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Point-of-care tests for tuberculous meningitis (TBM) are needed. We studied the diagnostic accuracy of the lipoarabinomannan (LAM) lateral flow assay (LFA), LAM enzyme-linked immunosorbent assay (ELISA), and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent postmortem from the next of kin. A complete autopsy was done and CSF obtained. We performed LAM LFA (on unprepared and supernatant CSF after heating and spinning), LAM ELISA, and Xpert MTB/RIF on the CSF samples. Accuracy parameters were calculated for histopathological TBM and also for the composite standard, including Xpert MTB/RIF-positive cases. We tested CSF of 91 patients. LAM LFA had a sensitivity of 75% for definite histopathological TBM, ELISA a sensitivity of 43%, and Xpert MTB/RIF a sensitivity of 100% and specificities of 87%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 50% for definite and probable histopathological TBM, ELISA a sensitivity of 38%, and Xpert MTB/RIF a sensitivity of 86% and specificities of 70%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 68% for the composite standard and ELISA a sensitivity of 48% and specificities of 78% and 98%, respectively. The rapid diagnostic tests detected TBM in 22% to 78% of patients not on anti-TB treatment. Point-of-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool.
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Líquido Cefalorraquidiano/química , DNA Bacteriano/análise , Infecções por HIV/complicações , Imunoensaio/métodos , Lipopolissacarídeos/análise , Técnicas de Diagnóstico Molecular/métodos , Tuberculose Meníngea/diagnóstico , Adulto , Autopsia , Estudos de Coortes , DNA Bacteriano/genética , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , UgandaRESUMO
BACKGROUND: Research on cardiac arrest and cardiopulmonary resuscitation (CPR) has considerably increased in recent decades, and international guidelines for resuscitation have been implemented and have undergone several changes. Very little is known about the prevalence and management of in-hospital cardiac arrest in low-resource settings. We therefore sought to determine the prevalence, outcomes and associated factors of adult inpatients with cardiac arrest at a tertiary referral hospital in a low-income country. METHODS: Upon obtaining institutional approval, we conducted a prospective observational period prevalence study over a 2-month period. We recruited adult inpatients with cardiac arrest in the intensive care unit and emergency wards of Mulago Hospital, Uganda during the study period. We reviewed all files and monitoring charts, and also any postmortem findings. Data were analyzed with Stata 12 and statistical significance was set at p < 0.05. RESULTS: There was a cardiac arrest in 2.3% (190) of 8,131 hospital admissions; 34.5% occurred in the intensive care unit, 4.4% in emergency operating theaters, and 3.0% in emergency wards. A majority (63.2%) was unwitnessed, and only 35 patients (18.4%) received CPR. There was return of spontaneous circulation (ROSC) in 14 (7.4%) cardiac arrest patients. Survival to 24 h occurred in three ROSC patients, which was only 1.6% of all cardiac arrest patients during the study period. Trauma was the most common primary diagnosis and HIV infection was the most common co-morbidity. CONCLUSION: Our hospital has a high prevalence of cardiac arrest, and low rates of CPR performance, ROSC, and 24-hour survival. Single provider CPR; abnormal temperatures as well as after hours/weekend CAs were associated with lower survival rates.
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Países em Desenvolvimento , Parada Cardíaca/epidemiologia , Hospitalização , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Uganda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Percutaneous needle autopsy can overcome a number of barriers that limit the use of complete autopsies. We performed blind-and ultrasound guided needle autopsies in HIV-infected adults in Uganda. In this study we describe in detail the methods we used, the ability of both procedures to obtain sufficient tissue for further examination and the learning curve of the operators over time. METHODS: If written informed consent was granted from the next of kin, we first performed a blind needle autopsy, puncturing brain, heart, lungs, liver, spleen and kidneys using predefined surface marking points. We then performed an ultrasound guided needle autopsy puncturing heart, liver, spleen and kidneys. The number of attempts, expected success and duration of the procedure were noted. A pathologist read the slides and indicated if the target tissue was present and of sufficient quality for pathological review. We report the predicted and true success rates, compare the yield of blind to ultrasound guided needle biopsies and evaluate the failure rate over time. RESULTS: Two operators performed 96 blind needle autopsies and 95 ultrasound guided needle autopsies. For blind needle biopsies true success rates varied from 56-99% and predicted success rates from 89-99%. For ultrasound guided needle biopsies true success rates varied from 72-100% and predicted success rates from 84-98%. Ultrasound guidance led to a significantly higher success rate in heart and left kidney. A learning curve was observed over time with decreasing failure rates with increasing experience and a shorter duration of the needle autopsy. CONCLUSION: Needle autopsy can successfully obtain tissue for further pathological review in the vast majority of cases, with a decrease in failure rate with increasing experience of the operator. The benefit of ultrasound guidance will depend on the population, the disease and organ of interest and the local circumstances. Our results justify further evaluation of needle autopsies as a method to establish a cause of death.
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The incidence and economic burden of cancer in sub-Saharan Africa is increasing, and innovative strategies are needed to improve prevention and care in this population. This article uses a case of cutaneous T-cell lymphoma in Uganda to propose guidelines for the diagnosis and treatment of this disease in resource-limited settings. These guidelines were developed from the consensus opinion of specialists at the Uganda Cancer Institute and Fred Hutchinson Cancer Research Center as part of an established collaboration. Areas for future investigation that can improve the care of patients in this region are identified.
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Países em Desenvolvimento , Linfoma Cutâneo de Células T/diagnóstico , Neoplasias Nasais/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Recursos em Saúde , Humanos , Masculino , Guias de Prática Clínica como Assunto , UgandaRESUMO
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma that histologically resembles embryonic skeletal muscle. It can occur anywhere in the body, including tissues devoid of skeletal muscles. RMS is a common malignancy in children, and it accounts for Ë50% of all soft tissue sarcomas in children. Embryonal rhabdomyosarcoma (ERMS) mostly affects children younger than 10 years of age. The head and neck area, the genitourinary tract and the retroperitoneum are described as the preferred anatomic sites for ERMS development. However, the mesentery location is extremely rare. We report a rare case of an ERMS occurring in the mesentery of a 17-year-old male.
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Background: The loss of health workers through death is of great importance and interest to the public, media and the medical profession as it has very profound social and professional consequences on the delivery of health services. Objective: To describe the profile, causes and patterns of death among medical doctors and dental surgeons in Uganda between 1986 and 2016. Methods: We conducted a retrospective descriptive study of mortality among registered medical doctors and dental surgeons. Information on each case was collected using a standard questionnaire and analysed. Cause of death was determined using pathology reports, and if unavailable, verbal autopsies. We summarized our findings across decades using means and standard deviations, proportions and line graphs as appropriate. Cuzick's test for trend was used to assess crude change in characteristics across the three decades. To estimate the change in deaths across decades adjusted for age and sex, we fit a logistic regression model, and used the margins command with a dy/dx option. All analyses were done in Stata version 14.0 (Stata Corp, College Station, TX). Results: There were 489 deaths registered between 1986 and 2016. Of these, 59 (12.1%) were female. The mean age at death was 48.8 years (Standard Deviation (SD) 15.1) among male and 40.1 years (SD 12.8) among females. We ascertained the cause of death for 468/489 (95.7%). The most common causes of death were HIV/AIDS (218/468, 46.6%), cancer (68/468, 14.5%), non-communicable diseases (62/48, 13.3%), alcohol related deaths (36, 7.7%), road traffic accidents (34, 7.3%), gunshots (11, 2.4%), among others. After adjusting for age and sex, HIV/AIDs attributable deaths decreased by 33 percentage points between the decade of 1986 to1995 and that of 2006 to 2016 -0.33 (-0.44, -0.21. During the same period, cancer attributable deaths increased by 13 percentage periods 0.13 (0.05,0.20). Conclusion: The main causes of death were HIV/AIDS, cancer, non-communicable diseases, alcohol-related diseases and road traffic accidents. There was a general downward trend in the HIV/AIDS related deaths and a general upward trend in cancer related deaths. Doctors should be targeted for preventive and support services especially for both communicable and non-communicable diseases.
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Síndrome da Imunodeficiência Adquirida , Neoplasias , Doenças não Transmissíveis , Cirurgiões , Humanos , Masculino , Feminino , Causas de Morte , Uganda , Estudos RetrospectivosRESUMO
Introduction: SARS-CoV-2 is a fatal disease of global public health concern. Measures to reduce its spread critically depend on timely and accurate diagnosis of virus-infected individuals. Biobanks can have a pivotal role in elucidating disease etiology, translation, and advancing public health. In this article, we show how a biobank has been a critical resource in the rapid response to coronavirus disease of 2019 (COVID-19) in Uganda. Materials and Methods: The Integrated Biorepository of H3Africa Uganda established a COVID-19 biobank. Standard Operating Procedures for sample and data collection, sample processing, and storage were developed. An e-questionnaire data tool was used to collect sociodemographic factors. Samples were collected at 7-day intervals from patients, analyzed for key parameters, processed, annotated, characterized, and stored at appropriate temperatures. Results: Stored samples have been used in validation of 17 diagnostic kits, the Cepheid Xpert Xpress SARS-CoV-2 assay, as well as a sample pooling technique for mass screening and polymerase chain reaction assay validation. Kits that passed validation were deployed for mass screening boosting early detection, isolation, and treatment of COVID-19 cases. Also, 10 applications from researchers and biotech companies have been received and approved and 4 grants have been awarded Conclusion: The CoV-Bank has proven to be an invaluable resource in the fight against the COVID-19 pandemic in Uganda, as samples have been resources in the validation and development of COVID-19 diagnostic tools, which are important in tracing and isolation of infected cases to confront, delay, and stop the spread of the SARS-CoV-2 virus.
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COVID-19 , Bancos de Espécimes Biológicos , COVID-19/epidemiologia , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Humanos , Pandemias , SARS-CoV-2 , Uganda/epidemiologiaRESUMO
Burkitt lymphoma accounts for approximately 50% of pediatric cancers in equatorial Africa and a majority of NHL in Uganda. The aim of the study was to examine the expression profile of the RB (pRb2 or p16) and p53 (p53, p14, or p21) pathways in biopsies of endemic BL, and compare it to the pattern found in reactive lymphoid hyperplasia (RLH). A total of 51 BL and 10 RLH biopsy specimens were included in the study. p16 expression was found in 8 (16.3%) BL and 2 (20%) RLH cases. p27 was revealed in 29 (65.9%)BL and 9(90%) RLH cases, whereas 29(59.2%) BL and only 1 RLH expressed p53. Positivity for pRb2 was found in 42 (84.0%) of the BL and 8(80%)of the RLH cases. p21 and p14 were negative in all BL and RLH cases. In conclusion, our data indicate that heterogeneous RB (pRb2 or p16) and p53 (p53, p14, or p21) pathway alterations occur frequently in BL. Except for a much higher frequency of p53 protein expression in BL, close similarities were found between BL and RLH.
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Linfoma de Burkitt/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Pseudolinfoma/metabolismo , Proteína p130 Retinoblastoma-Like/biossíntese , Proteína Supressora de Tumor p14ARF/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adolescente , Linfoma de Burkitt/genética , Criança , Pré-Escolar , Proteína Substrato Associada a Crk/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/genética , Doenças Endêmicas , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pseudolinfoma/genética , Transdução de Sinais/fisiologia , Análise Serial de TecidosRESUMO
BACKGROUND: Cancer burden in sub-Saharan Africa is on the rise with one-third of cancers estimated to be caused by infectious agents. Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy in sub-Saharan Africa and includes tumors in the Upper Aero-digestive Tract (UADT). The established risk factors are tobacco and alcohol exposure with a recent recognition of the role of Human Papilloma Virus (HPV). The HPV related HNC is seen predominantly in the oropharynx, presents at a younger age and has a better prognosis. With a rapidly increasing incidence of these cancers in the developed world, it was important to study HPV in HNC in Uganda. The HPV can be detected using P16 immunohistochemistry as a surrogate marker thus making it suitable for screening. The study aimed at establishing the presence of HPV and the commonly affected sites in UADT squamous cell carcinoma (SCC) at Uganda Cancer Institute (UCI) using P16 immunohistochemistry. METHODOLOGY: This was a cross sectional study in which 59 patients with histologically proven SCC from the oral cavity, oropharynx, larynx and hypopharynx were recruited. These patients' demographics and clinical data were collected. Tissue sections from retrieved histology samples were stained by Haematoxylin and Eosin to reconfirm SCC. Subsequently, P16 expression was determined using P16 immunohistochemistry. RESULTS: Seventy-one patients were enrolled and 59 patients with confirmed SCC of the sites of interest were analyzed. The majority (79.7%) of the participants were male and over 50 years. 59.3% were tobacco smokers, 66.1% used alcohol, 52.2% used both. Only 27.1% used none of the substances. Only 27.1% of the participants were HIV positive. Most of the tumors were in the larynx (37.3%) and 64.4% were overall TNM stage 4. The overall prevalence of HPV in UADT SCC at UCI was 20.3, 95%CI 10.9-32.8. The oropharynx had the highest prevalence (30.8%). CONCLUSION: The prevalence of HPV in UADT SCC at UCI is significant at 20.3%. The most affected site, is the oropharynx. Vigilant HPV screening of these sites with confirmation where possible is recommended.
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BACKGROUND: The expression of estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor-2 (HER2) has been reported to have an invaluable prognostic role. The aim of this study was to determine the expression of ER, PR and HER2 in women with breast cancer (BC) in Kampala, Uganda. METHODS: Expression of ER, PR and HER2 was determined immunohistochemically. Logistic regression was performed to determine the effect of the independent factors in predicting the risk of not expressing the breast markers. A two-tailed p<0.05 was regarded to be statistically significant. RESULTS: ER, PR and HER2 were expressed in 53.4%, 46.6% and 18.5%, respectively. ER and PR co-expression was present in 42.7% and 37.9% patients had triple negative breast cancer (TNBC). Age was an independent predictor of expression of ER (AOR = 0.18, 95% CI = 0.062-0.541, p = 0.002) and PR (AOR = 0.35, 95% CI = 0.129-0.968, p = 0.043). CONCLUSION: The majority of patients in this study had less than 50 years with high tumour grade. Interestingly, most of them had high expression of HER2 with TNBC which are molecular subtypes of BC with poor prognosis. Age was an independent predictor of expression of both ER and PR.
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BACKGROUND: The members of the retinoblastoma protein family, pRb, p107 and pRb2 (p130), are central players in controlling the cell cycle. Whereas disturbed function of pRb is commonly seen in human cancers, it is still an open question whether pRb2 is involved in tumorigenic processes. However, altered subcellular localization of pRb2 and mutations in the pRb2-encoding gene RBL2 have been described for some tumours, including Burkitt lymphomas (BL). METHODS: We retrieved 51 biopsy specimens of endemic BL cases from Uganda. The expression of pRb2 was determined by immunohistochemistry. Exons 1922 of the RBL2 gene, the region known to contain a nuclear localization signal, were screened for mutations by PCR amplification and direct DNA sequencing. RESULTS: Nearly all of our cases (84.0%) were positive for pRb2 protein expression although this protein is a marker for growth arrest and Burkitt lymphoma is characterized by a high proliferation rate. Of the positive cases, 73.8% were scored as expressing the protein at a high level. Subcellular pRb2 localization was predominantly nuclear and no cases with expression restricted to the cytoplasm were observed. We did not detect any RBL2 mutations in the part of the gene that encodes the C-terminal end of the protein. CONCLUSION: The majority of endemic BL cases from Uganda express pRb2, but somatic RBL2 mutations affecting the protein's nuclear localization signal appear to be rare.
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AIM: To evaluate the efficacy of a pediatric multidisciplinary tumor board (MTB) in Uganda. PATIENTS & METHODS: We documented the discussion of cases presented at a pediatric MTB and subsequently, though retrospective chart review, determined the degree to which decision were implemented. RESULTS: 95 patients were discussed. In total, 129 of 226 (57%) distinct management decisions reached during the MTBs were implemented. Of these, 15 resulted in changes in diagnosis and 53 were classified as major changes in management. Decisions on chemotherapy were the most likely to be successfully enacted (51/58), followed by radiotherapy (18/30) and surgery (12/21). Labs/consults were less likely to be implemented. CONCLUSION: Key improvements, specifically in the documentation and implementation of management decisions, are needed to improve the MTB's efficacy.
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OBJECTIVE: The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults. METHODS: We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings. RESULTS: Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death. CONCLUSION: Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.
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Infecções por HIV/urina , Rim/patologia , Lipopolissacarídeos/urina , Tuberculose Renal/urina , Adulto , Biomarcadores/urina , Estudos de Coortes , Feminino , Humanos , Rim/microbiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , UgandaRESUMO
INTRODUCTION: Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda. METHODS: We subsequently performed a blind and ultrasound-guided needle autopsy followed by a complete autopsy in HIV-infected adults who died during hospitalization. Two teams of pathologists reviewed the tissue from either the needle autopsies or the complete autopsy and formulated the major diagnoses, that is, diseases directly contributing to death. The primary outcome was concordance in major diagnosis between needle and complete autopsies. RESULTS: We performed 96 blind needle and complete autopsies and 95 ultrasound-guided needle autopsies. Concordance in major diagnosis between blind needle and complete autopsy was 50%. For the main major diagnosis, tuberculosis (TB) concordance was higher (71%; P < 0.01). Blind needle autopsy identified at least 1 major diagnosis in 60% of patients; and in 46%, there was complete concordance for all major diagnoses. The main reason for discordance was sampling error of the lesion. Concordance with the addition of ultrasound guidance was 52% for all major diagnoses and 79% for TB. Major diagnoses were mainly identified in tissue cores from the liver (76%) and the spleen (82%). DISCUSSION: Blind needle autopsy identified half of the major diagnosis. The addition of ultrasound guidance did not significantly improve the performance of needle autopsy. Needle autopsy is a valuable method to confirm causes of death in HIV-infected patients, especially for highly prevalent diseases like TB.
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Autopsia/métodos , Biópsia por Agulha/métodos , Causas de Morte , Infecções por HIV/mortalidade , Adulto , Feminino , Humanos , Masculino , UgandaRESUMO
Burkitt lymphoma (BL) accounts for 80% of Non-Hodgkin lymphoma in Uganda. The tumour is fast growing with a very short doubling time. Inhibition of apoptosis, achieved through the apoptosis inhibitor family of proteins enhances survival of cancer cells. The aim of this study was to explore the expression of apoptosis related proteins Survivin, Livin and Thrombospondin-1 (TSP-1) in BL and comparing it with the expression in reactive follicular hyperplasia. Among the BL cases, survivin was positive in 37 (75%) and negative in 12 (25%). Livin staining was positive in 23 (48%) and negative in 25 (52%) of the BL cases. TSP-1 was positive in 40 (87%) and negative in 6 (13%) of the BL cases. All the 10 reactive lymphoid hyperplasia (RLH) were positive for survivin, livin expression was found in 4 (40%), whereas TSP-1 was positive in 7 (70%) of the RLH cases. Among the BL, there was no statistically significant association between survivin and livin expression (p = 0.6), livin and TSP-1 (p = 1.0) or survivin and TSP-1 (p = 0.6). Likewise no statistical association was found between the expressions of the proteins in RLH. There was no statistically significant difference between the expression frequency of the apoptosis associated proteins examined in BL and RLH. In conclusion, we have demonstrated the expression of inhibitor of apoptosis proteins, survivin and Livin and the pro-apoptotic protein TSP-1 in endemic BL. No significant difference was found between BL and RLH.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfoma de Burkitt/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Trombospondina 1/metabolismo , Apoptose , Humanos , Imuno-Histoquímica , Pseudolinfoma/metabolismo , Survivina , UgandaRESUMO
In Uganda, a large number of biopsied enlarged lymph nodes is diagnosed as reactive lymphoid hyperplasia (RLH) not indicative of a specific etiologic agent. The aim of this study was to examine the spectrum of RLH in lymph node biopsies in Ugandan patients and their possible association with HIV and EBV infection. Ninety biopsies were retrieved and included in the study. The predominant RLH type was follicular, found in 45 (50.0%) of the cases. Positive staining for LMP-1 was found in six cases (6.7%), EBNA-1 in 36 cases (40.0%) and HIV1-p24 in 15 cases (16.7%), respectively. A combination of EBV and HIV positivity was found in 46 (52.2%) of the cases. EBV infection was associated with hyperplastic germinal centers (p<0.01). HIV1-p24 positive staining was associated with follicle fragmentation (p<0.01) but not hyperplastic GC (p=0.08). In conclusion, RLH in Ugandan patients is frequently associated with EBV and HIV infection. The histologic features of the lymph nodes are not specific for any individual infection, but a high number of EBV-positive cases are associated with hyperplastic GC, and follicular fragmentation is characteristic of HIV infection.