In this study we evaluate the reliability of the Regional Climate Model (RegCM4.6) by performing several sensitivity tests at 50 km horizontal resolution using 10 convection schemes or combination of ...convection schemes. Emphasis on model output is made for the September–October–November 2017–2019 seasonal period. Part of the Central African region, five sub‐regions, was identified. The simulated temperatures are compared to the daily climatology of near‐surface temperature of the European Centre for Medium‐Range Weather Forecasts Reanalysis fifth‐generation and the National Center for Environmental Prediction datasets, while the simulated precipitations are compared to the precipitation of the Global Precipitation Climatology Project and Climate Hazards Group Infrared Precipitation with Stations datasets. In most analyses, the Grell scheme with Arakawa–Schubert closure assumption tends to have the best index of agreement but its spatial distribution shows underestimation of rainfall. Generally, the Emanuel convection scheme is more suitable to represent rainfall and temperature over Central Africa. Compared to our previous study (Komkoua Mbienda et al., International Journal of Climatology, 2017, 37, 328–342), the present study shows that we have to pay attention to the choice of convective scheme when using any version of RegCM4 released for climate study over Central Africa. This choice is strictly related to the RegCM version released, the study years and the season. It is important to note, however, that the results presented are a preliminary study of the response to the selected convection schemes. The analysis uses a limited sample of climate model simulation (three model years for each convection scheme). Follow‐up work, featuring longer duration climate simulations and a full assessment of statistical significance, is therefore required to confirm the robustness of the analysis presented.
The Regional Climate Model 4.6 (RegCM4.6) is sensitive to the choice of convective scheme or mixed convective scheme to simulate precipitation.
The Emanuel convective scheme tends to be the most suitable option in RegCM4.6 among other convective schemes and mixed convective schemes to simulate precipitation.
The different RegCM experiments generally underestimate near‐surface temperature over the continental area.
The choice of convective scheme is strictly related to the RegCM version released, the study year and the season.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In this open-label trial of first-line treatment for HIV-1 in Cameroon, a dolutegravir-based regimen was found to be noninferior to a low-dose efavirenz–based regimen as initial antiretroviral ...therapy. However, more weight gain and a higher incidence of obesity occurred in the dolutegravir group.
Objectives
Evidence comparing the economic and patient values of the World Health Organization’s preferred (dolutegravir 50 mg DTG-based) and alternative (low-dose 400 mg efavirenz EFV400-based) ...first-line antiretroviral regimens is limited. We compared patient-reported outcomes (PROs), costs, and the cost-utility of DTG- versus EFV400-based regimens in treatment-naive HIV-1 adults in the randomised NAMSAL ANRS 12313 trial in Yaoundé, Cameroon.
Methods
We used clinical data, PROs, and health resource use data collected in the trial’s first 96 weeks (2016–2019). Quality-adjusted life-years (QALYs) were computed using utility scores obtained from the 12-item Short Form (SF-12) generic health scale. Other PROs included perceived symptoms, depression, anxiety, and stress. In the 96-week base-case analysis, we estimated the unadjusted and multivariate-adjusted (1) mean costs (in US$, 2016 values) and QALYs/patient, (2) incremental costs and QALYs/patient, and (3) net health benefit (NHB). Outcomes were extrapolated over 5 and 10 years. Uncertainty was assessed using the cost-effectiveness acceptability curve and scenario and cost-effective price threshold analyses.
Results
In the base-case analysis, the NHB (95% confidence interval) for the DTG-based regimen relative to the EFV400-based regimen was 0.056 (− 0.037 to 0.153), corresponding to an 88% probability of DTG being cost-effective. A 10% decrease in this regimen’s price (from $5.2 to $4.7/month) would increase its cost-effectiveness probability to 95%. When extrapolating outcomes over 5 and 10 years, the DTG-based regimen had a 100% probability of being cost-effective for a large range of cost-effectiveness thresholds.
Conclusions
At 2020 antiretroviral drug prices, a DTG-based first-line regimen should be preferred over an EFV400-based regimen in sub-Saharan Africa.
Trial Registration
ClinicalTrials.gov Identifier: NCT02777229.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A prospective study was extended to the new antiretroviral and monitoring strategies in HIV-infected adults in low-income countries (NAMSAL-ANRS)-12313 trial, a 96-week open-label, multicenter, ...randomized phase 3 trial comparing dolutegravir (DTG) 50 mg with efavirenz 400 mg (EFV400), both administered with tenofovir disoproxil fumarate and lamivudine (TDF/3TC) as first-line treatment for antiretroviral therapy (ART)-naive people living with human immunodeficiency virus type 1 (HIV). Noninferiority of DTG to EFV400 was demonstrated at 48-week and sustained at 96 weeks. Here, we present results at 192-week.
Previous trial participants were reconsented and followed up on their initial randomization arm (1:1 DTG/TDF/3TC:EFV400/TDF/3TC). Assessments included changes in viral suppression, biological parameters, and new serious adverse events (SAEs).
Among the participants enrolled in the trial, 81% (499/613) were analyzed at week 192: 84% (261/310) on DTG/TDF/3TC and 78% (238/303) on EFV400/TDF/3TC. HIV RNA suppression was maintained in 69% (214/310) on DTG/TDF/3TC-based and 62% (187/303) on EFV400/TDF/3TC-based regimens (difference, 7.3% 95% confidence interval, -.20 to 14.83;
= .057). Five (DTG/TDF/3TC = 2; EFV400/TDF/3TC = 3) new viral failures (World Health Organization definition) without related resistance DTG mutations and 24 new SAEs were observed (DTG/TDF/3TC = 13; EFV400/TDF/3TC = 11). Mean weight gain was +9.4 kg on DTG/TDF/3TC and +5.9 kg on EFV400/TDF/3TC. The percentage of participants with obesity increased from 6.9% to 27.7% on DTG/TDF/3TC (
< .0001) and from 8.3% to 16.7% on EFV400/TDF/3TC (
= .0033).
Four-year follow-up of people with HIV on DTG- and EFV400-based regimens showed long-term efficacy and safety of both ARTs, markedly among participants on DTG/TDF/3TC with high baseline viral load. However, unexpected substantial weight gain over time was prominent among participants on DTG/TDF/3TC, which should be closely monitored.
NCT02777229.
Immune Response to Dengue and Zika Elong Ngono, Annie; Shresta, Sujan
Annual review of immunology,
04/2018, Volume:
36, Issue:
1
Journal Article
Peer reviewed
Open access
Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral ...diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell-mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.
A year after the COVID-19 pandemic started, there are still few scientific reports on COVID-19 in Africa. This study explores the clinical profiles and factors associated with COVID-19 in Cameroon.
...In this prospective cohort study, we followed patients admitted for suspicion of COVID-19 at Djoungolo Hospital between 01st April and 31st July 2020. Patients were categorised by age groups and disease severity: mild (symptomatic without clinical signs of pneumonia), moderate (with clinical signs of pneumonia without respiratory distress) and severe cases (clinical signs of pneumonia and respiratory distress not requiring invasive ventilation). Demographic information and clinical features were summarised. Multivariable analysis was performed to predict risk.
A total of 313 patients were admitted during the study period; 259 were confirmed cases of COVID-19 by Polymerase Chain Reaction (PCR). Among the confirmed cases, the male group aged 40 to 49 years (13.9%) was predominant. Disease severity ranged from mild (26.2%; n = 68) to moderate (59%; n = 153) to severe (14.7%; n = 38); the case fatality rate was 1% (n = 4). Dysgusia (46%; n = 119) and hyposmia/anosmia (37.8%; n = 98) were common features of COVID-19. Nearly one-third of patients had comorbidities (29%; n = 53), of which hypertension was the most common (18.9%; n = 49). Participation in mass gatherings (Odds Ratio (OR) = 2.37; P = 0.03) and dysgusia (OR = 2.09, P = 0.02) were predictive of diagnosis of COVID-19. Age groups 60 to 69 (OR = 7.41; P = 0.0001), 50 to 59 (OR = 4.09; P = 0.03), 40 to 49 (OR = 4.54; P = 0.01), male gender (OR = 2.53; P = 0.04), diabetes (OR = 4.05; P = 0.01), HIV infection (OR = 5.57; P = 0.03), lung disease (OR = 6.29; P = 0.01), dyspnoea (OR = 3.70; P = 0.008) and fatigue (OR = 3.35; P = 0.02) significantly predicted COVID-19 severity.
Most COVID-19 cases in this study were benign with low fatality. Age (40-70), male gender, HIV infection, lung disease, dyspnoea and fatigue are associated with severe COVID-19. Such findings may guide public health decision-making.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dengue virus (DENV) is a member of the Flavivirus family that includes Zika virus (ZIKV), West Nile virus, Japanese encephalitis virus, and yellow fever virus. As the most prevalent of the ...flaviviruses, DENV is responsible for tens of millions of infections each year. The clinical manifestations of infection with one of the four DENV serotypes (DENV1-4) range from no symptoms to hemorrhagic fever and shock ("severe dengue"), which is fatal in ~25,000 patients annually. Many factors contribute to the development of severe dengue, including the DENV serotype and host expression of certain HLA alleles; however, it now seems clear that pre-existing immunity to DENV-and possibly other flaviviruses-is a major precipitating factor. While primary infection with one DENV serotype elicits strong cellular and humoral immune responses that likely confer long-lived protection against the same serotype, subsequent infection with a different serotype carries an increased risk of developing severe dengue. Thus, primary DENV infection elicits cross-reactive immunity that may be protective or pathogenic, depending on the context of the subsequent infection. Many flaviviruses share high sequence homology, raising the possibility that cross-reactive immunity to one virus may contribute to protection against or pathogenesis of a second virus in a similar manner. In addition, several flaviviruses are now endemic in overlapping geographic regions, underscoring the need to gain more knowledge about the mechanisms underlying cross-reactive immunity to different DENV serotypes and flaviviruses. Here, we review our current understanding of T cell immunity to DENV, focusing on cross-reactivity with other serotypes and flaviviruses such as ZIKV, and the role of DENV-elicited CD4
and CD8
T cells in protection. Recent work in this area supports a beneficial role for cross-reactive T cells and provides new insights into the design of safe and efficient flavivirus/pan-flavivirus vaccines.
The idea that dark matter could be made of stable relics of microscopic black holes is not new. In this article, we revisit this hypothesis, focusing on the creation of black holes by the scattering ...of trans-Planckian particles in the early Universe. The only new physics required in this approach is an unusually high-energy scale for inflation. We show that dark matter emerges naturally and we study the question of fine-tuning. We finally give some lines of thoughts for a possible detection.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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