Prevalence of hepatitis B and C and relationship to liver damage in HIV infected patients attending Joint Clinical Research Centre Clinic (JCRC), Kampala, Uganda.

Background: Hepatitis B and C viruses cause death due to liver disease worldwide among Human Immunodeficiency Virus (HIV) positive individuals. Hepatitis B (HBV) and HIV have similar routes of transmission primarily; sexual, intravenous injections and prenatal while hepatitis C (HCV) is transmitted mainly through blood transfusion. Human immunodeficiency virus increases the pathological effect of hepatitis viruses and potentiates re-activation of latent hepatitis infections as a result of reduced immunity. The increase in use of antiretroviral (ARVs) drugs has led to longer period for patient survival and apparent increase in liver disease among HIV positive individuals.Objective: This study aimed at determining the prevalence of HBV, HCV, their co-infection with HIV and their effect on liver cell functionMethod: This was a cross sectional study conducted at the Joint Clinical Research Centre (JCRC) among HIV positive individuals attending the clinic. Patients were enrolled after obtaining a signed informed consent or assent for children below 17 years. Serum samples were collected for detection of Hepatitis B surface antigen (HBsAg), HCV specific antibodies and alanine aminotransferase (ALT) liver enzyme.Results: Of the 89 patients enrolled, 20 (22.5%) had at least one hepatitis virus, 15 tested positive for HBsAg (16.9%) and 5 for HCV (5.6%), one had both viruses. Hepatitis B was more prevalent among women (13 out of 57, 22.8%) than men, (2 out of 32, 6.2%), while HCV was higher among men (4 out of 32, 12.5%) than women (1 out of 57, 1.8%). Seven of 89 patients (7.9%) had elevated ALT, indicative of liver cell injury. Of these with liver cell injury, one individual tested positive for HBsAg and another one individual tested positive for HCV specific antibodies.Conclusion: The prevalence of HBV is high in HIV positive individuals with more women commonly infected. The Prevalence of HCV is lower than that of HBV with more men commonly infected. Co-infection of Hepatitis B and C viruses was uncommon. This study reveals a high prevalence of liver cell injury among HIV positive individuals although the injury due to HBV or HCV infection was lower than that which has been documented. From this study, the high prevalence of HBV and HCV among HIV positive individuals point to a need for screening of HIV positive individuals for the hepatitis viruses.Key words: Hepatitis B virus, HBV surface antigen, Hepatitis C virus, Hepatitis C virus antibodies, HIV, Liver damage

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/mm3. 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.Keywords: Fine needle aspiration cytology, cervical lymphadenopathy, HI

Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial

Background HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its eff ect on HIV risk is uncertain and methods to improve linkage to care have not been studied. Methods We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data offi cer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). Findings We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], diff erence –0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a signifi cant eff ect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96). Interpretation Abbreviated HIV counselling and testing did not adversely aff ect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might aff ect secondary HIV transmission and improve treatment outcomes

Concise gene signature for point‐of‐care classification of tuberculosis

There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real‐time PCR analysis, we evaluated the expression profiles from a large panel of genes in TB patients and healthy individuals in an Indian cohort. Classification models were built and validated for their capacity to discriminate samples from TB patients and controls within this cohort and on external independent gene expression datasets. A combination of only four genes distinguished TB patients from healthy individuals in both cross‐validations and on separate validation datasets with very high accuracy. An external validation on two distinct cohorts using a real‐time PCR setting confirmed the predictive power of this 4‐gene tool reaching sensitivity scores of 88% with a specificity of around 75%. Moreover, this gene signature demonstrated good classification power in HIV (+) populations and also between TB and several other pulmonary diseases. Here we present proof of concept that our 4‐gene signature and the top classifier genes from our models provide excellent candidates for the development of molecular point‐of‐care TB diagnosis in endemic areas

Neutrophil activation and enhanced release of granule products in HIV-TB immune reconstitution inflammatory syndrome

Background: Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and, in particular, the role of neutrophils. Setting: Two observational, prospective cohort studies in HIV/TB coinfected patients starting antiretroviral therapy (ART), 1 to analyze gene expression and subsequently 1 to explore neutrophil biology. Methods: nCounter gene expression analysis was performed in patients with TB-IRIS (n = 17) versus antiretroviral-treated HIV/TB coinfected controls without IRIS (n = 17) in Kampala, Uganda. Flow cytometry was performed in patients with TB-IRIS (n = 18) and controls (n = 11) in Cape Town, South Africa to determine expression of neutrophil surface activation markers, intracellular cytokines, and human neutrophil peptides (HNPs). Plasma neutrophil elastase and HNP1-3 were quantified using enzyme-linked immunosorbent assay. Lymph node immunohistochemistry was performed on 3 further patients with TB-IRIS. Results: There was a significant increase in gene expression of S100A9 (P = 0.002), NLRP12 (P = 0.018), COX-1 (P = 0.025), and IL-10 (P = 0.045) 2 weeks after ART initiation in Ugandan patients with TB-IRIS versus controls, implicating neutrophil recruitment. Patients with IRIS in both cohorts demonstrated increases in blood neutrophil count, plasma HNP and elastase concentrations from ART initiation to week 2. CD62L (L-selectin) expression on neutrophils increased over 4 weeks in South African controls whereas patients with IRIS demonstrated the opposite. Intense staining for the neutrophil marker CD15 and IL-10 was seen in necrotic areas of the lymph nodes of the patients with TB-IRIS. Conclusions: Neutrophils in TB-IRIS are activated, recruited to sites of disease, and release granule contents, contributing to pathology

Contact investigation for active tuberculosis among child contacts in Uganda.

BACKGROUND: Tuberculosis is a large source of morbidity and mortality among children. However, limited studies characterize childhood tuberculosis disease, and contact investigation is rarely implemented in high-burden settings. In one of the largest pediatric tuberculosis contact investigation studies in a resource-limited setting, we assessed the yield of contact tracing on childhood tuberculosis and indicators for disease progression in Uganda. METHODS: Child contacts aged <15 years in Kampala, Uganda, were enrolled from July 2002 to June 2009 and evaluated for tuberculosis disease via clinical, radiographic, and laboratory methods for up to 24 months. RESULTS: Seven hundred sixty-one child contacts were included in the analysis. Prevalence of tuberculosis in our child population was 10%, of which 71% were culture-confirmed positive. There were no cases of disseminated tuberculosis, and 483 of 490 children (99%) started on isoniazid preventative therapy did not develop disease. Multivariable testing suggested risk factors including human immunodeficiency virus (HIV) status (odds ratio [OR], 7.90; P < .001), and baseline positive tuberculin skin test (OR, 2.21; P = .03); BCG vaccination was particularly protective, especially among children aged ≤5 years (OR, 0.23; P < .001). Adult index characteristics such as sex, HIV status, and extent or severity of disease were not associated with childhood disease. CONCLUSIONS: Contact tracing for children in high-burden settings is able to identify a large percentage of culture-confirmed positive tuberculosis cases before dissemination of disease, while suggesting factors for disease progression to identify who may benefit from targeted screening

Equitable Access to Health Professional Training in Uganda: A Cross Sectional Study

Objective: We set out to assess inequalities to access health professional education, and the impact of an education improvement program supported by MEPI (Medical Education Partnership Initiative). Inequalities in the higher education system in sub-Saharan Africa remain despite some transformative policies and affirmative action. Methods: We reviewed enrollment data from four universities for the period 2001–2014 for various health professional training programs, and conducted group discussions through an iterative process with selected stakeholders, and including a group of education experts. Two time periods, 2001–2010 and 2011–2014, were considered. In 2010–11, the MEPI education program began. Gender ratios, regional representation, secondary schools, and the number of admissions by university and year were analysed. We used SPSS version 17 software to analyse these data with level of significance p < 0.05. We collated qualitative data along predetermined and emerging themes. Results: The overall male-to-female ratio among the student population was 2.3:1. In total, there were 7,023 admissions, 4,403 between 2001–2010 (440 per annum) and 2,620 between 2011–2014 (655 per annum) with p = 0.018. There were no significant increases in admissions in the central and western regions over the two time periods, 1,708 to 849 and 1,113 to 867 respectively, both p = 0.713 and p = 0.253. We propose improving the university admission criteria and increasing enrollment to health professions training schools. Conclusion: There were significant inequalities for higher education training in Uganda by gender, regional representation and school attended. Modifying the admission criteria and increasing enrollment may reduce these inequalities

Metabolite changes in blood predict the onset of tuberculosis

Immunogenetics and cellular immunology of bacterial infectious disease