Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB.

BackgroundHIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated.MethodsWe stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined.ResultsAST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03).ConclusionWe identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

OBJECTIVE: T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. METHODS: A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. RESULTS: Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. CONCLUSION: Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa

The incidence of scarring on the dorsum of the hand

When undertaking image comparison of the hand between accused and perpetrator, it is not unusual for scars to be identified on the back of the hand. To investigate the occurrence of scarring in a discreet sample, a database of 238 individuals was examined, and the dorsum of the right and left hands was gridded for each individual. The position, size and type of scar were recorded within each grid. It was found that, in general, males exhibited a higher incidence of scarring than females. However, males were more likely to show scarring on their left hand whereas females were more likely to exhibit scarring on their right hand. Contrary to the literature, scarring was not most prevalent along the borders of the hand but occurred more frequently in association with the index and middle finger corridor regions. Surgical scars were rare as were large scars whereas linear scars smaller than 6 mm were the most frequently identified. Close to half of the sample did not exhibit scarring on one hand. The importance of understanding the pattern of scarring on the back of the hand is discussed in the light of forensic image comparison analysis

Media and Mental Health in Uganda

Objective: The media is largely regarded as an important stakeholder in health service delivery, with a great influence on publicattitudes. However, little is known about its interest in mental health and the guiding factors that influence media coverage of mentalhealth issues. This article describes the importance accorded to mental health by the media and the factors that influence mediacoverage of mental health issues in Uganda. Method: Semi-structured interviews were held with representatives from sixprominent media houses as part of the situational analysis of the mental health system in Uganda. Data was analyzed using Nvivo7 qualitative data analysis software. Results: The media was found to be interested and actively involved in health initiatives, butwith little attention devoted to mental health. Coverage and interest in mental health was noted to be mainly dependent on theindividual journalists’ interests, and mostly for personal reasons. Low interest was largely attributed to mental health beingperceived as a non-priority area, and the fact that mental illness is not a major contributor to mortality. Media coverage andreporting is guided by prioritization of the Health Department. Conclusion: The media in Uganda is an important stakeholderin the health care system with a key role of advocacy, publicity and mass education. Media houses however are less interested inmental health as evidenced by low coverage of mental health issues. This calls for advocacy and sensitization as a way ofpersuading media for more involvement in mental health initiatives.Key words: Media; Mental health; Uganda; Publi

Integration of Mental Health into Primary Health Care in a rural district in Uganda

Objective: Mental health has been identified as a major priority in the Ugandan Health Sector Strategic Plan. Efforts are currently underway to integrate mental health services into the Primary Health Care system. In this study, we report aspects of the integration of mental health into primary health care in one rural district in Uganda. Method: Qualitative methods were used for data collection. Semi-structured interviews and focus group discussions were conducted with various stakeholders within the ministry of health as well as line ministries. Data analysis was done using Nvivo 7, specifically adopting framework analysis approach. Results: Attempts to offer organized mental health services were found to be present in only a few health facilities. The district had only a single mental health nurse, and very few General Health Workers adequately equipped with the knowledge and skills to provide mental health services. The vertical referral system was not being followed as planned and there was no evidence of any organized community interventions for those with mental disorders. The mental health nurse and a few PHC nurses however expressed interest and commitment to providing services for persons with mental illness, despite the challenges. Conclusion: Although mental healthis expected to be integrated into primary health care, mental health services in this district have not yet achieved the expected level of integration. This implies that this important policy requirement has not yet been effectively realized in this rural district, which could be the case in many other districts of a similar status. There is thus a need to direct more efforts towards realization of this important policy requirement.Key words: Mental health; Primary Health Care; Integration; Ugand

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results: Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions: The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations

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

A blood RNA signature for tuberculosis disease risk: a prospective cohort study.

BACKGROUND: Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. METHODS: In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease. FINDINGS: Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis. INTERPRETATION: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. FUNDING: Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council