Enza Viviano

Human herpesvirus type 8 DNA sequences in biological samples of HIV-positive and negative individuals in Sicily.

Objective:To evaluate the circulation of a new human herpesvirus (HHV), HHV-8 or Kaposis sarcoma (KS)-associated herpesvirus in a geographical area where a high incidence rate of classical KS was already present before the appearance of the AIDS epidemic. Design and methods:The study was carried out by analysing: (i) bioptic samples from classic, AIDS-associated KS, and controls; (ii) peripheral blood mononuclear cells (PBMC) from classic KS, HIV-positive subjects with and without KS and healthy HIV-negative individuals; (iii) semen samples from heterosexual HIV-positive and HIV-negative individuals affected or not by KS; and (iv) cervical swabs from HIV-negative healthy heterosexual females. All specimens were tested for the presence of HHV-8 DNA sequences by a two-step polymerase chain reaction. Results:Positive results were obtained in 90% of bioptic samples of classic KS and in 100% of AIDS-associated KS. Viral sequences were also present in 50% of PBMC of subjects with classic KS and AIDS-associated KS, in 10% of AIDS patients without the angiosarcoma, and in 11% of healthy HIV-negative individuals. Finally, HHV-8 DNA was detected in 13% of semen of HIV-negative heterosexual individuals and in 10% of AIDS patients without KS. Both PBMC and ejaculates from the same individual gave positive results. No HHV-8 sequences were found in cervical swabs. Conclusions:HHV-8 is widespread in the general population in Sicily since it was detected in PBMC and semen of heterosexual HIV-negative individuals and is not found only in high-risk groups. The viral load appears to be more elevated in a high-risk population and it may be ascribed to a viral reactivation. The higher incidence rates of KS in Sicily compared with northern Italy and other European countries might be related to the presence of HHV-8 in the general population.

Penile, Urethral, and Seminal Sampling for Diagnosis of Human Papillomavirus Infection in Men

ABSTRACT Methods that used specimens from three genital sites (penile brushing [PB], urethral brushing [UB], and the retrieval of semen [SE]) from 50 men were examined for human papillomavirus (HPV) DNA detection. The rates of detection by PB, UB, SE, PB and UB, and PB and SE were 88.9%, 50.0%, 33.3%, 100%, and 97.2%, respectively. The use of PB and UB appears to be the most accurate method; as an alternative to UB, the use of SE with PB could be used to improve the rate of HPV DNA detection in men.

MDM2 and CDKN1A gene polymorphisms and risk of Kaposi’s sarcoma in African and Caucasian patients

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi’s sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0–5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients.

Transmission of Drug-Resistant HIV Type 1 Strains in HAART-Naive Patients: A 5-Year Retrospective Study in Sicily, Italy

The transmission of drug-resistant HIV-1 strains might compromise the efficacy of current first-line antiretroviral (ARV) regimens. Between 2004 and 2008, HIV-1 reverse transcriptase (RT) and protease (PR) genes of 108 ARV-naive Sicilian patients were amplified and sequenced to describe the prevalence of ARV resistance mutations among HAART-naive HIV-1-infected individuals. The frequency of transmitted drug resistance mutations (DRAMs) was determined by using genotypic interpretation algorithms. The proportion of HAART-naive HIV-1-infected patients in Sicily increased from 18.4% to 23.5% during 2004-2008. Among naive patients, the overall prevalence of DRAMs was 15.7% [17/108; 95% CI: 9.4-24.0]. DRAMs to nonnucleoside reverse transcriptase inhibitors (nNRTI) were detected most frequently [11/108 (10.2%)], of which K103N was the most prevalent (4.6%), whereas the prevalence of DRAMs was lowest for protease inhibitors (PI) [3/108 (2.8%)]. Drug resistance substitutions associated with two or three drug classes were rarely observed. The prevalence of HIV-1 DRAMs in Sicily was relatively higher than that observed in Italy and other European geographic areas and much higher than in resource-limited countries. However, the possible clinical role played by DRAMs in HAART-naive HIV-1-infected individuals will require further assessment.

Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily

Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non‐specifically and specifically against the KS‐associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non‐AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV‐seronegative controls were tested for interferon‐γ T‐cell (enzyme‐linked immunospot [Elispot]) responses to KSHV‐latency‐associated nuclear antigen (LANA), KSHV‐K8.1 and CMV/Epstein–Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed‐type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV‐LANA responses had current KS lesions, whereas five of six cases with KSHV‐K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55–0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02–1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86–30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03–0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV‐specific and KSHV‐non‐specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution. (Cancer Sci 2011; 102: 1769–1773)

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

BackgroundTo clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV).MethodsIn a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods.ResultsComparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07) and anti-VCA (P = 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03), and they were marginally lower with older age and cortisone use (Padj ≤ 0.09).ConclusionsAnti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.

Avian mite dermatitis: an Italian case indicating the establishment and spread of Ornithonyssus bursa (Acari: Gamasida: Macronyssidae) (Berlese, 1888) in Europe.

Avian mite dermatitis is a skin disease caused in mammals by the incidental bites of blood‐sucking mites which customarily parasitize wild and domestic birds. It manifests in the form of pruritic, erythematous, or urticarial papules, with a central sting mark, in skin regions normally covered by clothing. The species mainly implicated in human bite cases are Dermanyssus gallinae, Ornithonyssus sylviarum and, less frequently, Ornithonyssus bursa. The latter is mainly a tropical and subtropical mite and its – presumably transitory – presence has been recorded only once in Europe, in migratory birds.

Dermatitis due to Mesostigmatic mites (Dermanyssus gallinae, Ornithonyssus [O.] bacoti, O. bursa, O. sylviarum) in residential settings

Since early recorded history, people who live in urban areas have shared their environment with pets and synanthropic animals, mainly birds and rodents. These animals harbor zoonotic parasites, including mites of the suborder Mesostigmata [ 1 ] . Among them, the avian mites Dermanyssus (D.) gallinae , Ornithonyssus (O.) sylviarum, O. bursa and the tropical rat-mite, O. bacoti are the most dermatologically relevant species. They are non-burrowing, bloodsucking ectoparasites of similar shape and size (about 1 mm in length) [ 1 ] . With the exception of O. sylviarum, which usually lives permanently on its host, they are temporary and nocturnal visitors of their victims, hiding in daytime in their close proximity. The resting/breeding sites of birds/ rodents, mainly pigeons and feral rats/mice and occasionally pets, act as mite reservoirs [ 2, 3 ] ; in the absence of their natural host, hungry mites may migrate into nearby human buildings and bite their inhabitants. Patients develop itching urticarial papules, often bearing a red punctiform mark, on covered and/or exposed body areas. These lesions are usually unrecognized unless there is a high degree of clinical suspicion. From 2001 to September 2017, we used transmission light microscopy and/or scanning electron microscopy to analyze the arthropods supposedly related to 26 urban outbreaks of pruritic dermatitis, with a total of 66 subjects (60 adults and 6 children) living and/or working in southern peninsular and insular Italian regions (Campania, Molise, Basilicata, Apulia and Sicily). The dermatitis had started in spring/summer and lasted from a week to nine months. In eleven cases, it remained undiagnosed for more than four weeks and underwent several relapses after systemic and local treatment with antihistamines and corticosteroids. The patients presented with eruptions of urticarial papules, most of which had a central red puncture mark, readily detectable with a magnifi cation lens (Figures 1, 2 ). The clinical picture was highly suggestive of mite bite dermatitis and the parasites were searched for. They were collected from the patients’ bedrooms, workplaces (hospitals, offi ces, animal facilities) and from the patients’ skin. In a few cases, the parasites were delivered to our laboratory by the patients themselves, who had found them crawling on their skin and/or in their bedrooms or workplaces. The parasites were identifi ed as D. gallinae (20/26; peninsular regions), O. bacoti (4/26; Sicily/peninsular regions), O. bursa and O. sylviarum (both 1/26; Sicily) based on morphological key characters [ 1, 4 ] (Figure 3 ). Abandoned bird nests (20/26; pigeon/sparrow/ swallow) close to buildings, pet canaries (1/26) and poultry in backyards (1/26) were the sources of avian mite species; the source of O. bacoti was ascribed to laboratory holdings (1/26) or colonies of wild rats (3/26). Considering the patients’ medical histories, clinical fi ndings and laboratory data, we diagnosed Mesostigmata mite infestation in all cases. Showering and washing clothes, removal of mite sources and