Salvage Therapy with Rezafungin for Candida parapsilosis Spondylodiscitis: A Case Report from Expanded Access Program.

Candida spp. spondylodiscitis is a rare condition for which treatment options are often limited. A further obstacle is the duration of therapy, which should be administered for up to twelve months. In view of the long duration of therapy, azoles are, so far, the only oral treatment strategy that can be given as home therapy. In the case of resistance or reduced susceptibility to azoles, there are not enough comfortable treatment opportunities with adequate bone penetration and limited toxicity. We report the first case of the successful use of rezafungin for spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. A 68-year-old patient, affected by paraplegia and short bowel syndrome, was diagnosed with Candida parapsilosis spondylodiscitis, confirmed with a culture on vertebral biopsy after an 18-FDG PET/CT scan. He received 200 mg of rezafungin weekly for 26 weeks, after 10 weeks of previous antifungal treatment that was not well tolerated with voriconazole plus liposomal amphotericin B. He had a full clinical, radiologic, and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin can be a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective, poorly tolerated, or contraindicated.

Risk Factors for Pneumocystis jirovecii Pneumonia in Non-HIV Patients Hospitalized for COVID-19: A Case-Control Study.

BACKGROUND: Very few cases of Pneumocystis jirovecii pneumonia (PJP) have been reported in COVID-19 so far, and mostly in patients with concomitant HIV infection or in solid-organ transplant recipients. Despite COVID-19 being associated with lymphopenia and the use of steroids, there are no studies specifically aimed at investigating the risk factors for PJP in COVID-19. METHODS: A retrospective case-control study was performed. We matched PJP cases with controls with a 1:2 ratio, based on age ± 10 years, solid-organ transplantation (SOT), hematological malignancies, and in the setting of PJP development (ICU vs. non-ICU). A direct immunofluorescence assay on bronchoalveolar lavage fluid was used to diagnose PJP. RESULTS: We enrolled 54 patients. Among 18 cases of PJP, 16 were diagnosed as "proven". Seven of the eighteen cases were immunocompromised, while the other patients had no previous immunological impairment. Patients with PJP had significantly lower median lymphocyte values (p = 0.033), longer COVID-19 duration (p = 0.014), a higher dose of steroid received (p = 0.026), higher CRP values (p = 0.005), and a lower SARS-CoV-2 vaccination rate than the controls (p = 0.029). Cumulative steroid dose is the independent risk factor for PJP development (OR = 1.004, 95%CI = 1-1.008, p = 0.042). CONCLUSIONS: PJP develops in COVID-19 patients regardless of immunosuppressive conditions and the severity of disease, and it is correlated to the corticosteroid dose received.

Impact of an anti-infective screening and monitoring protocol together with infectious disease consultation in preventing infective adverse events in patients treated with anti-CD20/CD52 agents for multiple sclerosis.

BACKGROUND: Monoclonal antibodies have been a milestone in the treatment of multiple sclerosis (MS). Infective complications have been observed in patients on agents targeting lymphoid cells' surface antigens, namely anti-CD52 (alemtuzumab) and anti-CD20 agents (ocrelizumab and rituximab). Despite increasing emerging data, there is no standardized consensus regarding pre-treatment testing, vaccinations, and patient education before and during MS therapy or optimal infection-control strategies. METHODS: We led a retrospective/prospective real-life study to evaluate the effectiveness of a program of screening and prophylaxis for infective adverse events in patients with multiple sclerosis and related disorders treated with drugs directed against CD20/52 antigens. All patients referring to the MS Clinical Care and Research Center, University of Naples "Federico II", who started on alemtuzumab, ocrelizumab or rituximab (off-label use) from 1 November 2015 to 30 June 2019 were recruited. From the 1st of February 2018 patients underwent a microbiological screening and were evaluated by an infectious disease specialist (IDs) before monoclonal antibodies infusion to rule out active infections. We evaluated incidence of infective complications and predictors before (retrospectively)and after (prospectively) the introduction of the above-mentioned anti-infective program. RESULTS: We enrolled 275 patients, 104 retrospectively (pre-intervention group, PRE) and 171 prospectively (post-intervention group, POST). In PRE group, most patients were treated with alemtuzumab (58% vs 32%, p < 0.001), were more frequently DMT naïve (48% vs 36%, p = 0.044) or had received fingolimod in the past (48% vs 28%, p = 0.044) and the follow-up period was longer than in POST group (750 vs 191 days, p < 0.001). In POST group, patients were older (median age 47 vs 42 years, p = 0.030) and mostly received OCR (54% vs 14%, p < 0.001). Lymphopenia at baseline was significantly more commonly observed in PRE arm (47% vs 8%, p < 0.001). A total of 39 patients (38%) in PRE arm and 42 patients (25% in POST) group experienced one or more infections (p = 0.022); severe infections were significantly more common in PRE patients (23% vs 14%, p = 0.022). Our anti-infective program was associated with a lower IAE incidence both at univariate and multivariate analysis (aHR of infective events in PRE group: 3.652 [CI: 9.03-94.19], p < 0.001). Moreover, DMT naïve patients significantly experienced fewer infective complications (aHR: 0.470, [CI: 1.02-2.55], p = 0.040). CONCLUSIONS: A risk mitigation program including infectious disease consultation and standardized screening and prophylactic protocols was effective in reducing infective adverse events in patients receiving anti CD20/CD52 agents for MS.

Case Report: Discovery a Novel SARS-CoV-2 Variant in a Six-Months Long-Term Swab Positive Female Suffering From Non-Hodgkin Lymphoma.

BACKGROUND: We report the case of a woman with non-Hodgkin lymphoma who remained positive on the molecular assay for SARS-CoV-2 for six months: she has never experienced a severe form of COVID-19 although in absence of seroconversion. METHODS: The whole SARS-CoV-2 genome analysis was performed by the CleanPlex SARS-CoV-2 Research and Surveillance NGS Panel (PARAGON GENOMICS, Hayward, USA). RESULTS: We found twenty-two mutations in SARS-CoV-2 genome and a novel deleterious ORF3a frameshift c.766_769del corresponding to a unique and novel lineage. The region affected by this frameshift variant is reported as being important in determining SARS-CoV-2 immunogenicity. Patient's immunophenotype showed the absence of B lymphocytes and significantly reduced T-cell count. Only after the treatment with hyperimmune plasma she finally became negative on the swab. CONCLUSIONS: Our findings could be helpful in the management of patients with immunodeficiency, particularly when novel variants, potentially altering the virus immune response, are present.

Epilobium angustifolium L. extract with high content in oenothein B on benign prostatic hyperplasia: A monocentric, randomized, double-blind, placebo-controlled clinical trial.

Benign prostatic hyperplasia (BPH) is a common condition in adult men. Especially in Europe, increasing attention has been focused on E. angustifolium extracts (EAEs), which are widely used for their positive effects on the symptoms of BPH, although human clinical trials are limited. The aim of this monocentric, randomized, double-blind, placebo-controlled clinical trial is to evaluate if a daily intake of hard, gastric-resistant capsules containing a chemically characterized EAE (500 mg) for 6 months may allow a significant improvement in symptoms in subjects with BPH. This study was conducted in 128 adult men, randomly assigned to receive either EAE food supplement (N = 70) or placebo (N = 58), who underwent four visits (baseline = t0, after 15 days = t1, after 2 months = t2 and after 6 months = t3) in an outpatient setting to evaluate post-void residual (PVR) and prostate volume (PV) by means of prostate ultrasound, prostate-specific antigen (PSA) and neutrofile/lymphocyte ratio (N/L), nocturia before the clinical visits and International Prostate Specific Score (IPSS) registered by the physicians. EAE food supplement induced a significant decrease in the PVR and consequently nocturia improving the quality of life as suggested by the decrease of IPSS. No subjects reported adverse effects related to oral intake of EAE food supplement. Moreover, EAE food supplement did not show hepatic or renal toxicity. In conclusion, EAE food supplements can be used in subjects with BPH, to improve their quality of life and general renal function.

A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): A monocentric, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: The most common symptoms of mild upper respiratory tract infections (URTIs) are sore throat, muffled dysphonia, and swelling and redness of the throat, which result from the inflammation process following acute bacterial or viral infection. HYPOTHESIS/PURPOSE: As propolis is a natural resinous substance traditionally used to maintain oral cavity and upper respiratory tract health due to its antimicrobial and anti-inflammatory properties, the aim of this study is to evaluate the efficacy of an oral spray based on poplar-type propolis extract with a known and standardized polyphenol content, on the remission of the symptoms associated with mild uncomplicated URTIs. STUDY DESIGN: A monocentric, randomized, double-blind, placebo-controlled clinical trial was performed. METHODS: This study was conducted in 122 healthy adults who had perceived mild upper respiratory tract infections. Participants, randomly assigned to receive either propolis oral spray (N = 58) or placebo (N = 64), underwent four visits (baseline = t0, after 3 days = t1 and after 5 days = t2 and after a follow-up of 15 days = t3) in an outpatient setting. Propolis oral spray total polyphenol content was 15 mg/ml. The dosage was 2-4 sprays three times/day (corresponding to 12-24 mg of polyphenols/day), for five days. The duration of the study was 8 weeks. RESULTS: After 3 days of treatment, 83% of subjects treated with propolis oral spray had remission of symptoms, while 72% of subjects in the placebo group had at least one remaining symptom. After five days, all subjects had recovered from all symptoms. This means that resolution from mild uncomplicated URTIs took place two days earlier, instead of taking place in five days as recorded in the control group. There was no relationship between the ingestion of propolis oral spray or placebo and adverse reactions. CONCLUSION: Propolis oral spray can be used to improve both bacterial and viral uncomplicated URTI symptoms in a smaller number of days without the use of pharmacological treatment, leading to a prompt symptom resolution.

Direct acting antivirals treatment for hepatitis C virus infection does not increase the incidence of de novo hepatocellular carcinoma occurrence: Results from an Italian real-life cohort (LINA cohort).

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection is ascertained. However, some authors raised the issue of an increased incidence of de novo hepatocellular carcinoma (HCC) in patients treated with DAAs. Aim of the study was to evaluate the rate of HCC occurrence in a real-life cohort of patients who received anti-HCV treatment with DAAs.A prospective multicentre study was conducted. All adult patients with HCV infection who received treatment between March 2015 and December 2017 in 4 hospital of Campania region (South Italy) with at least 6 months of follow-up were enrolled.A total of 323 patients were included in the study. Most patients had HCV genotype 1b (61.8%). The overall SVR12 rate was 95.5%. Median time of observation was 10 months. The incidence rate of HCC was 0.2 per 100 person-months (crude incidence rate 3.4%, 95 confidence interval: 1.5%-5.3%). The median time for HCC occurrence was 11 months. HCC occurrence rate was significantly higher among patients who did not achieve SVR12 compared with patients who did (28.6% vs 2.8%, P < 0.05). No patient with F0-F3 fibrosis developed HCC. Among patients with cirrhosis, at the multivariate time-to-event analysis, no covariates were independently associated with the risk of HCC occurrence.Treatment with DAAs did not increase the risk of HCC occurrence. Patients who achieved SVR12 had a lower rate of HCC occurrence. Further studies are needed to estimate the incidence and the risk for HCC in the long-term follow-up among patients undergoing treatment with DAAs.

Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C.

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.

Interferon-free regimens improve kidney function in patients with chronic hepatitis C infection.

BACKGROUND AND AIM: The impact of directly acting antiviral agent (DAA) regimens on renal function is not well defined and quite controversial. We evaluated the effect of DAAs on kidney function and the factors associated with an improvement or worsening. PATIENTS AND METHODS: The changes in estimated glomerular filtration rate (eGFR) in a cohort of 403 patients treated with a DAA regimen were evaluated. RESULTS: The overall sustained virological response (SVR12) rate was 98%. The median eGFR progressively increased throughout treatment from 84.54 ml/min/1.73 m2 (IQR 70.8-97.3) to 88.12 ml/min/1.73 m2. Conversely, rates of patients with a eGFR more than 60 ml/min/1.73 m2 progressively increased from 83.1% at baseline to 87.8% at 12 weeks post-treatment (p < 0.05). Considering the change in eGFR according to the different factors, a significant improvement in eGFR was observed in the patients without diabetes (p < 0.001), in those with cirrhosis (p < 0.05), in those receiving a Sof-based regimen (p < 0.01) or not receiving RBV (p < 0.05), in those with a baseline eGFR less than 60 ml/min/1.73 m2 (p < 0.001) and in those with SVR (p < 0.05). An improvement in eGFR (defined as an increase in baseline eGFR of at least 10 ml/min/1.73 m2) was observed in 148 patients (36.7%). At multivariate analysis, age (aHR 0.96; 95 CI 0.93-0.99, p < 0.01) and a diagnosis of diabetes (aHR 0.02; 95 CI 0.20-0.87, p < 0.05) were inversely and independently associated with improvement in renal function, while the presence of Child-Pugh B cirrhosis at baseline was associated with an improvement in renal function (aHR 3.07; 95 CI 1.49-6.30, p < 0.01). CONCLUSIONS: DAAs correlate with an improvement in renal function, underlining the importance of hepatitis C virus eradication to achieve also an improvement in extra-hepatic disorders.

Severe Vitamin D Deficiency Increases Mortality Among Patients With Liver Cirrhosis Regardless of the Presence of HCC.

BACKGROUND: The aim of this study was to investigate the association between vitamin D deficiency (<10 mg/ml) and mortality in patients with and without hepatocellular carcinoma (HCC) in a cohort of patients with liver cirrhosis. MATERIALS AND METHODS: A prospective study was conducted among 345 patients with liver cirrhosis. RESULTS: At enrolment, 46 (13.3%) patients had HCC. Severe vitamin D deficiency was associated with mortality (p<0.01). At the survival analysis, alpha-fetoprotein >10 ng/ml (p=0.003), vitamin D deficiency (p<0.001), a Model for End-Stage Liver Disease score ≥15 (p<0.001), Child-Pugh class B and C (versus A) (p<0.001) and the presence of active HCC (p<0.001) were strongly associated with death. At the multivariate Cox regression analysis, only Child-Pugh class B and C (versus A) and vitamin D deficiency were found to be significantly associated with death during the follow-up period (p<0.001 and p=0.006, respectively). CONCLUSION: Vitamin D deficiency is common in patients with HCC, it is associated with active HCC and it negatively affects the overall survival of patients with cirrhosis.

Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis.

INTRODUCTION: Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia. AREAS COVERED: The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare, and unexpected infections. EXPERT OPINION: Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients' history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.

Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis.

OBJECTIVES: To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis. METHODS: We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses. RESULTS: Vitamin D deficiency (<20ng/mL) was diagnosed in 68.3% of patients, and a total of 102 infections were detected. Urinary tract infections were the most common infections diagnosed (41.2%). Vitamin D deficiency rates were higher in patients with decompensated cirrhosis (Child-Pugh B vs A p=0.008, and Child-Pugh C vs A p=0.024). Infection was significantly associated with vitamin D deficiency (p<0.001), MELD score >15 (p=0.003), Child-Pugh class B/C vs A (p<0.001), and active hepatocellular carcinoma (HCC) (p<0.001). At multivariate analysis, vitamin D deficiency (p<0.01), HCC (p<0.05), hospitalization (p<0.001) and exposure to immunosuppressant agents (p<0.05) were independent risk factors for infection at baseline. CONCLUSIONS: Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials.

Diagnostic Accuracy of PIVKA-II, Alpha-Fetoprotein and a Combination of both in Diagnosis of Hepatocellular Carcinoma in Patients Affected by Chronic HCV Infection.

BACKGROUND/AIM: Patients affected by liver cirrhosis are at high risk for developing hepatocellular carcinoma (HCC). The aim of this study was to evaluate the feasibility of PIVKA-II (protein induced by vitamin K absence or antagonist-II) alone or in combination with α-1 fetoprotein (AFP), as a screening marker for development of HCC. MATERIALS AND METHODS: A case-control study was conducted in 2 hospital wards in Naples. All anti-HCV-positive patients affected by HCC were considered as cases, while consecutive anti-HCV-positive patients without HCC were considered as controls. RESULTS: Overall, 160 patients were enrolled, 56 cases and 104 controls. At the set cut-off of 36 mAU/ml, PIVKA-II was more sensitive (78.6% vs. 60%), but less specific than AFP at the set cut-off of 12 ng/ml (66.3% vs. 77.2%). The negative predictive value of PIVKA in combination with AFP was 93.2%. CONCLUSION: PIVKA II, when combined with AFP, may be considered as a screening test for HCC due to its high negative predictive value.

The therapeutic potential of new investigational hepatitis C virus translation inhibitors.

INTRODUCTION: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma and liver-related death worldwide. Currently, the anti-HCV armamentarium encompasses several direct-acting antivirals (DAA) that achieve very high response rates and have an excellent tolerability profile. However, they do not represent a final solution for HCV global eradication for at least these two reasons: i) some patients harbour resistant strains to DAAs and cannot benefit from currently available treatments; ii) the cost of these drugs remains very high. AREAS COVERED: This review summarizes pre-clinical and clinical data regarding HCV translation inhibitors, a new class of drugs currently in the pipeline with novel mechanisms of action. EXPERT OPINION: The availability of DAAs resolved most issues related to HCV treatment compared with the previous interferon-based therapies. However, there are some patients that cannot achieve a viral clearance with currently available treatments. Therefore, there is still room for new drugs in this setting, providing that they demonstrate an advantage in terms of efficacy, safety, cost or or simplicity of use. Based on preliminary results, at least for some promising molecules (e.g. miravirsen and RG-101), studies on safety and efficacy on this intriguing class of drugs are needed.

Beclabuvir for the treatment of hepatitis C.

INTRODUCTION: About 185,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). Currently, the most successful HCV infection antiviral therapies reduce the chance of progression towards the advanced phases of the hepatopathy (liver cirrhosis, hepatocellular carcinoma and death). Recently, however, several new direct-acting antivirals against HCV are available or are in an advanced phase of clinical development. AREAS COVERED: This review focuses on beclabuvir , an allosteric non-nucleotide inhibitor of HCV polymerase. The article covers its pharmacokinetics, mechanism of action, in addition to its tolerability and safety profile as well as its resistance pattern. EXPERT OPINION: The pharmacokinetic, efficacy and tolerability profile of beclabuvir, as well as its barrier to resistance, are very favorable. In particular, the combination of beclabuvir with asunaprevir and daclatasvir achieves very high rates of viral eradication (about 90%) in patients infected with HCV genotype 1, which is the most common genotype worldwide. Therefore, beclabuvir represents a powerful weapon against HCV infection and has to be considered an optimal option in tailored IFN-free combinations.

Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) chronically infects about 150,000,000 people worldwide and is a relevant cause of liver cirrhosis, hepatocellular carcinoma and death. Antiviral treatment is rapidly moving from interferon (IFN)-based therapy to IFN-free approaches. This review focuses on the mechanism of action, pharmacokinetics, efficacy, tolerability, safety and resistance of ombitasvir, which is an inhibitor of the HCV nonstructural protein 5A. The pharmacokinetics of ombitasvir enables its once daily administration. In vivo, in combinations with other oral direct acting antivirals, ombitasvir achieves very high rates of sustained virological response (about 95%) in patients with HCV genotype 1 infection with a good tolerability. Resistance profiling revealed a low barrier to resistance when given as monotherapy. However, coadministration of ombitasvir and other antivirals enhances its barrier to resistance. In conclusion, ombitasvir is a good drug to be used in IFN-free combinations for the treatment of chronic hepatitis C.

Prevalence and titre of antibodies to cytomegalovirus and epstein-barr virus in patients with autism spectrum disorder.

BACKGROUND/AIM: The etiology of autism spectrum disorders (ASD) is currently unknown. Few studies have explored the role of Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) as potential etiological factors of ASD. The aim of the present study was to evaluate the seropositivity rate and antibody titre to CMV and EBV in children with ASD compared to same-aged healthy controls. PATIENTS AND METHODS: We compared the seropositivity rate and titre of antibodies to CMV and EBV in 54 children with ASD (19 with autistic disorder and 35 with non-autistic disorder ASD) and in 46 controls. RESULTS: Seropositivity rate and titre of the two antibodies were not dissimilar between cases and controls. However, considering only patients with ASD, those seropositive for CMV tended to test worse to the major severity scales than the seronegative ones. CONCLUSION: Titre and seropositivity rate of antibodies to CMV and EBV are similar between children with ASD and healthy controls.