Quantitative Analysis of Viral Load per Haploid Genome Revealed the Different Biological Features of Merkel Cell Polyomavirus Infection in Skin Tumor

Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen’s disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119–42.8) and AK (0.02–0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4+ and CD8+ T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models

Factors Associated with Pruritic Papular Eruption of Human Immunodeficiency Virus Infection in the Antiretroviral Therapy Era

Background—Pruritic papular eruption (PPE) of HIV is common in HIV-infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure. Objectives—To determine factors associated with PPE in HIV-infected persons receiving ART. Methods—A case–control study nested within a 500-person cohort from a teaching hospital in Mbarara, Uganda. Forty-five cases and 90 controls were enrolled. Cases had received ART for ≥ 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration. Results—Twenty-five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA \u3c 400 copies mL–1 (96% vs. 85%, P = 0·31). The odds of having PPE increased fourfold with every log increase in viral load at ART initiation (P · 0.02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8 T-cell activation measured 6 and 12 months after ART commencement were not associated with PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8.3, P \u3c 0.001] or PPE cases (OR 8.6, P = 0.01). Conclusions—Pruritic papular eruption in HIV-infected persons receiving ART for ≥ 15 months was associated with greater HIV viraemia at ART commencement, independent of CD4 count. Skin biopsies are important to distinguish between PPE and other itchy papular eruptions