Immunological and biochemical biomarker alterations among SARS-COV-2 patients with varying disease phenotypes in Uganda.

Every novel infection requires an assessment of the host response coupled with identification of unique biomarkers for predicting disease pathogenesis, treatment targets and diagnostic utility. Studies have exposed dysregulated inflammatory response induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as significant predictor or cause of disease severity/prognosis and death. This study evaluated inflammatory biomarkers induced by SARS-CoV-2 in plasma of patients with varying disease phenotypes and healthy controls with prognostic or therapeutic potential. We stratified SARS-CoV-2 plasma samples based on disease status (asymptomatic, mild, severe, and healthy controls), as diagnosed by RT-PCR SARS-CoV-2. We used a solid phase sandwich and competitive Enzyme-Linked Immunosorbent Assay (ELISA) to measure levels of panels of immunological (IFN-γ, TNF-α, IL-6, and IL-10) and biochemical markers (Ferritin, Procalcitonin, C-Reactive Protein, Angiotensin II, Homocysteine, and D-dimer). Biomarker levels were compared across SARS-CoV-2 disease stratification. Plasma IFN-γ, TNF-α, IL-6, and IL-10 levels were significantly (P < 0.05) elevated in the severe SARS-CoV-2 patients as compared to mild, asymptomatic, and healthy controls. Ferritin, Homocysteine, and D-dimer plasma levels were significantly elevated in severe cases over asymptomatic and healthy controls. Plasma C-reactive protein and Angiotensin II levels were significantly (P < 0.05) higher in mild than severe cases and healthy controls. Plasma Procalcitonin levels were significantly higher in asymptomatic than in mild, severe cases and healthy controls. Our study demonstrates the role of host inflammatory biomarkers in modulating the pathogenesis of COVID-19. The study proposes a number of potential biomarkers that could be explored as SARS-CoV-2 treatment targets and possible prognostic predictors for a severe outcome. The comprehensive analysis of prognostic biomarkers may contribute to the evidence-based management of COVID-19 patients.

Aneurysmal bone cyst of the mandible: a rare case report and literature review.

Introduction and importance: Aneurysmal bone cysts (ABCs) are benign, non-neoplastic cystic lesions composed of multiple blood-filled cavities, which are separated by connective tissue septa and they constitute ~6 and 1.5% of all cases of the skull and jaws lesions, respectively. Case presentation: Herein, the case of an 80-year-old male with a histologically confirmed diagnosis of ABC involving the body of the left mandible was presented. The patient underwent partial mandiblectomy after confirmation of the diagnosis using orthopantomography, a computed tomography scan, and a tissue biopsy. The patient was free from pain after 1-year of follow-up, and the control orthopantomography showed no evidence of recurrence. This was followed by reconstruction of the healed part of the bone with titanium plates and a piece of bone from the lateral two-thirds of the left femur and thereafter he was cosmetically well. Clinical discussion: Patients with ABCs present with expansile and radiolucent bone lesions, which may be associated with displacement and loss of teeth due to alveolar bone erosion. Complete excision of the lesions is mandatory for the prevention of recurrence and increased morbidity. Conclusion: ABCs that involve the jaws are extremely rare and are more likely to pose a diagnostic challenge as they are more likely to be confused clinically with other expansile radiolucent bone lesions such as ameloblastoma, osteoblastoma, and giant cell tumor among many others. Also, those with extensive bone matrix formation may sometimes be confused histologically with other bone forming tumors including osteosarcoma. Recurrence is common but it can be avoided or minimized by complete resection of the lesion.

Immunohistochemical expression of P53 protein in nephroblastoma: a predictor of unfavorable prognosis.

OBJECTIVE: Immunohistochemical expression of P53 protein is so closely related to status of mutation of P53 gene which is tightly linked with pathogenesis of nephroblastoma or Wilms tumor. This study aims to determine the immunohistochemical expression of P53 protein and its predictors in formalin-fixed paraffin-embedded tissue blocks of patients with nephroblastoma. MATERIALS AND METHODS: A series of 83 histologically diagnosed cases of nephroblastoma from formalin-fixed paraffin-embedded tissue blocks archived at the Department of Pathology, Makerere University, in Kampala, Uganda, were analyzed. Monoclonal anti-p53 antibody (DO-7, DAKO) was used to assess the expression of P53 protein expression. Multivariable logistic regression analysis was performed to determine the predictors of P53 protein immunohistochemical expression, and statistical significance was considered when p-value was less than 0.05. RESULTS: Most (42.2%, n = 35) of the cases were in advanced tumor stages (III-V), and almost one-quarter (21.7%, n = 18) of the cases were in high-risk group. The immunohistochemical expression of P53 protein was (8.4%, n = 7), and there were more (83.3%, n = 5) positive anaplastic cases for P53 protein compared with (2.6%, n = 2) of P53 expression for non-anaplastic cases. High risk (AOR = 3.42, 95% CI = 7.91-12.55, p = 0.037) and anaplasia (AOR = 1.41, 95% CI = 13.85-4.46, p = 0.001) were potential predictors of immunohistochemical expression of P53 protein. CONCLUSION: Most of patients with nephroblastoma in resources-limited settings are diagnosed with advanced clinical stages. Association of P53 protein with anaplasia found in this study indicates the possibility of having novel target therapy for treatment of patients with anaplastic form of nephroblastoma with a focus of identifying molecules that lead to its suppression in such subpopulations of patients with nephroblastoma.

Invasive ductal carcinoma of breast in a 73-year old male: A rare case report and literature review.

INTRODUCTION AND IMPORTANCE: Male breast cancers despite being similar to female breast cancers in various aspects; however, they have important distinctive characteristics such as molecular biology, increased tendency for axillary lymph node metastasis and late age at presentation. PRESENTATION OF CASE: We present the case of a 73-year old indigenous African male who had a 3-year history of right breast swelling which was associated with episodes of pain and tenderness. The assigned clinical stage for the patient was T2aNoMo. The mass was histologically confirmed to be invasive ductal carcinoma, not specified type (NST) without axillary lymph node involvement or distant metastasis. Immunohistochemistry also showed positive results for ER and PR hormonal receptors but negative for HER2. CLINICAL DISCUSSION: Considering the rarity nature of male breast cancers, this contributes to lack of evidence of the specific treatment approaches despite the noticeable difference in clinical presentation and even biological characteristics of male breast cancers, which are more likely to contribute to poor prognosis. CONCLUSION: The prevalence of male breast cancers has been reported to be less than 1 % of all male cancers. This contributes to the lack of analytical large studies that address the comprehensive data regarding the clinical outcomes of breast cancer among men and their predictors. Therefore, having prospective multicenter studies in future would help in providing high level of evidence on prognosis.

Frequency and distribution of ABO and Rh blood group systems among blood donors at the Northern Zone Blood Transfusion Center in Kilimanjaro, Tanzania: a retrospective cross-sectional study.

OBJECTIVES: ABO and Rh blood group systems are the major factors affecting the blood transfusion safety. The frequency and distribution of these blood group systems vary worldwide. We aimed to determine the frequency and distribution of ABO and Rh blood group systems among first-time blood donors at the Northern Zone Blood Transfusion Center in Kilimanjaro, Tanzania. DESIGN: Cross-sectional descriptive population-based study. SETTING: Data on ABO and Rh blood group systems were obtained and analysed from the Northern Zone Blood Transfusion Center among first-time blood donors. PARTICIPANTS: There were 65 535 first-time blood donors aged 15-55 years who donated at the Northern Zone Blood Transfusion Center from January 2017 to December 2019. OUTCOME MEASURES: The percentage of ABO and Rh blood group systems among different categories of blood donors was calculated. RESULTS: Retrospective data from Blood Establishment Computer System of 65 535 first-time blood donors were analysed in the present study. The mean age of the blood donors was 30.6±11.2 years (range: 15-55 years). The vast majority of the blood donors 84.2% (n=55 210) were men. Also, the majority 69.6% (n=45 595) were aged ≥35 years. Blood group O was the most common blood group which was found in over half 52.4% (n=34 333) of the blood donors and majority 95.3% (n=62 461) of the donors were Rh positive. Moreover, the majority 78.3% (n=51 336) were voluntary donors and the remaining 21.7% (n=14 199) were replacement donors. CONCLUSION: Majority of the donors had blood group O and also the vast majority of the donors were Rh positive. Considering the large size of our study population, this has provided a more comprehensive information regarding the frequency and patterns of ABO and Rh blood group systems in Tanzania. The observed association of blood group A with one of the regions from which donors were coming from, is intriguing and further studies may confirm possible related genetic evolution.

Disseminated peritoneal leiomyomatosis as an incidental finding: A case report.

We present the case of a 23-year-old female with multiple diffuse and nodular masses of different sizes involving predominantly the posterior wall of the uterus, omentum, and peritoneum which were histopathologically confirmed to be disseminated peritoneal leiomyomatosis. Meticulous investigation and accurate diagnosis are of utmost importance for the establishment of the correct diagnosis. Additionally, proper management of the patient while considering choice of the patients including close follow-up of the patients is mandatory for the reason of ensuring early detection of recurrence.

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing in Women with Breast Cancer in Kampala, Uganda.

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.

Knowledge, Attitude, and Beliefs of Communities and Health Staff about Echinococcus granulosus Infection in Selected Pastoral and Agropastoral Regions of Uganda.

A descriptive cross-sectional survey was done to determine knowledge, attitudes, and beliefs of the communities and health workers about cystic echinococcosis (CE) in pastoral region of Northeastern (NE) and agropastoral regions of Eastern (E) and Central (C) Uganda. Overall a total of 1310 participants were interviewed. Community respondents from NE region were more aware of CE infection than those from Eastern (OR 4.85; CI: 3.60-6.60; p < 0.001) and Central (OR 5.73; CI: 4.22-7.82; p < 0.001) regions. 19.8% of the respondents from EA region had positive attitude towards visiting witch doctors for treatment compared with 62.0% and 60.4% from NE and Central regions, respectively (p < 0.001). Notably, the awareness of CE increased with level of education (p < 0.001). There was no statistical difference between male and female respondents as far as awareness of CE was concerned (p > 0.05). 51.7% of the community respondents from Central believed CE is caused by witchcraft, compared with 31.3% and 14.3% from NE and EA regions, respectively (p < 0.001). There was no statistical difference between health staff regarding their knowledge, attitude, and beliefs about CE infection (p > 0.05). None of the participants knew his/her CE status. The communities need to be sensitized about CE detection, control, and management and health staff need to be trained on CE diagnosis.

Knowledge, attitudes and practices towards cystic echinococcosis in livestock among selected pastoral and agro-pastoral communities in Uganda.

A cross-sectional study was done from March 2013 to May 2014 to assess knowledge, attitudes, and practices towards cystic echinococcosis (CE) or hydatidosis among selected pastoral and agro-pastoral communities in Uganda. A structured questionnaire was administered to 381 respondents. Multivariate logistic regression analysis was done to find the relationship between knowledge about CE and factors such as age, sex, and level of education across all regions. The odds ratio and confidence interval were used to determine the difference in responses across regions. It was shown that age above 36 years was significantly (p < 0.001) associated with awareness about CE in livestock. Likewise, uneducated (p < 0.0001) and agro-pastoralists (p = 0.01) were significantly less knowledgeable than the educated and pastoralists across all regions. The overall knowledge towards CE in livestock was low 17.8% (95% CI = 14.0-21.6). Dog ownership was high and they never dewormed their freely roaming dogs. Dogs shared water with livestock. In conclusion, knowledge about CE in livestock was low across all regions. Therefore, public health education and formulation of policies towards its control by the relevant stakeholders should be done. Also, the true prevalence of CE in livestock needs to be done so that the magnitude and its public health significance are elucidated.

Identification of Echinococcus granulosus strains using polymerase chain reaction-restriction fragment length polymorphism amongst livestock in Moroto district, Uganda.

A descriptive study was conducted to identify the different strains of Echinococcus granulosus occurring in livestock in Moroto district, Uganda. Echinococcus cysts from 104 domestic animals, including cattle, sheep, goats and camels, were taken and examined by microscopy, polymerase chain reaction with restriction fragment length polymorphism and Sanger DNA sequencing. Echinococcus granulosus genotypes or strains were identified through use of Bioinformatics tools: BioEdit, BLAST and MEGA6. The major finding of this study was the existence of a limited number of E. granulosus genotypes from cattle, goats, sheep and camels. The most predominant genotype was G1 (96.05%), corresponding to the common sheep strain. To a limited extent (3.95%), the study revealed the existence of Echinococcus canadensis G6/7 in three (n = 3) of the E. granulosus-positive samples. No other strains of E. granulosus were identified. It was concluded that the common sheep strain of Echinococcus sensu stricto and G6/7 of E. canadensis were responsible for echinococcal disease in Moroto district, Uganda.

Prevalence and risk factors of Echinococcus granulosus infection in dogs in Moroto and Bukedea districts in Uganda.

A cross sectional study was conducted in Moroto and Bukedea districts of Uganda from May to September 2013 to determine the prevalence and risk factors of Echinococcus granulosus infection in dogs. Fresh dog faecal samples were collected, preserved in 70 % ethanol, and later screened for presence of taeniid eggs using zinc chloride floatation method. Positive samples were confirmed by a copro-PCR (polymerase chain reaction) for E. granulosus using NADH dehydrogenase sub-unit 1 gene (NADH1) as a target molecular marker. Structured questionnaires and focus group discussions were used to collect quantitative and qualitative data for risk factor identification. Study sub-counties were selected by simple random sampling. Overall apparent prevalence of taeniid infection in dogs of 14.9 % (39/261, confidence interval 10.6-19.2) in both districts was recorded using the faecal floatation test. The sensitivity of the faecal floatation test was found to be 78 % (25/32), while the specificity was 93 % (215/229). Copro-PCR results revealed a true prevalence of 14.4 % (9.91-19.0, 95 % CI) in dogs in Moroto district and 7.4 % (2.14-12.60, 95 % CI) in Bukedea district. The overall true prevalence of cystic echinococcosis (CE) was 12.2 % (8.70-15.76, 95 % CI) in both districts. The major risk factors identified using logistic regression were uncontrolled access of dogs to animal slaughter facilities, higher cattle herd sizes and lack of knowledge about the disease. It was recommended that restricting dog access to infected tissues and public health education about epidemiology of CE should be done.

Diagnostic accuracy of fine needle aspiration cytology in providing a diagnosis of cervical lymphadenopathy among HIV-infected patients.

BACKGROUND: Opportunistic infections and malignancies cause lymphadenopathy in HIV-infected patients. The use and accuracy of fine needle aspiration cytology in diagnosing of cervical lymphadenopathy among HIV-infected patients is not well studied in Uganda. OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of fine needle aspiration cytology in providing a diagnosis of cervical lymphadenopathy among HIV-infected patients in Uganda. METHODS: We consecutively recruited adult HIV-infected patients with cervical lymphadenopathy admitted to Mulago Hospital medical wards. Clinical examination, fine needle aspiration and lymph node biopsy were performed. We estimated the sensitivity, specificity; negative and positive predictive values using histology as the gold standard. RESULTS: We enrolled 108 patients with a mean age of 33 years (range, 18-60), 59% were men and mean CD4 was 83(range, 22-375) cells/mm(3). The major causes of cervical lymphadenopathy were: tuberculosis (69.4%), Kaposi's sarcoma-KS (10.2%) and reactive adenitis (7.4%). Overall fine needle aspiration cytology accurately predicted the histological findings in 65 out of 73 cases (89%) and missed 7 cases (9.5%). With a sensitivity of 93.1%, specificity of 100%, positive predictive value of 100% and negative predictive value of 78.7% for tuberculosis and 80%; 98.4%;88.9% and 98.9% for KS respectively. No fine needle aspiration complications were noted. CONCLUSIONS: Fine needle aspiration cytology is safe and accurate in the diagnosis of tuberculosis and KS cervical lymphadenopathy among HIV-positive patients.

Breast carcinoma in Uganda: microscopic study and receptor profile of 45 cases.

CONTEXT: Histologic and receptor data on breast carcinoma in Uganda are scarce. Estrogen receptor status is not routinely available. Breast cancer blocks from Uganda were studied in Montreal, Canada, and clinical correlations subsequently discussed in Kampala, Uganda. OBJECTIVE: To correlate histologic features (tumor type, histologic grade), receptor profile (estrogen receptor, progesterone receptor, and HER2/neu), and age in Ugandan women. DESIGN: Pathology reports for 2000-2004 from Nsambya Hospital, reporting invasive breast carcinoma, provided 45 microscopically confirmed cases. RESULTS: Seventy-three percent of patients were 50 years or younger. Histologic types were invasive ductal carcinoma (78%) and "good" prognosis types (11%). Overall 40% were grade 3, but 48% of invasive ductal carcinomas were grade 3. Estrogen receptor was positive in 60% overall and in 51% of invasive ductal carcinomas. HER2/neu was overexpressed in 11%; 36% were "triple" negative (estrogen receptor, progesterone receptor, HER2/neu negative). CONCLUSIONS: Breast carcinoma in Ugandan women presents at a younger age and is histologically and by receptor profile more aggressive than carcinoma in Caucasian women.

Immunohistochemical and other prognostic factors in B cell non Hodgkin lymphoma patients, Kampala, Uganda.

BACKGROUND: Non Hodgkin lymphomas are the most common lymphomas in Uganda. Recent studies from developed countries have shown differences in survival for the different immunophenotypes. Such studies are lacking in Africa where diagnosis is largely dependent on morphology alone. We report immunohistochemical and other prognostic factors in B cell non Hodgkin lymphoma patients in Kampala, Uganda. METHODS: Non Hodgkin lymphoma tissue blocks from the archives of the Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda, from 1991-2000, were sub typed using haematoxylin and eosin, Giemsa as well as immunohistochemistry. Using tissue micro array, 119 biopsies were subjected to: CD3, CD5, CD10, CD20, CD23, CD30, CD38, CD79a, CD138, Bcl-6, Bcl-2, IRTA-1, MUM1/IRF4, Bcl-1/cyclin D1, TdT, ALKc, and Ki-67/Mib1. Case notes were retrieved for: disease stage, chemotherapy courses received and retrospective follow up was done for survival. RESULTS: Non Hodgkin B cell lymphomas comprised of Burkitt lymphoma [BL] (95/119) diffuse large B cell lymphoma (19/119), mantle cell lymphoma (4/119) and precursor B lymphoblastic lymphoma (1/119). For Burkitt lymphoma, good prognosis was associated with receiving chemotherapy, female gender and CD30 positivity. Only receiving chemotherapy remained significant after Cox regression analysis. Diffuse large B cell lymphomas with activated germinal centre B cell (GCB) pattern (CD10+/-, BCL-6+/-, MUM+/-, CD138+/-) had better survival (98.4 months; 95% CI 89.5 -107.3) than the others (57.3 months; 95% CI 35.5 - 79.0) p = 0.027 (log rank test). CONCLUSIONS: Activated GCB diffuse large B cell lymphoma had a better prognosis than the others. For Burkitt lymphoma, not receiving chemotherapy carried a poor prognosis. Availability of chemotherapy in this resource limited setting is critical for survival of lymphoma patients.

Kaposi sarcoma-associated herpesvirus in non-Hodgkin lymphoma and reactive lymphadenopathy in Uganda.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma and is also associated with primary effusion lymphoma, a subset of diffuse large B-cell lymphomas, and multicentric Castleman disease. Because KSHV infection is endemic in sub-Saharan Africa, we sought to identify cases of KSHV-positive non-Hodgkin lymphomas (NHLs) and reactive lymphadenopathy in this region. One hundred forty-four cases (80 NHLs, 64 reactive lymph nodes) from the major pathology laboratory in Uganda were reviewed. One NHL was KSHV-positive, as indicated by staining for the viral latent nuclear antigen. This NHL was a diffuse large B-cell lymphoma in a 5-year-old boy. The tumor was also Epstein-Barr virus-positive. In addition, 2 reactive lymph nodes, both classified histologically as follicular involution, stained KSHV latent nuclear antigen-positive and thus most likely represent multicentric Castleman disease. In all 3 KSHV-positive cases, a minority of cells expressed KSHV viral interleukin 6, a biologically active cytokine homolog. In conclusion, we show that KSHV is rarely associated with lymphoproliferative disorders in sub-Saharan Africa. We describe the first case of a KSHV-positive NHL from this region; this case is also the first reported pediatric lymphoma associated with KSHV infection.