Khat distorts the prefrontal cortex histology and function of adult Wistar rats

Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive behaviors however; it is linked to many psychological disorders such as depression, schizophrenia and memory loss. We studied the effects exerted by khat on the PFC cytoarchitecture and functions since this part of the brain is highly interconnected with various cortical regions. This was an experimental study of 6 weeks. A total of 24 male adult wistar rats of 130g-155g were divided into four groups of 6 animals that received respective khat doses of 2000mg/kg, 1000mg/kg, 500mg/kg and 10ml/kg of distilled water for the controls. Brain to body weight ratio was determined at week 6 using an analytical balance (Fisher Science Education™, RS232C; USA). Histology of the brain was determined using H and E and Kulvers staining technique. Khat exhibited features of prefrontal cortex disorientation such as necrosis, vacuolations, chromatolysis, demyelination, cortical degeneration and hemorrhage in a dose dependent manner. Selective attention and working memory were impaired well as brain to body weight ratio was reduced significantly (P ≤ 0.05). Repeated exposure to khat distorts the prefrontal cortex cytoarchitecture and impairs selective attention and working memory accuracy due to ischemia and cell exhaustion by khat toxicity.Keywords: Khat, prefrontal cortex histology, working memory, selective attentio

Neuroprotective potential of Lantana trifolium ethanolic extract against ethambutol induced histological changes in the optic nerve

Ethambutol is an anti-tuberculosis drug important in treatment of multidrug resistant tuberculosis which is on a rise due to emergence of Human Immunodeficiency Virus. However, it has been associated with side effects on optic nerve histology leading to severe neuropathy. The purpose of this study was to establish the protective potential of Lantana trifolium ethanolic extract against ethambutol induced histological changes in the optic nerve. Twenty five male adult wistar rats of 110-130g average weight were used. These were divided into five groups each comprising five animals. Group A received distilled water only. Group B was treated with 100 mg/kg/day of ethambutol. Groups C, D, and E were treated with 25, 50, and 100 mg/kg/day of Trifolium Extract respectively, one hour before administering 100 mg/kg/day of ethambutol. After five weeks the optic nerves were excised, processed and stained for histological studies. It was observed that Lantana trifolium ethanolic extract had a dose dependent protective potential against ethambutol induced histological changes in the optic nerve. The histology of the optic nerve showed that the numbers of vacuoles were significantly few in group A (2.2±0.37), D (6.2±1.07), and E (5±0.71) when compared against the positive control group (37.4±1.54). Axons were mildly demyelinated in group D and E compared to group B and C. The protective potential of Latana trifolium is possibly present due to its anti-oxidative and anti-inflammatory activities. Studies to determine the exact phytochemical component and mechanism of action responsible for the neuroprotective potential of Latana trifolium should be conducted.Keywords: Ethambutol, Optic Nerve, Lantana Trifolium, Optic Neuropath

Risk Perception and Condom Use in Uganda

The paper examines the risk perception and condom use in Uganda, based on 600 respondents drawn from Kabale, Kampala and Lira districts. The majority of the respondents were aged 35 and above, were married and engaged in subsistence farming. HIV risk perception was found to be associated with condom use, religion, educational attainment, marital status, residence, number of sexual partners and having contracted an STD. Predictors of high HIV risk perception were non use of condoms, rural residence, having ever engaged in sex for gain and ever discussed sex. Mistrust of partners, past social history, having many sexual partners, and having undergone blood transfusion are the main reasons why people consider themselves at risk of contracting HIV. Ever use of condoms was at 46% among males and 27% among females. Respondents who do not consider themselves at risk of contracting HIV and those who have never contracted STDs are less likely to use condoms. Respondents who had ever engaged in gainful sex were more likely to use condoms than those who engage in sex for pleasure. Post-primary education and urban residence are strong contributors to condom use.Cet article examine la perception du risque et l'utilisation du condom en Ouganda \ue0 partir de donn\ue9es obtenues aupr\ue8s de 600 r\ue9pondants choisis dans les districts de Kabala, Kampala et Lira. La plupart des r\ue9pondants sont \ue2g\ue9s de plus de 35 ans, sont mari\ue9s et pratiquent une agriculture de subsistance. Les r\ue9sultats ont montr\ue9 que les risques de contamination du VIH sont associ\ue9s \ue0 la non utilisation du condom, la r\ue9sidence rurale, la pratique de rapports sexuels \ue0 des fins commerciales, l'absence de discussions autour des rapports sexuels. Les principales raisons pour lesquelles les personnes se consid\ue8rent en risque de contamination du VIH/SIDA sont le manque de confiance entre partenaires, l'histoire sociale pass\ue9e, la pratique de rapports sexuels avec plusieurs partenaires ainsi que la transfusion sanguine. 46 % des hommes ont jamais utilis\ue9 les condoms alors seules 27 % des femmes l'utilisent. Les r\ue9pondants qui ne se consid\ue8rent pas en situation de risque de contamination du VIH et ceux qui n'ont jamais eu de MST sont ceux qui peu probablement utiliseront les condoms. Les r\ue9pondants qui ont jamais pratiqu\ue9 des rapports sexuels \ue0 des fins commerciales \ue9taient ceux qui avaient plus certainement utilis\ue9s les condoms que ceux qui pratiquaient des rapports sexuels par simple plaisir. L'enseignement post-primaire ainsi que la r\ue9sidence urbaine contribuent pour beaucoup \ue0 l'utilisation du condom

Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

Background International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15–49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population. Findings Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4–7·3) of transmissions occurred within lakeside areas, 89·2% (86·0–91·8) within inland areas, 1·3% (0·6–2·6) from lakeside to inland areas, and 3·7% (2·3–5·8) from inland to lakeside areas. Interpretation Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics. Funding The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Has the HIV/AIDS epidemic changed sexual behaviour of high risk groups in Uganda?

Background: Uganda, was the first country in sub-Saharan Africa to reverse its HIV/AIDS epidemic. Long distance drivers, prostitutes and barmaids have been identified as the groups that engage in risky sex, which promotes HIV transmission in Uganda and other countries across the continent. This paper investigates whether and why there were changes of sexual behaviour and practices among five risky groups in Uganda as a consequence of HIV/AIDS epidemic. Methodology: The paper is based on data generated from a survey on ‘resistance to sexual behaviour change in the African AIDS epidemic', which was conducted in the districts of Kabale, Kampala and Lira in 1999. For purposes of this paper, only data from the focus group discussions with high-risk groups have been analysed. These include commercial sex workers, street children, long haul truck drivers, bar maids and adolescents in three towns of Uganda (Kabale, Kampala, Lira). Results:Results indicate that despite the HIV/AIDS epidemic, these groups had only changed their sexual behaviour a little, and they reported to be continuing with multiple sexual partners for a variety of reasons. The adolescents and street children were under peer pressure and a lot of sexual urge; commercial sex workers and bar maids attributed their risky behaviour to the need to survive due to the existing poverty; and the truck drivers reflected on the need for female company to reduce their stress while on the long lonely travels across Africa. Nevertheless, they are all aware and perceive people with multiple sexual partners as being highly vulnerable to contracting HIV and they all reported to have adopted condom use as an HIV preventive strategy. They also observed that married people were at a high risk of contracting HIV due to non-use of condoms in marital relationships and unfaithfulness of spouses. Conclusions: Females engage in high-risk sexual relations as a means of economic survival, and perceive their acts as a strategy to improve their socio-economic well being. On the contrary, men in these high-risk categories do such acts out of pleasure and as avenues for attaining fulfilled sexual lives. The search for money among women and the constant desire for men to have sexual pleasure, which are greatly facilitated by their financial status are the forces behind reckless sexual behaviour among high-risk groups. (African Health Sciences: 2003 3(3): 107-116

Risk Perception And Condom Use In Uganda

The paper examines the risk perception and condom use in Uganda, based on 600 respondents drawn from Kabale, Kampala and Lira districts. The majority of the respondents were aged 35 and above, were married and engaged in subsistence farming. HIV risk perception was found to be associated with condom use, religion, educational attainment, marital status, residence, number of sexual partners and having contracted an STD. Predictors of high HIV risk perception were non use of condoms, rural residence, having ever engaged in sex for gain and ever discussed sex. Mistrust of partners, past social history, having many sexual partners, and having undergone blood transfusion are the main reasons why people consider themselves at risk of contracting HIV. Ever use of condoms was at 46% among males and 27% among females. Respondents who do not consider themselves at risk of contracting HIV and those who have never contracted STDs are less likely to use condoms. Respondents who had ever engaged in gainful sex were more likely to use condoms than those who engage in sex for pleasure. Post-primary education and urban residence are strong contributors to condom use

Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda

International audienceBackground: International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda.Methods: We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15-49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population.Findings: Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4-7·3) of transmissions occurred within lakeside areas, 89·2% (86·0-91·8) within inland areas, 1·3% (0·6-2·6) from lakeside to inland areas, and 3·7% (2·3-5·8) from inland to lakeside areas.Interpretation: Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics.Funding: The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention