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Margaret Lubwama,1 David P Kateete,2 George Katende,1 Edgar Kigozi,2 Jackson Orem,3 Warren Phipps,4,5 Freddie Bwanga2 1Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda; 3Uganda Cancer Institute, Kampala, Uganda; 4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; 5Allergy and Infectious Diseases Division, Department of Medicine, University of Washington, Seattle, WA, USACorrespondence: Margaret Lubwama, Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P. O Box 7072, Kampala, Uganda, Tel +256 774 440 332, Email margaret.lubwama@mak.ac.ugPurpose: We determined the phenotypic resistance to third-generation cephalosporins, phenotypic extended spectrum beta-lactamase (ESBL) prevalence, and genotypic prevalence of ESBL-encoding genes blaCTX-M, blaTEM, and blaSHV in Enterobacteriaceae isolated from hematologic cancer patients with febrile neutropenia and bacteremia at the Uganda Cancer Institute (UCI).Patients and Methods: Blood cultures from hematologic cancer patients with febrile neutropenia were processed in BACTEC 9120. E. coli, K. pneumoniae, and Enterobacter spp. isolates were identified using conventional biochemical methods. Antimicrobial susceptibility tests, phenotypic ESBL characterization, and genotypic characterization of the ESBL-encoding genes blaCTX-M, blaTEM, and blaSHV were determined for pure isolates of E. coli, K. pneumoniae, and Enterobacter spp.Results: Two hundred and two patients were included in the study. Median age of patients was 19 years (IQR: 10– 30 years). Majority (N=119, 59%) were male patients. Sixty (30%) of the participants had at least one febrile episode due to Enterobacteriaceae. Eighty-three organisms were isolated with E. coli being predominant (45, 54%). Seventy-nine (95%) Enterobacteriaceae were multidrug resistant. The ESBL phenotype was detected in 54/73 (74%) of Enterobacteriaceae that were resistant to third-generation cephalosporins. A higher proportion of Enterobacteriaceae with ESBL-positive phenotype were resistant to piperacillin-tazobactam (p=0.024), gentamicin (p=0.000), ciprofloxacin (p=0.000), and cotrimoxazole (p=0.000) compared to Enterobacteriaceae, which were sensitive to third-generation cephalosporins. The organisms were more susceptible to carbapenems and chloramphenicol than resistant. ESBL-encoding genes (blaCTX-M, blaTEM, and blaSHV) were detected in 55 (75%) of the 73 Enterobacteriaceae that were resistant to third-generation cephalosporins. BlaCTX-M, was the most common ESBL-encoding gene identified with 50 (91%).Conclusion: ESBL-producing Enterobacteriaceae are a predominant cause of bacteremia in hematologic cancer patients at UCI. The most common ESBL-encoding gene identified in the ESBL-PE was blaCTX-M. Resistance to imipenem and meropenem was low.Keywords: antimicrobial resistance, extended spectrum beta-lactamases, enterobacteriaceae, CTX-M, Uganda, cancer

Jackson Orem,1–3 Sven Sandin,1 Caroline E Weibull,1 Michael Odida,4 Henry Wabinga,4 Edward Mbidde,2,3 Fred Wabwire-Mangen,5 Chris JLM Meijer,6 Jaap M Middeldorp,6 Elisabete Weiderpass1,7,81Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 2Uganda Cancer Institute, 3School of Medicine, 4School of Biomedical Sciences, 5School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda; 6Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; 7Cancer Registry of Norway, Oslo; Department of Community Medicine, University of Tromsø, Tromsø, Norway; 8Samfundet Folkhälsan, Helsinki, FinlandBackground: Correct diagnosis is key to appropriate treatment of cancer in children. However, diagnostic challenges are common in low-income and middle-income countries. The objective of the present study was to assess the agreement between a clinical diagnosis of childhood non-Hodgkin lymphoma (NHL) assigned in Uganda, a pathological diagnosis assigned in Uganda, and a pathological diagnosis assigned in The Netherlands.Methods: The study included children with suspected NHL referred to the Mulago National Referral Hospital, Kampala, Uganda, between 2004 and 2008. A clinical diagnosis was assigned at the Mulago National Referral Hospital, where tissue samples were also obtained. Hematoxylin and eosin-stained slides were used for histological diagnosis in Uganda, and were re-examined in a pathology laboratory in The Netherlands, where additional pathological, virological and serological testing was also carried out. Agreement between diagnostic sites was compared using kappa statistics.Results: Clinical and pathological diagnoses from Uganda and pathological diagnosis from The Netherlands was available for 118 children. The agreement between clinical and pathological diagnoses of NHL assigned in Uganda was 91% (95% confidence interval [CI] 84–95; kappa 0.84; P < 0.001) and in The Netherlands was 49% (95% CI 40–59; kappa 0.04; P = 0.612). When Burkitt's lymphoma was considered separately from other NHL, the agreement between clinical diagnoses in Uganda and pathological diagnoses in Uganda was 69% (95% CI 59–77; kappa 0.56; P < 0.0001), and the corresponding agreement between pathological diagnoses assigned in The Netherlands was 32% (95% CI 24–41; kappa 0.05; P = 0.326). The agreement between all pathological diagnoses assigned in Uganda and The Netherlands was 36% (95% CI 28–46; kappa 0.11; P = 0.046).Conclusion: Clinical diagnosis of NHL in Uganda has a high probability of error compared with pathological diagnosis in Uganda and in The Netherlands. In addition, agreement on the pathological diagnosis of NHL between Uganda and The Netherlands is very low.Keywords: Africa, Epstein-Barr virus, non-Hodgkin lymphoma, Burkitt's lymphoma, cancer

The statistical analysis of continuous longitudinal data may be complicated since quantitative levels of bioassay cannot always be determined. Values beyond the limits of detection (LOD) in the assays may not be observed and thus censored, rendering complexity to the analysis of such data. This article examines how both left-censoring and right censoring of HIV-1 plasma RNA measurements, collected for the study on AIDS-related Non-Hodgkin's lymphoma (AR-NHL) in East Africa, affects the quantification of viral load and explores the natural history of viral load measurements over time in AR-NHL patients receiving anticancer chemotherapy. Data analyses using Monte Carlo EM algorithm (MCEM) are compared to analyses where the LOD or LOD/2 (left censoring) value is substituted for the censored observations, and also to other methods such as multiple imputation, and maximum likelihood estimation for censored data (generalized Tobit regression). Simulations are used to explore the sensitivity of the results to changes in the model parameters. In conclusion, the antiretroviral treatment was associated with a significant decrease in viral load after controlling the effects of other covariates. A simulation study with finite sample size shows MCEM is the least biased method and the estimates are least sensitive to the censoring mechanism. [ABSTRACT FROM AUTHOR]