Merkel cell polyomavirus (MCPyV) is thought to be the etiological agent of Merkel cell carcinoma, but little is known about its distribution and modes of transmission. We conducted seroepidemiological surveys in more than 1000 individuals, from two populations from Cameroon. Overall MCPyV seroprevalence was high in both populations (>75% in adults). Data from the first population, comprising mainly children, indicated that MCPyV infections mostly occurred during early childhood, after the disappearance of specific maternal antibodies. Results from the second family-based population provided evidence for familial aggregation of MCPyV infection status. We observed significant sib-sib correlation (odds ratio=3.42 [95% CI 1.27-9.19], p=0.014), particularly for siblings close together in age, and a trend for mother-child correlation (OR=2.71 [0.86-8.44], p=0.08). Overall, our results suggest that MCPyV infection is acquired through close contact, possibly involving saliva and/or the skin, especially between young siblings and between mothers and their children.
Regional chemotherapy has been proposed as a treatment modality in a number of cancer settings. In primary or metastatic lung cancer, administration of chemotherapy via inhalation could increase exposure of lung tumor to the drug, while minimizing systemic side effects. Several proof of concept studies in animal models of metastatic or primary lung cancer have demonstrated the safety, pharmacokinetic advantage, and antitumor effect of aerosol administration of several chemotherapeutic agents including doxorubicin, gemcitabine and liposome-encapsulated formulations of paclitaxel and 9-nitrocamptothecin (9-NC). Recent phase I studies have demonstrated the feasibility of aerosol delivery of doxorubicin and liposomal formulations of 9-NC and cisplatin in patients with primary and metastatic lung cancer with a limited pharmacokinetic profile consistent with the observed low systemic toxicity. Further studies integrating safety, pharmacokinetic, and efficacy considerations are required to determine whether there is a place for local administration of chemotherapy via inhalation in lung cancer.
The seroprevalence of the recently discovered human Malawi polyomavirus (MWPyV) was determined by virus-like particlebased enzyme-linked immunosorbent assay (ELISA) in age-stratified Italian subjects. The findings indicated that MWPyV infection occurs early in life, and seroprevalence was shown to reach 42% in adulthood.T welve human polyomaviruses have been described to date, including JC and BK polyomaviruses (JCPyV and BKPyV), Karolinska Institute polyomavirus (KIPyV), Washington University polyomavirus (WUPyV), Merkel cell polyomavirus (MCPyV), human polyomaviruses 6 and 7 (HPyV6 and HPyV7), trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 9 (HPyV9) (1), and three recently identified polyomaviruses, i.e., Malawi polyomavirus/human polyomavirus 10 (MWPyV/HPyV10), Saint Louis polyomavirus (STLPyV) isolated from stools (2-4), and human polyomavirus 12 (HPyV12) identified in the liver (5).Polyomavirus infections are ubiquitous, with seroprevalence ranging from 40 to 90% in adults, and asymptomatic infections occur early in childhood (6-12).Four human polyomaviruses are associated with disease. JCPyV causes progressive multifocal leukoencephalopathy, BKPyV is the cause of hemorrhagic cystitis in allogeneic hematopoietic stem cell transplant patients and induced nephropathy frequently followed by graft loss in renal transplant patients. MCPyV is responsible for Merkel cell carcinoma (MCC), which occurs mainly in elderly individuals and immunocompromised subjects, and TSPyV is associated with trichodysplasia spinulosa. JCPyV-, BKPyV-, and TSPyV-associated diseases have been observed only in immunocompromised subjects (1,13).In this study, we investigated the seroepidemiology of the recently identified Malawi polyomavirus in an Italian population using a virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) and evaluated the existence of crossreactivity with MCPyV, HPyV6, HPyV7, TSPyV, and HPyV9 polyomaviruses.MWPyV seroprevalence was determined in 825 Italian subjects 1 to 100 years of age. This study population has previously been investigated for reactivity against five other polyomaviruses (12), and the approach here was similar. Antibodies against MWPyV were determined using a VLP-based ELISA (14). The MWPyV VP1 coding sequence (GenBank accession no. NC_018102.1) was codon optimized for expression in Spodoptera frugiperda cells (Genscript, Piscataway, NJ) and used to generate a recombinant baculovirus. The presence of 45-to 50-nm VLPs and smaller particles was observed by electron microscopy (Fig. 1). Purified MWPyV VLPs (100 ng/well in phosphate-buffered saline [PBS]) were used to sensitize microplates (Maxisorp; Nunc) overnight at 4°C. Briefly, sera were diluted 1:100, and peroxidase-conjugated anti-human IgG (Southern Biotech, Clinisciences, Nanterre, France) diluted 1:20,000 was used to detect human IgG binding (14). A histogram of the ELISA optical density (OD) values in 1-to 10-year-old children (data not shown) revealed a bimodal distribution of seroreacti...
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