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Abstract: Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform. Subsequently, the data were validated using multiplex and combined immunostaining. Based on unsupervised clustering of differentially expressed genes, BL samples formed 3 distinct clusters differentially enriched in BL with a diffuse granulomatous reaction (cluster 1), EBV+ BL with typical starry sky pattern (cluster 2), EBV- BL with typical "starry sky" (cluster 3). We observed variations in the immune response signature among BL with granulomatous reaction and BL with typical "starry sky," both EBV+ and EBV-. The TME signature in BL with diffuse granulomatous reaction showed a proinflammatory response, whereas BLs with "starry sky" were characterized by upregulation of M2 polarization and protumor response. Moreover, the analysis of additional signatures revealed an upregulation of the dark zone signature and epigenetic signature in BL with a typical starry sky. Tumor-associated macrophages and epigenetic regulators may be promising targets for additional therapies for BL lymphoma, opening novel immunotherapeutic strategies., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Aim: Hypertension and diabetes mellitus (DM) are major causes of morbidity and mortality, with growing burdens in low-income countries where they are underdiagnosed and undertreated. Advances in machine learning may provide opportunities to enhance diagnostics in settings with limited medical infrastructure., Materials and Methods: A non-interventional study was conducted to develop and validate a machine learning algorithm to estimate cardiovascular clinical and laboratory parameters. At two sites in Kenya, digital retinal fundus photographs were collected alongside blood pressure (BP), laboratory measures and medical history. The performance of machine learning models, originally trained using data from the UK Biobank, were evaluated for their ability to estimate BP, glycated haemoglobin, estimated glomerular filtration rate and diagnoses from fundus images., Results: In total, 301 participants were enrolled. Compared with the UK Biobank population used for algorithm development, participants from Kenya were younger and would probably report Black/African ethnicity, with a higher body mass index and prevalence of DM and hypertension. The mean absolute error was comparable or slightly greater for systolic BP, diastolic BP, glycated haemoglobin and estimated glomerular filtration rate. The model trained to identify DM had an area under the receiver operating curve of 0.762 (0.818 in the UK Biobank) and the hypertension model had an area under the receiver operating curve of 0.765 (0.738 in the UK Biobank)., Conclusions: In a Kenyan population, machine learning models estimated cardiovascular parameters with comparable or slightly lower accuracy than in the population where they were trained, suggesting model recalibration may be appropriate. This study represents an incremental step toward leveraging machine learning to make early cardiovascular screening more accessible, particularly in resource-limited settings., (© 2024 AstraZeneca. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Kenya is among the countries endemic for soil-transmitted helminthiasis (STH) with over 66 subcounties and over 6 million individuals being at-risk of infection. Currently, the country is implementing mass drug administration (MDA) to all the at-risk groups as the mainstay control strategy. This study aimed to develop and analyze an optimal control (OC) model, from a transmission interruption model, to obtain an optimal control strategy from a mix of three strategies evaluated. The study used the Pontryagin's maximum principle to solve, numerically, the OC model. The analysis results clearly demonstrated that water and sanitation when implemented together with the MDA programme offer the best chances of eliminating these tenacious and damaging parasites. Thus, we advocate for optimal implementation of the combined mix of the two interventions in order to achieve STH elimination in Kenya, and globally, in a short implementation period of less than eight years., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

While tremendous progress has been made on attaining HIV treatment goals (95-95-95), children's viral load suppression remains a challenge particularly among the orphans and vulnerable groups. In Sub Saharan Africa, there is limited evidence of specific interventions in orphans and vulnerable children (OVC) programs to support children and adolescents living with HIV (CALHIV) to attain durable viral load suppression. Through a large OVC cohort, the study sought to identify correlates of optimal viral load suppression among CALHIV in the Kenya OVC program. This cross-sectional study utilized data on CALHIV below the age of 18 years who were enrolled in the OVC program and actively receiving HIV care and treatment services from ART clinics across Kenya and with documented VL results between October 2019 and September 2020. To obtain a nationally representative sample, data was retrieved from USAID implementing partners' databases across the country. Association between selected variables and VL suppression (outcome of interest) were assessed using a multivariate mixed effect logistic regression model, using glmer function in the LME4 package in R. Factors associated with VL suppression included child's education status (aOR = 1.33; 95% CI: 1.07, 1.65), membership of a psychosocial support group (aOR = 1.258; 95% CI: 1.15, 1.38), and membership of a voluntary savings and lending association (VSLA) (aOR = 1.226; 95% CI: 1.129, 1.33). In addition, child's sex (aOR = 0.88; 95% CI: 0.83, 0.94), caregiver sex (aOR = 0.909; 95% CI: 0.839, 0.997) and "high" status for caregiver household vulnerability (aOR = 0.81; 95% CI: 0.71, 0.924), had an inverse relationship with VL suppression. CALHIV characteristics including child's sex, child's education status (whether currently active in school or inactive) and child's membership in a psychosocial support group were key determinants of VL suppression. Similarly, caregiver sex and membership in a voluntary savings and lending association also influence VL suppression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Acute myeloid leukemia (AML) is an infrequent disease, and it is associated with high morbidity and mortality. It harbors a unique configuration of cytogenetic abnormalities and molecular mutations that can be detected using microscopic and molecular methods respectively. These genetic tests are core elements of diagnosis and prognostication in high-income countries. They are routinely incorporated in clinical decision making, allowing for the individualization of therapy. However, these tests are largely inaccessible to most patients in Kenya and therefore no data has been reported on this group of patients. The main purpose of this study is to describe the cytogenetic and molecular abnormalities of acute myeloid leukemia patients seen at the hemato-oncology unit of Kenyatta National Hospital. A cross-sectional descriptive study was carried out over a 3-month period on ten patients with a diagnosis of AML. Social demographics and clinical data were collected through a study proforma. A peripheral blood sample was collected for conventional metaphase G-banding technique and next generation sequencing. Particularly, targeted DNA sequencing (Illumina myeloid panel) and whole exome sequencing (WES) were performed. Cytogenetic analysis failed in 10/10 cases. Targeted sequencing was successfully obtained in 8 cases, whereas WES in 7. Cytogenetic studies yielded no results. There were 20 mutations detected across 10 commonly mutated genes. All patients had at least one clinically relevant mutation. Based on ELN criteria, NGS identified three patients with high-risk mutations, affecting TP53 ( n = 2) and RUNX1 ( n = 1). One patient was classified as favorable ( PML-RARA ) while 4 were standard risk. However, WT1 mutations associated with unfavorable prognosis were recorded in additional 2 cases. WES showed concordant results with targeted sequencing while unveiling more mutations that warrant further attention. In conclusion , we provide the first molecular profiling study of AML patients in Kenya including application of advanced next generation sequencing technologies, highlighting current limitations of AML diagnostics and treatment while confirming the relevance of NGS in AML characterization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gatua, Navari, Ong’ondi, Onyango, Kaggia, Rogena, Visani, Abinya and Piccaluga.)

The risk of unintended pregnancy is high in the postpartum period, especially during the first year of delivery. Yet, short birth intervals are associated with increased risk of adverse maternal and infant outcomes. In Kenya, despite women having multiple contacts with healthcare providers during their pregnancy and postpartum journeys, uptake of contraceptives during the postpartum period remains low. We examine factors that determine contraceptive use among postpartum women in Kitui County, Kenya.A cross-sectional study was conducted in six sub-counties of Kitui County covering a random sample of 768 postpartum women in April 2019. Logistic regression was used to study the association between uptake of contraceptives among women 0-23 months postpartum and several explanatory variables that included socio-demographic characteristics and facility-level factors. Overall, 68% of women in Kitui County reported using contraceptives. The likelihood of contraceptive use increased with the increase in the number of known family planning methods. Women who discussed family planning with a health worker within the last 12 months were 2.58 (95%CI: 1.73, 3.89) times more likely to use contraceptives during the postpartum period compared to those who did not. There was an increased odds of contraceptive uptake among women who received family planning information or service during postnatal care than those who did not (aOR = 2.04, 95%CI: 1.30, 3.24). A positive association was also found between contraceptive use and receipt of family planning information or service during immunization visits or during child well visits. It is evident that facility-level factors such as discussing family planning with women; educating women about different family planning methods; providing family planning information or services during postnatal care, immunization, or well child visits are associated with increased likelihood of contraceptive uptake by women during postpartum period. Programs targeting enhancing women's attendance of postnatal care clinics should be encouraged., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

As the world rallies toward the endgame of soil-transmitted helminths (STH) elimination by the year 2030, there is a need for efficient and robust mathematical models that would enable STH programme managers to target the scarce resources and interventions, increase treatment coverage among specific sub-groups of the population, and develop reliable surveillance systems that meet sensitivity and specificity requirements for the endgame of STH elimination. However, the considerable complexities often associated with STH-transmission models underpin the need for specifying a large number of parameters and inputs, which are often available with considerable degree of uncertainty. Additionally, the model may behave counter-intuitive especially when there are non-linearities in multiple input-output relationships. In this study, we performed a global sensitivity analysis (GSA), based on a variance decomposition method: extended Fourier Amplitude Sensitivity Test (eFAST), to a recently developed STH-transmission model in Kenya (an STH endemic country) to; (1) robustly compute sensitivity index (SI) for each parameter, (2) rank the parameters in order of their importance (from most to least influential), and (3) quantify the influence of each parameter, singly and cumulatively, on the model output. The sensitivity analysis (SA) results demonstrated that the model outcome (STH worm burden elimination in the human host) was significantly sensitive to some key parameter groupings: combined effect of improved water source and sanitation (ϕ), rounds of treatment offered (τ), efficacy of the drug used during treatment ( h ), proportion of the adult population treated ( g a : akin to community-wide treatment), mortality rate of the mature worms in the human host (μ), and the strength of the -dependence of worm egg production (γ). For STH control programmes to effectively reach the endgame (STH elimination in the entire community), these key parameter groupings need to be targeted since together they contribute to a strategic public health intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Okoyo, Onyango, Orowe, Mwandawiro and Medley.)

Introduction: human leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease., Methods: an analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status., Results: the HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040)., Conclusion: the higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population., Competing Interests: The authors declare no competing interest., (Copyright: Susan Odera et al.)

Background: Soil-transmitted helminths (STH) are among the most common parasitic infections globally, disproportionately affecting children. Treatment of STH in Kenya is often targeted at preschool (PSAC) and school aged (SAC) children delivered through annual mass drug administration (MDA) in primary schools. Understanding group-specific prevalence and dynamics between treatment and coverage is critical for continued treatment success. This study aims to provide detailed information on group-specific infection prevalence and relative reductions (RR), and their relationships with treatment coverage over time. Additionally, it aims to quantify the correlation between the observed school level infection prevalence and treatment coverage. Methods: Secondary analysis of existing data collected between 2012 and 2018 by the monitoring and evaluation (M&E) program of the National School-Based Deworming (NSBD) program was used. The M&E program conducted surveys utilizing cross-sectional study design, at four survey time points, in a nationally-representative sample of schoolchildren across counties in Kenya. In each participating school, the program randomly sampled 108 children per school, of both groups. Infection prevalence was estimated using binomial regression, RR in prevalence using multivariable mixed effects model, statistical correlations using structural equation modeling, and change-point-analysis using the binary segmentation algorithm. Results: Overall, STH prevalence for PSAC was 33.7, 20.2, 19.0, and 17.9% during Year 1 (Y1), Year 3 (Y3), Year 5 (Y5), and Year 6 (Y6) surveys, respectively with an overall RR of 46.9% ( p = 0.001) from Y1 to Y6. Similarly, overall STH prevalence for SAC was 33.6, 18.4, 14.7, and 12.5% during Y1, Y3, Y5, and Y6 surveys, respectively with an overall RR of 62.6% ( p < 0.001). An overall (all time points) significant but very weak negative correlation was found between treatment coverage and undifferentiated STH prevalence ( r = -0.144, p = 0.002) among PSAC but not in SAC. Further, we observed inter-county heterogeneity variation in infection prevalence, RR, as well as correlations. Conclusion: The analysis showed that after six rounds of MDA, prevalence of STH has significantly declined among both groups of children, however not to a point where it is not a public health problem (below 1%). The analysis, additionally established an overall significant but weak negative correlation between treatment coverage and prevalence, indicating that the current treatment coverage might not be sufficient to drive the overall STH prevalence to below 1%. These findings will allow STH control programs in Kenya to make decisions that will accelerate the attainment of STH elimination as a public health problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Okoyo, Campbell, Minnery, Owaga, Onyango, Medley and Mwandawiro.)

According to the Kenya National School-Based Deworming program launched in 2012 and implemented for the first 5 years (2012-2017), the prevalence of soil-transmitted helminths (STH) and schistosomiasis substantially reduced over the mentioned period among the surveyed schools. However, this reduction is heterogeneous. In this study, we aimed to determine the factors associated with the 5-year school-level infection prevalence and relative reduction (RR) in prevalence in Kenya following the implementation of the program. Multiple variables related to treatment, water, sanitation, and hygiene (WASH) and environmental factors were assembled and included in mixed-effects linear regression models to identify key determinants of the school location STH and schistosomiasis prevalence and RR. Reduced prevalence of Ascaris lumbricoides was associated with low (< 1%) baseline prevalence, seven rounds of treatment, high (50-75%) self-reported coverage of household handwashing facility equipped with water and soap, high (20-25°C) land surface temperature, and community population density of 5-10 people per 100 m2. Reduced hookworm prevalence was associated with low (< 1%) baseline prevalence and the presence of a school feeding program. Reduced Trichuris trichiura prevalence was associated with low (< 1%) baseline prevalence. Reduced Schistosoma mansoni prevalence was associated with low (< 1%) baseline prevalence, three treatment rounds, and high (> 75%) reported coverage of a household improved water source. Reduced Schistosoma haematobium was associated with high aridity index. Analysis indicated that a combination of factors, including the number of treatment rounds, multiple related program interventions, community- and school-level WASH, and several environmental factors had a major influence on the school-level infection transmission and reduction.

Kenya, just like other countries with endemic soil-transmitted helminths (STH), has conducted regular mass drug administration (MDA) program for the last 5 years among school aged children as a way to reduce STH infections burden in the country. However, the point of interruption of transmission of these infections still remains unclear. In this study, we developed and analyzed an age structured mathematical model to predict the elimination period (i.e., time taken to interrupt STH transmission) of these infections in Kenya. The study utilized a deterministic age structured model of the STH population dynamics under a regular treatment program. The model was applied to three main age groups: pre-school age children (2-4 years), school age children (5-14 years), and adult populations (≥15 years) and compared the impact of two interventions on worm burden and elimination period. The model-simulated results were compared with the 5 year field data from the Kenyan deworming program for all the three types of STH ( Ascaris lumbricoides, Trichuris trichiura , and hookworm). The model demonstrated that the reduction of worm burden and elimination period depended heavily on four parameter groups; drug efficacy, number of treatment rounds, MDA and water, sanitation and hygiene (WASH) coverage. The analysis showed that for STH infections to be eliminated using MDA alone in a short time period, 3-monthly MDA plan is desired. However, complementation of MDA with WASH at an optimal (95%) coverage level was most effective. These results are important to the Kenyan STH control program as it will guide the recently launched Breaking Transmission Strategy ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Okoyo, Medley, Mwandawiro and Onyango.)

The Epstein-Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a "hit-and-run" mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

Background: Diversity within the medical workforce remains a topic of discussion in academia, particularly when it comes to the underrepresentation of certain ethnic groups and gender in the surgical specialties. In this article, we look at how the gender and ethnicity of surgeons at a large academic institution in a rural setting compare with those of the population it serves., Methods: We looked at demographic data from 2008 to 2018 and compared population trends among surgeons and patients., Results: We found that while whites represent the large majority in both the surgeon and patient populations, absolute number and percentage of whites in the patient population seem to be trending downward from 2008 to 2018, but trending upward among surgeons (attendings and residents). In addition, we found that while Asians make up only 1% of the patient population, they represent the second largest group (17%) among surgeons, with more than twice the proportion percentage of the second largest group within the patient population, composed of Hispanics (6%). Finally, we found a significant gender difference between the 2 populations with almost two-thirds of the surgeons being men, compared with the nearly even split of men and women within the patient population., Conclusions: Ultimately, understanding how gender and ethnic diversity in the surgical workforce compares with that of the patient population being served may aid in designing training programs to address cultural competency and awareness as well as in impacting administrative decisions and hiring., Competing Interests: Disclosure: The authors have no financial or other conflicts of interest to disclose. No funding was received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and RCUK., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: Household Contacts (HHCs) of Pulmonary Tuberculosis (PTB) patients have a higher risk of latent tuberculosis infection (LTBI). However, its prevalence and risk factors among adults living with PTB patients are poorly documented in Kenya., Objective: to determine the prevalence and risk factors for LTBI among adult HHCs of PTB patients in Kenya., Methods: this was an analytical cross-sectional study of HHCs of PTB patients in Nairobi, Kenya. Socio-demographic data was captured on questionnaires and blood samples drawn for Interferon gamma (IFN-γ) quantification. Univariate and multivariate analyses using the Statistical Package for Social Scientists (SPSS) was used to determine the prevalence of LTBI and risk factors at 95% Confidence Interval (CI)., Results: a total of 166 PTB patients yielded 175 HHCs of whom 29.7% (52/125) were males and 70.3% (123/125) were females. A majority of HHCs [65.7% (115/175)] lived in a single-room house with the patient and [37.7% (66/175)] were in the age group 30-39-years. The overall prevalence of LTBI was 55.7%, peaking among spouses of the patients [70.0% (14/20) and the 30-39 year age group [63.5% (42/66)]. Potential risk factors for LTBI included cohabiting with a PTB patient for 8 to 12 weeks [OR = 3.6 (0.70-18.5), p = 0.107], being a spouse of the patient [OR = 2.0 (0.72-5.47), p = 0.173] and sharing a single room with the patient [OR = 1.58 (0.84 - 2.97), p = 0.158]., Conclusion: the high prevalence of LTBI among adult HHCs of PTB patients in this population demonstrates the need for targeted contact-screening programs in high TB transmission settings., Competing Interests: The authors declare no competing interests., (Copyright: Susan Odera et al.)

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood., Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis., Results: Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway., Conclusion: In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL. Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN. Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.

Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run . Early during oncogenesis, viral genes are essential for initiating disease. Progressively, viral genome is lost to escape the immune system and host mutations accumulate in proto-oncogenic cell. The main problem with the hit-and-run hypothesis is the lack of evidence in primary tumors. The routine methods applied to detect the virus [i.e., immunohistochemistry and EBV-encoded RNAs (EBER) in situ hybridization (ISH)] have a low specificity and accuracy. The aim of this study was to identify the most suitable method to detect EBV infection in pathology samples by applying conventional and non-conventional methods (i.e., EBV-microRNAs detection and EBV viral load measurement). We investigated a total of 10 cases and we found that all the samples ( n = 6) diagnosed as EBV negative by immunohistochemistry and EBER-ISH demonstrated the presence of EBV-microRNAs and EBV genome. This points at the possibility that EBV might have contributed to lymphomagenesis in all our patients, and propose microRNAs detection as the most specific and sensitive tool to recognize EBV vestiges. It is worth noting that our data would have considerable implications for EBV-related diseases control. By using anti-EBV vaccines, one could potentially prevent also some cancers less suspected of a viral origin because of viral genome loss.

Background: Although prevention and control of spread of multi-drug resistant tuberculosis strains is a global challenge, there is paucity of data on the prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya. The present study assessed patients' characteristics and prevalence of drug resistant TB in sputa smear positive TB patients presenting to Coast Provincial General Hospital (CPGH) in Mombasa, Kenya., Methods: Drug resistance was evaluated in 258 randomly selected sputa smear TB positive cases between the periods of November 2011 to February 2012 at the CPGH-Mombasa. Basic demographic data was obtained using administered questionnaires, and clinical history extracted from the files. For laboratory analyses, 2mls of sputum was obtained, decontaminated and subjected to mycobacteria DNA analyses. Detection of first line drug resistance genes was done using MDRTDR plus kit. This was followed with random selection of 83 cases for second line drug resistance genes testing using Genotype MDRTBsl probe assay kit (HAINS Lifesciences, GmbH, Germany), in which ethambutol mutation probes were included. The data was then analyzed using SPSS statistical package version 19.0., Results: Male to female ratio was 1:2. Age range was 9 to 75 years, with median of 30 years. New treatment cases constituted 253(98%), among which seven turned out to be PTB negative, and further grouped as 4 (1.6%) PTB negative and 3(1.1%) NTM. 237(91.7%) new cases were fully susceptible to INH and RIF. The remaining, 8 (3.1%) and 1(0.4%) had mono- resistance to INH and RIF, respectively. All the retreatment cases were fully susceptible to the first line drugs. HIV positivity was found in 48 (18.6%) cases, of which 46(17.8%) were co-infected with TB. Of these, 44 (17.1%) showed full susceptibility to TB drugs, while 2 (0.8%) were INH resistant. For the second line drugs, one case each showed mono resistance to both and FQ. Also, one case each showed drug cross poly resistance to both ETH and FQ, with second line injectable antibiotics. However, no significant statistical correlation was established between TB and resistance to the second line drugs p = 0.855., Conclusion: The findings of this study showed the existence of resistance to both first and second line anti-tubercular drugs, but no MDR-TB and XDR-TB was detected among patients attending TB clinic at CPGH using molecular techniques., Competing Interests: The authors have declared that no competing interests exist.

Background: Malaria and HIV infections are both highly prevalent in sub-Saharan Africa, with HIV-infected patients being at higher risk of acquiring malaria. HIV-1 infection is known to impair the immune response and may increase the incidence of clinical malaria. However, a positive association between HIV-1 and malaria parasitaemia is still evolving. Equally, the effect of malaria on HIV-1 disease stage has not been well established, but when fever and parasitemia are high, malaria may be associated with transient increases in HIV-1 viral load, and progression of HIV-1 asymptomatic disease phase to AIDS., Objective: To determine the effects of HIV-1 infection on malaria parasitaemia among consented residents of Milo sub-location, Bungoma County in western Kenya., Study Design: Census study evaluating malaria parasitaemia in asymptomatic individuals with unknown HIV-1 status., Methods: After ethical approvals from both Moi University and MTRH research ethics committees, data of 3,258 participants were retrieved from both Webuye health demographic surveillance system (WHDSS), and Academic Model Providing Access to Healthcare (AMPATH) in the year 2010. The current study was identifying only un-diagnosed HIV-1 individuals at the time the primary data was collected. The data was then analysed for significant statistical association for malaria parasitemia and HIV-1 infection, using SPSS version 19. Demographic characteristics such as age and sex were summarized as means and percentages, while relationship between malaria parasitaemia and HIV-1 (serostatus) was analyzed using Chi square., Results: Age distribution for the 3,258 individuals ranged between 2 and 94 years, with a mean age of 26 years old. Females constituted 54.3%, while males were 45.8%. In terms of age distribution, 2-4 years old formed 15.1% of the study population, 5-9 years old were 8.8%, 10-14 years old were 8.6% while 15 years old and above were 67.5%. Of the 3,258 individuals whose data was eligible for analysis, 1.4% was newly diagnosed HIV-1 positive. Our findings showed a higher prevalence of malaria in children aged 2-10 years (73.4%), against the one reported in children in lake Victoria endemic region by the Kenya malaria indicator survey in the year 2010 (38.1%). There was no significant associations between the prevalence of asymptomatic malaria and HIV-1 status (p = 0.327). However, HIV-1/malaria co-infected individuals showed elevated mean malaria parasite density, compared to HIV-1 negative individuals, p = 0.002., Conclusion: HIV-1 status was not found to have effect on malaria infection, but the mean malaria parasite density was significantly higher in HIV-1 positive than the HIV-1 negative population.

Background: Squamous cell carcinoma of conjunctiva has increased tenfold in the era of HIV/AIDS. The disease pattern has also changed in Africa, affecting young persons, with peak age-specific incidence of 30-39 years, similar to that of Kaposi sarcoma, a well known HIV/AIDS defining neoplasm. In addition, the disease has assumed more aggressive clinical course. The contributing role of exposure to high risk HPV in the development of SCCC is still emerging., Objective: The present study aimed to investigate if immunohistochemical expressions of EGFR, pEGFR and p16, could predict infection with high risk HPV in HIV-related SCCC., Methods: FFPE tissue blocks of fifty-eight cases diagnosed on hematoxylin and eosin with SCCC between 2005-2011, and subsequently confirmed from medical records to be HIV positive at the department of human pathology, UoN/KNH, were used for the study. Immunohistochemistry was performed to assess the expressions of p16INK4A, EGFR and pEGFR. This was followed with semi-nested PCR based detection and sequencing of HPV genotypes. The sequences were compared with the GenBank database, and data analyzed for significant statistical correlations using SPSS 16.0. Ethical approval to conduct the study was obtained from KNH-ERC., Results: Out of the fifty-eight cases of SCCC analyzed, twenty-nine (50%) had well differentiated (grade 1), twenty one (36.2%) moderately differentiated (grade 2) while eight (13.8%) had poorly differentiated (grade 3) tumours. Immunohistochemistry assay was done in all the fifty eight studied cases, of which thirty nine cases (67.2%) were positive for p16INK4A staining, forty eight cases (82.8%) for EGFR and fifty one cases (87.9%) showed positivity for p-EGFR. HPV DNA was detected in 4 out of 40 SCCC cases (10%) in which PCR was performed, with HPV16 being the only HPV sub-type detected. Significant statistical association was found between HPV detection and p16INK4 (p=0.000, at 99% C.I) and EGFR (p=0.028, at 95% C.I) expressions, but not pEGFR. In addition, the expressions of these biomarkers did not show any significant association with tumor grades., Conclusion: This study points to an association of high risk HPV with over expressions of p16INK4A and EGFR proteins in AIDS-associated SCCC.