Pietro Caramello

A short course of pegylated interferon-alpha in acute HCV hepatitis

Summary.  Acute hepatitis C virus (HCV) infection evolves to chronicity in 50–84% cases. Treatment with interferon‐α (IFN‐α) was repeatedly found to provide sustained cure rates higher than that in chronic HCV infection, but the optimal treatment strategy has not yet been defined. In a multicentre open‐label study, we investigated the therapeutic performance of a short course of pegylated (peg) IFN‐α in patients with acute HCV hepatitis. Peg IFN‐α2b, 1.0–1.5 μg/kg weekly, was administered for 12 weeks. Forty‐six patients were enrolled; 26 of them were intravenous drug users. Eleven patients had jaundice. Treatment was started within 1–90 days from the peak alanine aminotransferase. Treatment was well tolerated with a single dropout (2%). Thirty‐three of 46 patients (72%) had a sustained virological response (SVR) after a 6 months post‐treatment follow‐up, 8 (17%) relapsed after treatment and 4 were nonresponders (9%). A lower peak viraemia, receiving at least 1.2 μg/kg of peg IFN‐α, and a negative HCV‐RNA at week 4 and week 12 were predictors of SVR. Thus, in patients with early (week 4) viral response, a short course of peg IFN‐α at a weekly dose >1.2 μg/kg, may be a valuable option for the treatment of acute HCV hepatitis.

Viral interference between hepatitis B, C, and D viruses in dual and triple infections in HIV-positive patients.

Objective:To investigate the reciprocal inhibitory effects of hepatitis B virus (HBV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) infections in naive and previously antiretroviral-experienced HIV-positive patients. Design:This retrospective study involved 72 consecutive patients of the Italian Cohort Naive Antiretroviral cohort: 21 coinfected with HBV/HCV (group 1BC), 18 infected with HBV (group 2B), and 33 infected with HCV (group 3C). Methods:Viral interference between HBV and HCV was assessed by means of the qualitative detection, quantification, and genotyping of each virus; HDV infection was assessed by means of genomic amplification. Results:Univariate analysis showed that HBV DNA was less frequently detected in group 1BC than in group 2B (16 of 21 vs 18 of 18; P = 0.02), their HBV load was significantly lower (median 3.9 vs 5.4 log10 HBV DNA copies/mL; P = 0.002), and they more frequently carried HBV genotype D (12 of 13 vs 4 of 11; P = 0.0071). HCV RNA was less frequently detected in group 1BC than in group 3C (12 of 21 vs 33 of 33; P < 0.0001), and HDV RNA was more frequently detected in group 1BC than in group 2B (9 of 21 vs 2 of 18; P = 0.028). Multivariate analysis of the HBV-infected subjects showed that the risk of HCV coinfection was associated with older age [relative risk 0.28, 95% confidence interval (CI): 0.09 to 0.90; P = 0.033 for every 10 years older] and intravenous drug use (relative risk 73, 95% CI: 2.4 to >999.999; P = 0.013). The only predictor of HBV coinfection in HCV-infected individuals was a lower HCV load (relative risk 0.30, 95% CI: 0.11 to 0.79 for every additional log10 HCV RNA; P = 0.015). Conclusion:HBV and HCV showed alternative dominant replication in the I.Co.N.A. cohort, with HBV having a more unfavorable effect on HCV replication.

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.

Combination of conventional blood cultures and the SeptiFast molecular test in patients with suspected sepsis for the identification of bloodstream pathogens

We evaluated performances of the molecular test SeptiFast (SF) for the detection of agents of bloodstream infection (BSI) in patients with suspected sepsis, the majority of them under antibiotic treatment and at high prevalence of HIV-1 infection (10.5%). Matched SF and blood culture (BC) samples (n=1186) from 1024 patients were studied. Two hundred fifty-one episodes of BSI out of 1144 were identified with the combined methods (22%). SF identified more episodes of BSI than BC: 206 versus 176 (χ(2)=7.008, P=0.0081) and a significantly higher number of Gram-negative bacteria than BC (77 versus 53, χ(2)=9.12; P=0.0025), as well as of polymicrobial infections (χ(2)=4.50, P=0.0339). In conclusion, SF combined with BC improved the diagnosis of sepsis, especially in immunocompromised patients.

Severe malaria, artesunate and haemolysis

Sir, Intravenous artesunate is the treatment of choice for severe and complicated malaria, according to the WHO 2010 guidelines, after large clinical trials in Africa (AQUAMAT) and South-East Asia (SEAQUAMAT) demonstrated a substantial benefit in terms of survival when this drug was compared with quinine; artesunate also proved to be very well tolerated. We report the case of a 22-year-old Italian woman who presented to Amedeo di Savoia Hospital in Turin in September 2011, with fever, chills and headache after a 4 week stay in Sierra Leone, without taking malaria chemoprophylaxis. Her physical examination showed a temperature of 408C, dehydration and splenomegaly. Blood tests showed a normal leucocyte count, haemoglobin 14.4 g/dL, thrombocyte count 32000/mm, lactate dehydrogenase (LDH) 2722 U/L and total bilirubin 5.7 mg/dL. Peripheral thick and thin blood films showed Plasmodium falciparum trophozoites (3.8% parasitized red blood cells). A treatment with oral artemether/lumefantrine was started. The following day, the parasitaemia was 6.9%; since the parasitaemiawas increasing and the patient was fulfilling WHO 2010 criteria for severe malaria (hyperparasitaemia and jaundice), intravenous artesunate (Guilin Pharmaceutical Co., Shanghai, China) dosed at 2.4 mg/kg every 12 h was started. After 6 h, the parasitaemia had dropped to 2% and was 0.01% after 24 h. After 36 h, the patient was switched to oral artemether/lumefantrine. On day 4, parasitaemia was absent and LDH was 1449 U/L. On day 8 she had another febrile peak and laboratory signs of haemolytic anaemia (haemoglobin 8.1 g/dL, LDH 2406 U/L, bilirubin 3.1 mg/dL, reticulocytes 150/1000 and haptoglobin ,2 mg/dL). No parasites were found on the blood smear. Immunohaematological haemolysis and glucose-6-phosphate dehydrogenase deficiency were ruled out by a cold agglutinins test, Coombs test, autoantibodies and glucose-6-phosphate dehydrogenase test. On day 14 (haemoglobin 5.6 g/dL), a blood transfusion was prescribed. In the following days the patient’s condition improved and she was discharged on day 18. On day 40, the patient was asymptomatic, thin and thick blood films were negative, and haematological and biochemical parameters were within the normal range. The patient gave written informed consent for the publication of these data. Haemolysis is not reported as a side effect of artesunate treatment in the cited trials (only some expected cases of blackwater fever occurred immediately after treatment). Nonetheless, subclinical haemolysis could be undiagnosed in such settings. Zoller et al. recently published a case series in European travellers with artesunate-treated imported malaria, including six cases with haemolysis occurring 14–31 days and resolving 3–6 weeks after treatment. The event was more frequent when high doses were used. In the reported case, an LDH flare and decrease in haemoglobin reappeared after parasite and fever clearance, and were associated with fever (37.5–388C) and conjunctival jaundice, indicating a haemolytic syndrome. A direct drug toxicity is unlikely, given the short half-life of the molecule (time to final detection: 2 h); although, due to the drug’s production outside European standards of good manufacturing practice, the presence of contaminants cannot be excluded. A further possibility is haemolysis due to lumefantrine, which has a longer half-life; however, this has never been reported, despite the long-term worldwide use of artemether/lumefantrine. Overall, a clear explanation for the haemolysis in this reported case is lacking. Since unexplained haemolysis has been repeatedly observed, specific surveillance in artesunate-treated patients is required.

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‐Hodgkins 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. Am. J. Hematol. 2012.

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.

Puumala virus pulmonary syndrome in a Romanian immigrant

Hantaviruses belong to the Bunyaviridae family, which is comprised of Bunyavirus, Phlebovirus, Nairovirus, and Hantavirus. Euroasiatic Hantaviruses belong to two distinct subfamilies: Murinae (comprising Hantaan, Dobrava, and Seoul viruses), which are responsible for hemorrhagic fever with renal syndrome (HFRS), and Arvicolinae (comprising Puumala virus), responsible for nephropathia epidemica (NE) and HFRS. On the contrary, the New World Hantavirus belongs to the Sigmodontinae subfamily and includes the North American viruses: Sin Nombre, Monongahela; New York, Bayou, Black Creek Canal, and the South American, which comprise the Andes, Oran, Lechiguanas, Laguna Negra, Juquitiba; both groups are responsible for the hantavirus pulmonary syndrome (HPS).

Variability in Malaria Prophylaxis Prescribing Across Europe: A Delphi Method Analysis

BACKGROUND The indications for prescribing malaria chemoprophylaxis lack a solid evidence base that results in subjectivity and wide variation of practice across countries and among professionals. METHODS European experts in travel medicine, who are members of TropNetEurop, participated in a survey conducted using the Delphi method. This technique aims at evaluating and developing a consensus through iterations of questionnaires, controlled feedback, and statistical group responses. RESULTS A first questionnaire, including questions about controversial issues in prescribing malaria prophylaxis, required responses on a visual scale between 1 and 10. The questionnaire included issues on problematic prescribing, characteristics of drugs, relevance of geography, and importance of insect bite prevention. The repeat questionnaire with the group response from the first round revealed an increasing consensus on most issues. A second survey considered 14 practical scenarios (including two internal standards) and investigated preferred choice of prophylaxis. A significant consensus was noted in 8 of 14 scenarios, which did not increase after a second round. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice, and a greater willingness to prescribe in northern and southern Europe than in central Europe. The second round showed a 9.5% change of opinion. CONCLUSIONS The study shows that improving the evidence base on efficacy and tolerability and risk of malaria for prescribing chemoprophylaxis is needed as is further discussion across Europe to achieve harmonization of prescribing practice.

Unmet Needs for a Rapid Diagnosis of Chikungunya Virus Infection

Rapid Diagnosis of Chikungunya Virus Infection