Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

BACKGROUND: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. METHODS: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. RESULTS: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. CONCLUSIONS: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals.

Incidence and predictors of single drug discontinuation according to the presence of HCV coinfection in HIV patients from the ICONA Foundation Cohort Study.

To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation. Inverse probability weighting method to control for potential informative censoring was applied. Data from 10,637 patients were analyzed and 1,030 (9.7%) were HCV-Ab positive. Overall, there were 15,464 ART discontinuations due to any reason in 82,415.9 person-years of follow-up (PYFU) for an incidence rate (IR) of 18.8 (95% confidence interval [95%CI] 18.5-19.1) per 100 PYFU. No difference in IR of ART discontinuation due to any reason between HCV-infected and -uninfected patients was found. In a multivariable Poisson regression model, HCV-infected participants were at higher risk of darunavir/r discontinuation due to any reason (adjusted incidence rate ratio = 1.5, 95%CI 1.01-2.22, p value = 0.045) independently of demographics, HIV-related, ART and life-style factors. Among DRV/r treated patients, we found that HCV-viremic patients had twice the risk of ART discontinuation due to any reason than HCV-aviremic patients. In conclusion, HIV/HCV coinfected patients had a marginal risk increase of DRV/r discontinuation due to any reason compared with those without coinfection.

A retrospective study of viral central nervous system infections: relationship amongst aetiology, clinical course and outcome.

PURPOSE: To describe the clinical pattern of viral central nervous system (CNS) infections and compare meningitis and encephalitis. METHODS: This is a retrospective study reporting the clinical characteristics and outcome of 138 cases of viral meningitis and meningoencephalitis in a real life experience at a referral centre in Turin, Northern Italy. RESULTS: Enteroviruses were predominant in younger patients who were mainly presenting with signs of meningitis, had shorter hospital admission and absence of complications, whereas herpesviruses had more often signs of encephalitis, were more frequent in elderly patients, had longer hospital admission and frequent complications and sequelae. CONCLUSIONS: Two main clinical entities with different epidemiology, clinical aspects and prognosis may be identified within the group of viral CNS inefctions.

Unmet Needs for a Rapid Diagnosis of Chikungunya Virus Infection.

Rapid Diagnosis of Chikungunya Virus Infection.

Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Role of serum free light chains in predicting HIV-associated non-Hodgkin lymphoma and Hodgkin's lymphoma and its correlation with antiretroviral therapy.

A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.

Malaria chemoprophylaxis recommendations for immigrants to Europe, visiting relatives and friends--a Delphi method study.

BACKGROUND: Numbers of travellers visiting friends and relatives (VFRs) from Europe to malaria endemic countries are increasing and include long-term and second generation immigrants, who represent the major burden of malaria cases imported back into Europe. Most recommendations for malaria chemoprophylaxis lack a solid evidence base, and often fail to address the cultural, social and economic needs of VFRs. METHODS: European travel medicine experts, who are members of TropNetEurop, completed a sequential series of questionnaires according to the Delphi method. This technique aims at evaluating and developing a consensus through repeated iterations of questionnaires. The questionnaires in this study included questions about professional experience with VFRs, controversial issues in malaria prophylaxis, and 16 scenarios exploring indications for prescribing and choice of chemoprophylaxis. RESULTS: The experience of participants was rather diverse as was their selection of chemoprophylaxis regimen. A significant consensus was observed in only seven of 16 scenarios. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice and increased prescribing seen in Northern Europe compared to Central Europe. CONCLUSIONS: Improving the evidence base on efficacy, adherence to chemoprophylaxis and risk of malaria and encouraging discussion among experts, using techniques such as the Delphi method, may reduce the variability in prescription in European travel clinics.

Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures.

BACKGROUND: Although the kinetics of CD4(+) cell counts have been extensively studied in antiretroviral-naive HIV-infected patients, data on individuals who have failed combination antiretroviral therapy (cART) are lacking. METHODS: This analysis was based on the ICONA Foundation Study. Subjects with > or = 1 episode of viral suppression after starting first-line cART were included (n = 3537). Following a viral rebound, patients who achieved another episode of viral suppression could reenter the analysis. The percentage of patients with an increase in CD4(+) cell count >300 cells/mm(3) was estimated using Kaplan-Meier techniques; the rate of CD4(+) cell count increase per year was estimated using a multivariable, multilevel linear model with fixed effects of intercept and slope. Multivariable models were also fitted to include several covariates. RESULTS: The median time to reach a CD4(+) cell count increase >300 cells/mm(3) from baseline was significantly associated with the number of failed regimens: 34 months, 41 months, 51 months, and 45 months in subjects without evidence of previous virological failure, or 1, 2, or > or = 3 previous virologically failed regimens, respectively (P < .001, by log-rank test). The annual estimated increases in CD4(+) cell count were 36 cells/mm(3) (95% confidence interval [CI], 34-38 cells/mm(3)), 28 cells/mm(3) (95% CI, 11-21 cells/mm(3)), 31 cells/mm(3) (95% CI, 26-36 cells/mm(3)), and 26 cells/mm(3) (95% CI, 18-33 cells/mm(3)), respectively. Differences in the annual CD4(+) cell count increase were observed between specific antiretrovirals. CONCLUSIONS: Subjects with > or = 1 virological failure took a longer time to reach a CD4(+) cell count >300 cell/mm(3) and had a slower annual increase than those without virological failure. Efforts should be made to optimize first-line cART, because this represents the best chance of achieving an effective CD4(+) response.

Klebsiella pneumoniae meningitis in a 38-year-old Chinese traveller with impaired glucose tolerance: a new emerging syndrome?

Early diagnosis and appropriate empirical treatment of bacterial meningitis reduce morbidity and mortality. Prevalence rates of different causative pathogens associated with bacterial meningitis can depend on age, the underlying medical condition, way of infection and geographical distribution. Klebsiella pneumoniae represents an infrequent cause of community-acquired meningitis in South-East Asia and North-East Asia, where it accounts for 20% of all bacterial meningitis, frequently associated with septic metastatic complications. We describe a case of K. pneumoniae meningitis, diplopia and chemosis in a recently immigrated patient with impaired glucose tolerance. The reason for the high prevalence of metastatic septic infections caused by K. pneumoniae in Taiwan and South-East Asia remains unclear: high prevalence in this area of serotype K1 and K2 and the expression of a novel locus called magA conferring to bacterium an elevated phagocytosis resistance and an active proliferation ability have been suggested. A high degree of suspicion for this etiology must be taken into account in immigrants from China and Taiwan. Due to a very high lethality, guidelines on empiric treatment should be considered in the management of bacterial meningitis, with the patients geographical origin and the clinical syndrome (meningitis and endophtalmitis) as potential risk factors for K. pneumoniae infection.

[Primary soft tissue and tenosynovial tuberculosis after needlestick injury in a surgeon]. / Tubercolosi primaria tenosinoviale e dei tessuti molli da inoculazione in un chirurgo.

We describe the case of a surgeon, who pricked himself with a needle used to drain a paravertebral abscess in a patient from Sudan. He lost this patient at follow up. Six weeks later, the surgeon developed oedema of his left hand and wrist. He started antibiotics, amoxicillin/clavulanate plus ciprofloxacin 2 weeks, without any improvement. He came to our centre for examination, and by chance his patient had been admitted to our ward the day before, and had died during the night of disseminated tuberculosis. The surgeon was treated with rifampin, isoniazid and pyrazinamide (3 drugs 2 months, followed by rifampin plus isoniazid for further 7 months) with rapid improvement. He could start his job again after 5 months. To our knowledge, this is the first case of inoculation tuberculosis transmitted to a surgeon, while other cases in health care workers (internists, pathologists, nurses...) have already been well described.

Proportion and factors associated with recent HIV infection in a cohort of patients seen for care in Italy over 1996-2014: Data from the ICONA Foundation Study cohort.

In Italy the prevalence of recent HIV infection (RHI) isn't currently monitored. Early diagnosis is crucial to allow introduction of antiretroviral therapy (cART) in the recent phase of infection. We aimed to estimate the proportion and the determinants of RHI among patients enrolled in the ICONA cohort; we explored differences in the median time from HIV diagnosis to cART initiation and in the viro-immunological response between RHI and Less Recent HIV infections (NRHI). We included antiretroviral-naïve HIV-positive patients enrolled in the cohort with documented dates of HIV-negative and positive antibodies tests, grouped in RHI (estimated date of seroconversion within 12 months of enrolment) and NRHI. Proportion of RHI and the trend of this proportion by calendar period (1996-2014) were investigated (Chi-square test). Logistic regression analysis was employed to identify factors associated with RHI. The time from seroconversion to cART initiation was compared in RHI and NRHI overall and after stratification by calendar period (survival analysis). We finally explored the time from starting cART to HIV-RNA <50 copies/mL and to CD4+ gain ≥200 cells/mmc by Cox regression. HIV seroconversion could be estimated for 2608/12,616 patients: 981/2608 (37.6%) were RHI. Proportion of RHI increased in recent calendar periods and was associated with younger age, baseline higher HIV-RNA and CD4+ count. There wasn't difference in the 2-year estimates of cART start between RHI and NRHI, regardless of calendar period. Rates and hazards of virological response were similar in RHI versus NRHI. RHI showed a 1.5-fold higher probability of CD4+ gain, also following adjustment for calendar period and cART regimen, and for age, HCV and smoking; the difference in probability was however attenuated after further controlling for baseline HIV-RNA and CD4+ T-cells. The increased proportion of RHI over time suggests that in recent years in Italy HIV infections are more likely to be detected earlier than before. The similar rates of cART introduction and viro-immunological response in RHI and NRHI probably reflect the efficacy of the modern cART regimens. An improvement of the prevention services is warranted to allow an early cART access, also in the perspective of therapy as prevention.

Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa.

The development in Plasmodium falciparum of the resistance to chloroquine (CQ) constitutes a public health priority, due to its direct influence in childhood mortality. The molecular basis for CQ resistance (CQR) is still unclear but, recently, a new relevant gene, named pfcrt, with several point mutations was identified in P. falciparum. Two mutations, K76T and A220S, have been considered crucial for CQR in further studies, making the pfcrt a good candidate as determinant for CQR in P. falciparum. To contribute to this topic, we have undertaken a molecular screening on 164 P. falciparum isolates from Africa: 120 isolates were Italian imported malaria cases, 27 and 17 isolates were from a school-children survey from Congo and Tanzania, respectively. In vitro tests (pLDH and WHO-Mark III tests) for CQ sensitivity have been also carried out on 28 plasmodial isolates and results compared to those obtained by molecular analysis in the same isolates. The SVIET pfcrt haplotype has been identified in the samples from Congo, and this is the first time that this haplotype is detected in Africa. Our results give further evidence to the reliability of the 76T (and the linked 74I-75E) pfcrt point mutation as molecular marker for CQR.

[Molecular epidemiology of imported malaria in Italy: the use of genetic markers and in vitro sensitivity test in a study of chloroquine resistance in Plasmodium falciparum]. / Epidemiologia molecolare della malaria d'importazione in Italia: l'impiego di marcatori genetici e di saggi di sensibilità in vitro nello studio della clorochino-resistenza in Plasmodium falciparum.

The emergence of Plasmodium falciparum drug-resistance, especially chloroquine resistance, represents one of the main obstacles to the control of malaria. Several studies have shown that in P. falciparum the mechanism of chloroquine resistance is linked to specific point mutations in the pfcrt gene of the parasite. In the present study we have analyzed 120 Italian imported malaria cases to evaluate the prevalence of 76T and 220S mutantions in the pfcrt gene. Moreover, the correlation between the presence of pfcrt point mutations and in vitro chloroquine resistance has been evaluated on 25 plasmodial isolates. The results showed a high prevalence of the pfcrt point mutations in isolates analyzed and a significant association between point mutations and in vitro chloroquine resistance. Molecular screening on imported malaria cases can be a useful tool to be employed in surveillance activity and also in monitoring the development and spread of drug resistance in endemic areas.

High-density lipoprotein-cholesterol levels and risk of cancer in HIV-infected subjects: Data from the ICONA Foundation Cohort.

Investigation of the relationship between high-density lipoprotein-cholesterol (HDL-c) and the risk of developing cancer in a prospective cohort of human immunodeficiency virus (HIV)-infected patients.The Italian Cohort of Antiretroviral-naïve Patients Foundation Cohort is an Italian multicenter observational study recruiting HIV-positive patients while still antiretroviral treatment-naïve, regardless of the reason since 1997.Patients with at least 1 HDL-c value per year since enrollment and one such value before antiretroviral treatment initiation were included. HDL-c values were categorized as either low (<39 mg/dL in males or <49 mg/dL in females) or normal. Cancer diagnoses were classified as AIDS-defining malignancies (ADMs) or non-AIDS-defining malignancies (NADMs). Kaplan-Meier curves and Cox proportional-hazards regression models were used.Among 4897 patients (13,440 person-years of follow-up [PYFU]), 104 diagnoses of cancer were observed (56 ADMs, 48 NADMs) for an overall incidence rate of 7.7 (95% confidence interval [CI] 6.3-9.2) per 1000 PYFU.Low HDL-c values at enrollment were associated with higher risk both of cancer (crude hazard ratio [HR] 1.72, 95% CI 1.16-2.56, P = 0.007) and of NADM (crude HR 2.50, 95% CI 1.35-4.76, P = 0.003). Multivariate analysis showed that the risk of cancer diagnosis was higher in patients with low HDL-c values (adjusted HR [AHR] 1.87, 95% CI 1.18-2.95, P = 0.007) in older patients, those patients more recently enrolled, and in those with low current cluster of differentiation 4+ levels, and/or high current HIV-ribonucleic acid.The multivariate model confirmed an association between HDL-c (AHR 2.61, 95% CI 1.40-4.89, P = 0.003) and risk of NADM.Low HDL-c is an independent predictor of cancer in HIV-1-infected subjects.

Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression.

Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated.This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated.One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P = 0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P = 0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1.Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P = 0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio = 4.06, 95% CI: 1.20-13.80, P = 0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL.Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.

Chemosusceptibility analysis of Plasmodium falciparum imported malaria in Italy.

A constant surveillance of susceptibility to antimalarials allows to optimize prevention and treatment of malaria in nonendemic countries. In vitro susceptibility of imported Plasmodium falciparum isolates to chloroquine, quinine, mefloquine, halofantrin, pyronaridine, and amodiaquine was analyzed by WHO Micro-test Mark III; IC50 and IC90 were calculated by WHO Log-probit. Sixty-seven tests were performed. All the infections were acquired in Africa: 14.9% in East Africa and 85.1% in West Africa (WA). IC50 and IC90 (micromol/L) were chloroquine: 0.129 and 0.648; amodiaquine: 1.134 and 5.445; mefloquine: 0.38 and 0.868; quinine: 0.193 and 0.478; halofantrin: 3.27 and 25.35; pyronaridine: 11.504 and 51.996. Higher IC50 and IC90 were observed in East Africa versus West Africa strains. All strains were susceptible to quinine and mefloquine; chloroquine resistance, 14%; amodiaquine resistance, 33%, with cross-resistance to chloroquine (r = 0.93; P < .0001); halofantrin resistance, 3.6%, no cross-resistance with chloroquine; low susceptibility to pyronaridine (66.7%), with cross-resistance with chloroquine (r = 0.38, P < 0.05). Lower levels of chloroquine resistance were observed in 2000-2003 as compared with prior data; thus, the reemergence of chloroquine susceptibility in Africa may be hypothesized.

Pharmacodynamic analysis of antimalarials used in Plasmodium falciparum imported malaria in northern Italy.

BACKGROUND: Conventional treatment of imported malaria in Italy consists of quinine or mefloquine. Since beta-arthemeter is now available, an open-label pharmacodynamic analysis was performed in 73 adults with uncomplicated Plasmodium falciparum malaria. In vitro susceptibility to mefloquine and quinine was evaluated at admission. METHODS: According to clinical status, baseline parasitemia (P(0)), and premunition, the patients received intravenous quinine, oral mefloquine, or beta-arthemeter. The following parameters were measured: parasitemia at 0, 6, 12, and 24 hours and then every 24 hours until negative; time to 50%, 90%, and 100% reduction in parasite density (PC(50), PC(90), and PCT); parasite reduction ratio at 24 and 48 hours (PRR(24) and PRR(48)); percentage of patients with undetectable parasitemia at 48 hours (PPUP(48)); time required to eradication; in vitro susceptibility to mefloquine and quinine by World Health Organization Microtest Mark III. RESULTS: Of the study patients, 54.8% were immigrants from malaria-endemic countries. All the infections were acquired in Africa. All the patients were treated successfully. According to the pharmacodynamic parameters measured, no significant differences were recorded among patients with or without prior exposure to malaria. Pharmacodynamic comparison was performed between quinine and beta-arthemeter. Significantly higher clearance times were recorded for beta-arthemeter vs quinine (PC(50), PC(90), and PCT: 16.8, 42.6, and 72 h for quinine vs 7.9, 12.2, and 48 h for beta-arthemeter; p values: .02, < .0001, and .008, respectively). The number of patients who obtained a PPUP(48) with beta-arthemeter was higher than with quinine (66.7 vs 9.1%, p < .003), and PRR(24) was significantly higher in beta-arthemeter-treated patients (617 vs 3.15, p = .0001). PRR(48) and time to eradication were not measurable in the beta-arthemeter group (negative P at 48 h in most cases). Two recrudescences occurred after 5 and 7 days of beta-arthemeter monotherapy. All strains were fully susceptible to quinine and mefloquine. CONCLUSIONS: Pharmacodynamic properties of mefloquine and quinine are in the range reported in literature. The better PCT and pharmacodynamics of beta-arthemeter suggest that it could be used as a first-line agent, coadministered with mefloquine.