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Nature Communications May 2024Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that...
Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
Topics: Humans; Anti-Bacterial Agents; Neonatal Sepsis; Infant, Newborn; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Acinetobacter baumannii; Microbial Sensitivity Tests; Klebsiella pneumoniae; Amikacin; Fosfomycin; beta-Lactamases; Escherichia coli; Developing Countries; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Serratia marcescens; Enterobacter cloacae; Bacterial Proteins
PubMed: 38729951
DOI: 10.1038/s41467-024-48296-z -
Journal of Clinical Microbiology Jun 2024Herpes simplex virus (HSV) infections are one of the most common and stigmatized infections of humankind, affecting more than 4 billion people around the world and more... (Comparative Study)
Comparative Study
Herpes simplex virus (HSV) infections are one of the most common and stigmatized infections of humankind, affecting more than 4 billion people around the world and more than 100 million Americans. Yet, most people do not know their infection status, and antibody testing is not recommended, partly due to poor test performance. Here, we compared the test performance of the Roche Elecsys HSV-1 IgG and HSV-2 IgG, DiaSorin LIAISON HSV-1/2 IgG, and Bio-Rad BioPlex 2200 HSV-1 and HSV-2 IgG assays with the gold-standard HSV western blot in 1,994 persons, including 1,017 persons with PCR or culture-confirmed HSV-1 and/or HSV-2 infection. Across all samples, the Bio-Rad and Roche assays had similar performance metrics with low sensitivity (<85%) but high specificity (>97%) for detecting HSV-1 IgG and both high sensitivity (>97%) and high specificity (>98%) for detecting HSV-2 IgG. The DiaSorin assay had a higher sensitivity (92.1%) but much lower specificity (88.7%) for detecting HSV-1 IgG and comparatively poor sensitivity (94.5%) and specificity (94.2%) for detecting HSV-2 IgG. The DiaSorin assay performed poorly at low-positive index values with 60.9% of DiaSorin HSV-1 results and 20.8% of DiaSorin HSV-2 results with positive index values <3.0 yielding false positive results. Based on an estimated HSV-2 seroprevalence of 12% in the United States, positive predictive values for HSV-2 IgG were 96.1% for Roche, 87.4% for Bio-Rad, and 69.0% for DiaSorin, meaning nearly one of every three positive DiaSorin HSV-2 IgG results would be falsely positive. Further development in HSV antibody diagnostics is needed to provide appropriate patient care.IMPORTANCESerological screening for HSV infections is currently not recommended in part due to the poor performance metrics of widely used commercial HSV-1 and HSV-2 IgG assays. Here, we compare three Food and Drug Administration (FDA)-cleared automated HSV-1 and HSV-2 IgG assays to the gold-standard western blot across nearly 2,000 samples. We find that not all commercially available HSV assays are created equal, with comparably low sensitivities for HSV-1 IgG across platforms and high false positivity rates for DiaSorin on HSV-2 IgG. This study is the first large-scale comparison of performance metrics for the Bio-Rad and Roche assays in over 10 years. Our study confirms that there remains room for improvement in HSV serological diagnostic testing-especially in regard to low sensitivities for HSV-1 IgG detection-and highlights that some previously less-studied assays may have better performance metrics than previously considered typical of commercially available HSV-2 IgG assays.
Topics: Humans; Immunoglobulin G; Herpesvirus 1, Human; Herpesvirus 2, Human; Antibodies, Viral; Sensitivity and Specificity; Herpes Simplex; Male; Female; Adult; Middle Aged; Adolescent; Young Adult; Aged; Automation, Laboratory; Child; Aged, 80 and over; Immunoassay; Child, Preschool
PubMed: 38687020
DOI: 10.1128/jcm.00263-24 -
Journal of Korean Medical Science Apr 2024is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant at our institution, we...
BACKGROUND
is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in , with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and β-lactamase production.
METHODS
Among isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of β-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via gene sequencing.
RESULTS
Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant isolates, eighteen were non-typeable and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L.
CONCLUSION
The emergence of ceftriaxone-resistant with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in isolated from pediatric patients in Korea.
Topics: Ceftriaxone; Haemophilus influenzae; Humans; Anti-Bacterial Agents; Microbial Sensitivity Tests; Republic of Korea; beta-Lactamases; Child; Haemophilus Infections; Penicillin-Binding Proteins; Child, Preschool; Drug Resistance, Bacterial; Infant; Female; Male; Bacterial Proteins
PubMed: 38651222
DOI: 10.3346/jkms.2024.39.e136 -
Parasites & Vectors May 2024Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli....
BACKGROUND
Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known.
METHODS
The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection.
RESULTS
Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was -4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected.
CONCLUSIONS
Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated.
Topics: Animals; China; Rats; Mice; Phylogeny; Trypanosoma; Triatoma; RNA, Ribosomal, 18S; Insect Vectors; Trypanosomiasis; Feces; HSP70 Heat-Shock Proteins; DNA, Protozoan; Female; Male
PubMed: 38730303
DOI: 10.1186/s13071-024-06274-w -
Environmental Microbiology Reports Jun 2024Common carp (Cyprinus carpio) were fed food with different protein concentrations following different feeding regimes, which were previously shown to affect growth,...
Common carp (Cyprinus carpio) were fed food with different protein concentrations following different feeding regimes, which were previously shown to affect growth, nitrogen excretion and amino acid catabolism. 16S rRNA gene amplicon sequencing was performed to investigate the gut microbiota of these fish. Lower dietary protein content increased microbial richness, while the combination of demand feeding and dietary protein content affected the composition of the gut microbiota. Hepatic glutamate dehydrogenase (GDH) activity was correlated to the composition of the gut microbiota in all dietary treatments. We found that demand-fed carp fed a diet containing 39% protein had a significantly higher abundance of Beijerinckiaceae compared to other dietary groups. Network analysis identified this family and two Rhizobiales families as hubs in the microbial association network. In demand-fed carp, the microbial association network had significantly fewer connections than in batch-fed carp. In contrast to the large effects of the feeding regime and protein content of the food on growth and nitrogen metabolism, it had only limited effects on gut microbiota composition. However, correlations between gut microbiota composition and liver GDH activity showed that host physiology and gut microbiota are connected, which warrants functional studies into the role of the gut microbiota in fish physiology.
Topics: Animals; Carps; Gastrointestinal Microbiome; Animal Feed; RNA, Ribosomal, 16S; Dietary Proteins; Bacteria; Glutamate Dehydrogenase; Nitrogen; Liver; Phylogeny; Diet
PubMed: 38725141
DOI: 10.1111/1758-2229.13262 -
Viruses Jun 2024Bovine coronavirus (BCoV) poses a threat to cattle health worldwide, contributing to both respiratory and enteric diseases. However, few contemporary strains have been...
Bovine coronavirus (BCoV) poses a threat to cattle health worldwide, contributing to both respiratory and enteric diseases. However, few contemporary strains have been isolated. In this study, 71 samples (10 nasal and 61 fecal) were collected from one farm in Ohio in 2021 and three farms in Georgia in 2023. They were screened by BCoV-specific real-time reverse transcription-PCR, and 15 BCoV-positive samples were identified. Among them, five BCoV strains from fecal samples were isolated using human rectal tumor-18 (HRT-18) cells. The genomic sequences of five strains were obtained. The phylogenetic analysis illustrated that these new strains clustered with US BCoVs that have been detected since the 1990s. Sequence analyses of the spike proteins of four pairs of BCoVs, with each pair originally collected from the respiratory and enteric sites of one animal, revealed the potential amino acid residue patterns, such as D1180 for all four enteric BCoVs and G1180 for three of four respiratory BCoVs. This project provides new BCoV isolates and sequences and underscores the genetic diversity of BcoVs, the unknown mechanisms of disease types, and the necessity of sustained surveillance and research for BCoVs.
Topics: Cattle; Animals; Coronavirus, Bovine; Phylogeny; Feces; Cattle Diseases; Coronavirus Infections; Genome, Viral; Spike Glycoprotein, Coronavirus; Humans; Genetic Variation; Ohio
PubMed: 38932257
DOI: 10.3390/v16060965 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Aug 2023Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can... (Review)
Review
Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.
Topics: Humans; Autoantibodies; Female; Breast Neoplasms; Ovarian Neoplasms
PubMed: 37654151
DOI: 10.3881/j.issn.1000-503X.15320 -
Viruses May 2024(1) Background: Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease endemic in Africa, Asia, the Middle East, and the Balkan and Mediterranean...
(1) Background: Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease endemic in Africa, Asia, the Middle East, and the Balkan and Mediterranean regions of Europe. Although no human CCHF cases have been reported, based on vector presence, serological evidence among small vertebrates, and the general human population, Hungary lies within high evidence consensus for potential CCHF introduction and future human infection. Thus, the aim of our pilot serosurvey was to assess CCHF seropositivity among cattle and sheep as indicator animals for virus circulation in the country. (2) Methods: In total, 1905 serum samples taken from free-range cattle and sheep in 2017 were tested for the presence of anti-CCHF virus IgG antibodies using commercial ELISA and commercial and in-house immunofluorescent assays. (3) Results: We found a total of eleven reactive samples (0.58%) from five administrative districts of Hungary comprising 8 cattle and 3 sheep. The most affected regions were the south-central and northwestern parts of the country. (4) Conclusions: Based on these results, more extended surveillance is advised, especially in the affected areas, and there should be greater awareness among clinicians and other high-risk populations of the emerging threat of CCHF in Hungary and Central Europe.
Topics: Animals; Hemorrhagic Fever, Crimean; Sheep; Hungary; Cattle; Hemorrhagic Fever Virus, Crimean-Congo; Seroepidemiologic Studies; Antibodies, Viral; Livestock; Sheep Diseases; Cattle Diseases; Immunoglobulin G; Enzyme-Linked Immunosorbent Assay; Humans
PubMed: 38932166
DOI: 10.3390/v16060875 -
The Journal of General Virology May 2024High-throughput sequencing for uncultivated viruses has accelerated the understanding of global viral diversity and uncovered viral genomes substantially larger than any...
High-throughput sequencing for uncultivated viruses has accelerated the understanding of global viral diversity and uncovered viral genomes substantially larger than any that have so far been cultured. Notably, the Lak phages are an enigmatic group of viruses that present some of the largest known phage genomes identified in human and animal microbiomes, and are dissimilar to any cultivated viruses. Despite the wealth of viral diversity that exists within sequencing datasets, uncultivated viruses have rarely been used for taxonomic classification. We investigated the evolutionary relationships of 23 Lak phages and propose a taxonomy for their classification. Predicted protein analysis revealed the Lak phages formed a deeply branching monophyletic clade within the class which contained no other phage genomes. One of the interesting features of this clade is that all current members are characterised by an alternative genetic code. We propose the Lak phages belong to a new order, the 'Grandevirales'. Protein and nucleotide-based analyses support the creation of two families, three sub-families, and four genera within the order 'Grandevirales'. We anticipate that the proposed taxonomy of Lak megaphages will simplify the future classification of related viral genomes as they are uncovered. Continued efforts to classify divergent viruses are crucial to aid common analyses of viral genomes and metagenomes.
Topics: Genome, Viral; Bacteriophages; Phylogeny; High-Throughput Nucleotide Sequencing; Genetic Variation; Humans; Animals; Evolution, Molecular; Viral Proteins
PubMed: 38814706
DOI: 10.1099/jgv.0.001997 -
Journal of Obstetrics and Gynaecology :... Dec 2024The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the...
OBJECTIVE
The vaginal flora has been reported to be associated with human papillomavirus (HPV) infection. The purpose of this study was to investigate the characteristics of the cervical microbiota in patients with HPV infection and to analyse the changes in the vaginal flora and enzyme profiles in females with HPV infection.
METHODS
We conducted a cross-sectional study involving 206 participants who underwent HPV genotyping, sexually transmitted diseases pathogen testing, cytology examination, and microbiome analysis. Additionally, we collected 115 HPV-negative samples and 48 HPV-positive samples for 16S rRNA amplicon sequencing. The vaginal microbial communities of both groups were analysed for diversity and differences to explore their association with HPV infection.
RESULTS
The abundance of was found to be reduced, while was significantly more prevalent in the HPV + group. In terms of alpha diversity indices, the Shannon index ( = .0036) and Simpson index ( = .02) were higher in the HPV + group compared to the HPV - group, indicating greater community diversity in the HPV + group. Among the 10 sexually transmitted diseases pathogens analysed, Uup3 and Uup6 were significantly associated with HPV infection. Statistically significant differences were observed in Nugent scores and bacterial vaginosis between the two groups ( < .05). In functional analysis, 11 proteins and 13 enzymes were found to be significantly altered in the HPV + group.
CONCLUSION
Our study demonstrates that disruptions in the vaginal flora are associated with HPV infection. Reduced levels of , increased prevalence of , and abnormal enzyme profiles are closely linked to HPV infection.
Topics: Humans; Female; Papillomavirus Infections; Cross-Sectional Studies; Vagina; Adult; Microbiota; Lactobacillus; Gardnerella vaginalis; Vaginosis, Bacterial; Middle Aged; RNA, Ribosomal, 16S; Papillomaviridae; Young Adult; Cervix Uteri
PubMed: 38861397
DOI: 10.1080/01443615.2024.2361847