Incidence and Risk Factors for Chronic Elevation of Alanine Aminotransferase Levels in HIV-Infected Persons without Hepatitis B or C Virus Co-Infection

Background. Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. Methods. We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at ⩾2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. Results. A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/µL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI ⩾30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. Conclusions. Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortalit

Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950-2017: protocol for a systematic review.

IntroductionCryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa.Methods and analysisWe will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2 test on Cochrane's Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines.Ethics and disseminationThere is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era.Prospero registration numberCRD42017081312

Hepatitis E Virus Seroprevalence among Blood Donors in Southwest Switzerland

Aim: The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.Background: HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.Methods: We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.Results: The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.Conclusions: Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration

Hepatitis E Virus Seroprevalence and Chronic Infections in Patients with HIV, Switzerland

We screened 735 HIV-infected patients in Switzerland with unexplained alanine aminotransferase elevation for hepatitis E virus (HEV) immunoglobulin G. Although HEV seroprevalence in this population is low (2.6%), HEV RNA can persist in patients with low CD4 cell counts. Findings suggest chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation

Urinary culture sensitivity after a single empirical antibiotic dose for upper or febrile urinary tract infection: a prospective multicenter observational study

Objectives: Urinary culture sensitivity after antibiotics administration is unknown. This study aimed to describe the diagnostic sensitivity of urine cultures from patients' first, second, and third micturition samples after a single dose of empirical antibiotics given for upper and/or febrile urinary tract infections, as well as searched for factors influencing diagnostic sensitivity over time. Methods: We collected consecutive urine samples from adult patients with an upper or febrile urinary tract infection diagnosed at four secondary hospital emergency rooms. One sample was collected before a first dose of empirical antibiotic treatment and up to three samples were collected from consecutive postadministration micturition. The main outcome was the number of positive cultures growing uropathogens with ≥103 colony forming units (CFUs) for men and ≥104 for women. Identical analyses were performed for any identified CFU and ≥105 CFU cut-off points. Time between antibiotic administration and first negative urinary culture was noted, which could have been at the time of any of the three postantibiotic urine samples. We used a Cox regression analysis for age-and sex-adjusted analyses. Results: A total of 86 of 87 patients' preantibiotic cultures (99%) were positive compared with 26 of 75 (35%; p &lt; 0.001), 15 of 50 (30%; p &lt; 0.001), and 1 of 15 (7%; p &lt; 0.001) of the first, second, and third postantibiotic samples, respectively, and missing 14 of 21 (67%), 13 of 17 (76%), and 7 of 7 (100%) of uropathogens with antibiotic resistance, respectively. The times needed for 25%, 50%, and 75% of cultures to be negative were 1.5, 2.9, and 9 hours, respectively, after antibiotic administration. Older age, male sex, non-Escherichia coli pathogens, urinary tract disease, comorbidity burdens, and urinary catheters prolonged time to negative culture, but were not significantly associated after adjustment. Uropathogens were found at ≥105 CFU in 15 of 75 (20%), 7 of 50 (14%), and 0 of 15 (0%) of the three postantibiotic micturition samples, respectively, and in any identified CFU in 48 of 75 (64%), 23 of 50 (46%), and 1 of 15 (7%), respectively. Conclusion: Urinary culture sensitivity decreases rapidly after administering antibiotics.</p