Volume 16, Issue 1, 2008
Review
New treatment options in chronic hepatitis B
Mondelli Mario
To date, four different nucleoside/nucleotide analogues are available in the treatment of chronic hepatitis B (CHB): lamivudine, adefovir dipivoxil and entecavir; telbivudine, a deoxythymidine analogue that specifically inhibits polymerase-DNA of HBV, approved by the European Medicines Agency (EMEA), has recently become obtainable in Italy. Lamivudine, the first antiviral drug to be used in the treatment of chronic hepatitis B, shows an excellent bioavailability, a virtual absence of significant adverse drug reactions, and a high efficacy in reducing the viral load.
Such good pharmacological features are not paralleled by a high genetic barrier. Adefovir dipivoxil, a nucleotide analogue, is considered an effective alternative option to lamivudine, due to the better genetic barrier (almost 30% of resistant mutants after 5 years of treatment). However, at the therapeutic approved doses (10 mg/die), adefovir demonstrates sub-optimal efficacy in suppressing viral replication. By contrast, it has proved highly effective against viral strains resistant to lamivudine. Entecavir, the nucleoside analogue most recently introduced in Italy, exhibits a substantial inhibition of viral replication and a high genetic barrier both in naïve patients (<1% of resistant mutants after three years), and in patients resistant to lamivudine treatment.
Telbivudine appears a new, promising antiviral agent, characterised by a rapid and sustained virologic response, together with a good genetic barrier. Its excellent tolerability and safety profile (FDA Pregnancy Category B), specific mechanism of activity (no activity against HIV) and efficacy characteristics make telbivudine a first choice therapeutic option for treatment of patients affected by CHB.
Original article
Carotid artery intima-media thickness in highly treated HIV-1 patients
Leone Sebastiano,
Amitrano Maria,
D’Avanzo Antonio,
Acone Nicola,
Giglio Sergio
The authors used ultrasonography to measure carotid artery intima-media thickness in a cohort of antiretroviral-experienced patients. Overall, 52 patients were enrolled in the study. Twenty-two patients (42.3%) showed a IMT >1 mm and among these 14 (26.9%) showed a atheromatous plaque. Data analysis showed that IMT >1 mm was associated with the duration of HIV infection (p=0.03), nadir CD4 cell count (p<0.01), and conventional cardiovascular risk factors. No association was found between IMT and type or duration of antiretroviral therapy. These data confirm the direct role of HIV in the development of endothelial damage.
Serological screening for Leishmania infantum in asymptomatic blood donors and HIV+ patients living in an endemic area
Scarlata Francesco,
Li Vecchi Valentina,
Abbadessa Vincenzo,
Giordano Salvatore,
Infurnari Laura,
Saporito Laura,
Mancuso Salvatrice,
Occhipinti Francesco,
Vitale Fabrizio,
Reale Stefano,
Titone Lucina
Visceral leishmaniasis (VL) is endemic in Sicily (48 new cases in 2004, of which nine were in Agrigento). In southern Europe between 25-70 per cent of adult VL cases are related to HIV infection. The HIV cases have a high risk (1.5-9%) of developing VL either as a new infection or as the revival of a latent infection. We therefore carried out serologic screening to detect antibodies against L. infantum by IFAT in 1449 blood donors in Agrigento and the surrounding area (May-December 2005) and in 120 HIV+ in western Sicily, all of whom were asymptomatic and had no history of VL. L. DNA was assessed by nested PCR in blood samples of some seropositive donors.
Of the 1449 blood donors, 11 (0.75%) were positive by IFAT and three of them were also positive in PCR. L. infantum seropositivity is most probably the expression of recent infection because the clearance of serum antibodies is rather fast (6-12 months) after VL. This is why blood donation by Leishmania seropositive donors, whether positive or negative by PCR, could constitute an infection risk especially for immunosuppressed recipients, who should receive deleukocyted blood. Moreover it could be useful to monitor HIV/Leishmania coinfection cases to avoid the risk of slatentization of L. infection when CD4+ levels are very low.
Infezione materno-fetale da Toxoplasma gondii: analisi critica della diagnosi pre e post-natale
Di Carlo Paola,
Romano Amelia,
Schimmenti Maria Gabriella,
Mazzola Angela,
Titone Lucina
Various critical issues still surround the management of toxoplasmosis in pregnant women and neonates. Although the study of specific antibodies remains an essential parameter for diagnosing materno-fetal infection and establishing time of infection, the method needs to be carefully and critically reviewed due to the distinctive immunological sensitivity of the neonate. We began a retrospective epidemiological study of the pre-natal management of Toxoplasma gondii (TG) infection to evaluate the incidence of congenital toxoplasmosis in children in a southern Italian area (Sicily). 230 children born between 1999 and 2005 to mothers with TG infection during pregnancy enrolled in the G. Di Cristina Children’s Hospital of Palermo.
Retrospective analysis of the maternal sample established that 150 (65%) of the 230 infants enrolled in the study were born to a mother with probable infection, while the remaining 80 (35%) were born to a mother with definite infection. To date, the results of the neonatal follow-up programme have confirmed the diagnosis of congenital infection in 16 infants (7%); for 43%, diagnosis was made early due to the presence, at birth or in the first month of life, of specific anti-TG IgM. Sequelae were observed in 8/16 infected infants. Sequelae in infected born to mothers with infection in the third trimester opens up the problematic issue of which therapeutic approach to adopt for these women: even without consensus support, a combined regimen of Pyrimethamine-Sulfadiazine could be advocated, even in the absence of prenatal diagnosis. Currently, the best diagnostic strategy involves the sequential or contemporaneous combination of more than one of the currently available methods, as no method on its own can ensure an appropriate level of accuracy.
Case report
Primary soft tissue and tenosynovial tuberculosis after needlestick injury in a surgeon
Lipani Filippo,
Canta Francesca,
Carosella Sinibaldo,
Marrone Rosalia,
Boglione Lucio,
Sacchi Claudia,
Caramello Pietro
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.
Acute abdomen due to massive intestinal ascaridiasis: a case report
Scarlata Francesco,
Giordano Salvatore,
Infurnari Laura,
Rubino Raffaella,
Iacono Maurizio,
Nasta Roberto,
Romano Amelia
Ascaridiasis is a geohelminthiasis with a worldwide distribution, especially occurring in countries with hot-humid climates. The infection occurs most frequently in children between three and nine years of age. We report a case of ascaridiasis regarding a ten-year-old girl born in Bangladesh who arrived in Italy about one year before. During laparotomy for suspected acute appendicitis, a large number of ascaridia nematodes were seen in the small intestine.
Infected atrial myxoma: a rare cause of fever
Falasca Katia,
Ucciferri Claudio,
Mancino Paola,
Di Girolamo Arturo,
Vecchiet Jacopo
We report the case of a patient complaining of intermittent fever for two years. After three episodes which were well controlled in a few days by antibiotic therapy, in October 2004 she came to our observation for the reappearance of fever. Our findings included high levels of inflammation indexes, a left atrial power at ECG, and an enlargement of the heart at chest radiography. Finally, transthoracic echocardiography showed the presence of a mass in the left atrium, subsequently identified as a myxoma after its surgical excision. To date the patient has reported no new episodes of fever. We recommend careful examination of all patients with unexplained fever so to avoid failure to identify rare but potentially fatal causes of fever (e.g.: myxoma).
Relapsing infection of cranial prosthesis sustained by Enterobacter cloacae and methicillin-resistant Staphylococcus aureus
Garazzino Silvia,
De Rosa Francesco Giuseppe,
Bargiacchi Olivia,
Di Perri Giovanni
We describe the case of a young man who suffered from relapsing infections of a cranial prosthesis implanted in 1982 after a serious accident. The presence of a bacterial infection was diagnosed by microbiological assays performed on purulent drainage from the surgical wound, removed prosthetic material and bone biopsies obtained intraoperatively. The first prosthesis infection was sustained by two nosocomial pathogens, Enterobacter cloacae and methicillin-resistant Staphylococcus aureus (MRSA); it was treated for eight weeks with parenteral antibiotic therapy, including teicoplanin and piperacillin/tazobactam, in association with surgical debridement and prosthesis removal. The following relapse, sustained by Enterobacter cloacae, was treated with a prolonged course of parenteral antibiotic therapy and prosthesis substitution. A third infection was diagnosed two months after the last cranioplasty: cultures of purulent drainage grew MRSA and Staphylococcus gallinarum. In addition to radical debridement, oral antibiotic treatment including linezolid was introduced. Antibiotic therapy was stopped after 10 weeks; at a follow-up visit performed after three years no signs or symptoms of relapse were evident. This case shows the difficulty in eradicating prosthesis infections, and demonstrates the central role of radical surgical debridement and the need of appropriate antibiotic treatment in dosing and duration.
The Infections in the History of Medicine
The Semmelweis reasoning and the puerperal fever
Sabbatani Sergio
Ignaz Philipp Semmelweis is probably one of the most important personalities of the history of medicine in nineteenth century before the microbiological Pasteur’s revolution. Young doctor, troubled by the numerous deaths occurring at the obstetrician department in Wien, were he had been temporarily employed, despite the unavailability of laboratory instruments, he could get, by means of empirical observation and deductive reasoning, what all the other contemporary scientists had not been able to perceive: the responsibility of puerperae’s mortality was to ascribe to genital contamination that occurred through the hands of doctors visiting them after having performed autopsies.
Semmelweis is a romantic figure, who also paid for his political and cultural engagement in Wien in 1848 with social isolation. His uneasy temperament, and some difficulties in the relationship with his colleagues, didn’t promote his ideas to be accepted and spread. Few years following his death, prematurely occurred in unclear circumstances, thanks to Pasteur’s discoveries, his battle was eventually recognized.