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

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

Depression symptoms and cognitive function among individuals with advanced HIV infection initiating HAART in Uganda

Background Among patients with HIV infection, depression is the most frequently observed psychiatric disorder. The presence of depressive symptoms and cognitive dysfunction among HIV patients has not been well studied in Sub-Saharan Africa. Initiation of highly active antiretroviral therapy (HAART) may have an effect on the prevalence and the change over time of depression symptoms and cognitive impairment among HIV-positive individuals. Methods We recruited 102 HIV-positive individuals at risk of cognitive impairment who were initiating HAART and 25 HIV-negative individuals matched for age and education. Depression was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D). Neurocognitive assessment included the International HIV Dementia Scale (IHDS), an 8 test neuropsychological battery and the Memorial Sloan Kettering scale. Assessments were carried out at 0, 3 and 6 months. Results The HIV-positive group had more respondents with CES-D score > 16 than the HIV-negative group at all 3 clinic visits (54%Vs 28%; 36% Vs 13%; and 30% Vs 24% respectively; all p < 0.050 OR 2.86, 95% CI: 1.03, 7.95, p = 0.044). The HIV positive group had higher likelihood for cognitive impairment (OR 8.88, 95% CI 2.64, 29.89, p < 0.001). A significant decrease in the mean scores on the CES-D (p = 0.002) and IHDS (p = 0.001) occurred more in the HIV-positive group when compared to the HIV-negative group. There was no association between clinical Memorial Sloan Kettering score and depression symptoms (p = 0.310) at baseline. Conclusion Depression symptomatology is distinct and common among cognitively impaired HIV patients. Therefore individuals in HIV care should be screened and treated for depression

Reproducibility of the ribosomal RNA synthesis ratio in sputum and association with markers of mycobacterium tuberculosis burden

The MIND-IHOP study was funded by the IHOP grant (NIH R01 HL090335), Lung MicroCHIP grant (NIH U01 HL098964), and K24 grant (NIH K24 HL087713). These sources provided the funding to support participant enrollment and specimen collection. Emmanuel Musisi was supported by a scholarship from the Pulmonary Complications of AIDS Research Training Program (NIH D43 TW009607). N.D.W., R.M.S., J.L.D., and P.N. acknowledge funding from the U.S. National Institutes of Health (1R01AI127300-01A1). N.D.W. and M.I.V. acknowledge funding from the U.S. National Institutes of Health (1R21AI135652-01). N.D.W. acknowledges funding from Veterans Affairs (1IK2CX000914-01A1 and 1I01BX004527-01A1) and from the Doris Duke Charitable Foundation Clinical Scientist Development Award.There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. Importance This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.Publisher PDFPeer reviewe

Possibilities for the future of global mental health: a scenario planning approach.

BACKGROUND: Global mental health is a widely used term describing initiatives in policies, research and practice to improve the mental health of people worldwide. It has been gaining momentum over the last 10 years, reflected in increasing funding opportunities, training programmes, and publications. In light of the rising importance of global mental health and the various uncertainties about its future directions, this paper explores what the future may hold for global mental health in 30 years' time. METHOD: A scenario planning method was used, involving a workshop with experts from four continents and a range of backgrounds, including clinical and academic psychiatry, psychology, art and music therapy, service user advisory role, funder of global health research and post-graduate students. RESULTS: Six distinct scenarios that describe potential future situations were developed: universal standards for care; worldwide coordination of research; making use of diversity; focus on social factors; globalised care through technology; mental health as a currency in global politics. CONCLUSIONS: These scenarios consider different social, economic, scientific and technological drivers and focus on distinct aspects. Some reflect a global application of possible trends in mental health, whilst others apply general global developments to mental health care. They are not fixed forecasts, but instead may help to promote discussion and debate about further developments and decisions

Developing mental health research in sub-Saharan Africa: capacity building in the AFFIRM project.

BACKGROUND: There remains a large disparity in the quantity, quality and impact of mental health research carried out in sub-Saharan Africa, relative to both the burden and the amount of research carried out in other regions. We lack evidence on the capacity-building activities that are effective in achieving desired aims and appropriate methodologies for evaluating success. METHODS: AFFIRM was an NIMH-funded hub project including a capacity-building program with three components open to participants across six countries: (a) fellowships for an M.Phil. program; (b) funding for Ph.D. students conducting research nested within AFFIRM trials; (c) short courses in specialist research skills. We present findings on progression and outputs from the M.Phil. and Ph.D. programs, self-perceived impact of short courses, qualitative data on student experience, and reflections on experiences and lessons learnt from AFFIRM consortium members. RESULTS: AFFIRM delivered funded research training opportunities to 25 mental health professionals, 90 researchers and five Ph.D. students across 6 countries over a period of 5 years. A number of challenges were identified and suggestions for improving the capacity-building activities explored. CONCLUSIONS: Having protected time for research is a barrier to carrying out research activities for busy clinicians. Funders could support sustainability of capacity-building initiatives through funds for travel and study leave. Adoption of a train-the-trainers model for specialist skills training and strategies for improving the rigor of evaluation of capacity-building activities should be considered

Pattern of neuropsychological performance among HIV positive patients in Uganda

BACKGROUND: Few studies have examined cognitive functioning of HIV positive patients in sub-Saharan Africa. It cannot be assumed that HIV positive patients in Africa exhibit the same declines as patients in high-resource settings, since there are differences that may influence cognitive functioning including nutrition, history of concomitant disease, and varying HIV strains, among other possibilities. Part of the difficulty of specifying abnormalities in neuropsychological functioning among African HIV positive patients is that there are no readily available African normative databases. The purpose of the current study was to evaluate the pattern of neuropsychological performance in a sample of HIV positive patients in comparison to HIV negative control subjects in Uganda. METHODS: The neuropsychological test scores of 110 HIV positive patients (WHO Stage 2, n = 21; WHO Stage 3, n = 69; WHO Stage 4, n = 20) were contrasted with those of 100 control subjects on measures of attention/concentration, mental flexibility, learning/memory, and motor functioning. RESULTS: Analysis of covariance (ANCOVA) revealed significant group differences on measures of verbal learning and memory, speed of processing, attention and executive functioning between HIV seropositive and seronegative subjects. CONCLUSION: Ugandan patients with HIV demonstrated relative deficits on measures of verbal learning and memory, speed of processing, attention, and executive functioning compared to HIV negative controls. These results from a resource limited region where clades A and D are prevalent are consistent with previous findings in the developed world where clade B predominates

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>There is limited data on Methicillin resistant <it>Staphylococcus aureus </it>(MRSA) in Uganda where, as in most low income countries, the routine use of chromogenic agar for MRSA detection is not affordable. We aimed to determine MRSA prevalence among patients, healthcare workers (HCW) and the environment in the burns units at Mulago hospital, and compare the performance of CHROMagar with oxacillin for detection of MRSA.</p> <p>Results</p> <p>One hundred samples (from 25 patients; 36 HCW; and 39 from the environment, one sample per person/item) were cultured for the isolation of <it>Staphylococcus aureus</it>. Forty one <it>S. aureus </it>isolates were recovered from 13 patients, 13 HCW and 15 from the environment, all of which were oxacillin resistant and <it>mecA/femA/nuc</it>-positive. MRSA prevalence was 46% (41/89) among patients, HCW and the environment, and 100% (41/41) among the isolates. For CHROMagar, MRSA prevalence was 29% (26/89) among patients, HCW and the environment, and 63% (26/41) among the isolates. There was high prevalence of multidrug resistant isolates, which concomitantly possessed virulence and antimicrobial resistance determinants, notably biofilms, hemolysins, toxin and <it>ica </it>genes. One isolate positive for all determinants possessed the <it>bhp </it>homologue which encodes the biofilm associated protein (BAP), a rare finding in human isolates. SCC<it>mec </it>type I was the most common at 54% prevalence (22/41), followed by <it>SCCmec </it>type V (15%, 6/41) and <it>SCCmec </it>type IV (7%, 3/41). <it>SCCmec </it>types II and III were not detected and 10 isolates (24%) were non-typeable.</p> <p>Conclusions</p> <p>Hyper-virulent methicillin resistant <it>Staphylococcus aureus </it>is prevalent in the burns unit of Mulago hospital.</p

Prevalence of severe mental distress and its correlates in a population-based study in rural south-west Uganda

BACKGROUND: The problem of severe mental distress (SMD) in sub-Saharan Africa is difficult to investigate given that a substantial proportion of patients with SMD never access formal health care.This study set out to investigate SMD and it's associated factors in a rural population-based cohort in south-west Uganda. METHODS: 6,663 respondents aged 13 years and above in a general population cohort in southwestern Uganda were screened for probable SMD and possible associated factors. RESULTS: 0.9% screened positive for probable SMD. The factors significantly associated with SMD included older age, male sex, low socio-economic status, being a current smoker, having multiple or no sexual partners in the past year, reported epilepsy and consulting a traditional healer. CONCLUSION: SMD in this study was associated with both socio-demographic and behavioural factors. The association between SMD and high risk sexual behaviour calls for the integration of HIV prevention in mental health care programmes in high HIV prevalence settings

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

Background: HIV 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. Methods: We stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-na\uefve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-na\uefve (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. Results: AST (p&lt;0.001), GGT (p&lt;0.001), total protein (p=0.001) and MDA (p&lt;0.001) were higher in HIV patients compared to controls. Vitamin C (P&lt;0.0001) and albumin (p&lt;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). Conclusion: We 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