[Anti-rabies measures by the Infectious Disease Prevention Service at the "La Sapienza" University of Rome in the years 2005-2007]. / Attività Antirabbica del Servizio di Profilassi delle Malattie Infettive della Sapienza Università di Roma nel 2005-2007.

Antirabies service activities of the Infectious Diseases Prophylaxis Centre of the Sapienza University of Rome during the period 2005-2007. Authors analyzed data, of antirabies activity, from 3206 patients treated at the Infectious Diseases Prophylaxis Centre of the University of Rome "La Sapienza" during the period 2005-2007 Dogs were responsible for most bites (92.1%). All patients went first to the Emergency Room where tetanus prophylaxis was administrated only with specific immunoglobulins (51.5%): to such patients we suggested to implement prophylaxis with vaccination. For other patients (19.4%) we prescribed only vaccine tetanus prophylaxis. Antirabies vaccine (PCEC) has been injected in 604 patients (18.8%). Rabies immunoglobulins have been prescribed only to 11 (0.4%) patients that were bitten during travel to Asia or Africa (0.4%). The authors emphasize the opportunity to reduce the administration of anti-tetanus immunoglobulin in Emergency Room by a deeper evaluation of patient's immunity; moreover the authors confirm a clear quantitative reduction of prophylactic interventions against rabies in Italy.

Measurement of the sensitivity of different commercial assays in the diagnosis of CMV infection in pregnancy.

To evaluate the performance of different commercial assays for the detection of recent cytomegalovirus (CMV) in pregnancy, the sensitivity and specificity of assays for CMV-specific IgM antibodies were compared. Routine specimens from pregnant women were screened for CMV IgM using the Abbott AxSYM assay. Sera that were reactive according to AxSYM were further tested for IgM by other commercial assays. In selected IgM positive samples a CMV IgG avidity assay (Radim) and virus isolation from urine (shell vial) were also performed. The positivity rate for IgM anti-CMV by AxSYM was relatively high (140 out of 492, combining reactive and grayzone results). Only 26 of the 140 samples were positive for IgM according to Radim. The IgG avidity was low in 16 of the 43 samples tested, and the Radim and DiaSorin IgM assays were negative in 5 of them; 2 of the latter cases were also positive for viral isolation according to a shell vial method. There are differences in the sensitivity of the commercially available tests for CMV antibodies. CMV screening in pregnancy is performed as a first step by immunoassays and the choice of highly sensitive IgM test associated with further serological and virological methods could help to identify early primary infections.

[Role of sonography in the evaluation of parotid gland in HIV+ children undergone highly active antiretroviral therapy (HAART)]. / Ruolo dell'ecografia nello studio della ghiandola parotide in bambini HIV+ sottoposti a terapia farmacologica antiretrovirale combinata. (HAART: "Highly active antiretroviral therapy").

PURPOSE: To evaluate the role of sonography (US) in the evaluation of parotid gland alterations in HIV+ children, in order to show their presence, severity, specificity, relationship with clinical and laboratory data and sensitivity to new drugs. MATERIAL AND METHODS: From June 2000 to December 2000 twenty-two consecutive HIV+ children (12 males and 10 females, mean age 9.7) undergoing HAART were prospectively examined with US. A multi-frequency linear probe (7.5-10 MHz) was used for the examination. The glands were assessed for alterations in gland volume and vasculature, hypoechoic foci, hyperechoic striae, lympho-epithelial cysts and solid nodules and the enlargement of intraparotid and adjacent lympho nodes. The US findings on HIV+ patients were compared with the patients'clinical and laboratory data and with US exams performed on HIV- children. Finally, we made a comparison with US exams performed on the same patients before HAART: RESULTS: In HIV+ children the most frequent US findings were hypoechoic foci (68.2% of patients), hyperechoic striae (68.2%) and the enlargement of intraparotid and adjacent lympho nodes (86.3% and 95.4%, respectively). No relationship between US outline and clinical and laboratory data was found. In the control group (HIV-negative children) hypoechoic foci and hyperechoic striae were rare (4.7% and 14.3%, respectively), while the enlargement of intraparotid and adjacent lympho nodes was very common (76.2% and 100%, respectively). The comparison with US exams performed on the same patients before HAART showed an improvement in 59.1% of patients, no improvement in 13.6% and a worsening in 13.6% (3 patients were lost to follow-up). DISCUSSION AND CONCLUSIONS: US is useful in the study of parotid gland alterations in HIV+ children. The most frequent specific US findings were hypoechoic foci and hyperechoic striae, whereas the enlargement of intraparotid and adjacent lympho nodes was frequent but completely aspecific. The analysis of results did not show any relationship between the US findings and clinical and laboratory data. HAART can be correlated to an improvement and/or a stabilization of the US pattern in most patients.

HPV and intraepithelial neoplasia recurrent lesions of the lower genital tract: assessment of the immune system.

OBJECTIVE: To evaluate the immune state in patients with genital relapse HPV and intraepithelial lesions of the lower genital tract. METHOD: Forty-three patients were selected. Twenty-one were affected by recurrent HPV infection either alone or combined with intraepithelial neoplasia treated by laser surgery, and 22 had been previously-treated and clinically cured without recurrence during a follow-up from 18 to 24 months. The diagnostic protocol included colposcopy with eso- and endocervical cytology histologically confirmed by directed biopsy. Afterwards patients underwent a systemic immunogenic evaluation. RESULTS: NK cell reduction was strictly related to HPV infection associated with intraepithelial lesions; B-lymphocyte reduction was percentually greater in patients affected by HPV alone; activation of R-IL2 increased in a percentage overlapping in the two groups indicating patient reaction to the virus. CONCLUSION: Our study supports the theory that immune response directed against viral antigens is one of the most important effectors in the control of HPV infections and that HPV is the cause of a systemic rather than local lesion.

Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues.

OBJECTIVE: A severe dose limiting axonal peripheral neuropathy may develop in subjects on treatment with the nucleoside analogues didanosine (ddl), zalcitabine (ddC), and stavudine (d4T). The impairment of mitrochondrial DNA synthesis is crucial to the pathogenesis of this disorder although other mechanisms have not been ruled out. The depletion of acetyl-carnitine, which regulates the metabolism and function of peripheral nerves could contribute to the neurotoxicity of these compounds. DESIGN: Non-randomized, cross-sectional study of selected patients. METHODS: We measured the serum levels of acetyl- and total carnitine in 12 subjects with axonal peripheral neuropathy developed on treatment with different regimens of neurotoxic nucleoside analogues (ddl, ddC, d4T). Subjects who did not develop peripheral neuropathy while staying on treatment with ddl (n = 10) or zidovudine (n = 11) served as the control groups. HIV-negative subjects with axonal on demyelinating autoimmune neuropathies (n = 10) and healthy individuals (n = 13) were additional control groups. RESULTS: Subjects experiencing axonal peripheral neuropathy on treatment with ddl, ddC and d4T had significantly reduced levels of acetyl-carnitine in comparison to the control groups. No difference was observed in the levels of total carnitine between study subjects and the control groups. CONCLUSIONS: Our results demonstrate that subjects who developed peripheral neuropathy while staying on treatment with ddl, ddC and d4T had acetyl-carnitine deficiency. The normal levels of total carnitine in the study group appear to indicate the specificity of the defect and rule out coexisting relevant nutritional problems. The critical role of acetyl-carnitine for the metabolism and function of the peripheral nerves supports the view that the acetyl-carnitine deficiency found in these subjects may contribute to the neurotoxicity of ddl, ddC and d4T, even though the interference with mitochondrial DNA synthesis is regarded as the main cause of their toxicity.

[Seroepidemiologic study of the prevalence of anti-HAV antibodies in children in Rome]. / Studio sieroepidemiologico della prevalenza degli anticorpi anti HAV nei bambini di Roma e Provincia.

The authors evaluated the incidence of infection by hepatitis A virus (HAV) in a paediatric population through a seroepidemiological investigation in a group of 278 children (0-12 years old), apparently healthy. The determination of anti-HAV antibodies was carried out by ELISA-test. Of the 287 examined sera, 27 cases turned out HAV positive antibodies (9.7%), with the following distribution, according to the groups of age: 0-3 months: 2 of 6 children were positive (mother's antibodies); 3 months-2 years: 6 of 112 (5.35%); 2-6 years: 10 of 93 (10.75%); 6-12 years: 11 of 67 (16.41%). With regard to distribution of anti-HAV antibodies by sex, 23 (15.03%) males of 153 resulted positive, whereas 4 (3.2%) females of 125 resulted positive. The decline of HAV infection in the paediatric age involves a possible shift of the risk to the adult age. It's advisable that the vaccination against hepatitis A in first period should be reserved for the subjects at risk and later both for unweaned and children in order to eradicate the infection.

[Acyclovir in the treatment of varicella in immunocompetent children]. / L'acyclovir nel trattamento della varicella nei bambini immunocompetenti.

We evaluated safety and tolerance of acyclovir ACV per os in immunocompetent children affected by chicken-pox admitted to our department from January 1993 to December 1994. 183 subjects (102 males and 81 females) aged between 0 and 14 years were treated by ACV (80 mg/kg/daily in 4 divided doses): 88 children were treated within 24 hours and 95 subjects within 48 hours from the onset of symptoms. The control group consisted of 83 children (52 males and 31 females) aged between 0 to 14 years. In all patients routine blood-test were performed and in those with respiratory illness Chest-Rx was also done. We evaluated clinical course, degree of eruption, the appearance and kind of complications, duration of hospitalization, the compliance and the potential consequences on specific antibody response. Our results show a faster improvement of clinical symptoms in treated patients with respect to the control group with shortening of the period of the fever, itch and appearance of new vescicles. The percentage of complications was lower in treated than in untreated patients. 16 cases tested for specific antibody response showed protective titers six months after treatment. In conclusion, ACV administered per os within 48 hours from onset of exanthema causes reduction of the period and the degree of general symptoms and exanthema, a lower incidence of complications even if non statistically significant. The drug is safe and well-tolerated.

Activity of terbinafine against Pneumocystis carinii in vitro and its efficacy in the treatment of experimental pneumonia.

The antiprotozoan and antifungal agent, the terbinafine, was investigated for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley rats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post inoculation. With respect to trimethoprim-sulphamethoxazole and pentamidine isethionate P. carinii organisms decreased at the same time interval but cyst form elimination was less apparent than with terbinafine. The results of the in-vitro culture were consistent with the in-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats (group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among terbinafine treated rats (group 1), P. carinii pneumonia was present in one rat (3.3%), while no P. carinii infection occurred in the pentamidine isethionate and in trimethoprim-sulphamethoxazole treatment rat groups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P. carinii pneumonia.

[Treatment and prevention of Mycobacterium avium complex infection in AIDS]. / Terapia e profilassi dell'infezione da Mycobacterium avium complex in corso di AIDS.

Since Mycobacterium avium complex (MAC) infects most, if not all, HIV-positive patients, effective regimens for its treatment and prophylaxis are a necessity. We review here the available literature in an attempt to establish clear-cut criteria for the administration of antibiotics and immunotherapy and for the prophylactic treatment of MAC infections. Several antibiotics, chiefly in combination regimens, are active against MAC. Recent data indicate rifabutin as a first-line antibiotic for the treatment of MAC infections. However, since this antibiotic accelerates hepatic metabolism of many drugs (zidovudine in particular), it has the potential to reduce their serum concentrations and hence limit their antiviral activity. Moreover, rifabutin is active against retroviruses only at extremely high concentrations which are not reached in vivo at normally-prescribed dosages. The recent demonstration that the cytokine interferon-gamma (IFN-gamma) in combination with conventional antibiotic therapy may be effective for disseminated MAC infections indicates that immunotherapy could play a pivotal role in the treatment of MAC infections. Lifetime prophylaxis with rifabutin (300 mg/die) is advised for all patients with HIV infection and fewer than 100 CD4 T lymphocytes/mm3 in the peripheral blood: this antibiotic regimen significantly reduces the frequency of disseminated MAC infections. Further studies are required to evaluate the effectiveness of other prophylactic regimens such as azithromycin and clarithromycin. We conclude that rifabutin and immunotherapy with IFN-gamma will play a key role in the treatment of MAC infections.

Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine.

OBJECTIVE: Reduced levels of serum carnitines (3-hydroxy-4-N-trimethyl-ammonio-butanoate) are found in most patients treated with zidovudine. However, since serum carnitines do not strictly reflect cellular concentrations we examined whether a carnitine depletion could be found in peripheral blood mononuclear cells (PBMC) from AIDS patients with normal serum carnitine levels. In addition, we explored whether it was possible to relate the host's immunoreactivity to the content of carnitine in PBMC and whether carnitine levels can be corrected by oral supplementation of L-carnitine. DESIGN: Immunopharmacologic study. METHODS: Twenty male patients with advanced AIDS (Centers for Disease Control and Prevention stage IVCI) and normal serum levels of carnitines were enrolled. Patients were randomly assigned to receive either L-carnitine (6 g/day) or placebo for 2 weeks. At baseline and at the end of the trial, we measured carnitines in both sera and PBMC, serum triglycerides, CD4 cell counts, and the frequency of cells entering the S and G2-M phases of cell cycle following mitogen stimulation. RESULTS: Concentrations of total carnitine in PBMC from AIDS patients was lower than in healthy controls. A significant trend towards the restoration of appropriate intracellular carnitine levels was found in patients treated with high-dose L-carnitine and was associated with an increased frequency of S and G2-M cells following mitogen stimulation. Furthermore, at the end of the trial we found a strong reduction in serum triglycerides in the L-carnitine group compared with baseline levels. CONCLUSIONS: Our data indicate that carnitine deficiency occurs in PBMC from patients with advanced AIDS, despite normal serum concentrations. The increase in cellular carnitine content strongly improved lymphocyte proliferative responsiveness to mitogens. Because carnitine status is an important contributing factor to immune function in patients with advanced AIDS, we therefore believe that L-carnitine supplementation could have a role as a complementary therapy for HIV-infected individuals.

High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients.

Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.

L-carnitine: a partner between immune response and lipid metabolism ?

The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

Regulation of normal human polyrnorphonuclear leucocytes by carnitine.

The effect of carnitine, a drug that plays an essential role in mitochondria metabolism, on some of the most important human polymorphonuclear leucocytes (PMN) activation steps including modulation of adhesion molecule density, reactive oxygen species production, and tumour necrosis factor-alpha (TNFalpha) production was investigated. The capability of carnitine in protecting PMN from deter ioration on storage was also studied. Data shows that carnitine exerts considerable effects on all PMN functions investigated. Although the ultimate effect was often donor dependent, TNFalpha production was exceptional in that carnitine was able to consistently reduce TNFalpha production in Staphylococcus aureus stimulated PMN in a clear dose-dependent fashion. It is concluded that carnitine may represent a useful active agent in situations characterized by PMN mobilization/activation.

AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin.

In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin.

L-carnitine deficiency in AIDS patients.

OBJECTIVE: To evaluate carnitine (3-hydroxy-4-N-trimethyl-ammoniobutanoate) deficiency in AIDS patients by measuring serum total, free and short-chain carnitine concentrations. DESIGN: We conducted an open study. SETTING: All patients were seen at the Infectious Diseases Clinic, Università 'La Sapienza', Rome, Italy. PATIENTS, PARTICIPANTS: Twenty-nine AIDS patients, aged 27-41 years, with a previous history of drug use; and 14 healthy age- and sex-matched controls were studied. INTERVENTIONS: Study subjects were administered 500-800 mg zidovudine daily for 2 to 28 months (8 +/- 6 months). MAIN OUTCOME MEASURES: Carnitine deficiency was suspected in study participants prior to data collection because of previously reported cardiac symptoms, muscle weakness, hypometabolism and/or cachexia. RESULTS: A marked decrease in total and free carnitine was observed in 21 (72%) subjects. Nine of these patients also had low levels of short-chain carnitine. CONCLUSIONS: AIDS patients may become carnitine-depleted and therefore at risk for alterations in fatty-acid oxidation and energy supply.

Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes.

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.