Mental disorder, sexual risk behaviour, sexual violence and HIV in Uganda

Aim The overall aim of this thesis was to investigate the association between mental disorder and risk of sexual HIV transmission in a low-income country with a generalized HIV epidemic. Specific objectives were to investigate in Uganda, (1) the association between common mental disorder and sexual risk behaviour, (2) how severe mental disorder could influence sexual risk behaviour, (3) the prevalence of HIV in persons with severe mental disorder, and (4) the association of severe mental disorder with sexual risk behaviour and sexual violence exposure. Methods (1) Population-based household survey of 646 Ugandans. Depression, psychological distress and alcohol use were assessed, and questions asked about sexual risk behaviour. (2) Facility-based qualitative semi-structured interview study of 20 Ugandans, exploring sexual risk behaviour and violence exposure. (3) Facility-based study of HIV prevalence among 602 persons with severe mental disorder. (4) Facility-based study of prevalence of sexual risk behaviour and sexual violence among 602 persons with severe mental disorder, with nationally representative comparison data. Results (1) Depression, psychological distress and alcohol use were all associated with sexual risk behaviour, with stronger associations found in women than in men. (2) Severe mental disorder can influence sexual risks by contributing to casual sex during episodes, to rape by non-partners, to exploitation by partners, to non-monogamy in partners, and to sexual inactivity. (3) HIV prevalence was higher in women with severe mental disorder than in women in the general population, but no similar difference was found in men. (4) Severe mental disorder was associated with sexual risk behaviour in women, but not men. In women, severe mental disorder was associated with exposure to sexual violence by a non-partner. The above associations were not confounded by basic socio-demographic variables. Conclusions Mental disorder is associated with risk of sexual HIV transmission in a low-income country with a generalized HIV epidemic. Associations were found across levels of mental disorder severity and in relationship to several indicators of sexual risk. Stronger associations were found in women. By design we were not able to show that mental disorder preceded the development of sexual risk behaviour, or first sexual violence exposure. However, qualitative and quantitative findings were consistent. Our findings suggest that women with mental disorder in Uganda may be at higher risk of HIV, and at higher risk of sexual violence, than women in the general population

Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy

Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR) of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence

Single Nucleotide Polymorphisms in TLR9 Are Highly Associated with Susceptibility to Bacterial Meningitis in Children

Background. Bacterial meningitis (BM) is a severe infection mainly caused by Streptococcus pneumoniae and Neisseria meningitidis (NM). However, genetically determined susceptibility to develop severe infections by these microorganisms is variable between individuals. Toll-like receptor 9 (TLR9) recognizes bacterial DNA leading to intracellular inflammatory signaling. Single nucleotide polymorphisms (SNPs) within the TLR9 gene are associated with susceptibility to several diseases, no such association with meningitis has been described. Methods. We studied the role of TLR9 SNPs in host defense against BM. Two TLR9 SNPs and 4 TLR9 haplotypes were determined in 472 survivors of BM and compared to 392 healthy controls. Results. Carriage of the TLR912848-A mutant was significantly decreased in meningococcal meningitis (MM) patients compared with controls (p: .0098, odds ratio [OR]: .6, 95% confidence interval [CI]: .4-.9). TLR9 haplotype I was associated with an increased susceptibility to MM (p: .0237, OR 1.3, 95% CI: 1.0-1.5). In silico analysis shows a very strong immunoinhibitory potential for DNA of NM upon recognition by TLR9 (CpG index of -106.8). Conclusions. We report an association of TLR9 SNPs with susceptibility to BM, specifically MM indicating a protective effect for the TLR912848-A allele. We hypothesize that the TLR912848-A mutant results in an upregulation of TLR9 induced immune response compensating the strong inhibitory potential of NM CpG DNA. BACKGROUN

Search for polarization in Ξ0 hyperons

Inclusive hyperon production by 400 GeV protons at Fermilab has shown that the hyperons are produced with significant polarization. However no polarization has been seen for Λ’s produced at these energies. In this paper we present the results of a searcch for Ξ0 polarization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87405/2/126_1.pd

Polarization of inclusively produced hyperons

We report here polarization results from a series of Fermilab experiments from the years 1974 through 1980, with some preliminary data from a high pT polarization experiment completed in February 1982. The Λ polarization has a remarkably simple and interesting behavior when expressed as a function of xF and pT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87407/2/83_1.pd

Poor mental health and sexual risk behaviours in Uganda: A cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>Poor mental health predicts sexual risk behaviours in high-income countries, but little is known about this association in low-income settings in sub-Saharan Africa where HIV is prevalent. This study investigated whether depression, psychological distress and alcohol use are associated with sexual risk behaviours in young Ugandan adults.</p> <p>Method</p> <p>Household sampling was performed in two Ugandan districts, with 646 men and women aged 18-30 years recruited. Hopkins Symptoms Checklist-25 was used to assess the presence of depression and psychological distress. Alcohol use was assessed using a question about self-reported heavy-episodic drinking. Information on sexual risk behaviour was obtained concerning number of lifetime sexual partners, ongoing concurrent sexual relationships and condom use.</p> <p>Results</p> <p>Depression was associated with a greater number of lifetime partners and with having concurrent partners among women. Psychological distress was associated with a greater number of lifetime partners in both men and women and was marginally associated (p = 0.05) with having concurrent partners among women. Psychological distress was associated with inconsistent condom use among men. Alcohol use was associated with a greater number of lifetime partners and with having concurrent partners in both men and women, with particularly strong associations for both outcome measures found among women.</p> <p>Conclusion</p> <p>Poor mental health is associated with sexual risk behaviours in a low-income sub-Saharan African setting. HIV preventive interventions should consider including mental health and alcohol use reduction components into their intervention packages, in settings where depression, psychological distress and alcohol use are common.</p