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1.  HIV Associated Neurocognitive Disorders (HAND) in Malawian Adults and Effect on Adherence to Combination Anti-Retroviral Therapy: A Cross Sectional Study 
PLoS ONE  2014;9(6):e98962.
Background
Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.
Methods
HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery.
Results
One hundred and six HIV positive patients, with median (range) age 39 (18–71) years, 73% female and median (range) CD4 count 323.5 (68–1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition.
Discussion/Conclusion
Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI.
doi:10.1371/journal.pone.0098962
PMCID: PMC4051684  PMID: 24915530
2.  Social Desirability Bias in Sexual Behavior Reporting: Evidence from an Interview Mode Experiment in Rural Malawi 
CONTEXT
Social desirability bias is problematic in studies that rely on self-reported sexual behavior data. Where gender norms create different expectations about socially acceptable behavior, males and females face distinct pressures in reporting certain outcomes, which can distort assessments of risk for HIV and STIs.
METHODS
In 2009, relationship and sexual behavior data were collected from 1,750 never-married males and females aged 16–18 via audio computer-assisted self-interviewing (audio-CASI) during the third round of the Malawi Schooling and Adolescent Study. A comparison group of 311 youth completed an identical questionnaire in face-to-face interviews. To assess whether interview mode may have influenced participants’ reporting of sensitive behavior, reports of sexual experience in the two groups were compared. Multiple logistic regression analysis was used to identify associations between interview mode and reports of these behaviors, by gender.
RESULTS
In adjusted regression models, males were less likely to report ever having had a girlfriend in audio-CASI than in face-to-face interviews (odds ratio, 0.4), but they were more likely to report having had sex with a relative or teacher (3.5). For females, reports of ever having had a boyfriend or having had sex did not differ between modes. A small proportion of females reported ever having had sex with a relative or teacher in audio-CASI, while none did so in face-to-face interviews.
CONCLUSIONS
The method used for collecting relationship and sexual behavior data may influence the reported prevalence of some key behaviors, particularly among males. Further research is needed to improve methods of collecting sensitive data.
doi:10.1363/3901413
PMCID: PMC4023461  PMID: 23584464
3.  Herpes simplex virus type 2 cross-sectional seroprevalence and the estimated rate of neonatal infections among a cohort of rural Malawian female adolescents 
Sexually transmitted infections  2013;89(7):561-567.
Objective
To assess herpes simplex virus type 2 (HSV-2) seroprevalence among rural Malawian adolescent women and estimate the number of neonatal herpes infections among infants of these adolescents.
Methods
A longitudinal cohort study of adolescents (14–16 years at entry) residing in rural Malawi was initiated in 2007 with annual observation. HSV-2 testing was introduced in 2010. In this study, we (1) determined, using cross-sectional analysis, risk factors for positive serostatus, (2) adjusted for non-response bias with imputation methods and (3) estimated the incidence of neonatal herpes infection using mathematical models.
Results
A total of 1195 female adolescents (age 17–20 years) were interviewed in 2010, with an observed HSV-2 seroprevalence of 15.2% among the 955 women tested. From a multivariate analysis, risk factors for HSV-2 seropositivity include older age (p=0.037), moving from the baseline village (p=0.020) and report of sexual activity with increasing number of partners (p<0.021). Adjusting for non-response bias, the estimated HSV-2 seroprevalence among the total female cohort (composed of all women interviewed in 2007) was 18.0% (95% CI 16.0% to 20.2%). HSV-2 seropositivity was estimated to be 25.6% (95% CI 19.6% to 32.5%) for women who refused to provide a blood sample. The estimated number of neonatal herpes infections among the total female cohort was 71.8 (95% CI 57.3 to 86.3) per 100 000 live births.
Conclusions
The risk of HSV-2 seroconversion is high during adolescence, when childbearing is beginning, among rural Malawian women. Research on interventions to reduce horizontal and vertical HSV-2 transmission during adolescence in resource-limited settings is needed.
doi:10.1136/sextrans-2012-050869
PMCID: PMC3923533  PMID: 23794069
4.  Characteristics of Female Sex Workers in Southern India Willing and Unwilling to Participate in a Placebo Gel Trial 
AIDS and behavior  2013;17(2):585-597.
Respondent-Driven Sampling was used to recruit female sex workers (FSWs) for a community survey conducted in southern India. After survey completion, participants were given a brochure describing a clinical trial that entailed daily use of a placebo vaginal gel for four months. This study assessed predictors of screening among survey respondents, predictors of enrollment among those eligible for the trial, and predictors of visit attendance and retention among those enrolled. FSWs who reported STI symptoms, engaging in sex work in the past month, and living in a subdistrict easily accessible by public transportation with a high concentration of FSWs, were more likely to screen. FSWs never before tested for HIV were more likely to enroll. This analysis suggests that the primary reason FSWs participated in the trial was a desire for health care—not other factors hypothesized to be important, e.g., HIV risk perception and poverty status.
doi:10.1007/s10461-012-0259-1
PMCID: PMC3629903  PMID: 22907287
microbicides; willingness to participate; female sex workers; Southern India
5.  Suboptimal management of central nervous system infections in children: a multi-centre retrospective study 
BMC Pediatrics  2012;12:145.
Objective
We aimed to audit the regional management of central nervous system (CNS) infection in children.
Methods
The study was undertaken in five district general hospitals and one tertiary paediatric hospital in the Mersey region of the UK. Children admitted to hospital with a suspected CNS infection over a three month period were identified. Children were aged between 4 weeks and 16 years old. Details were recorded from the case notes and electronic records. We measured the appropriateness of management pathways as outlined by national and local guidelines.
Results
Sixty-five children were identified with a median age of 6 months (range 1 month to 15 years). Ten had a CNS infection: 4 aseptic meningitis, 3 purulent meningitis, 3 encephalitis [2 with herpes simplex virus (HSV) type 1]. A lumbar puncture (LP) was attempted in 50 (77%) cases but only 43 had cerebrospinal fluid (CSF) available for analysis. Of these 24 (57%) had a complete standard set of tests performed. Fifty eight (89%) received a third generation cephalosporin. Seventeen (26%) also received aciclovir with no obvious indication in 9 (53%). Only 11 (65%) of those receiving aciclovir had CSF herpes virus PCR. Seventeen had cranial imaging and it was the first management step in 14. Treatment lengths of both antibiotics and aciclovir were highly variable: one child with HSV encephalitis was only treated with aciclovir for 7 days.
Conclusions
The clinical management of children with suspected CNS infections across the Mersey region is heterogeneous and often sub-optimal, particularly for the investigation and treatment of viral encephalitis. National guidelines for the management of viral encephalitis are needed.
doi:10.1186/1471-2431-12-145
PMCID: PMC3443041  PMID: 22958329
Encephalitis; Meningitis; Central nervous system infection; Aciclovir; Lumbar puncture
6.  Control and Function of the Homeostatic Sleep Response by Adenosine A1 Receptors 
During sleep, the mammalian CNS undergoes widespread, synchronized slow wave activity (SWA) that directly varies with prior waking duration (Borbely, 1982;Dijk et al., 1990a). When sleep is restricted, an enhanced SWA response follows in the next sleep period. The enhancement of SWA is associated with improved cognitive performance (Huber et al., 2004c), but it is unclear either how the SWA is enhanced or whether SWA is needed to maintain normal cognitive performance. A conditional, CNS knockout of the adenosine receptor, AdoA1R gene, shows selective attenuation of the SWA rebound response to restricted sleep, but sleep duration is not affected. During sleep restriction, wild phenotype animals, express a rebound SWA response and maintain cognitive performance in a working memory task. However, the knockout animals not only show a reduced rebound SWA response but they also fail to maintain normal cognitive function, although this function is normal when sleep is not restricted. Thus, AdoA1R activation is needed for normal rebound SWA, and when the SWA rebound is reduced, there is a failure to maintain working memory function suggesting a functional role for SWA homeostasis.
doi:10.1523/JNEUROSCI.2942-08.2009
PMCID: PMC2754857  PMID: 19193874
Sleep; Delta; Adenosine; working memory; Hippocampal function; Memory; Cre-transgenic; metabolism

Results 1-8 (8)