HIV-1: towards understanding the nature and quantifying the latent reservoir.

The human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) pandemic constitutes one of the greatest public health issues, since 36.9 million people worldwide were living with HIV in 2017 and 940,000 died from AIDS- related illnesses in the same year. One of the main obstacles in the effort to achieve viral eradication or long-term virologic remission is the existence of the HIV-reservoir. Except for resting memory CD4+ T cells there is a plethora of innate immunity cells including macrophages, dendritic cells, follicular T helper cells and NK cells which are now considered to play a role in viral latency and persistence. Hematopoietic precursor cells and progenitor mast cells, astrocytes, fibrocytes, renal and liver epithelial cells could also contribute to the reservoir, but their role remains controversial. Tissue reservoirs, such as the central nervous system (CNS), lymphoid tissue, adipose tissue and the gut-associated-lymphoid-tissue (GALT) are usually referred to as anatomic sanctuaries, where it is difficult to achieve high concentration and efficacy of antiretroviral agents. Accurate quantification of this reservoir is of the utmost importance and multiple assays have been developed for this purpose. The role of several cell populations in viral latency needs to be clarified by further studies. Furthermore, there is an urgent need for new assays, which will accurately measure the size of the reservoir, which plays a key role in predicting the timing of viral rebound upon cessation of antiretroviral treatment, since the currently available ones either overestimate or underestimate the size and have significant limitations. Keywords: HIV-1; cellular reservoirs; tissue reservoirs; quantification.

West Nile virus meningitis in a patient with human immunodeficiency virus type 1 infection.

The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.

Soluble receptor for advanced glycation end products in male infertility.

BACKGROUND: Soluble receptor of advanced glycation end-products (sRAGE) is widely expressed in various organs including male genital tract and spermatozoa. Their regulation depends on many simultaneous conditions that may occur. Male fertility is a multifactorial condition which is influenced by various parameters, some of which are detrimental to the spermatozoa. The aim of this study was to detect possible differences in sRAGE concentrations between serum and seminal plasma of infertile men, compared to fertile men population. METHODS: Seventy-five men were included in the study and divided into three groups: a group of fertile controls (age 34.8 ± 4.6 years, n =12) and two groups of men from infertile couples (age 36.1 ± 5.2 years) with normal (NS, n =10) and abnormal (AS, n =53) semen parameters, respectively. sRAGE was measured by ELISA in serum, and seminal plasma samples of all participants and biochemical, hormonal examinations, as well as anthropometric characteristics, were co-evaluated. Data were statistically analyzed using the chi-square test and the independent samples t-test. A two-tailed p <0.05 was considered significant. RESULTS: Serum sRAGE levels of fertile men were higher than those of men of infertile couples with AS or NS semen parameters (2,061 ± 884 pg/ml vs 1,673 ± 613 pg/ml and 1,411 ± 405 pg/ml, respectively; p <0.058). Seminal plasma sRAGE levels in fertile men were similar to the ones measured in both groups of men from infertile couples AS and NS (327 ± 81 pg/ml vs 322 ± 162 - 413 ± 207 pg/ml; p =0.197). Interestingly, the seminal plasma sRAGE levels in those three groups were significantly lower than the corresponding serum sRAGE levels (p <0.001). CONCLUSION: Serum and seminal plasma sRAGE concentrations seem to show variations worth considering between fertile and infertile men. Moreover, further research is required to elucidate the role of the sRAGEs and oxidative stress in male infertility. HIPPOKRATIA 2017, 21(1): 19-24.

An unusual case of Streptococcus agalactiae meningitis in a patient with sys-temic lupus erythematosus.

BACKGROUND: Streptococcus agalactiae (group B Streptococcus) is a major cause of sepsis and meningitis in neonates and an important cause of invasive disease in adults. CASE DESCRIPTION: We describe an unusual case of fatal bacterial meningitis caused by Streptococcus agalactiae in a young man suffering from systemic lupus erythematosus for over 20 years. The young man was transferred intubated in AHEPA University Hospital in a coma; twenty-four hours upon arrival and despite intense invasive treatment, he died from multiple organ failure. CONCLUSION: The risk of serious infections in patients with systemic lupus erythematosus even under treatment with moderate doses of corticosteroids is high. Hippokratia 2015; 19 (4):372-373.

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009-2011.

We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009-11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.

HIV infection and periodontal diseases: an overview of the post-HAART era.

HIV infection remains a global health problem of unprecedented dimensions, although the development of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease into a manageable chronic disease with longer survival and improved quality of life in HIV-infected subjects. Among the HIV-associated infections, oral lesions have been recognized as prominent features since the beginning of the epidemic and continue to be important. Periodontal diseases strongly associated with HIV infection are classified as linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis and are included among the cardinal oral lesions. Although oral candidiasis appears to be the infection more significantly decreased after the introduction of HAART, the current literature suggests that the prevalence and course of periodontal lesions have also been modified. Higher prevalence of opportunistic microorganisms has been frequently detected in the subgingival flora of HIV-infected individuals, probably due to the immune status of those patients, as colonization and overgrowth of atypical pathogenic species is facilitated by immunosuppression. Additional research is required regarding biological issues such as the role of oral immune factors and periodontal disease in the persistency of HIV infection, the possibility of oral transmission and the re-emerging of HIV infection.

Association between the heme oxygenase-1 promoter polymorphism and renal transplantation outcome in Greece.

BACKGROUND: Heme oxygenase-1 (HO-1) is the enzyme that catabolizes heme into carbon monoxide, biliverdin, and free iron. The induction of this enzyme is an important cytoprotective mechanism, which occurs as an adaptive and beneficial response to a wide variety of oxidant stimuli. HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. HO-1 inducibility is mainly modulated by a (GT)(n) repeat polymorphism in the promoter region, and has been shown that short repeats (S) are associated with greater upregulation of HO-1, compared with long repeats (L). In the present study we investigated the influence of this HO-1 gene polymorphism on clinical outcome after transplantation and on renal transplant function. METHODS: DNA from 175 donor/recipient pairs who underwent transplantation between October 2002 and June 2007 was genotyped. We divided the HO-1 alleles into 2 subclasses, the S ≤ 27 repeats and L > 27 repeats. RESULTS: There has been significant relevance between the genotype of the donor and the outcome of the graft, as far as recipients with normal graft function and recipients with deteriorated graft function are concerned (P = .021). In patients with normal graft function, grafts from L-homozygotes were found in 24%, whereas in patients with deteriorated function, grafts from L-homozygotes exhibited in higher rate (50%). Neither the donor's nor the recipient's polymorphism influenced the graft survival (log-rank test P = .228 for the donors and log-rank test P = 0.844 for the recipients). There was no evidence of a gene-dose effect on graft survival (P = .469). Recipients of allografts from S-carriers donors had significantly lower serum creatinine levels at 24 months compared with recipients of allografts from L-homozygotes donors (P = .016).

Molecular epidemiology of Echovirus 6 in Greece.

The objective was to investigate the genetic relationships among Echovirus 6 (E6) strains circulating in Greece and to compare them with the respective strains from other geographic regions. Cerebrospinal fluid samples collected during the period 2006-2007 from 84 patients with aseptic meningitis or encephalitis were tested for a probable enteroviral infection. Two RT-PCRs amplifying overlapping regions of the VP1 gene were performed, while isolation procedures were applied in one third of cases. All PCR products were sequenced, and further phylogenetic analysis was performed for E6 strains. Enteroviruses were detected in 27 out of 84 cases (32.14%) and E6 was the predominant serotype (11 out of 27, 40.74%). Three distinct clades of Greek E6 sequences were seen in the phylogenetic tree: sequences of the present study were placed in clades A and B, while sequences of a former study in Greece were clustered in clade C. Sequences of clades A and C presented high genetic homology (>95%) with sequences from other countries, while sequences of clade B were unique, differing by more than 15% from all known E6 sequences. The most prevalent enterovirus in Greece during the period 2006-2007 was E6, and was associated with aseptic meningitis. A high degree of heterogeneity was observed among Greek E6 strains.

Aseptic meningitis and encephalitis because of herpesviruses and enteroviruses in an immunocompetent adult population.

BACKGROUND AND AIM: Human herpesviruses (HHVs) and enteroviruses (EVs) are the major causative agents of CNS viral infections. The aim of the study was to identify the etiology and determine the frequency of aseptic meningitis and encephalitis due to HHVs and EVs in an immunocompetent adult population. METHODS: Eighty-one patients (ages >or=15) with aseptic meningitis or encephalitis treated in the Infectious Diseases Hospital of Thessaloniki, Greece, during 2003-2006, were included in the study. Polymerase chain reaction for detection of herpes- and enterovirus genome direct in cerebrospinal fluid samples was performed. RESULTS: Based on clinical and laboratory data, 36/81 patients had meningitis and 45/81 had encephalitis. Etiology was defined in 11 patients (31%) with aseptic meningitis. EVs were the major causative agents (8/36, 22%), followed by varicella zoster virus (2/36, 5%) and herpes simplex virus-2 (HSV-2) (1/36, 3%). Etiology was identified in 8 of 45 (18%) patients with encephalitis, EV (4/45, 9%) and HSV-1 (4/45, 9%) being the most common pathogens. CONCLUSION: Enteroviruses are the most common cause of adult aseptic meningitis and together with HSV-1 the main causes of encephalitis.

Study on the use of an enzyme-linked immunosorbent assay in determining human antibodies to diphtheria toxin as compared with a reference toxin neutralization assay.

Serum samples from 156 Greek persons were assessed by an IgG-specific enzyme-linked immunosorbent assay (ELISA) and a reference tissue culture toxin-neutralization (TN) assay for the quantitation of diphtheria toxin antibodies. By the reference method, 7.7% of the persons were susceptible to diphtheria (antitoxin < 0.01 IU/ml), 28.8% had basic protection (antitoxin 0.01-0.09 IU/ml) and 63.5% were fully protective (antitoxin > or = 0.1 IU/ ml), while the corresponding figures were 17.9, 36.5 and 45.5% when they were tested by the immunoassay. None of the samples been susceptible by the TN assay were found to have some protection when tested by ELISA. However, three (6.7%) of the 45 samples showing a basic protection with TN, were fully protective when titrated by the immunoassay. In addition, 31 (31.3%) of the 99 samples been fully protective by the bioassay, were found to be either basically protective or susceptible by means of the ELISA. Overall, validity features of the immunoassay were: sensitivity 68.7%, specificity 94.7%, positive predictive value 95.8% and negative predictive value 63.5%. The ELISA tested in our study could be used to determine diphtheria antitoxin in individuals needed a booster immunization (susceptible or basic protective samples), although it might falsely include in the above categories samples that are within the fully protective levels of antibodies.

Diphtheria immunity of Albanian and other eastern European immigrants in Greece compared with the local population--the risk of reemergence in Greece.

A large number of immigrants have come to Greece from diphtheria-endemic countries during the past 8 years. Information on the immune status against diphtheria among immigrants from Albania and the New Independent States (NIS) of the former USSR, as well as the Greek population, is essential in planning public health control measures. The main objective of the study was to determine the risk of the spread of diphtheria if new cases arrived in the country. Diphtheria antitoxin (DAT) in sera from 185 healthy individuals from northern Greece and 227 immigrants from Albania and the NIS was titrated using a quantitative ELISA test. The participants were adults aged 22 to 46 years. Titers were considered as protective when DAT levels were higher or equal to 0.1 IU/ml. Albanian immigrants exhibited the highest rates of protective titers (99 of 167, 59.3%), while lower immunity rates were detected among immigrants from the NIS (20 of 60, 33.3%) (1.5 < OR = 2.9 < 5.4, p = 0.0007) as well as among Greek participants (47 of 185, 25.4%) (2.8 < OR = 4.4 < 7.0, p = 0.00001). Immunity rates did not differ between Greek and NIS participants. DAT levels of persons with protective titers differed between the three population groups (analysis of variance, p = 0.0005), with the highest mean DAT values detected among NIS immigrants (0.613 IU/ml). Lower values were found among protected Albanians (0.482 IU/ml) and Greeks (0.314 IU/ml). There was no significant age- and sex-related difference in immunity rates and DAT levels among the groups. The low immunity rates among Greek adults might suggest that they have had no natural contact with toxigenic strains of corynebacteria. A booster dose of diphtheria toxoid for local adults is recommended, to reduce their risk of acquiring toxigenic strains from individuals who may carry the bacteria without exhibiting clinical disease.