Browsing by Author "Mbidde, Edward Katongole"
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Item Burkitt’s Lymphoma In Africa, A Review Of The Epidemiology And Etiology(African health sciences, 2007) Orem, Jackson; Mbidde, Edward Katongole; Lambert, Bo; Sanjose, Silvia de; Weiderpass, ElisabeteBurkitt\'s lymphoma (BL) was first described in Eastern Africa, initially thought to be a sarcoma of the jaw. Shortly it became well known that this was a distinct form of Non Hodgkin\'s lymphoma.The disease has given insight in all aspects of cancer research and care. Its peculiar epidemiology has led to the discovery of Epstein Barr virus (EBV) and its importance in the cause of several viral illnesses and malignancies.The highest incidence and mortality rates of BL are seen in Eastern Africa. BL affects mainly children, and boys are more susceptible than girls. Evidence for a causal relationship between EBV and BL in the endemic form is fairly strong. Frequency of association between EBV and BL varies between different patient groups and different parts of the world. EBV may play a role in the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal translocation.Although several studies suggest an association between malaria and BL, there has never been a conclusive population study in support of a direct role of malaria in causation of BL.The emergence of HIV and a distinct subtype of BL in HIV infected have brought a new dimension to the disease particularly in areas where both HIV and BL are endemic. BL has been reported as a common neoplasmin HIV infected patients, but not in other forms of immuno-depression, and the occurrence of BL seems to be higher amongst HIV positive adults, while the evidence of an association amongst children is still disputed.The role of other possible risk factors such as low socio-economical status, exposure to a plant species common in Africa called Euphorbiaceae, exposure to pesticies and to other infections such as schistosomiasis and arbovirus (an RNA virus transmitted by insect vectors) remain to be elucidated.Item Capacity Building For The Clinical Investigation Of AIDS Malignancy In East Africa(Cancer Detection and Prevention, 2005) Orem, Jackson; Otieno, Mwanda W.; Banura, Cecily; Mbidde, Edward Katongole; Johnson, John L.; Ayers, Leona; Ghannoum, Mahmoud; Fu, Pingfu; Feigal, Ellen G.; Black, Jodi; Whalen, Christopher; Lederman, Michael; Remick, Scot C.To build capacity in the resource-poor setting to support the clinical investigation and treatment of AIDS-related malignancies in a region of the world hardest hit by the AIDS pandemic.An initial MEDLINE database search for international collaborative partnerships dedicated to AIDS malignancies in developing countries failed to identify any leads. This search prompted us to report progress on our collaboration in this aspect of the epidemic. Building on the formal Uganda-Case Western Reserve University (Case) Research Collaboration dating back to 1987, established NIH-supported centers of research excellence at Case, and expanding activities in Kenya, scientific and training initiatives, research capital amongst our institutions are emerging to sustain a international research enterprise focused on AIDS and other viral-related malignancies.A platform of clinical research trials with pragmatic design has been developed to further enhance clinical care and sustain training initiatives with partners in East Africa and the United States. An oral chemotherapy feasibility trial in AIDS lymphoma is near completion; a second lymphoma trial of byrostatin and vincristine is anticipated and a feasibility trial of indinavir for endemic Kaposi's sarcoma is planned.In the absence of published reports of evolving international partnerships dedicated to AIDS malignancy in resource constrained settings, we feel it important for such progress on similar or related international collaborative pursuits to be published. The success of this effort is realized by the long-term international commitment of the collaborating investigators and institutions to sustain this effort in keeping with ethical and NIH standards for the conduct of research; the provision of formal training of investigators and research personnel on clinical problems our East African partners are faced with in practice and the development of pragmatic clinical trials and therapeutic intervention to facilitate technology transfer and enhance clinical practice.Item Clinical characteristics, treatment and outcome of childhood Burkitt’s lymphoma at the Uganda Cancer Institute(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2011) Orem, Jackson; Mulumba, Yusuf; Algeri, Sara; Bellocco, Rino; Mangen, Fred Wabwire; Mbidde, Edward Katongole; Weiderpass, ElisabeteBurkitt's lymphoma (BL) is a major cause of death among Ugandan children. We studied clinical characteristics and outcomes of childhood BL over time at the Uganda Cancer Institute (UCI). A total of 1217 children (766 boys, 451 girls, mean age 6.69 years) diagnosed with BL between 1985 and 2005 were included. There were no significant changes in the proportion of boys and girls diagnosed, or in mean age at diagnosis. Facial tumor (n = 945, 77.65%) and abdominal disease (n = 842, 69.19%) were the most common presentations. The proportion of children presenting with hepatic mass, malignant pleocytosis, and advanced-stage (stage C and D) BL increased during the study period (P < 0.01). A total of 1085 children out of 1206 (89.97%) received at least one cycle of chemotherapy, and 832 of 1099 (75.71%) demonstrated objective response (i.e. complete or partial remission). The most common symptoms at BL diagnosis were fever (n = 621, 51.03%), anemia (n = 593, 48.73%), and weight loss (n = 588, 48.32%). Significant increases in the proportion of children with fever, and significant changes in the proportion of children with anemia, night sweats and severe infection were observed. HIV positivity was 3.87%, but no substantial differences in the proportion of HIV-positive children were observed. Mortality was not significantly different over time: it was similar in boys and girls, higher in older children (compared with younger ones), in those with advanced-stage BL, and HIV-positive children, but lower in children with facial tumors compared with other tumor presentations, and among those who received chemotherapy.Item Current Investigations And Treatment Of Burkitt’s Lymphoma In Africa(Tropical doctor, 2008) Orem, Jackson; Mbidde, Edward Katongole; Weiderpass, ElisabeteWe reviewed the scientific literature on Burkitt's lymphoma (BL) in Africa in order to provide information on the current status of clinical care and the existing research challenges. BL epidemiology led to the discovery of the Epstein Barr virus, an important cause of several viral illnesses and malignancies. The incidence of BL has increased in the endemic areas of Africa, overlapping with the epidemic of HIV and increase of malaria. The impact of this on the clinical care of BL in the region is therefore of interest, especially in HIV-infected children. Rapid methods must be developed which enable the correct diagnosis to be made. It is important to improve supportive care to allow fairly aggressive treatment, to research into salvage therapy for those who fail first-line treatment, and to develop less toxic drug combinations for HIV-infected patients. Documentation of HIV status through counselling should be offered to all patients.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 Evaluation of HIV-1 Rapid Tests and Identification of alternative Testing Algorithms for Use in Uganda(BMC Infectious Diseases, 2018) Kaleebu, Pontiano; Kitandwe, Paul Kato; Lutalo, Tom; Kigozi, Aminah; Watera, Christine; Nanteza, Mary Bridget; Musinguzi, Joshua; Opio, Alex; Downing, Robert; Mbidde, Edward KatongoleThe World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated.Item Human Herpesvirus Type 8 Variants Circulating In Europe, Africa And North America In Classic, Endemic And Epidemic Kaposi's Sarcoma Lesions During Pre-AIDS and AIDS Era(Virology, 2010) Tornesello, Maria Lina; Biryahwaho, Benon; Downing, Robert; Hatzakis, Angelo; Alessi, Elvio; Cusini, Marco; Ruocco, Vincenzo; Mbidde, Edward Katongole; Loquercio, Giovanna; Buonaguro, Luigi; Buonaguro, Franco M.Human herpesvirus-8 (HHV-8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in Kaposi's sarcoma development remains controversial. In the present study, HHV-8 variant distribution has been analyzed in classic, iatrogenic, endemic as well as epidemic Kaposi's sarcoma (KS) during pre-AIDS and AIDS period (1971–2008) in countries with different KS incidence rate. DNA samples from cutaneous KS lesions of 68 patients living in Africa (n = 23, Cameroon, Kenya and Uganda), Europe (n = 34, Greece and Italy) and North America (n = 11) have been subjected to PCR amplification of HHV-8 ORF 26, T0.7, K1 and K14.1/15, followed by direct nucleotide sequencing and phylogenetic analysis. Among the 23 African samples, the majority of HHV-8 ORF 26 variants clustered with the subtype R (n = 12) and B (n = 5). Conversely, the viral sequences obtained from 45 European and North European tumors belonged mainly to subtype A/C (n = 36). In general, HHV-8 and K1 variant clustering paralleled that of ORF 26 and T0.7. Genotyping of the K14.1/15 loci revealed a large predominance of P subtype in all tumors. In conclusion, comparison of the HHV-8 sequences from classic or endemic versus AIDS-associated KS showed a strong linkage of the HHV-8 variants with specific populations, which has not changed during AIDS epidemic.Item Human Herpesvirus Type 8 Variants In Kaposi’s Sarcoma Before And After AIDS Era(BioMed Central, 2010) Tornesello, Maria Lina; Biryahwaho, Benon; Downing, Robert; Hatzakis, Angelo; Alessi, Elvio; Cusini, Marco; Ruocco, Vincenzo; Loquercio, Giovanna; Mbidde, Edward Katongole; Buonaguro, Luigi; Buonaguro, Franco M.Human herpesvirus 8 (HHV- 8) variants have been found heterogeneously distributed among human populations living in diverse geographic regions, but their differential pathogenicity in Kaposi's sarcoma (KS) development remains controversial. The aim of the present study was to analyze variations of HHV-8 genomes in tumor biopsies collected before and in the course of HIV epidemic (1971 - 2008), from patients with classic, iatrogenic, endemic as well as epidemic KS living in Africa, Europe, and North America.Item Isolation of Genetically Diverse Marburg Viruses from Egyptian Fruit Bats(PLoS pathogens, 2009) Towner, Jonathan S.; Amman, Brian R.; Sealy, Tara K.; Carroll, Serena A. Reeder; Comer, James A.; Kemp, Alan; Swanepoel, Robert; Paddock, Christopher D.; Balinandi, Stephen; Khristova, Marina L.; Formenty, Pierre B. H.; Albarino, Cesar G.; Miller, David M.; Reed, Zachary D.; Kayiwa, John T.; Mills, James N.; Cannon, Deborah L.; Greer, Patricia W.; Byaruhanga, Emmanuel; Farnon, Eileen C.; Atimnedi, Patrick; Okware, Samuel; Mbidde, Edward Katongole; Downing, Robert; Tappero, Jordan W.; Zaki, Sherif R.; Ksiazek, Thomas G.; Nichol, Stuart T.; Rollin, Pierre E.In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.Item Kaposi’s Sarcoma In Childhood: An Analysis Of 100 Cases From Uganda And Relationship To HIV Infection(International Journal of Cancer, 1996) Ziegler, John L.; Mbidde, Edward KatongoleWe report 100 cases of Kaposi's sarcoma (KS) in children under 15 years of age treated at the Uganda Cancer Institute in the 6-year period 1989–1994. The incidence of childhood KS has risen more than 40-fold in the era of AIDS, and 78% of 63 cases tested were seropositive for HIV-I. There were 63 boys and 37 girls. The median age was 4 years and the median age of onset was 33 months. Tumour distribution was lymphadenopathic and muco-cutaneous, with 2 major patterns: pattern I, oro-facial dominant (79%); and pattern II, inguinal-genital dominant (13%). A newly described herpes-like virus is implicated as the cause of KS (KSHV), and DNA sequences of this virus were present in all of 8 childhood cases tested. If KSHV is a direct cause of KS, this tumour distribution in children suggests mucosal routes of virus entry, possibly during birth or breast feeding. The dramatic increase of childhood KS implies that the prevalence of causative factors is rising in Uganda.Item Risk Of Being Seropositive For Multiple Human Papillomavirus Types Among Finnish And Ugandan Women(Scandinavian journal of infectious diseases, 2010) Namujju, Proscovia Bazanya; Surcel, Heljä-Marja; Kirnbauer, Reinhard; Kaasila, Marjo; Banura, Cecily; Byaruhanga, Romano; Muwanga, Moses; Mbidde, Edward Katongole; Koskela, Pentti; Lehtinen, MattiAlthough infections with multiple human papillomavirus (HPV) types have been reported widely, more information is needed on the occurrence of the different types. We determined the distribution of seroprevalences to multiple HPV types in Finland and Uganda to compare the epidemiology of the different HPV types in the 2 populations. Serum samples were obtained from 2784 Finnish and 1964 Ugandan women (mean ages 22 y and 25 y, respectively) of whom 44% and 57%, respectively, had antibodies to at least 1 of the 7 HPV types (6, 11, 16, 18, 31, 33, 45) tested ( p 0.001). Multiple HPV antibody positivity was common. HPV45-seropositive Finns had a higher risk of having antibodies to other high-risk HPV types: HPV18 (odds ratio (OR) 10.9), HPV31 (OR 6.1), HPV33 (OR 12.2), than their Ugandan counterparts: HPV18 (OR 3.4), HPV31 (OR 2.2), HPV33 (OR 3.3). Increased estimates for being double antibody-positive were also noted among HPV18- and HPV16- seropositive women, but there were no major differences between HPV16-seropositive Finns and Ugandans. In addition to biological and behavioural factors, iatrogenic and societal factors (screening vs no screening) may also result in the different occurrence of infections with the high-risk HPV types in Finland and Uganda.Item 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.Item Successful Treatment Of Human Plague With Oral Ciprofloxacin(Emerging infectious diseases, 2017) Apangu, Titus; Griffith, Kevin; Abaru, Janet; Candini, Gordian; Apio, Harriet; Okoth, Felix; Okello, Robert; Kaggwa, John; Acayo, Sarah; Ezama, Geoffrey; Yockey, Brook; Sexton, Christopher; Schriefer, Martin; Mbidde, Edward Katongole; Mead, PaulThe US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.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.