New Italian guidelines for malaria prophylaxis in travellers to endemic areas.

BACKGROUND AND METHODS: As a consequence of the rapid evolution of malaria prophylaxis recommendations throughout the world, the Italian Society of Tropical Medicine (SIMET-Società Italiana di Medicina Tropicale) has set up a working group in charge of preparing a new national guideline. Other scientific societies interested in the topic were also involved in the project. RESULTS AND CONCLUSIONS: The group stated that awareness about malaria risk and characteristics, as well as protection from mosquito bites, are recommended for all travellers visiting malaria-endemic countries. The risk and benefit of malaria chemoprophylaxis must be carefully balanced before prescribing drugs: the disease-related risk must outweigh the possibility of drugs' side effects. As a general rule, malaria pills are the first choice for travellers to high-risk areas, such as sub-Saharan Africa, Eastern India, Myanmar, Eastern Indonesia, Papua New Guinea and, with some limitations, South-East Asia, and the Amazon part of Venezuela, Guyana and French Guyana. However, several other factors, such as itinerary, season, duration of trip, availability of insect bite protection, pre-existing conditions and compliance, must be taken into account. In low-risk areas, stand-by emergency treatment is the first option. In minimal-risk areas and in Plasmodium vivax areas, a prompt diagnosis only is advised (Central America, South America outside the Amazon basin, Middle East, China, Thailand, Nepal). Recommendations may be modified when particular groups of travellers are concerned, such as long-term residents, visiting friends and relatives, patients with pre-existing conditions, pregnant women and children.

Infections are a global issue: infection addresses global issues.

Infections are of unifying global concern, despite regional differences in disease epidemiology, clinical appearance and the instruments to tackle them. The primary aim of Infection is "to be a forum for the presentation and discussion of clinically relevant information on infectious diseases… from all over the world". To that end, and as a reflection of the global burden of infectious diseases, we intend to increase the number of high-quality contributions from authors addressing the aetiology, pathogenesis, diagnosis and treatment of infectious diseases from outside Europe and the affluent North (Chang et al. Infection 40:359-365, 2012; Misra et al. Infection 40:125-130, 2012). The Editorial Board of Infection envisages the journal as an interface between where infectious diseases meet and mix between "North and South"--i.e., the field of travel medicine--frequently functioning as a sentinel for altered/novel disease activities that are encountered as imported conditions. With the change in generation on the Editorial Board, Infection aims to expand the areas of tropical medicine, travel medicine and global health with its own section editors (GC and MPG). Contributions from outside Europe are actively encouraged.

[Imported dengue in two tertiary Italian hospitals: Use of rapid diagnostic tests]. / Dengue importée dans deux hôpitaux tertiaires en Italie : utilisation des tests de diagnostic rapides.

Dengue fever is growing at a global level both as number of cases and as geographic area of endemicity. Italy is not in endemic area, but the competent vector Aedes albopictus is widespread in this country, so that the possibility of introduction of the infection cannot be ruled out. We retrospectively collected demographic, clinical, and laboratory data about consecutive cases diagnosed in Torino and Negrar-Verona in the period 2010-2015. One hundred thirteen cases of dengue were observed, with an increasing trend during years. The infection was imported mostly from south-east Asia, but the risk appears to be higher in Latin America. More than half of the patients were admitted to the hospital but only one case of severe dengue was observed. Many patients presented after the resolution of symptoms. Rapid diagnostic tests were done in the majority of patients and allowed a diagnosis both in the acute (NS1 antigen) and convalescent (IgMantibodies) phases of the disease. An early diagnosis is paramount to avoid the spreading of the infection.

A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin.

BACKGROUND: There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. AIM: To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. METHODS: 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).

Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients.

Cimetidine induces reversible dose-related central nervous system (CNS) toxicity. Trough serum concentrations and the development of CNS toxicity correlate. We compared cimetidine kinetics in 12 healthy subjects and 31 patients. Six of the latter had normal renal and liver function, five had renal disease only, 12 had liver disease only, and eight had both renal and liver disease. Postmortem tissue distribution was assessed in 11 patients, and expressed as tissue:serum ratio. Average cimetidine total clearance (ClB) in milliliters per minute for each group was as follows: patients with renal and liver disease (182 +/- 105), renal disease only (193 +/- 24), liver disease only (463 +/- 145), normal patients (510 +/- 93), and healthy subjects (583 +/- 140). Renal function was the major determinant for ClB, and the relationship was described by ClB = 4.2(CCr) + 140, r = 0.87, where CCr is creatinine clearance. Cimetidine clearance was affected little by age. Tissue:serum ratios from highest to lowest were as follows: kidney greater than stomach greater than liver greater than bone greater than brain greater than fat. Central and steady-state distribution volumes were not influenced by age or disease. There was enchanced CNS penetration in liver disease patients; their cerebrospinal fluid (CSF):serum ratio was twice the normal. Our kinetic studies identify patient characteristics likely to result in elevated blood levels, and suggest that the greatest risk of CNS toxicity is in those with liver disease.

Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial.

PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.

Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.

OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated. METHODS: Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months. RESULTS: According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.

Severe and complicated Falciparum malaria in Italian travelers.

Imported malaria has been an important public health problem in Western countries in the last 20 years, since international travel has become an increasing habit for nonimmune populations and since chemoresistance to most antimalarial drugs has been spreading throughout the world. Moreover, immigration from African and Asian countries has been rapidly increasing, especially in Italy in the last few years. Malaria had been widespread in Italy in the past, but no new autochthonous cases have been reported since 1961. Nonetheless the number of reported cases throughout the country has been steadily growing because of imported malaria1-3 in nonimmune travelers as well as in immigrants from tropical countries. In our experience as well as according to other statistics, the vast majority of patients have Plasmodium falciparum malaria acquired in Africa.4,5 The clinical spectrum of this disease is wide, and severe cases are frequently observed, including a few fatal cases, which, although rare, are highlighted by mass media and impress the public opinion.5-8 The purpose of this study was to examine the clinical spectrum of malaria, with particular interest in severe falciparum malaria, and to define the frequency of this phenomenon and epidemiologic characteristics of patients who experience it as a life-threatening disease.

[Multiple cutaneous leishmaniasis after a stay in Central America]. / Leishmaniosi cutanea a lesioni multiple dopo un soggiorno in America Centrale.

Leishmaniasis is a protozoal disease affecting at least 12 millions persons, with 400,000 new cases per year. It is transmitted by a small insect, the phlebotomine sand fly. Clinical syndromes include visceral leishmaniasis and various cutaneous affections. We describe here the case of a patient affected by a multiple lesions New World cutaneous leishmaniasis, after staying in Costa Rica for tourism; we discuss the differential diagnosis and make a short summary of the principles of treatment.

Warthin's tumour in the parotid gland (an inflammatory or a neoplastic disease?).

Warthin's tumour has always been considered a peculiar neoplasm with specific anatomico-pathological characteristics. In this study we argue that it should not be considered a true neoplasm but simply an inflammatory process which is triggered by the indiscriminate use of tobacco and involves the parotid duct. In the 10 cases treated in our department, Warthin's tumour has predominantly affected males (9:1) and heavy smokers. Our treatment of choice has been enucleoresection. The results have been satisfactory, with no complications such as salivary fistula or permanent lesions of the facial nerve. In two subjects, treated by enucleoresection, there was a pleomorphic adenoma: in one on the same side as previous surgery performed two years earlier and, in the second, in the contralateral gland 4 years after surgery. Both patients, who underwent total parotidectomy, recovered perfectly without complications. Smoking appears to be involved in the development of Warthin's tumour and might be regarded as an inflammatory reaction to smoking or to ionising radiation. Ultrasound and FNAB are necessary for planning the correct surgical strategy, and enucleoresection, in our opinion, is the treatment of choice.

[Splenic abscess in typhoid fever]. / Ascesso splenico in corso di febbre tifoide.

We report the case of a young patient with typhoid fever who complained of pain in his left hypochondrium and shoulder and recrudescence of fever after 21 days of treatment with tiamphenicol and ampicilline. Ultrasonography lead to the diagnosis of splenic abscess; the patient was splenectomized and S. typhi was cultured from the pus. Splenic abscess was frequently observed before 1940; since then only 6 more cases are reported in literature.

[Hospital costs of patients with AIDS]. / Costo ospedaliero del malato di AIDS.

We carried out a retrospective research into the hospital care cost of 52 AIDS cases we observed in our department, in the period 1984-1988. These patients required an average of 3.2 hospital admissions per year, and 101.3 hospitalization days per year, spending more than one fourth of their life span after their diagnosis of AIDS, in a hospital. The total care cost was Lit. 1,133,614,000, mostly due to the hospital stay (65.0%), but the introduction of expensive drugs will increase the cost of treatment. The average daily cost per patient was Lit. 227,900. Prognosis and cost vary according to the kind of opportunistic infection or neoplasm. The prolongation of hospitalization in consequence of social and economic problems is very frequent. A better accessibility of diagnostic systems, and a development of day-hospital and social services could reduce AIDS patients costs.

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

Acute hepatitis C virus (HCV) infection evolves to chronicity in 50-84% cases. Treatment with interferon-alpha (IFN-alpha) 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-alpha in patients with acute HCV hepatitis. Peg IFN-alpha2b, 1.0-1.5 micro g/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 micro g/kg of peg IFN-alpha, 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-alpha at a weekly dose >1.2 micro g/kg, may be a valuable option for the treatment of acute HCV hepatitis.

Conscious sedation during endoscopic retrograde colangiopancreatography: implementation of SIED-SIAARTI-ANOTE guidelines in Belluno Hospital.

AIM: In this study we describe the results of adoption of local guidelines for conscious sedation (CS) during endoscopic-retrograde-cholangiopancreatography (ERCP) in Belluno Hospital. Local guidelines were created referring to SIED-SIAARTI-ANOTE guidelines for CS in gastrointestinal endoscopy. METHODS: Between January 2002 and February 2004, 300 ERCPs to be performed under CS have been scheduled. According to local guidelines CS was performed by the gastroenterologist assisted by an anesthesia nurse. An anesthesiologist was always on call in the intensive care unit (ICU) for emergencies and could be on the site in less than 5 min. RESULTS: In 278 patients the procedure was performed safely and effectively by the gastroenterologist without any anesthesiological assistance. At follow-up controls patients had either positive or no recollection of the procedure. An anesthesiologist was called in 13 cases to perform deep sedation and in 9 cases to deal with undesired effects (arterial hypertension in 5 patients, 1 episode of bradycardia, 1 of ventricular tachycardia, 1 of atrial fibrillation and 1 of hypoxia). CONCLUSION: In our experience, CS during ERCP can be safely performed autonomously by a gastroenterologist in the majority of cases. Drug prescription protocol and the presence of an anesthesia nurse create ideal conditions for the operator, patient comfort and good results with a low incidence of undesired events and few calls for the anesthesiologist. To allow safe and effective performance of CS, the Department of Anesthesia should promote the in-service training and up dating of gastroenterologists and anesthesia nurses.

[Interferon alpha treatment in chronic hepatitis C]. / Trattamento con alfa interferon nelle epatiti croniche di tipo C.

Alpha Interferon showed effective in the treatment of chronic type C hepatitis, but a consensus has not been reached about the selection of patients and therapy schedules so far. We treated 36 patients with chronic type C hepatitis in the outpatient ward of the 1st Infectious Diseases Dept., "Amedeo di Savoia" Hospital, Torino (Head of Dept.: Prof. W. Grillone) in the period 1990-1992. Alpha IFN 1-6 MU thrice weekly for 6-12 months was used. The average follow up period after therapy was 8.5 months. Four patients dropped out during the treatment period. The clinical response was evaluated using serum transaminases: 9 patients showed a full response, 9 patients had a hepatitis relapse after stopping the treatment, 6 patients had a partial response, and 9 were treatment failures. A better response was observed in young patients, drug addicts, with chronic persistent hepatitis and high transaminases levels. Side effects of the treatment were very frequent, but usually short lasting, and seldom responsible for dropping out.

[Microscopic diagnosis of Pneumocystis carinii. Comparison of various staining technics]. / La diagnosi microscopica di P. carinii. Confronto tra diverse tecniche di colorazione.

The toluidine blue 0 and methenamine-silver nitrate staining techniques allowed a good microscopic distinction of Pneumocystis carinii cysts in lung autoptic impression smears. Poor results we observed with methylene blue and modified Gram techniques. With Giemsa's stain the intracystic bodies are shown, however the microscopic examination requires experience and patience.

Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.

15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.

Dose and serum concentration relationships in cimetidine-associated mental confusion.

A patient with severe liver disease and mildly obnormal but stable renal function was given cimetidine on two occasions for gastrointestinal hemorrhage. In each course, dosing was initiated at half the recommended dosage of 600 mg daily, and mental status deteriorated shortly after dosing began. A further dosage decrease to 300 mg daily allowed continuation of cimetidine therapy in absence of mental status alterations. In this patient, mental status changes occurred at lower serum concentrations than we have previously reported. This discrepancy was explained by analysis of cimetidine CSF concentrations, as this patient had abnormally high cimetidine blood to CSF permeability. Although the cause of increased CSF concentrations is unclear, cimetidine-associated mental confusion was dose related and completely reversible upon a decrease in dosage. Patients who develop cimetidine-associated mental status changes and who cannot have treatment stopped may be safely treated by individualizing the dosing rate.