Building immunization decision-making capacity within the World Health Organization European Region

A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provides evidence-based recommendations to policy-makers, assisting them in making sound immunization policy and programme decisions. The World Health Organization (WHO) Regional Office for Europe is working to strengthen the capacity of newly-established NITAGs and has targeted efforts on low- and middle-income countries. The Regional Office, in collaboration with WHO Headquarters and USA Centers for Disease Control and Prevention (CDC), developed a new training strategy and held training workshops to improve NITAGs’ functioning and ability to make evidence-based recommendations. Feedback from countries that participated in trainings indicated that the updated training materials and interactive approach with follow-up technical support enabled them to align their NITAG charters and processes with WHO recommendations. To ensure continued progress, global and regional partners such as WHO and CDC should continue providing technical support to recently established NITAGs.     

Phage Display-directed Discovery of LEDGF/p75 Binding Cyclic Peptide Inhibitors of HIV Replication

The interaction between the human immunodeficiency virus (HIV) integrase (IN) and its cellular cofactor lens epithelium-derived growth factor (LEDGF/p75) is crucial for HIV replication. While recently discovered LEDGINs inhibit HIV-1 replication by occupying the LEDGF/p75 pocket in IN, it remained to be demonstrated whether LEDGF/p75 by itself can be targeted. By phage display we identified cyclic peptides (CPs) as the first LEDGF/p75 ligands that inhibit the LEDGF/p75–IN interaction. The CPs inhibit HIV replication in different cell lines without overt toxicity. In accord with the role of LEDGF/p75 in HIV integration and its inhibition by LEDGINs, CP64, and CP65 block HIV replication primarily by inhibiting the integration step. The CPs retained activity against HIV strains resistant to raltegravir or LEDGINs. Saturation transfer difference (STD) NMR showed residues in CP64 that strongly interact with LEDGF/p75 but not with HIV IN. Mutational analysis identified tryptophan as an important residue responsible for the activity of the peptides. Serial passaging of virus in the presence of CPs did not yield resistant strains. Our work provides proof-of-concept for direct targeting of LEDGF/p75 as novel therapeutic strategy and the CPs thereby serve as scaffold for future development of new HIV therapeutics.     

Proteases,actinidin, papain and trypsin reduce oral biofilm on the tongue in elderly subjects and in vitro

ObjectiveDental plaque is a causative factor for oral disease and a potential reservoir for respiratory infection in the elderly. Therefore, there is a critical need for the development of effective methods to remove oral biofilm. The objective of this study was to investigate the effect of proteases on oral biofilm formation andremoval.DesignThe in vivo effect of actinidin, a cysteine protease, on the removal of tongue coating was assessed after orally taking a protease tablet. Effects of the proteases trypsin, papain and actinidin on Actinomyces monospecies biofilm and multispecies biofilm that was reconstructed using a plaque sample from the tongue coating were investigated using the microtiter plate method. Antimicrobial tests and limited proteolysis of fimbrial shaft proteins were also performed to clarify underlying mechanisms of oral biofilm removal.ResultsTablets containing actinidin removed tongue coating in elderly subjects. Oral Actinomyces biofilm was significantly reduced by the proteases papain, actinidin and trypsin. Papain and trypsin effectively digested the major fimbrial proteins, FimP and FimA, from Actinomyces. Actinidin, papain and trypsin reduced multispecies biofilm that was reconstructed in vitro. Papain and trypsin inhibited formation of multispecies biofilm in vitro.ConclusionsThis study shows that proteases reduced oral biofilm in vivo in elderly subjects and in vitro, and suggests that protease digests fimbriae and inhibits biofilm formation.     

Enteric adenovirus epidemiology from historical fecal samples in Brazil (1998–2005): Pre-rotavirus vaccine era

Human adenovirus (HAdV) is recognized as frequent cause of acute gastroenteritis and enteric viruses can be preserved in frozen stored feces for long periods of times. The purpose of the present study was to investigate enteric HAdV genotypic diversity in archival fecal specimens stored from 1998 to 2005 in order to understand the natural history of HAdV in diarrheal patients in Brazil before rotavirus vaccine introduction. A total of 3346 specimens were tested for HAdV using conventional PCR. Genotypes were identified by sequencing. HAdV was detected in 6.8% (228/3346). Positivity was higher in children ≤ 5 years and males (p < 0.05). HAdV was most frequently observed during winter and spring seasons (p < 0.05). HAdV-F41 was the most prevalent genotype (59.2%;135/228), followed by HAdV-F40 (16.2%;37/228), HAdV-C1 (5.2%;12/228), HAdV-C2 (5.2%;12/228), HAdV-C5 (3.1%;7/228), HAdV-A12 (1.3%;3/228), HAdV-E4 (0.9%;2/228), HAdV-B3 (0.9%;2/228) and HAdV-B21 (0.4%;1/228). In 7.6% (17/228) only species D could be defined. HAdV-E4 strains were phylogenetic analyzed and classified as lineage (a)-like PG II. HAdV prevalence remained stable in Brazilian population, regardless rotavirus vaccine introduction. The predominant HAdV genotypes detected did not change over time, highlighting a high diversity of circulating strains in the country throughout decades. Due to the historical lack of HAdV genotyping surveillance in Brazil, HAdV-E4 epidemiology is virtually unknown in the country. The present study contributed significantly to the understanding of the natural history of HAdV in diarrheal patients in Brazil. The acquired data are important for clinical diagnosis, particularly for studies investigating enteric viruses' prevalence and molecular epidemiology of archival clinical specimens.