased risk of KSHV seropositivity, and higher KSHV antibody levels. We hypothesize that clinical malaria has an even larger association with KSHV seropositivity. In the current study, we investigated the association between clinical malaria and KSHV seropositivity and antibody levels.

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Background: We identified whether maternal human immunodeficiency virus (HIV) infection during pregnancy affects transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV)-specific antibodies and subsequent infant infection.

Methods: We followed pregnant Kenyan women through delivery and their infants until age 2 years. Children were classified as HIV-exposed uninfected (HEU) or HIV-unexposed uninfected (HUU) based on maternal HIV status.

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We previously found that age, sex and malaria were associated with KSHV in individuals from Uganda. In this study, we have evaluated these same factors in relation to EBV in the same specimens. Overall, 74% (oral fluids) and 46% (PBMCs) had detectable EBV.

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Background: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally.

Methods: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD).

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Background: Disparities in mortality in human immunodeficiency virus (HIV)-associated Kaposi sarcoma have been described, particularly in Black men in the southern United States. It is unclear if there are racial/ethnic differences in the seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) that may be contributing.

Methods: This is a cross-sectional study of men who have sex with men (MSM) and transgender women with HIV.

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We previously found that age, sex, and malaria were associated with KSHV viral load in individuals from Uganda. In this study, we have evaluated factors associated with presence of EBV DNA in blood and oral fluids among the same individuals, using the same biological samples. Overall, 74% of oral fluids samples and 46% of PBMCs had detectable EBV, compared to 24% and 11% for KSHV respectively Individuals with EBV in PBMCs were more likely to have KSHV in PBMCs (P=0.

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Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions.

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A biopsy of lymphoid tissue is currently required to diagnose Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease (KSHV-MCD). Patients showing clinical manifestations of KSHV-MCD but no pathological changes of KSHV-MCD are diagnosed as KSHV inflammatory cytokine syndrome. However, a lymph node biopsy is not always feasible to make the distinction.

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Article Synopsis
  • Seven viruses contribute to over 15% of cancer cases, with some considered easier to prevent or treat through vaccines.* -
  • Kaposi sarcoma herpesvirus (KSHV) is responsible for Kaposi sarcoma, mainly affecting disadvantaged communities.* -
  • A recent NIH workshop highlighted KSHV's unique features, suggesting that an effective and affordable vaccine could significantly reduce its cancer risk.*
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Objective: There are four conditions caused by Kaposi sarcoma herpesvirus (KSHV): Kaposi sarcoma, KSHV-associated multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS). These KSHV-associated disorders (KADs) often occur in people with HIV and can lead to multiorgan dysfunction requiring admission to the ICU. However, little is known about patient outcomes in this setting.

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Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that causes Kaposi's sarcoma (KS), primary effusion lymphoma, multicentric Castleman's disease and KSHV-induced cytokine syndrome. KSHV established lifelong infection and has evolved numerous ways in which to evade adaptive immune responses. Most KSHV infections are asymptomatic but when disease occurs it does so in the context of immune suppression especially HIV infection.

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