NRU :: Browsing by Author "Mbulaiteye, Sam M."

Browsing by Author "Mbulaiteye, Sam M."

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African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers
(The American journal of tropical medicine and hygiene, 2011) Emmanuel, Benjamin; Kawira, Esther; Ogwang, Martin D.; Wabinga, Henry; Magatti, Josiah; Nkrumah, Francis; Neequaye, Janet; Bhatia, Kishor; Brubaker, Glen; Biggar, Robert J.; Mbulaiteye, Sam M.
African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated agespecific patterns of 2,602 cases of African Burkitt lymphoma (60% male, mean ± SD age = 7.1 ± 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma.
A case-control study of Burkitt lymphoma in East Africa: are local health facilities an appropriate source of representative controls?
(Infectious Agents and Cancer, 2012) Baik, Sonya; Mbaziira, Mike; Williams, Makeda; Ogwang, Martin D.; Kinyera, Tobias; Emmanuel, Benjamin; Ziegler, John L.; Reynolds, Steven J.; Mbulaiteye, Sam M.
We investigated the feasibility and appropriateness of enrolling controls for Burkitt lymphoma (BL) from local health facilities in two regions in Uganda. Methods: BL case data were compiled from two local hospitals with capacity to diagnose and treat BL in Northwest and North-central regions of Uganda during 1997 to 2009. Local health facility data were compiled from children attending four representative local health facilities in the two regions over a two week period in May/June 2010. Age and sex patterns of BL cases and children at local facilities were compared and contrasted using frequency tables. Results: There were 999 BL cases diagnosed in the study area (92% of all BL cases treated at the hospitals): 64% were from North-central and 36% from North-west region. The mean age of BL cases was 7.0 years (standard deviation [SD] 3.0). Boys were younger than girls (6.6 years versus 7.2 years, P = 0.004) and cases from North-central region were younger than cases from North-west region (6.8 years versus 7.3 years, P = 0.014). There were 1012 children recorded at the four local health facilities: 91% at facilities in North-central region and 9% from facilities in North-west region. Daily attendance varied between 1 to 75 children per day. The mean age of children at health facilities was 2.2 years (SD 2.8); it did not differ by sex. Children at North-central region facilities were younger than children at North-west region facilities (1.8 years versus 6.6 years, P < 0.001). Conclusions: While many children attend local health facilities, confirming feasibility of obtaining controls, their mean age is much lower than BL cases. Health facilities may be suitable for obtaining young, but not older, controls.
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, Denise
Among 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.
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.
Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited
(International journal of cancer, 2008) Ogwang, Martin D.; Bhatia, Kishor; Biggar, Robert J.; Mbulaiteye, Sam M.
Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus and ecologically linked to Plasmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific BL incidence and standardized incidence ratios using data collected from 1997 to 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 500 patients, median age was 6 years (interquartile range 5–8) and male-to-female ratio was 1.8:1. Among those known, most presented with abdominal (56%, M:F 1.4:1) vs. only facial tumors (35%, M:F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p < 0.001) and more frequently in female children (68% vs. 50%; OR 2.2, 95% CI 1.5– 3.5). The age-standardized incidence was 2.4 per 100,000, being 0.6 in 1–4 year olds, 4.1 in 5–9 year olds and 2.8 in 10–14 year olds and varied 3- to 4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. Although districts close to Lacor were also more urbanized, the incidence was higher in the nearby perirural areas. We highlight high-BL incidence and geographic variation in neighboring districts in northern Uganda. Although distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation has shifted away from facial to mostly abdominal.
Mean platelet counts are relatively decreased with malaria but relatively increased with endemic Burkitt Lymphoma in Uganda, Tanzania, and Kenya
(British journal of haematology, 2020) Peprah, Sally; Ogwang, Martin D.; Kerchan, Patrick; Reynolds, Steven J.; Tenge, Constance N.; Were, Pamela A.; Kuremu, Robert T.; Wekesa, Walter N.; Masalu, Nestory; Kawira, Esther; Kinyera, Tobias; Otim, Isaac; Legason, Ismail D.; Nabalende, Hadijah; Dhudha, Herry; Mumia, Mediatrix; Ayers, Leona W.; Biggar, Robert J.; Bhatia, Kishor; Goedert, James J.; Mbulaiteye, Sam M.
Platelet counts are decreased in Plasmodium falciparum malaria, which is aetiologically linked with endemic Burkitt lymphoma (eBL). However, the pattern of platelet counts in eBL cases is unknown. We studied platelet counts in 582 eBL cases and 2 248 controls enrolled in a case-control study in Uganda, Tanzania and Kenya (2010–2016). Mean platelet counts in controls or eBL cases with or without malaria-infection in controls versus eBLcases were compared using Student’s t-test. Odds ratios (ORs) and two-sided 95% confidence intervals (95% CIs) were estimated using multiple logistic regression, controlling for age, sex, haemoglobin and white blood cell counts. Platelets were decreased with malaria infection in the controls [263 vs. 339 9 109 platelets/l, P < 0 0001; adjusted OR (aOR) = 3 42, 95% CI: 2 79–4 18] and eBL cases (314 vs. 367 9 109 platelets/ l, P-value = 0 002; aOR = 2 36, 95% CI: 1 49–3 73). Unexpectedly, platelets were elevated in eBL cases versus controls in overall analyses (mean: 353 vs. 307 9 109 platelets/l, P < 0 0001; aOR = 1 41; 95% CI: 1 12–1 77), and when restricted to malaria-positive (mean 314 vs. 263 9 109 platelets/ l, P < 0 0001; OR = 2 26; 95% CI: 1 56–3 27) or malaria-negative (mean 367 vs. 339 9 109 platelets/l, P < 0 001; OR = 1 46; 95% CI: 1 17–1 83) subjects. Platelets were decreased with malaria infection in controls and eBL cases but elevated with eBL.
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.
Sex-related alcohol expectancies and high-risk sexual behaviour among drinking adults in Kampala, Uganda
(Global Public Health, 2015) Nash, Scott D.; Katamba, Achilles; Kaawa Mafigiri, David; Mbulaiteye, Sam M.; Sethi, Ajay K.
Alcohol consumption, a risk factor for HIV transmission in sub- Saharan Africa, is considered high in Uganda. A cross sectional study was conducted to determine whether sex-related expectations about the effects of alcohol explain the association between alcohol use and risky sexual behaviours in a population based sample of adults in Kampala. Associations between alcohol use (current and higher risk drinking) and high-risk sexual behaviours (multiple regular partners and casual sex) were tested. In age–sex-adjusted models, having multiple regular partners was associated with current drinking (odds ratio [OR] = 2.76, 95% confidence intervals [CIs] = 1.15, 6.63) and higher risk drinking (OR = 3.35, 95% CI = 1.28, 8.71). Associations were similar but not statistically significant for having a causal sex partner. Sex-related alcohol outcome expectancy was associated with both alcohol use and high-risk sexual behaviour and attenuated relationships between multiple regular partners and both current drinking (OR = 1.94, 95% CI = 0.57, 6.73) and higher risk drinking (OR = 2.44, 95% CI = 0.68, 8.80). In this setting sexual behaviours related with alcohol consumption were explained, in part, by sex-related expectations about the effects of alcohol. These expectations could be an important component to target in HIV education campaigns.
Short Report: Intestinal Parasites in Kaposi Sarcoma Patients in Uganda: Indication of Shared Risk Factors or Etiologic Association
(The American journal of tropical medicine and hygiene, 2008) Lin, Cynthia J.; Mbidde, Edward Katongole; Byekwaso, Tadeos; Orem, Jackson; Rabkin, Charles S.; Mbulaiteye, Sam M.
Kaposi sarcoma (KS) is endemic in Uganda and shares several risk factors with intestinal parasite infestation, including rural residence, contact with surface water, and walking barefoot, however, the significance of these ecologic relationships is unknown. We investigated these relationships among 1,985 Ugandan patients with cancer. Odds ratios (OR) were calculated using logistic regression. KS patients had higher carriage of Strongyloides stercoralis larvae (OR 2.1, 95% CI 1.2–3.7) and lower carriage of hookworm ova (0.6, 0.4–1.0) and Entamoeba coli cysts (0.7, 0.5–1.0), after adjusting for region of residence, age, gender, and diagnosis. While our findings may be due to confounding, they are compatible with shared risk factors or etiological association between parasites and KS, and warrant well-designed follow up studies.
Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda
(British journal of haematology, 2020) Kirimunda, Samuel; Verboom, Murielle; Biggar, Robert J.; Prokunina-Olsson, Ludmila; Goedert, James J.; Blasczyk, Rainer; Mbulaiteye, Sam M.
Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein–Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology- based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0–15 years enrolled in northern Uganda and typed by accurate high-resolution HLA sequencing methods. HLA results were analyzed at one- or two-field resolution. Odds ratios and 95% confidence intervals (aOR, 95% CI) for eBL risk associated with common HLA alleles versus alleles that were rare (<1%) or differed by <2% between the cases and controls as the reference category, were estimated using multiple logistic regression adjusting for age, sex, microgeography, region, malaria positivity and treatment history, and genetic variants associated with eBL. Compared to the controls, eBL cases had a lower frequency of HLA-A*02 (aOR = 0 59, 95% CI 0 38–0 91), HLA-B*41 (aOR = 0 36, 95% CI 0 13–1 00), and HLA-B*58 alleles (aOR = 0 59, 95% CI 0 36–0 97). eBL cases had a lower frequency of HLA-DPB1 homozygosity (aOR = 0 57, 95% CI 0 40–0 82) but a higher frequency of HLA-DQA1 homozygosity (aOR = 2 19, 95% CI 1 42–3 37). Our results suggest that variation in HLA may be associated with eBL risk.
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.

Browsing by Author "Mbulaiteye, Sam M."

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