KSHV is endemic in Uganda and the HIV epidemic has dramatically increased the incidence of Kaposi sarcoma (KS). To investigate the role of KSHV in the development of KS, we obtained KS biopsies from ART-naïve, HIV-positive individuals in Uganda and analyzed the tumors using RNAseq to globally characterize the KSHV transcriptome. Phylogenetic analysis of ORF75 sequences from 23 tumors revealed 6 distinct genetic clusters with KSHV strains exhibiting M, N or P alleles. RNA reads mapping to specific unique coding sequence (UCDS) features were quantitated using a gene feature file previously developed to globally analyze and quantitate KSHV transcription in infected endothelial cells. A pattern of high level expression was detected in the KSHV latency region that was common to all KS tumors. The clear majority of transcription was derived from the downstream latency transcript promoter P3(LTd) flanking ORF72, with little evidence of transcription from the P1(LTc) latency promoter, which is constitutive in KSHV-infected lymphomas and tissue-culture cells. RNAseq data provided evidence of alternate P3(LTd) transcript editing, splicing and termination resulting in multiple gene products, with 90% of the P3(LTd) transcripts spliced to release the intronic source of the microRNAs K1-9 and 11. The spliced transcripts encode a regulatory uORF upstream of Kaposin A with alterations in intervening repeat sequences yielding novel or deleted Kaposin B/C-like sequences. Hierarchical clustering and PCA analysis of KSHV transcripts revealed three clusters of tumors with different latent and lytic gene expression profiles. Paradoxically, tumors with a latent phenotype had high levels of total KSHV transcription, while tumors with a lytic phenotype had low levels of total KSHV transcription. Morphologically distinct KS tumors from the same individual showed similar KSHV gene expression profiles suggesting that the tumor microenvironment and host response play important roles in the activation level of KSHV within the infected tumor cells.

Psychiatric manifestations after occurrence of epilepsy have often been noted. However, the association between newly diagnosed epilepsy and psychiatric disorders afterward is not completely understood. We conducted two longitudinal cohorts for patients with and without epilepsy to investigate the risk factors and hazard ratios of developing psychiatric disorders after patients were newly diagnosed with epilepsy.

To date there has been no population-based survey of the major risk factors for non-communicable diseases (NCD) in Uganda. Hospital-based data from urban centres report an increasing burden of NCDs in Uganda. This population-based survey aimed to describe the prevalence of risk factors for NCDs in a rural Ugandan district.

The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates, treatment response rates and adverse events in patients with HIV associated NHL treated with CHOP and dose adjusted-EPOCH regimens at the Uganda Cancer Institute.

Cancer incidence and mortality in sub-Saharan Africa are increasing and do account for significant premature death. The expertise of health care providers is critical to downstaging cancer at diagnosis and improving survival in low- and middle-income countries. We set out to determine the training needs of health care providers for a comprehensive oncology services package in selected hospitals in Uganda, in order to inform capacity development intervention to improve cancer outcomes in the East African region.

Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD.

The recent proliferation and application of digital technologies in public health has spurred interest in digital public health. However, as yet, there appears to be a lack of conceptual clarity and consensus on its definition.

Population based cancer registries (PBCRs) are accepted as the gold standard for estimating cancer incidence in any population. However, only 15% of the world's population is covered by high quality cancer registries with coverage as low as 1.9% in settings such as Africa. This study was conducted to assess the operational feasibility of estimating cancer incidence using a retrospective "catchment population" approach in Uganda.

A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy. However, the precise mechanisms affecting SR function and leading to arrhythmias remain elusive.

B cell non Hodgkin lymphomas account for the majority of lymphomas in Uganda. The commonest is endemic Burkitt lymphoma, followed by diffuse large-B-cell lymphoma (DLBCL). There has been an increase in incidence of malignant lymphoma since the onset of the HIV/AIDS pandemic. However, the possible linkages of HHV8 and EBV to the condition of impaired immunity present in AIDS are still not yet very clearly understood.

Globally, the incidence of sexually transmitted infections (STI) is rising, posing a challenge to its control and appropriate management. Text messaging has become the most common mode of communication among almost six billion mobile phone users worldwide. Text messaging can be used to remind patients about clinic appointments, to notify patients that it is time for STI re-testing, and to facilitate patient communication with their health professionals with any questions and concerns they may have about their sexual health. While there are a handful of systematic reviews published on short message service (SMS) interventions in a variety of health settings and issues, none are related to sexual health. We plan to conduct a systematic review to examine the impact text messaging might have on interventions for the prevention and care of patients with STIs.

HIV-positive and HIV-negative (gay, bisexual, and other) men who have sex with men (MSM) have experienced a dramatic increase in bacterial sexually transmitted infections (STIs)-syphilis, gonorrhea, and chlamydia. STI testing and treatment mitigate adverse health outcomes and substantially reduce transmission; yet, testing rates remain below recommended levels. Innovation is needed to produce the required increases in testing levels, frequency, and the use of appropriate testing technologies in ways that are engaging, nonstigmatizing, and acceptable to men.

Epstein-Barr virus (EBV) is transmitted by saliva and is a major cause of cancer, particularly in people living with HIV/AIDS. Here, we describe the frequency and quantity of EBV detection in the saliva of Ugandan adults with and without HIV-1 infection and use these data to develop a novel mathematical model of EBV infection in the tonsils. Eligible cohort participants were not taking antiviral medications, and those with HIV-1 infection had a CD4 count >200 cells/mm3. Over a 4-week period, participants provided daily oral swabs that we analysed for the presence and quantity of EBV. Compared with HIV-1 uninfected participants, HIV-1 coinfected participants had an increased risk of EBV detection in their saliva (IRR = 1.27, 95% CI = 1.10-1.47) and higher viral loads in positive samples. We used these data to develop a stochastic, mechanistic mathematical model that describes the dynamics of EBV, infected cells, and immune response within the tonsillar epithelium to analyse potential factors that may cause EBV infection to be more severe in HIV-1 coinfected participants. The model, fit using Approximate Bayesian Computation, showed high fidelity to daily oral shedding data and matched key summary statistics. When evaluating how model parameters differed among participants with and without HIV-1 coinfection, results suggest HIV-1 coinfected individuals have higher rates of B cell reactivation, which can seed new infection in the tonsils and lower rates of an EBV-specific immune response. Subsequently, both these traits may explain higher and more frequent EBV detection in the saliva of HIV-1 coinfected individuals.

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

There has been rapid development and application of digital technologies in public health domains, which are considered to have the potential to transform public health. However, this growing interest in digital technologies in public health has not been accompanied by a clarity of scope to guide policy, practice, and research in this rapidly emergent field.

Globally, young gay, bisexual and other men who have sex with men (gbMSM) continue to experience disproportionately high rates of HIV and other sexually transmitted and blood-borne infections (STBBIs). As such, there are strong public health imperatives to evaluate innovative prevention, treatment and care interventions, including online interventions. This study reviewed and assessed the status of published research (e.g. effectiveness; acceptability; differential effects across subgroups) involving online interventions that address HIV/STBBIs among young gbMSM.

Web-based sexual health resources are typically evaluated in terms of their efficacy. Information is lacking about how sexual health promotion websites are perceived and used. It is essential to understand website use to address challenges with adherence and attrition to Web-based health interventions. An existing theoretical framework for examining loyalty to electronic health (eHealth) interventions has been not yet been applied in the context of sexual health promotion nor has the association between e-loyalty and intended intervention efficacy outcomes been investigated.

HIV increases cancer incidence and mortality. In Uganda, the HIV epidemic has led to an elevated incidence of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). Limited information exists about how frequently HIV infection complicates the presentation and manifestations of cancer in sub-Saharan Africa.

Recent data have demonstrated that healthcare use after treatment for respiratory tuberculosis (TB) remains elevated in the years following treatment completion. However, it remains unclear which TB survivors are high healthcare users and whether any variation exists within this population. Thus, the primary objective of this study was to identify distinct profiles of high healthcare-use TB survivors to help inform post-treatment support and care.

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.