Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report.

BACKGROUND: Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual. CASE PRESENTATION: A 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air-fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice. CONCLUSIONS: Complicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.

Perceptions of Adolescents and Health Workers Towards Adolescents' TB Diagnosis in Central Uganda: A Cross-Sectional Qualitative Study.

PURPOSE: Prompt diagnosis of TB among adolescents may reduce transmission and improve individual outcomes. However, TB diagnosis in adolescents is challenging. This study sought to understand challenges to adolescent TB diagnosis. METHODS: We conducted qualitative focus group discussions (FGDs) to explore adolescents' and health workers' perspectives on challenges to TB diagnosis among adolescents seeking care at four secondary health care facilities in Uganda. Eight FGDs were conducted: four with 32 adolescents consulting for medical care and four with 34 health workers involved in TB care. RESULTS: Adolescents were aware of TB and associated risk factors and believed behaviours like smoking and alcohol use are risk factors for TB. They reported school schedules limit them from seeking TB care and have to miss school or wait for holidays to seek TB diagnosis. They noted school nurses do not take much interest in diagnosing TB and do not refer them to hospitals for further evaluation when they present with TB symptoms. Furthermore, adolescents reported cross-cutting issues like loss of trust in public health systems, encountering unfriendly, judgmental and uncooperative health workers. Health workers mentioned the school environment exposes adolescents to TB as the dormitories they sleep in are overcrowded. They indicated that it was difficult to make a diagnosis of TB in adolescents as the adolescents do not disclose health information. They reported fellow health workers perceive adolescents as being at low risk of TB as they believe most often adolescents are HIV negative and thus have reduced risk of TB. CONCLUSION: Adolescents present unique challenges that need to be addressed if TB diagnosis is to improve. These challenges could be handled by interventions that lead to minimal disruptions on school schedules, provision of adolescent-friendly services and intervention to build capacity of health care workers in the provision of adolescent-friendly services.

Trends of admissions and case fatality rates among medical in-patients at a tertiary hospital in Uganda; A four-year retrospective study.

BACKGROUND: Sub-Saharan Africa suffers from a dual burden of infectious and non-communicable diseases. There is limited data on causes and trends of admission and death among patients on the medical wards. Understanding the major drivers of morbidity and mortality would help inform health systems improvements. We determined the causes and trends of admission and mortality among patients admitted to Mulago Hospital, Kampala, Uganda. METHODS AND RESULTS: The medical record data base of patients admitted to Mulago Hospital adult medical wards from January 2011 to December 2014 were queried. A detailed history, physical examination and investigations were completed to confirm the diagnosis and identify comorbidities. Any histopathologic diagnoses were made by hematoxylin and eosin tissue staining. We identified the 10 commonest causes of hospitalization, and used Poisson regression to generate annual percentage change to describe the trends in causes of hospitalization. Survival was calculated from the date of admission to the date of death or date of discharge. Cox survival analysis was used to identify factors associate with in-hospital mortality. We used a statistical significance level of p<0.05. A total of 50,624 patients were hospitalized with a median age of 38 (range 13-122) years and 51.7% females. Majority of patients (72%) had an NCD condition as the primary reason for admission. Specific leading causes of morbidity were HIV/AIDS in 30% patients, hypertension in 14%, tuberculosis (TB) in 12%), non-TB pneumonia in11%) and heart failure in 9.3%. There was decline in the proportion of hospitalization due to malaria, TB and pneumonia with an annual percentage change (apc) of -20% to -6% (all p<0.03) with an increase in proportions of admissions due to chronic kidney disease, hypertension, stroke and cancer, with apc 13.4% to 24%(p<0.001). Overall, 8,637(17.1%) died during hospitalization with the highest case fatality rates from non-TB pneumonia (28.8%), TB (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%). HIV-status, age above 50yrs and being male were associated with increased risk of death among patients with infections. CONCLUSION: Admissions and case fatality rates for both infectious and non-infectious diseases were high, with declining trends in infectious diseases and a rising trend in NCDs. Health care systems in sub-Saharan region need to prepare to deal with dual burden of disease.