Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease.

The epidemiological transition has reduced infectious diseases mortality in most European countries, yet increased migrant influx risks importing diseases. All reported prevalence rates must be considered on a case-by-case basis depending on the disease in question, respective European Union (EU) country and migratory patterns at work. Tuberculosis has seen a re-emergence in Europe and is concentrated among migrants. Migrants arriving from North Africa (NA) and sub-Saharan Africa (SSA) carry higher rates of hepatitis C and B than the local EU population. The human immunodeficiency virus (HIV) impact of NA migrants to Europe is very low but a hallmark of the HIV epidemic is the penetration and circulation of non-B strains, recombinant forms and HIV-drug-resistant profiles through SSA migrants using NA as a transit point into Europe. Leishmaniasis is a re-emerging zoonotic disease prevalent to Southern Europe although not specifically isolated in migrant groups. Although not endemic in NA countries, malaria represent S: a risk in terms of re-emergence in Europe through transitory migrants arriving from SSA with the destination to Europe. Schistosomiasis has been largely eliminated from NA. High migrant flux into European countries has resulted in changing patterns of communicable disease and collectively requires a continuous surveillance. World Health Organization guidelines recommend targeted screening and preventative vaccination, followed by integration of migrants into the local health-care systems allowing for long-term treatment and follow-up. Finally, effective public health campaigns as a form of prevention are essential for the mitigation of disease dissemination in the migrant pool and for second-generation children of migrants.

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Cell surface-associated viral glycoproteins are thought to play a major role as target antigens in cellular cytotoxicity and antiviral immunosurveillance. One such glycoprotein is the Epstein-Barr virus (EBV)-encoded glycoprotein 350 (gp350), which is expressed on both virion envelope and EBV producer cells and carries the virus attachment protein moiety. Although it is known that some antibodies to gp350 can neutralize the virus, the role of this glycoprotein in EBV-specific cellular cytotoxicity is not yet clear. We describe here a study in which we successfully used a new approach to demonstrate that gp350 is a target antigen for EBV-specific antibody-dependent cellular cytotoxicity (ADCC). Transfection of gp350-negative cells resistant to natural killer (NK) cell activity (i.e., Raji) with a recombinant vector (pZIP-MA) containing the gene encoding the EBV-gp350 and the neomycin resistance gene enabled us to isolate cell clones with a stable and strong expression of gp350 on their surface membranes. ADCC determined by using two clones clearly demonstrated that gp350 is the target of the EBV ADCC. Interestingly, this ADCC was comparable to that obtained against the EBV-superinfected (coated) Raji cells expressing the same percentage of gp350 positivity as the two clones. No cytotoxic activity was detected against either nontransfected (gp350-negative) Raji cells or cells transfected with the vector [pZIP-neo-SV(X)1] lacking the gp350 gene. In addition to demonstrating that gp350 is a target molecule for EBV-specific ADCC, our approach in using NK-resistant transfectants provides a lead for probing the role of cell surface-associated viral antigens in specific cellular killing and immunosurveillance.

An NK cell activity-resistant human lymphoid T cell line (CEM-NKr) expressing the transfected Epstein-Barr virus (EBV) gp350 gene was used in membrane immunofluorescence (MIF) and antibody-dependent cellular cytotoxicity (ADCC) assays to analyze the gp350-specific humoral and ADCC responses in groups of EBV-seropositive persons. Results show that there is no correlation between gp350-specific ADCC-mediating antibody titers and MIF or EBV neutralizing antibody titers. For example, sera from patients in the acute phase of infectious mononucleosis, while positive by MIF assay or EBV neutralization test, were not reactive in the ADCC assay. Results also show that nasopharyngeal carcinoma (NPC) patients on MIF present high IgG titers against gp350 compared with healthy persons. Anti-gp350 IgA antibodies were detected in all groups tested; however, titers were highest in the NPC group.

The present meta-analysis was conducted to evaluate the prognostic value of pre and post-Epstein Barr Virus (EBV) DNA load testing and to assess the clinical benefit of using this molecular approach in the prognosis for a better nasopharyngeal carcinoma (NPC) management. Relevant studies were searched in different database until May 2020. Patient´s outcomes overall survival (OS), disease free survival (DFS), progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS), hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies. The association of pre and post-EBV DNA load and survival outcomes was assessed using review manager and the pooled HRs with 95% CIs were calculated. Twenty-six eligible studies were included in this meta-analysis, with a total of 9966 patients. Pooled HRs showed that EBV DNA levels before and after treatment are significantly associated with survival outcomes, with HR (95% CI) of 2.09 [1.74, 2.51] for OS, 1.77 [1.19, 2.62] for DFS, 2.53 [2.18, 2.92] for DMFS, 1.78 [1.45, 2.19] for LRFS and 2.17 [1.91, 2.47] for PFS in pre-EBV DNA, and an HR (95%) of 4.52 [2.44, 8.36], 4.08 [2.38, 6.99], 5.59 [ 3.58, 8.71] and 8.88 [5.29, 14.90] for OS, DFS and PFS and DMFS in post-EBV DNA, respectively. High pre and post-EBV DNA levels were significantly associated with poor NPC patient´s survival outcomes; which clearly confirm the high interest to introduce viral EBV DNA load as a prognostic biomarker for NPC management.

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Table of contentsA1 Hope and despair in the current treatment of nasopharyngeal cancerIB TanI1 NPC international incidence and risk factorsEllen T ChangI2 Familial nasopharyngeal carcinoma and the use of biomarkersChien-Jen Chen, Wan-Lun Hsu, Yin-Chu ChienI3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findingsAllan HildesheimI5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast AsiaJames D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena DeviI6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylationLi L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao QI7 Tumor exosomes and translational research in NPCPierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira DelhemI8 Host manipulations of the Epstein-Barr virus EBNA1 proteinSheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori FrappierI9 Somatic genetic changes in EBV-associated nasopharyngeal carcinomaLo Kwok WaiI10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern ChinaSui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei CaoI11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disordersDenise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan HildesheimI12 The nasopharyngeal carcinoma awareness program in IndonesiaRenske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB TanI13 Current advances and future direction in nasopharyngeal cancer managementBrian O’SullivanI14 Management of juvenile nasopharyngeal cancerEnis OzyarI15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapyAnne WM LeeI16 The predictive/prognostic biomarker for nasopharyngeal carcinomaMu-Sheng ZengI17 Effect of HLA and KIR polymorphism on NPC riskXiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary CarringtonI18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal CarcinomaAnna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I CohenI19 Advances in MR imaging in NPCAnn D KingO1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in TaiwanYin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan ...