Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding: Bill & Melinda Gates Foundation

Acute kidney injury in patients with Visceral Leishmaniasis in Northwest Ethiopia.

BackgroundVisceral Leishmaniasis (VL) is a neglected tropical disease endemic to several countries including Ethiopia. Outside of Africa, kidney involvement in VL is frequent and associated with increased mortality. There is however limited data on acute kidney injury (AKI) in VL patients in East-Africa, particularly in areas with high rates of HIV co-infection. This study aims to determine the prevalence, characteristics and associated factors of AKI in VL patients in Northwest Ethiopia.MethodsA hospital based retrospective patient record analysis was conducted including patients treated for VL from January 2019 to December 2019 at the Leishmaniasis Research and Treatment Center (LRTC), Gondar, Ethiopia. Patients that were enrolled in ongoing clinical trials at the study site and those with significant incomplete data were excluded. Data was analyzed using SPSS version 20. P values were considered significant if ResultsAmong 352 VL patients treated at LRTC during the study period, 298 were included in the study. All were male patients except two; the median age was 23 years (IQR: 20-27). The overall prevalence of AKI among VL patients was 17.4% (confidence interval (CI): 13.6%-22.2%). Pre-renal azotemia (57%) and drug-induced AKI (50%) were the main etiologies of AKI at admission and post-admission respectively. Proteinuria and hematuria occurred in 85% and 42% of AKI patients respectively. Multivariate logistic regression revealed HIV co-infection (adjusted odds ratio (AOR): 6.01 95% CI: 1.99-18.27, p = 0.001) and other concomitant infections (AOR: 3.44 95% CI: 1.37-8.65, p = 0.009) to be independently associated with AKI.ConclusionAKI is a frequent complication in Ethiopian VL patients. Other renal manifestations included proteinuria, hematuria, and pyuria. HIV co-infection and other concomitant infections were significantly associated with AKI. Further studies are needed to quantify proteinuria and evaluate the influence of AKI on the treatment course, morbidity and mortality in VL patients

Hematological and Clinical Features Associated with Initial Poor Treatment Outcomes in Visceral Leishmaniasis Patients with and without HIV Coinfection in Gondar, Northwest Ethiopia

Ethiopia is among the countries with a high leishmaniasis burden. In this retrospective review, we aimed to determine hematological and clinical features associated with initial poor treatment outcomes of visceral leishmaniasis (VL) patients. The majority of VL cases in this study had leucopenia (94.3%), thrombocytopenia (87.1%), and anemia (85.9%). HIV coinfection was present in 7.0% (n = 23) of VL cases. At the center, VL patients without HIV coinfection were treated with sodium stibogluconate and paromomycin combination, whereas HIV coinfected cases were treated with AmBisome and miltefosine combination therapy. End-of-treatment cure rates among HIV-positive and HIV-negative visceral leishmaniasis cases, respectively, were 52.2% and 96.9%. Case fatality rates were 34.8% and 2.7% in HIV-positive and HIV-negative cases, respectively. Overall, non-survivors in this study were more likely to have HIV (55.0% vs. 4.1%, p p = 0.019), and dyspnea (40.0% vs. 2.7%, p < 0.001) at admission. In this regard, particular attention to the management of superimposed disease conditions at admission, including sepsis, HIV, and dyspnea, is needed to improve VL patients’ treatment outcomes. The inadequacy of the current treatments, i.e., AmBisome and miltefosine combination therapy, for HIV coinfected visceral leishmaniasis patients requires further attention as it calls for new treatment modalities

Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN- γ, but not IL-10 Production

Abstract One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation

Successful treatment of human visceral leishmaniasis restores antigen-specific IFN-γ, but not IL-10 production

One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation

Arginase activity in plasma from activated whole blood cells.

<p>Blood from VL patients (n = 10) was collected with heparin and EDTA and was activated at 37°C with SLA, PHA or PBS (unstimulated). 24 hours later, the plasma was collected and the levels of arginase activity were measured by enzymatic assay as described in materials and methods. Each symbol represents the value for one individual, the straight lines represent the median. Statistical differences were determined using a Kruskal-Wallis test.</p

Arginase Activity in plasma from whole blood assay.

<p>Arginase Activity in plasma from whole blood assay.</p

IFN-γ and IL-10 levels in plasma of VL patients and controls.

<p>IFN-γ and IL-10 levels in plasma of VL patients and controls.</p

IL-10 production in plasma from whole blood assay.

<p>IL-10 production in plasma from whole blood assay.</p

Comparison of unstimulated versus stimulated cultures.

<p>Comparison of unstimulated versus stimulated cultures.</p