Genetic characterization of human immunodeficiency virus type 1 transmission in the Middle East and North Africa.

BACKGROUND: The HIV-1 spread in the Middle East and North Africa (MENA) has not been previously characterised using the phylogenetic approach. The aim of the current study was to investigate the genetic diversity and domestic transmission of HIV-1 in the MENA. METHODS: A total of 2036 HIV-1 sequences available in Genbank and collected in the MENA during 1988-2016 were used together with 715 HIV-1 reference sequences that were retrieved from Genbank based on genetic similarity with the MENA sequences. The REGA and COMET tools were used to determine HIV-1 subtypes and circulating recombinant forms. Maximum Likelihood and Bayesian phylogenetic analyses were used to identify and date HIV-1 transmission clusters. RESULTS: At least 21 HIV-1 subtypes and recombinant forms were prevalent in the MENA. Subtype B was the most common variant (39%), followed by CRF35_AD (19%) and CRF02_AG (14%). The most common genetic region was pol, and 675 partial pol sequences (average of 1005 bp) were eligible for detailed phylogenetic analysis. Fifty-four percent of the MENA sequences formed HIV-1 transmission clusters. Whereas numerous clusters were country-specific, some clusters indicated transmission links between countries for subtypes B, C and CRF02_AG. This was more common in North Africa compared with the Middle East (p < 0.001). Recombinant forms had a larger proportion of clustering compared to pure subtypes (p < 0.001). The largest MENA clusters dated back to 1991 (an Algerian CRF06_cpx cluster of 43 sequences) and 2002 (a Tunisian CRF02_AG cluster of 48 sequences). CONCLUSIONS: We found an extensive HIV-1 diversity in the MENA and a high proportion of sequences in transmission clusters. This study highlights the need for preventive measures in the MENA to limit HIV-1 spread in this region.

Variability in the precore and core promoter region of the hepatitis B virus genome.

There is increasing evidence that hepatitis B virus (HBV) infections with different genotypes and subgenotypes differ in response to treatment and long-term prognosis. The differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. Naturally occurring HBV strains covering the four major genotypes A-D were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction (PCR), sequenced, and analyzed for mutational differences in the precore and core promoter regions. The study confirmed that core promoter and precore mutations occur at key positions (A1762T, G1764A, G1896A, and G1899A), and that the proportions of strains with seroconvertion in patients differ between the four HBV genotypes. A rare double mutation (C1857T together with G1897A) was observed, and C1856T was found together with the emerging G1898A mutation, which itself was found to be more widespread geographically than previously described. We found a novel mutation (T1850C), never before observed in human HBV strains but known from woodchuck hepatitis virus (WHV). A novel association of mutation C1773T with G1764T, C1766A, and G1757A was also found within a site already suggested to be a putative binding site for HNF-3. This novel association is proposed by us to be of importance for additional binding of HNH-2 to this site and is a better indicator of the emergence of the double mutation G1764T and C1766A than the G1757A mutation proposed previously.

Clinical appearance of erythema migrans caused by Borrelia afzelii and Borrelia garinii--effect of the patient's sex.

AIM: The aim in this survey was to study the clinical characteristics of infections caused by Borrelia genospecies in patients with erythema migrans where borrelial origin was confirmed by polymerase chain reaction. The aim was also to study factors influencing the clinical appearance of erythema migrans. METHODS: The study was conducted in southern Sweden from May 2001 to December 2003 on patients 18 years and older attending with erythema migrans at outpatient clinics. All erythema migrans were verified by polymerase chain reaction, photographed and categorized as "annular" or "non-annular" lesions. A logistic regression model was used to analyze relations between the appearance of the erythema migrans (i.e. annular or non-annular) and factors that influenced its clinical appearance. RESULTS: A total of 118 patients, 54 women (45.8%) and 64 men (54.2%), fulfilled the inclusion criteria. Of these patients, 74% were infected by B. afzelii and 26% by B. garinii (p < 0.001). A total of 45% (38/85) of the erythema migrans were annular, 46% (39/85) were nonannular and 9.4% (8/85) were atypical. For men infected by B. afzelii, the odds ratio of developing non-annular erythema migrans was 0.09 (95% CI: 0.03-0.33) in comparison with women with the same infection. CONCLUSIONS: In this prospective study of a large series of erythema migrans, where infecting genospecies were confirmed by polymerase chain reaction, the sex of patients infected with B. afzelii had a strong influence on the appearance of the rash. Patients infected by B. garinii more often had non-annular erythema migrans and a more virulent infection with more individuals presenting with fever, raised levels of C-reactive protein and seroreactivity in the convalescence sera.

Elevated neutrophil, macrophage and dendritic cell numbers characterize immune cell populations in mice chronically infected with Salmonella.

The present study characterizes immune cell populations in mice chronically infected with Salmonella. Mice were characterized as chronically infected based on persistently high titers of Salmonella-reactive immunoglobulins in the serum >6 months after a single oral dose of S. enterica serovar Typhimurium. These mice had a visibly enlarged spleen but not liver, while both organs harbored bacteria and had increased total cellularity up to 11 months post-infection. Flow cytometry analysis revealed significantly elevated numbers of neutrophils, dendritic cells (DC) and macrophages in the spleen of chronically infected mice. In contrast, no significant increase in the absolute number of T and B cells was apparent in the spleen and DX5+ cells, which includes NK cells, some NK T cells and possibly some activated T cells, appears to correlate with chronic Salmonella infection in the liver but not the spleen. In situ analyses revealed that CD8alpha+ DC and Gr-1+ cells (neutrophils) increased in the splenic red pulp of chronically infected mice. In addition, Gr-1+ cells, CD68+ cells and CD11c+ cells (DC), the latter lacking detectable staining for CD8alpha and CD4, accumulated around hepatic blood vessels and in the hepatic network in the liver of mice chronically harboring bacteria. These data provide insight into changes that occur within immune cell populations, most notably within splenic and hepatic phagocytic cell populations, that accompany chronic infection with the intracellular bacterium Salmonella.