Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been ...intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
The spread of Plasmodium falciparum isolates carrying mutations in the kelch13 (Pfkelch13) gene associated with artemisinin resistance (PfART-R) in southeast Asia threatens malaria control and ...elimination efforts. Emergence of PfART-R in Africa would result in a major public health problem. In this systematic review, we investigate the frequency and spatial distribution of Pfkelch13 mutants in Africa, including mutants linked to PfART-R in southeast Asia. Seven databases were searched (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline, and Web of Science) for relevant articles about polymorphisms of the Pfkelch13 gene in Africa before January, 2019. Following PRISMA guidelines, 53 studies that sequenced the Pfkelch13 gene of 23 100 sample isolates in 41 sub-Saharan African countries were included. The Pfkelch13 sequence was highly polymorphic (292 alleles, including 255 in the Pfkelch13-propeller domain) but with mutations occurring at very low relative frequencies. Non-synonymous mutations were found in only 626 isolates (2·7%) from west, central, and east Africa. According to WHO, nine different mutations linked to PfART-R in southeast Asia (Phe446Ile, Cys469Tyr, Met476Ile, Arg515Lys, Ser522Cys, Pro553Leu, Val568Gly, Pro574Leu, and Ala675Val) were detected, mainly in east Africa. Several other Pfkelch13 mutations, such as those structurally similar to southeast Asia PfART-R mutations, were also identified, but their relevance for drug resistance is still unknown. This systematic review shows that Africa, thought to not have established PfART-R, reported resistance-related mutants in the past 5 years. Surveillance using PfART-R molecular markers can provide valuable decision-making information to sustain the effectiveness of artemisinin in Africa.
Helicobacter pylori is a bacterium that has infected more than half of the human population worldwide. This bacterium is closely associated with serious human diseases, such as gastric cancer, and ...identifying and understanding factors that predict bacterial virulence is a priority. In addition, this pathogen shows high genetic diversity and co-evolution with human hosts. H. pylori population genetics, therefore, has emerged as a tool to track human demographic history. As the number of genome sequences available is increasing, studies on the evolution and virulence of H. pylori are gaining momentum. This review article summarizes the most recent findings on H. pylori virulence factors and population genetics.
•Virulence factors are ever key points for H. pylori related pathogenesis.•The genetics of H. pylori prophage sequences bring interesting features.•New H. pylori populations will enounce the usefulness for tracing human migrations.
Background and Aim
To determine the application range of diagnostic kits utilizing anti‐Helicobacter pylori antibody, we tested a newly developed latex aggregation turbidity assay (latex) and a ...conventional enzyme‐linked immunosorbent assay (E‐plate), both containing Japanese H. pylori protein lysates as antigens, using sera from seven Asian countries.
Methods
Serum samples (1797) were obtained, and standard H. pylori infection status and atrophy status were determined by culture and histology (immunohistochemistry) using gastric biopsy samples from the same individuals. The two tests (enzyme‐linked immunosorbent assay and latex) were applied, and receiver operating characteristics analysis was performed.
Results
Area under the curve (AUC) from the receiver operating characteristic of E‐plate and latex curves were almost the same and the highest in Vietnam. The latex AUC was slightly lower than the E‐plate AUC in other countries, and the difference became statistically significant in Myanmar and then Bangladesh as the lowest. To consider past infection cases, atrophy was additionally evaluated. Most of the AUCs decreased using this atrophy‐evaluated status; however, the difference between the two kits was not significant in each country, but the latex AUC was better using all samples. Practical cut‐off values were 3.0 U/mL in the E‐test and 3.5 U/mL in the latex test, to avoid missing gastric cancer patients to the greatest extent possible.
Conclusions
The kits were applicable in all countries, but new kits using regional H. pylori strains are recommended for Myanmar and Bangladesh. Use of a cut‐off value lower than the best cut‐off value is essential for screening gastric cancer patients.
Abstract
Background
Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody ...maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated.
Methods
Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity.
Results
Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 interquartile range 28.4–45.1 vs 64.9 57.5–71.5, P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 wild-type; 0.18–0.52 vs 0.48–0.83 variants). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 Alpha; P < .01 Delta and Omicron). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25.
Conclusions
Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.
Avidity maturation augments host immunity following a natural infection and/or vaccination. For protection against SARS-CoV-2, avidity maturation was progressive beyond acute recovery from infection or became apparent after the booster vaccine dose, and granted broader neutralizing capacity against variant strains.
More people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the level of protection granted by 'hybrid immunity', the combined response of infection- and ...vaccine-induced immunity, may impact vaccination strategies through tailored dosing. A total of 36 infected ('prior infection') and 33 SARS-CoV-2 'naïve' individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and the receptor binding domain-ACE2 binding inhibition assays. The relationships between antibody titer, groups and age were explored. Anti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the 'prior infection' group. Semi-log regression models showed that participants with 'prior infection' demonstrated higher antibody titer compared with the 'naïve' even after adjusting for age. The enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the 'prior infection' group showed higher inhibition capacity against all six analyzed strains, including the Omicron variant. Prior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. While still pending any modifications of dosing recommendations (i.e. reduced doses for individuals with prior infection), our observation adds to the series of real-world data demonstrating the enhanced and more durable immune response evoked by booster vaccinations following prior infection.
Helicobacter pylori is involved in the etiology and severity of several gastroduodenal diseases; however, plasticity of the H. pylori genome makes complete genome assembly difficult. We report here ...the full genomes of H. pylori strains CHC155 and VN1291 isolated from a non-cardia gastric cancer patient and a duodenal ulcer patient, respectively, and their virulence demonstrated by in vitro infection. Whole-genome sequences were obtained by combining long- and short-reads with a hybrid-assembly approach. Both CHC155 and VN1291 genome possessed four kinds of genomic island: a cag pathogenicity island (cagPAI), two type 4 secretion system islands within an integrative and conjugative element (tfs ICE), and prophage. CHC155 and VN1291 carried East Asian-type cagA and vacA s1m1, and outer membrane protein genes, including two copies of oipA. Corresponded to genetic determinants of antibiotic resistance, chromosomal mutations were identified in CHC155 (rdxA, gyrA, and 23S rRNA) and VN1291 (rdxA, 23S rRNA, and pbp1A). In vitro infection of AGS cells by both strains induced the cell scattering phenotype, tyrosine phosphorylation of CagA, and promoted high levels of IL8 secretion, indicating fully intact phenotypes of the cagPAI. Virulence genes in CHC155 and VN1291 genomes are crucial for H. pylori pathogenesis and are risk factors in the development of gastric cancer and duodenal ulcer. Our in vitro studies indicate that the strains CHC155 and VN1291 carry the pathogenic potential.
Adults infected with Plasmodium spp. in endemic areas need to be re-evaluated in light of global malaria elimination goals. They potentially undermine malaria interventions but remain an overlooked ...aspect of public health strategies.
This study aimed to estimate the prevalence of Plasmodium spp. infections, to identify underlying parasite species, and to assess predicting factors among adults residing in an endemic area from the Democratic Republic of Congo (DRC). A community-based cross-sectional survey in subjects aged 18 years and above was therefore carried out. Study participants were interviewed using a standard questionnaire and tested for Plasmodium spp. using a rapid diagnostic test and a nested polymerase chain reaction assay. Logistic regression models were fitted to assess the effect of potential predictive factors for infections with different Plasmodium spp.
Overall, 420 adults with an estimated prevalence of Plasmodium spp. infections of 60.2% 95% CI 55.5; 64.8 were included. Non-falciparum species infected 26.2% 95% CI 22.2; 30.5 of the study population. Among infected participants, three parasite species were identified, including Plasmodium falciparum (88.5%), Plasmodium malariae (39.9%), and Plasmodium ovale (7.5%) but no Plasmodium vivax. Mixed species accounted for 42.3% of infections while single-species infections predominated with P. falciparum (56.5%) among infected participants. All infected participants were asymptomatic at the time of the survey. Adults belonging to the "most economically disadvantaged" households had increased risks of infections with any Plasmodium spp. (adjusted odds ratio, aOR = 2.87 95% CI 1.66, 20.07; p < 0.001), compared to those from the "less economically disadvantaged" households. Conversely, each 1 year increase in age reduced the risk of infections with any Plasmodium spp. (aOR = 0.99 95% CI 0.97, 0.99; p = 0.048). Specifically for non-falciparum spp., males had increased risks of infection than females (aOR = 1.83 95% CI 1.13, 2.96; p = 0.014).
Adults infected with malaria constitute a potentially important latent reservoir for the transmission of the disease in the study setting. They should specifically be taken into account in public health measures and translational research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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