Occult Hepatitis B Infection in Recent Immigrants to Italy: Occult B Infection in Immigrants.

This study determined the prevalence and clinical features of occult hepatitis B infection (OBI) in a population of recent immigrants to Italy. Two hundred-five immigrants were tested for HBV-infection and were classified as seropositive-OBI or false-OBI. Biochemical/virological activities and imaging diagnostics were determined in anti-HBc-positive subjects. Among the tested subjects, 39.0% were anti-HBc-positive/HBsAg-negative; 11.2% had persistently normal ALT levels with mild detectable HBV-DNA, seropositive-OBI; 6.2% had slightly elevated ALT and positive serum HBV-DNA with a mean level of viral load: 3275 copies/mL-false-OBI. The total prevalence of OBI was 6.8%; 4.4% were seropositive-OBI and 2.4% were false-OBI. Diagnosis by echo-tomography was achieved in 35.7% OBI subjects with alterations of the hepatic echo-texture. We found a moderate prevalence of occult hepatitis B-infection in immigrants. Frequently, these subjects present false-OBI.

Prevalence of antibodies to hepatitis E virus in immigrants: a seroepidemiological survey in the district of Foggia (Apulia-southern Italy).

Hepatitis E virus (HEV) is the etiologic agent of endemically transmitted viral hepatitis. HEV is endemic in developing countries where it occurs in sporadic and endemic forms, but autochthonous sporadic cases of hepatitis E have been reported in North America and in Europe, including Italy. The aim of the present study was to assess the seroprevalence of antibodies to HEV in immigrants from developing countries to the province of Foggia. The seroprevalence of HEV was determined in a cohort of 412 immigrants (mostly from countries in sub-Saharan Africa) who had arrived recently in Italy. Serum samples were tested for anti-HEV by a commercial enzyme immunoassay (EIA) based on recombinant proteins; positive results were confirmed by a Western blot assay (Recomblot HEV). A total of 88 (21.3%) of the 412 serum samples examined were reactive to IgG anti-HEV. Eighty-one of these samples (19.7%) were confirmed by Western blot. Anti-HEV IgM was found in 34/81 subjects (41.9%) of the anti-HEV IgG positive serum samples. Almost all anti-HEV positive subjects were asymptomatic clinically, but alanine aminotransferase serum values were elevated in 28/34 (82.3%) patients with IgM anti-HEV-positive. The results of this study indicate high circulation of HEV in the immigrant population. The high prevalence of acute hepatitis involved mainly subjects who arrived in Italy during the same period from the same countries (Eritrea, Ethiopia, and Somalia).

Congenital Zika Virus Syndrome: Microcephaly and Orofacial Anomalies.

The progressive reappearance of Zika virus (ZIKV) infections since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, and mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called congenital Zika syndrome (CZS), which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly or neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, and epidemiological aspects and modes of transmission of Zika virus infections, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

COVID-19 and Oral Lichen Planus: Between an "Intriguing Plot" and the "Fata Morgana Effect".

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant morbidity and mortality worldwide since its declaration as a global pandemic in March 2020. Alongside the typical respiratory symptoms, unusual clinical manifestations such as oral lichen planus (OLP) have been observed. OLP is a chronic inflammatory mucocutaneous dermatosis that results from a cell-mediated reaction, and its pathogenesis involves the loss of immunological tolerance. OLP has been associated with several triggering factors, such as certain drugs, stress, smoking, and even some viruses. Exposure to the spike protein antigen of SARS-CoV-2 during an infection can trigger autoimmune reactions and lead to the onset or flare of OLP. The E3 protein ligase TRIM21, which is identified in the lamina propria of OLP lesions, is overexpressed in COVID-19 patients and plays a critical role in autoimmune pathologies. Furthermore, the psychological stress of the lockdown and quarantine can be a trigger for the onset or exacerbation of OLP. However, the diagnosis of OLP is complex and requires a biopsy in order to confirm a clinical diagnosis, rule out other pathologies, and establish the most appropriate therapeutic procedure. Further research is needed to understand the potential link between Co-19 and OLP.

SARS-CoV-2 Infection and Taste Alteration: An Overview.

Since the worldwide spread of SARS-CoV-2 infection, the management of COVID-19 has been a challenge for healthcare professionals. Although the respiratory system has primarily been affected with symptoms ranging from mild pneumonia to acute respiratory distress syndrome, other organs or systems have also been targets of the virus. The mouth represents an important route of entry for SARS-CoV-2. Cells in the oral epithelium, taste buds, and minor and major salivary glands express cellular entry factors for the virus, such as ACE2, TMPRSS2 and Furin. This leads to symptoms such as deterioration of taste, salivary dysfunction, mucosal ulcers, before systemic manifestation of the disease. In this review we report and discuss the prevalence and socio-demographics of taste disturbances in COVID-19 patients, analysing the current international data. Importantly, we also take stock of the various hypothesized pathogenetic mechanisms and their impact on the reported symptoms. The literature indicated that COVID-19 patients frequently present with gustatory dysfunction, whose prevalence varies by country, age and sex. Furthermore, this dysfunction also has a variable duration in relation to the severity of the disease. The pathogenetic action is intricately linked to viral action which can be expressed in several ways. However, in many cases these are only hypotheses that need further confirmation.

[Prevalence of Plasmodium spp. in asymptomatic African immigrants assessed by nucleic acid sequence based amplification]. / Rilievo di Plasmodium spp. in immigrati asintomatici mediante tecniche molecolari innovative (NASBA) e valutazione del rischio.

Malaria is one of the most important infectious diseases in the world. Although most cases occur in the tropical regions of Africa, Asia, Central and South America, there is in Europe a significant increase in the number of imported cases in non-endemic countries, in particular due to the higher mobility in today's society. The prevalence of a possible asymptomatic infection with Plasmodium species was assessed using Nucleic Acid Sequence Based Amplification (NASBA) assays on clinical samples collected from 195 study cases with no clinical signs related to malaria and coming from sub-Saharan Africa. In addition, base-line demographic, clinical and socio-economic information was collected from study participants who also underwent a full clinical examination. Sixty-two study subjects (31.8%) were found positive for Plasmodium using a pan Plasmodium specific NASBA based on the small subunit 18S rRNA gene (18S NASBA). Twenty-four samples (38%) of the 62 positive study cases were found positive with a Pfs25 mRNA NASBA, which specifically detects gametocytes of Plasmodium falciparum. This study showed that a substantial proportion of people originating from malaria endemic countries harbour malaria parasites in their blood. If transmission conditions are available, they could be a reservoir.

Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification.

BACKGROUND: Malaria is one of the most important infectious diseases in the world. Although most cases are found distributed in the tropical regions of Africa, Asia, Central and South Americas, there is in Europe a significant increase in the number of imported cases in non-endemic countries, in particular due to the higher mobility in today's society. METHODS: The prevalence of a possible asymptomatic infection with Plasmodium species was assessed using Nucleic Acid Sequence Based Amplification (NASBA) assays on clinical samples collected from 195 study cases with no clinical signs related to malaria and coming from sub-Saharan African regions to Southern Italy. In addition, base-line demographic, clinical and socio-economic information was collected from study participants who also underwent a full clinical examination. RESULTS: Sixty-two study subjects (31.8%) were found positive for Plasmodium using a pan Plasmodium specific NASBA which can detect all four Plasmodium species causing human disease, based on the small subunit 18S rRNA gene (18S NASBA). Twenty-four samples (38%) of the 62 18S NASBA positive study cases were found positive with a Pfs25 mRNA NASBA, which is specific for the detection of gametocytes of Plasmodium falciparum. A statistically significant association was observed between 18S NASBA positivity and splenomegaly, hepatomegaly and leukopaenia and country of origin. CONCLUSION: This study showed that a substantial proportion of people originating from malaria endemic countries harbor malaria parasites in their blood. If transmission conditions are available, they could potentially be a reservoir. Therefore, health authorities should pay special attention to the health of this potential risk group and aim to improve their health conditions.

QuantiFERON-TB Gold In-Tube test (QFT-GIT) for the screening of latent tuberculosis in recent immigrants to Italy.

To evaluate the agreement between QuantiFERON-TB Gold In-Tube test (QFT-GIT) and tuberculin skin test (TST) for the screening of latent tuberculosis infection (LTBI) in recent immigrants to Italy, 279 subjects were submitted to concomitant TST and QFT-GIT. The agreement was analyzed using k statistics. A total of 72/279 (25.8%) individuals were TST positive, while 107/279 (38.3%) were QFT-GIT positive. The overall agreement between QFT-GIT and TST was 70.9%, with k statistic of 0.35. Using different TST and QFT-GIT cut-offs, the best concordance value was obtained for QFT-GIT at > 2.64 IU/ml and TST at > 10mm (k = 0.409). Discordant results were found for 58 subjects (21%) with QFT-GIT positive/TST negative and 23 (8%) with QFT-GIT negative/TST positive. A high amount of discordance QFT-GIT+/TST- was described. QFT-GIT might increase the identification of LTBI cases among recent immigrants.

Co-infection HBV and malaria: a striking association.

BACKGROUND: Many geographical areas are highly endemic for infectious tropical diseases, although in disproportional fashion. Various infections often overlap in terms of presentation of various epidemiological and clinical manifestations that are linked to the mutual influence of pathogens. The epidemiological and clinical aspects of hepatitis B virus and malaria co-infection remain little known because there have not been many studies until recently. METHODS: We performed a systematic search of the epidemiology of HBV/malaria co-infection, in particular, their overlapping clinical and histological features and their reciprocal conditioning. We examined published data regarding HBV and malaria. RESULTS: The data we obtained varied substantially. The interaction between malarial parasites and HBV viruses, both in chronic HBV hepatitis patients and in carriers, did not vary or change the clinical evolution of either infection. The diversity of epidemiological and clinical results depended both on the geographical areas in which the studies were carried out and on the various stages of the infections at the time of the study. CONCLUSION: Strategies to improve currently available diagnostic techniques, and studies dealing with vector control procedures and other operational tools and approaches are needed for better understanding of this health problem.

Screening for infectious diseases in newly arrived asymptomatic immigrants in southern Italy.

BACKGROUND: Screenings for infectious diseases in asymptomatic immigrants currently takes place when receiving new arrivals. AIMS: We describe the frequency of infections in a cohort of newly arrived asymptomatic immigrants in Southern Italy. METHODS: We studied a cohort of 238 Sub-Saharan African and Asian men hosted at a reception centre (CARA) in Foggia between January and December 2015. The tuberculin skin test for diagnosis of latent tuberculosis infection (LTBI) and serology/virology testing for HBV, HCV, HIV were performed. RESULTS: From this cohort, 205 individuals agreed to be tested for serological/virological markers only, while 82 agreed to be tested for LTBI only; 49 people agreed to have both tests. Among those tested for virological markers, 23/205 (11.2%) were HBsAg positive; 12/23 (52.2%) individuals had chronic active hepatitis; 77/205 (37.6%) individuals had only anti-HBc positivity. HCV infection was present in 8/205 (3.9%) individuals, and chronic HCV infection, was diagnosed in only two people. Only 2/205 (1.0%) individuals presented with anti-HIV and HIV-RNA positivity. We found LTBI in 29.6% of TB-tested individuals. CONCLUSIONS: Asymptomatic immigrants are at increased risk for some infections, mainly HBV and tuberculosis.

Early and sustained virological response in non-responders with chronic hepatitis C: a randomized open-label study of pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b.

OBJECTIVES: The purpose of this randomized open-label study was to assess the efficacy of treatment with pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b, both plus ribavirin, in inducing early and sustained virological response (EVR and SVR) in chronic hepatitis C non-responders. PATIENTS AND METHODS: A total of 108 patients with chronic hepatitis C who were non-responders to previous combined therapy (standard interferon-alpha plus ribavirin for > or = 3 months) were enrolled and equally randomized into two groups in this intention-to-treat analysis. The patients exhibited similar baseline features. One group received subcutaneous pegylated interferon-alpha-2a 180 microg once weekly, while the other was treated with subcutaneous pegylated interferon-alpha-2b 1.5 microg/kg once weekly. Ribavirin 15 mg/kg/day was included in both protocols. Treatment duration for EVR was 12 weeks. Patients who demonstrated non-detectable hepatitis C virus (HCV) RNA or a > or = 2 log(10) reduction in viral load at week 12 continued therapy up to 48 weeks, with assessments every 3 months during a follow-up of 24 weeks. RESULTS: All patients in both groups completed the EVR study, then seven patients receiving pegylated interferon-alpha-2a and seven patients receiving pegylated interferon-alpha2b discontinued treatment as a result of severe adverse effects. After 12 weeks of treatment, viral load reduction was >2 log(10) with both pegylated interferon-alpha-2a (-2.53) and pegylated interferon-alpha-2b (-2.48) with no significant difference. At the end of week 48, HCV RNA was undetectable in 14 of 54 patients (25.9%) receiving pegylated interferon-alpha-2a and in 15 of 54 patients (27.7%) receiving pegylated interferon-alpha-2b. When terminating follow-up, an SVR was observed in 11 of 54 patients (20.4%) who received pegylated interferon-alpha-2a and 10 of 54 patients (18.4%) receiving pegylated interferon-alpha-2b. The incidence and severity of adverse events was similar in both groups. CONCLUSIONS: Our results seem to show that in chronic hepatitis C patients who are non-responsive to previous therapy, EVR to the two pegylated interferons did not significantly differ with a similar therapeutic efficacy defined as SVR.

Hepatitis B and asymptomatic malaria coinfection in Sub-Saharan African immigrants: epidemiological and clinical features of HBV infection.

INTRODUCTION: Here, we conducted an epidemiological study of hepatitis B virus (HBV) mono-infected and asymptomatic malaria/HBV coinfected immigrants and further discussed the possibility of malaria disease modifying the clinical presentation of HBV infection. METHODS: A total of 195 African immigrants were examined for HBV infection or coinfection with HBV and asymptomatic malaria. HBV infection was diagnosed using serological tests and confirmed by PCR; furthermore, we performed a pan-Plasmodium-specific-nucleic-acid-sequence-based-amplification (NASBA) assay to detect asymptomatic malaria infection. The stage/grade of the liver disease was determined using echotomography and elastometry. RESULTS: PCR-NASBA results confirmed that 62 of 195 subjects (31.8%) were positive for Plasmodium infection, whereas 41 of 195 subjects (21%) tested positive for HBV chronic hepatitis (HBV-DNA positive). Among the HBV-positive subjects, 26 (63.4%) of them were mono-infected patients (Group A), whereas 15 (36.6%) patients had HBV chronic hepatitis and asymptomatic malaria coinfections (Group B). The HBV-DNA median levels were 1.4×105IU/mL in HBV-mono-infected patients and 2.0×105IU/mL in coinfected patients. Echotomography and hepatic elastometry presented similar findings for both groups of patients. CONCLUSIONS: Coinfected patients seem to present with the same clinical symptoms of the liver disease as HBV mono-infected patients.

Tuberculosis in the immigrant population in Italy: state-of-the-art review.

Although the incidence of tuberculosis (TB) has been decreasing in the European Union/European Economic Area (EU/EEA) in recent decades, specific subgroups of the population, such as immigrants, remain at high risk of the disease. Immigration from areas of high incidence is thought to have fuelled the resurgence of TB in areas of low incidence. Indeed, while immigrants have a high risk of acquiring TB prior to migration, after migration they are exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty, stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse and limited access to health care. In Italy as well, TB has increasingly become a disease for specific population subgroups such as immigrants and in urban settings often driven by reactivation of imported latent TB infection (LTBI). In this paper we present an analysis of the national scientific literature from recent years in order to estimate the burden of TB in foreign-born populations, to establish the burden of TB in migrants by gender, age group and country of origin as well as other relevant subgroups, and evaluate the clinical manifestations of latent or active tuberculosis and treatment response.

Efficacy and tolerability of lamivudine alone versus lamivudine plus alpha-interferon for treatment of chronic active hepatitis B in patients with a precore-mutant variant.

The aim of our study was to assess the efficacy and tolerability of lamivudine alone versus lamivudine plus alpha-interferon for treatment of chronic active hepatitis B, anti-HBe positive. In all, 59 patients were randomly divided into 3 groups: A) 21 patients received lamivudine at 100 mg/daily orally for 52 weeks; B) 20 patients received lamivudine at 100 mg/die plus alpha-interferon at 6 MU subcutaneously three times weekly for 52 weeks; C) 18 patients received the same combination therapy for 40 weeks after pre-treatment with lamivudine for 12 weeks. The complete sustained response in the three groups was 33.3% vs 35.0% vs 33.3%, respectively. Our study demonstrates that in anti-HBe positive chronic hepatitis B a 12-month course of lamivudine plus a-interferon combination therapy is as beneficial as lamivudine monotherapy. Moreover, the combination therapy for 40 weeks after pre-treatment with lamivudine for 12 weeks did not increase the sustained response.

Hepatitis C and immigration: a multicentre study.

This retrospective multicentre study aims to evaluate the clinical and epidemiological features of HCV infection in a cohort of immigrants in Italy. Tests were carried out on 194 HCV positive subjects, who represented 5.7% of the participants at baseline screening: the virological (viral load, genotype) and biochemical appearance of their infection was determined, and the disease was staged by histological examination in the patients who had indicated their willingness. Standard therapy (peg-interferon + ribavirin) was implemented in patients who agreed to undergo treatment. The majority of immigrants were of East-European origin (48.4%), females were globally slightly predominant and the average age was 41.4 years. Of the 194 patients, 119 (63.1%) proved to be viraemic: genotype 1 was the most frequent, followed by genotype 4, the latter mainly in African patients. The histological staging of liver disease conducted in 25 patients showed mild hepatitis in 13 subjects, moderate/severe hepatitis in eight subjects and cirrhosis in four. Although 45 out of 119 patients (37.8%) with determinable HCV RNA agreed to undergo treatment, 11 of them independently stopped taking medication before the course of therapy was completed, without any significant side effects. At the sixth month of follow-up, the overall sustained virological response (SVR) was shown by 22/45 patients (48.8%). In our study, migrant populations had higher rates of HCV-related chronic hepatitis than the indigenous population; in some cases the infections were contracted in the country of origin, but in others the infection took place in Italy. The most commonly represented genotype, besides 1, was 4, especially among Africans. The therapeutic management of immigrants proved to be very difficult, mostly but not exclusively because of social factors.

Treatment of genotype 1b HCV-related chronic hepatitis: efficacy and toxicity of three different interferon alfa-2b/ribavirin combined regimens in naive patients.

This prospective open-label randomized trial of chronic hepatitis C genotype-1b patients compared compared the efficacy and safety of peg-interferon alfa-2b administered once-weekly versus interferon alfa-2b thrice-weekly or daily, both in combination with ribavirin. Seventy-eight previously untreated patients, with biopsy-documented genotype 1 chronic HCV and persistently elevated ALT levels and detectable HCV RNA, were randomized (26 subjects each) to receive: interferon alfa-2b at 6MIUs.c./three-times-weekly (group A) or interferon alfa-2b, 3MIUs.c./daily (group B) or peg-interferon alfa-2b 1.5mcg/Kg s.c./once-weekly (group C). All regimens included standard weight-based doses of ribavirin (800, 1,000 or 1,200 mg/day) administered for 52-weeks. Patients in the three groups were comparable for age, sex, viral load, ALT value and histological-activity-index (HAI). Therapy was completed by 22, 20 and 23 patients in groups A, B and C, respectively. At the end of treatment, a complete (biochemical and virological) response was observed in 50.0% patients of group A, 57.7% of group B and 65.4% of group C. After an additional 24-weeks of follow-up, a sustained response was observed in 26.9%, 46.1% and 50.0% of patients in groups A, B or C, respectively. Therapy was discontinued by 4, 6 and 2 patients because of adverse events in the above three groups. In naive patients with chronic genotype-lb hepatitis C, a 48 week therapy with peg-interferon or interferon at daily doses combined with ribavirin were both more effective than treatment with thrice-weekly interferon in inducing end of treatment and sustained response. Peg-interferon treatment was better tolerated and provoked significantly fewer therapy discontinuations.

Clinical and virological response to adefovir dipovixil for lamivudine-resistant HBeAg-negative hepatitis B.

Adefovir dipivoxil (ADV), a new nucleotide analogue, has demonstrated activity against lamivudine-resistant HBV both in vivo and in vitro. Herein, we present eight lamivudine-resistant patients with chronic anti-HBe positive hepatitis B treated orally with adefovir dipivoxil at 10 mg/die to evaluate the efficacy and safety of this drug and to determine the possible development of clinical ADV resistance. After 48 weeks of therapy, 4/8 (50%) patients demonstrated a complete response with normalization of alaninoaminotransferase levels (ALT, normal value < 40 IU/L) and undetectable serum HBV- DNA (< 100 copies/ml tested by a PCR assay). In 3/8 subjects (37.5%), we observed a partial response with a > 50% reduction of both ALT and HBV DNA levels. Only one patient did not respond. Adefovir was well-tolerated and no patient presented adverse events related to treatment; there were no changes in renal parameters. We conclude that in patients with anti-HBe positive chronic hepatitis B resistant to lamivudine, a 48-week ADV treatment resulted in significant biochemical and virological improvement without major adverse effects.

Hepatitis E virus co-infection in HIV-infected patients in Foggia and Naples in southern Italy.

BACKGROUND: Hepatitis E virus (HEV) infection represents an emerging infection in developed countries and is thought to be a zoonotic infection. It has recently been described as a new causative agent of acute and chronic hepatitis in immunosuppressed subjects, including HIV-infected patients. The aim of this study was to assess the sero-virological prevalence of HEV in HIV patients and in the general population as control group. METHODS: A prospective and observational cohort study was carried out in two hospitals in southern Italy. The seroprevalence of HEV was determined in a cohort of 959 subjects, 509 (53%) of whom were HIV-positive patients and 450 were from the general population. Serum samples were tested for anti-HEV antibodies; repeatedly positive results were confirmed by a Western blot assay. In positive patients HEV RNA and genotypes were also determined. RESULTS: A total of 46 (4.8%) of the 959 serum samples examined were reactive to anti-HEV Ig and confirmed by Western blotting. The prevalence of HEV antibodies (IgG and/or IgM) was 2.7% in the control group and 6.7% in HIV-infected patients. Anti-HEV IgM was found in 6/46 (13.0%) of the anti-HEV Ig-positive serum samples, in 5/34 HIV patients and in 1/12 of the general population. No HIV-infected patient presented chronic hepatitis with HEV infection alone. CONCLUSIONS: This study indicates a higher circulation of HEV in HIV-infected patients, whereas a low prevalence of HEV antibodies in the general Italian population was shown. Chronic hepatitis with HEV alone was absent, while it was present in subjects with HIV-HEV, co-infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV).