Global existence of solutions for the relativistic Boltzmann equation with arbitrarily large initial data on a Bianchi type I space-time

We prove, for the relativistic Boltzmann equation on a Bianchi type I space-time, a global existence and uniqueness theorem, for arbitrarily large initial data.Comment: 17 page

Evaluation of treatment response, drug resistance and HIV-1 variability among adolescents on first- And second-line antiretroviral therapy: A study protocol for a prospective observational study in the centre region of Cameroon (EDCTP READY-study)

BackgroundSub-Saharan Africa (SSA) alone has nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million), with the potentials to reach adulthood. However, despite an overall reduction in HIV-related mortality, there are increasing deaths among adolescents living with HIV (ADLHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response and longer life expectancy. Interestingly, with uptakes in prevention of mother-to-child transmission, challenges in ART programs, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent ART options for SSA ADLHIV.ObjectivesAmong Cameroonian ADLHIV receiving ART, we shall evaluate the rate of immunovirologic failure, acquired HIVDR-associated mutations, HIV-1 subtype distribution, genetic variability in circulating (plasma) versus archived (cellular) viral strains, and HIVDR early warning indicators (EWIs) at different time-points.MethodsA prospective and observational study will be conducted among 250 ADLHIV (10-19years old) receiving ART in the centre region of Cameroon, and followed-up at 6 and 12months after enrollment. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia >=1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12months follow-up. Primary outcomes are rates of virological failure, acquired-HIVDR, and mortality.DiscussionOur findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ADLHIV within SSA

Viral suppression in adults, adolescents and children receiving antiretroviral therapy in Cameroon: Adolescents at high risk of virological failure in the era of "test and treat"

Background: After the launching of the "Test & Treat" strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon.Setting and methods: Cross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaounde, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and >= 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant.Results: 1946 patients (70% female) were enrolled (1800 adults, 105 adolescents, 41 children); 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at >= M48. The median (IQR) duration on was 48 months (24-48). Overall, VS was 79.4% (95% CI 77.6-81.2) and 67.1% (95% CI 64.9-69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (>= M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001.Conclusions: In this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings

po 8397 viral suppression among cameroonian adults adolescents and children receiving antiretroviral therapy in the test treat era

BackgroundGlobal efforts in meeting the 90–90–90 targets reveal that 70% of infected people know their HIV status, 77% of these are receiving antiretroviral therapy (ART) and 82% of treated patients have viral suppression. Since launching the 'test and treat' strategy and wider access to drugs that bring down the viral load (VL), evaluating viral suppression would help to identify those requiring interventions and to make progress towards meeting the targets in Cameroon.MethodsA study was conducted from October 2015 to August 2017 amongst adults (≥20 years), adolescents (10–19) and children (0–9) at 12, 24, 36 and ≥48 months on ART, monitored at the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon. VL was established using Abbott m2000RT-PCR. VS was defined as VL <1000 copies/ml; with p<0,05 considered significant.ResultsA total of 1979 patients (70% female) were enrolled (1825 adults, 112 adolescents, 42 children); 1865 were on first-line (NNRTI-based, duration: 48 [IQR 24–48] months) vs. 114 on second-line (PI/r-based, duration: 48 [IQR 36–48] months); with 19%(368) at Month2, 14%(274) at Month24, 10%(207) at Month36% and 54% (1130) at ≥Month48. Overall, viral suppression was 79.4%, and 64.3% had controlled viral replication (VL <40). On first-line, viral suppression was 79.7% (1487) vs. 72.2%(83) on second-line (p=0,076). By ART duration, viral suppression was 83.4%(Month12), 85.8%(Month24), 74.9%(Month36) and 77.3% (≥Month48); p=0,0011. By age-range, viral suppression was 76.2% in children, 54.5% in adolescents, and 80.9% in adults (p<0,0001). By age and ART-regimen, viral suppression on first vs. second line was: children 76.5% vs. 60%; adolescents 51.7% vs. 65.2%; and adults 81.2% vs. 74.7%.ConclusionAbout 80% of Cameroonian patients might be experiencing viral suppression, with a declining performance at adolescence and by 3 years of ART experience. Thus, meeting the viral suppression target by 2020 requires a closer VL monitoring strategy and an adapted adherence support mechanism for adolescents living with HIV in resource-limited settings sharing similar challenges

Alarming rates of virological failure and HIV-1 drug resistance amongst adolescents living with perinatal HIV in both urban and rural settings: evidence from the EDCTP READY-study in Cameroon

Objectives: Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location. Methods: A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL&nbsp;≥&nbsp;1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1. Results: Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were&nbsp;&lt;&nbsp;15%. In urban settings, the immunological failure (IF) rate (CD4 &nbsp;&lt;&nbsp;250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression. Conclusions: Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging

Melanin production inhibitors from the West African 'Cassipourea congoensis'

Cassipourea congoensis (syn. Cassipourea malosana) is used in African countries as a skin-lightening agent. Two previously unreported cycloartane triterpenoids, 26-hydroxy-3-keto-24-methy lenecycloartan-30-oic acid 1 and 24-methylene-cycloartan-3β,26,30-triol 2 along with the known mahuannin B 3, 7-methoxymahuannin B 4, 7-methoxygeranin A 5, methyl-3-(4-hydroxy-3-methoxyphenyl)-2E-propenoate, glycerol-1-alkanoate, (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enal 6, (-)-syringaresinol 7, and stigmast-5-en-3-O-β-D-glucoside, were isolated from the roots of C. congoensis. The crude extract and compounds 1 and 5 were found to inhibit the production of melanin at 10 μM with low cytotoxicity validating the ethno-medicinal use of this plan

The effect of isolates from 'Cassipourea flanaganii' (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition

Ethnopharmacological relevance The Zulu and Xhosa people of South Africa use the stem bark of Cassipourea flanaganii as a skin-lightning cosmetic. Aim of the study To isolate and identify compounds responsible for the skin lightning properties from the stem bark of Cassipourea flanaganii and to evaluate their cytotoxicity towards skin cells. Materials and methods Extracts from the stem bark of Cassipourea flanaganii were isolated using chromatographic methods and structures were determined using NMR, IR and MS analysis. The tyrosinase inhibitory activity and the ability to inhibit the production of melanin were determined using human primary epidermal melanocyte cells. Cytoxicity was established using the same melanocytes and a neutral red assay. Results One previously undescribed compound, ent-atis-16-en-19-al (1) along with the known ent-atis-16-en-19-oic acid (2), ent-atis-16-en-19-ol (3), ent-kaur-16-en-19-oic acid (4), ent-kaur-16-en-19-al (5), ent-manoyl oxide (6), guinesine A (7), guinesine B (8), guinesine C (9), lichenxanthone (10), 2,4-dihydroxy-3,6-dimethyl benzoic acid methyl ester (11), lynoside (12), lupeol (13), β-amyrin (14), docosyl ferulate (15), stigmasterol, sitosterol and sitosterol-O-glucoside were isolated in this investigation. An impure fraction containing compound 3 was acetylated to obtain 19-acetoxy-ent-atis-16-ene (3a). Compounds 10 and 11 are usually isolated from lichen, hence they are possible contaminants of lichen harvested with the bark. Compounds 1, 3a, 5–14 were not significantly cytotoxic to the primary epidermal melanocyte cells (P > 0.05) when compared to the negative and positive controls (DMSO, 0.1% and hydrogen peroxide, 30 wt% in water). Inhibition of tyrosinase was significantly greater with respect to the negative control (P < 0.001) for compounds 3a, 5–8 and 9–10 at 10 μM and for compounds 5–8 and 9–10 at 100 μM. Compared to hydroquinone (the positive control) at 10 μM, the level of inhibition was comparable or to that of compounds 3a, 5, 6, and 8–10 at 10 μM, with 9 and 10 showing a greater level of inhibition. Inhibition of melanin was both concentration and time dependent for all compounds tested with higher melanin content at 24 h compared to 48 h s and at 10 mM compared to100 mM at both time points; melanin content was significantly lower for hydroquinone at both time points and concentrations. Conclusions Compounds 1, 5–14, isolated from Cassipourea flanaganii and the derivative 3a showed low cytotoxicity. All compounds had a clear time and concentration dependent effect on melanin content which did not appear to be dependent on their inhibition of tyrosinase

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Anisotropic Heisenberg model for the mixed spin-3/2 and spin-1/2 under random crystal field

Thermodynamic properties of the mixed spin-3/2 and spin-1/2 Heisenberg model are examined within the Oguchi approximation in the presence of a random crystal-field (RCF). The RCF is either introduced with probability p or turned off with probability 1-p randomly. The thermal variations of the global magnetization and free energy of the system are investigated to construct the phase diagrams for the classical, quantum and anisotropic cases. Different results revealed that no qualitative changes exist between them. Quantum effects are found to be present and abundant in the quantum model in the negative D-range. This phenomenon has a strong decreasing effect on the critical temperature which becomes much lower than in the classical case. In the presence of an external field, it was observed that coercivity and remanence decrease in a wide range of the absolute temperature