Browsing by Author "Whitby, Denise"
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Item Association between malaria exposure and Kaposi’s sarcoma-associated herpes virus seropositivity in Uganda(Tropical medicine & international health, 2015) Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, RobertUnlike other herpes viruses, Kaposi’s sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparumapical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. results Kaposi’s sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP- 1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti- ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.Item Detection of Kaposi Sarcoma–Associated Herpesvirus DNA in Saliva and Buffy-Coat Samples from Children with Sickle Cell Disease in Uganda(The Journal of infectious diseases, 2004) Mbulaiteye, Sam M.; Pfeiffer, Ruth M.; Engels, Eric A.; Marshall, Vickie; Bakaki, Paul M.; Owor, Anchilla M.; Ndugwa, Christopher M.; Mbidde, Edward Katongole; Goedert, James J.; Biggar, Robert J.; Whitby, DeniseAmong 233 children, Kaposi sarcoma–associated herpesvirus (KSHV) DNA was detected in 43% of children seropositive for both K8.1 and orf73, in 29% of children seropositive for K8.1 only, in 14% of children seropositive for orf73 only, and in 7% of children seronegative for both K8.1 and orf73; among 228 mothers, KSHV DNA was detected in 27%, 25%, 4%, and 1%, respectively. KSHV DNA was detected more frequently and at higher levels in saliva than in buffy-coat samples and in children than in mothers. In both children and mothers, detection in saliva was associated with detection in peripheral blood. Detection was associated with K8.1 seropositivity, younger age, and high household density, indicating the importance of in-household person-to-person transmission, likely via saliva.Item High Levels of Epstein-Barr Virus DNA in Saliva and Peripheral Blood from Ugandan Mother-Child Pairs(The Journal of infectious diseases, 2006) Mbulaiteye, Sam M.; Walters, Michael; Engels, Eric A.; Bakaki, Paul M.; Ndugwa, Christopher M.; Owor, Anchilla M.; Goedert, James J.; Whitby, Denise; Biggar, Robert J.In Africa, Epstein-Barr virus (EBV) is associated with Burkitt lymphoma. We measured levels of EBV DNA in saliva and buffy coats from 233 asymptomatic Ugandan children with sickle cell disease and their mothers by quantitative real-time polymerase chain reaction. EBV DNA was detected in saliva from 90% of the children (median [interquartile range {IQR}] level, 5.2 [4.2–6.0] log10 copies/mL of saliva) and 79% of the mothers (median [IQR] level, 4.8 [3.7–5.6] log10 copies/mL of saliva) (P ! .001). EBV DNA was detected in buffy coats from 86% of the children (median [IQR] level, 2.5 [2.2–2.9] log10 copies/1 106 peripheral white blood cells [PWBCs]) and 72% of the mothers (median [IQR] level, 2.7 [2.4–3.1] log10 copies/1 106 PWBCs) (Pp.24). Detection of EBV DNA in saliva was positively correlated with detection in buffy coats. EBV DNA was detected more frequently in saliva and buffy coats than was human herpesvirus 8 DNA. Our results indicate that EBV infection persists, with virus readily detectable in saliva and buffy coats from persons without apparent symptoms in Africa.Item Parasite infection is associated with Kaposi’s sarcoma associated herpesvirus (KSHV) in Ugandan women(Infectious Agents and Cancer, 2011) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Muhangi, Lawrence; Miley, Wendell; Johnson, W. Thomas; Ndibazza, Juliet; Elliott, Alison M.; Whitby, Denise; Newton, RobertImmune 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. 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. Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.Item Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda(Cancer epidemiology,, 2018) Juan, Ravell; Otim, Isaac; Nabalende, Hadijah; Legason, Ismail D.; Reynolds, Steven J.; Ogwang, Martin D.; Ndugwa, Christopher M.; Marshall, Vickie; Whitby, Denise; Goedert, James J.; Engels, Eric A.; Bhatia, Kishor; Lenardo, Michael J.; Mbulaiteye, Sam M.Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (eBL). EBV control was improved by magnesium (Mg2+) supplementation in XMEN, an X-linked genetic disease associated with Mg2+ deficiency, high circulating EBV levels (viral loads), and EBV-related lymphomas. We, therefore, investigated the relationship between Mg2+ levels and EBV levels and eBL in Uganda. Methods: Plasma Mg2+ was measured in 45 women with low or high circulating EBV levels, 40 pediatric eBL cases, and 79 healthy children. Mg2+ uptake by T-lymphocytes was evaluated in samples from healthy donors. Results: Plasma Mg2+ deficiency (plasma level<1.8 mg/dl) was more likely in women with high- vs. low-EBV levels (76.0% vs. 35%; odds ratio [OR] 11.3, 95% CI 2.14–60.2), controlling for age, and in eBL cases than controls (42.0% vs. 13.9%; OR 3.61, 95% CI 1.32–9.88), controlling for sex, age group, and malaria status. Mg2+ uptake by T-lymphocytes was related to extracellular Mg2+ concentration. Interpretation: Plasma Mg2+ deficiency is associated with high EBV levels and eBL.Item Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda(Journal of acquired immune deficiency syndromes, 2013) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Miley, Wendell; Johnston, W. Thomas; Ndibazza, Juliet; Whitby, Denise; Newton, Robert; Elliott, Alison M.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. 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.Item SARS-CoV-2 seroprevalence among blood donors in Uganda: 2019–2022(John Wiley & Sons, Ltd, 2023-05-16) Bloch, Evan M; Kyeyune, Dorothy; White, Jodie L; Ddungu, Henry; Ashokkumar, Swetha; Habtehyimer, Feben; Baker, Owen; Kasirye, Ronnie; Patel, Eshan U.; Grabowski, M. Kate; Musisi, Ezra; Moses, Khan; Hume, Heather A; Lubega, Irene; Shrestha, Ruchee; Motevalli, Mahnaz; Fernandez, Reinaldo E; Reynolds, Steven J; Redd, Andrew D; Wambongo Musana, Hellen; Dhabangi, Aggrey; Ouma, Joseph; Eroju, Priscilla; Lange, Telsa; Fowler, Mary Glenn; Musoke, Philippa; Stramer, Susan L.; Whitby, Denise; Zimmerman, Peter A; McCullough, Jeffrey; Sachithanandham, Jaiprasath; Pekosz, Andrew; Goodrich, Raymond; Quinn, Thomas C; Ness, Paul M.; Laeyendecker, Oliver; Tobian, Aaron A. R.Abstract Abstract 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). Seropositivity for N and S was assigned using manufacturer‐provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November–December 2021 were assessed by chi‐square tests. Results A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January–April 2022. Among seropositive individuals, N and S antibody levels increased ≥9‐fold over the study period. In November–December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions ( p = .007). Seropositivity to S antibody was significantly lower among HIV‐seropositive individuals (58.8% vs. 84.9%; p = .009). Conclusions Despite previously reported low numbers of COVID‐19 cases and related deaths in Uganda, high SARS‐CoV‐2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.Item Water, Socioeconomic Factors, and Human Herpesvirus 8 Infection in Ugandan Children and Their Mothers(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2005) Mbulaiteye, Sam M.; Biggar, Robert J.; Pfeiffer, Ruth M.; Bakaki, Paul M.; Gamache, Christine; Owor, Anchilla M.; Mbidde, Edward Katongole; Ndugwa, Christopher M.; Goedert, James J.; Whitby, Denise; Engels, Eric A.Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its distribution is uneven. Transmission occurs during childhood within families by unclear routes.We evaluated 600 Ugandan children with sickle cell disease and their mothers for factors associated with HHV-8 seropositivity in a cross-sectional study. HHV-8 serostatus was determined using an HHV-8 K8.1 glycoprotein enzyme immunoassay. Odds ratios for seropositivity were estimated using logistic regression, and factor analysis was used to identify clustering among socioeconomic variables.One hundred seventeen (21%) of 561 children and 166 (34%) of 485 mothers with definite HHV-8 serostatus were seropositive. For children, seropositivity was associated with age, mother's HHV-8 serostatus (especially for children aged 6 years or younger), lower maternal education level, mother's income, and low-status father's occupation (P < 0.05 for all). Using communal standpipe or using surface water sources were both associated with seropositivity (OR 2.70, 95% CI 0.80-9.06 and 4.02, 95% CI 1.18-13.7, respectively) as compared to using private tap water. These associations remained, albeit attenuated, after adjusting for maternal education and child's age (P = 0.08). In factor analysis, low scores on environmental and family factors, which captured household and parental characteristics, respectively, were positively associated with seropositivity (Ptrend < 0.05 for both). For mothers, HHV-8 seropositivity was significantly associated with water source and maternal income.HHV-8 infection in Ugandan children was associated with lower socioeconomic status and using surface water. Households with limited access to water may have less hygienic practices that increase risk for HHV-8 infection.