BMC Infectious Diseases最新文献

Background: Trichomoniasis caused by Trichomonas vaginalis is the most prevalent nonviral sexually transmitted disease in women and has frequently damaged public health. To better use the animal model and take a step forward fully elucidating this pathogen, intraperitoneal infection of T. vaginalis in mice, one of the most common mouse models, was highly concerned.

Methods: By adjusting the number of parasites inoculated, acute and chronic infection models were established. Pathological changes and the presence of T. vaginalis in organs were observed at different timepoints post inoculation using histological and TV-α-actinin-based immunological detection.

Results: The results reconfirmed the correlation between inoculum size of parasites and infection duration, as well as the multiplication capacity of T. vaginalis in mouse enterocoelia or invaded organs. The progression and pathologic features of vital organs (e.g., liver and spleen) from mice intraperitoneally infected with T. vaginalis in both the acute and chronic groups were also revealed. In particular, a reliable immunological method based on TV-α-actinin was first verified to clearly present the invasion of T. vaginalis into infected mouse organs.

Conclusions: In brief, this study presented a clearer and more detailed pathologic characteristic of the intraperitoneal infection model, which probably provides more basic information for the use of this model in future studies. Especially, expanding on specific research applications of this model would be valuable.

Background: Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability.

Methods: A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods.

Results: Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate.

Conclusions: This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Background: Francisella tularensis, the causative agent of tularemia, is a facultative intracellular bacterium. Although the life cycle of this bacterium inside phagocytic cells (e.g., macrophages, neutrophils) has been well analyzed, the difficulty of gene silencing and editing genes in phagocytic cells makes it difficult to analyze host factors important for the infection. On the other hand, epithelial cell lines, such as HeLa, have been established as cell lines that are easy to perform gene editing. However, the infection efficiency of Francisella into these epithelial cells is extremely low.

Methods: In order to facilitate the molecular biological analysis of Francisella infection using epithelial cells, we constructed an efficient infection model of F. tularensis subsp. novicida (F. novicida) in HeLa cells expressing mouse FcγRII (HeLa-FcγRII), and the system was applied to evaluate the role of host GLS1 on Francisella infection.

Results: As a result of colony forming unit count, HeLa-FcγRII cells uptake F. novicida in a serum-dependent manner and demonstrated an approximately 100-fold increase in intracellular bacterial infection compared to parental HeLa cells. Furthermore, taking advantage of the gene silencing capability of HeLa-FcγRII cells, we developed GLS1, a gene encoding glutaminase, knockdown cells using lentiviral sh RNA vector and assessed the impact of GLS1 on F. novicida infection. LDH assay revealed that GLS1-knockdown HeLa-FcγRII cells exhibited increased cytotoxicity during infection with F. novicida compared with control HeLa-FcγRII cells. Furthermore, the cell death was inhibited by the addition of ammonia, the metabolite produced through glutaminase activity. These results suggest that ammonia plays an important role in the proliferation of F. novicida.

Conclusions: In this report, we proposed a new cell-based infection system for Francisella infection using HeLa-FcγRII cells and demonstrated its effectiveness. This system has the potential to accelerate cell-based infection assays, such as large-scale genetic screening, and to provide new insights into Francisella infection in epithelial cells, which has been difficult to analyze in phagocytic cells.

Background: Visceral leishmaniasis (VL) remains a significant public health concern in West Pokot County, Kenya, where a large outbreak between 2020 and 2022 emphasised the need for improved VL control strategies. However, these measures are partially hampered by limited insight into the geographical distribution of cases and localised outbreaks of the disease. This study aimed to describe the epidemiology and spatiotemporal patterns of VL in West Pokot between 2018 and 2022, in order to map the spread of VL transmission and identify regions that should be prioritised for control interventions.

Methods: VL patient demographics and village of residence were retrieved from admission records of Kacheliba Sub-County Hospital in West Pokot, Kenya. The temporal trend in VL admissions between 2018 and 2022 was analysed using seasonal decomposition analysis. To describe the spatial distribution of VL cases, geographic coordinates of villages of residence were collected from pre-established databases, and VL incidence was mapped at the sub-location level. Hotspot analysis was performed per study year to identify villages with high VL incidence, and scan statistics were applied to detect spatiotemporal clusters of VL cases during the study period.

Results: A total of 1948 VL patients were reported between 2018 and 2022. The annual number of cases increased from 245 in 2019 to 598 in 2022, and VL admissions were generally higher at the start of the wet seasons. 70% of the VL cases could be georeferenced, and mapping of VL incidence revealed high case rates in the east of West Pokot during the complete study period. The eastern villages Lotongot and Chepaywat were marked as VL hotspots at a 99% confidence level in all study years. In addition, five significant spatiotemporal clusters were detected in the east and north, suggestive of local VL outbreaks in these regions.

Conclusions: The increase in VL hospital admissions during the study period stresses the need for enhanced VL control and outbreak mitigation in West Pokot. These control measures should be focused on the hotspot regions in the east of the county.

Background: The Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) (UNAIDS) aims to eradicate AIDS by 2030 through 95:95:95 targets: identifying 95% of persons living with HIV (PLHIV), initiating 95% of those identified on antiretroviral therapy (ART), and ensuring that 95% of those initiated on ART are virally suppressed. Virally suppressed patients pose minimal risk of HIV transmission. ART aims to suppress the HIV-viral load (VL) and increase immunity, reducing morbidity and mortality. This study aimed to determine the trends in VL suppression among HIV patients on ART from 2019 to 2023 at Asante Mampong Municipal Hospital.

Methods: This study adopted a retrospective Hospital-based design in which secondary data from 842 patients on ART from 2019 to 2023 were used. The study design specifically involved conducting serial cross-sectional studies to measure the prevalence of VL suppression each year from 2019 to 2023. This approach allowed the researchers to analyse the annual prevalence of VL suppression among study participants without following individual participants longitudinally throughout the entire period. The data were analysed via STATA version 17.0. Chi-square and logistic regressions were used to determine the associations between VL suppression and the independent variables at p < 0.05 and 95% confidence intervals (CIs).

Results: In 2019, VL suppression was 79.6%, decreasing to 40.0% in 2020 and then rising to 82.7% in 2021, dropping to 67.8% in 2022 and 66.7% in the first quarter of 2023. Clients aged 40-49, 50-59, and 60-69 years were more likely to have VL suppression [aOR = 4.4 (1.36-14.25), p = 0.013], [aOR = 5.5 (1.65-18.39), p = 0.006] and [aOR = 5.0 (1.42-17.46), p = 0.012], respectively. Clients who were consistently on the same type of ART for more than a year were more likely to have VL suppression [aOR = 10.6 (4.18-26.76), p < 0.001].

Conclusion: VL suppression was low among patients. Advanced age and being on the same ART for more than 12 months were significantly associated with VL suppression. Health promotion activities are needed for people who have been suppressed to maintain and achieve a lifetime undetectable VL, targeting the younger age group.

Background: Although several genetic biomarkers have been reported in the tocilizumab (TCZ) response in rheumatoid arthritis, no studies have addressed the pharmacogenomics effect of TCZ in COVID-19.

Methods: In this prospective longitudinal study, 95 individuals with severe COVID-19 were selected between 2020-2022. The recovery process was measured at 24 h, 48 h, and 10 days before and after taking TCZ. All participants were genotyped using RFLP-PCR. Different genotypes of FCGR2A rs1801274 and IL-6R rs2228145 were compared in terms of the recovery process.

Results: 43.2% of patients were male and 56.8% were female with an average age of 58.20(± 16.214) years. The GA genotype for FCGR2A rs1801274 increased the risk of death (OR = 2.83, P = 0.038) and ventilation (OR = 2.71, P = 0.047) in TCZ-treated individuals. However, there was no risk of death and ventilation with IL-6R rs2228145 (P > 0.05). Additionally, docking analysis showed that not only IL6R but also FCGR2A can be a ligand for TCZ.

Conclusion: This study provides valuable insights into the impact of genetic variations on the response rate of TCZ in COVID-19 patients. The GA genotype for FCGR2A rs1801274 was associated with poor treatment outcomes.

Background: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children.

Methods: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ² or Fisher's exact tests were used for group comparisons.

Results: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022).

Conclusion: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Background: Malaria remains a significant public health concern, especially for the deadliest parasite, Plasmodium falciparum. During acute malaria, various cytokines, including osteopontin (OPN), regulate the immune response. OPN has been shown to be protective against malaria in mice. Nonetheless, its precise function and potential ability to control parasites during acute malaria in humans remain poorly understood.

Results: Blood samples were collected from Swedish adults with imported malaria, Ugandan children and adults with symptomatic malaria (including follow-up after 42 days), Ugandans with non-malarial fever and healthy individuals from both Uganda and Sweden. Parasitemia was determined by microscopy. Malaria-negative samples were verified by LAMP. OPN and interferon-γ (IFN- γ) levels were measured using ELISA. In children, OPN levels were significantly higher during acute infection compared to levels after 42 days, whereas Ugandan adults showed no difference. Swedish adults with imported malaria had elevated OPN levels compared to both Swedish controls and Ugandan adults with malaria. Parasitemia was significantly correlated with both OPN and IFN-γ levels across the entire cohort. While a significant correlation between OPN and IFN-γ was evident overall, it remained statistically significant only in Ugandan adults when analyzed by subgroups. This suggests that OPN is not just a general marker of inflammation but may be regulated differently during the development of malaria immunity.

Conclusions: In acute malaria, elevated OPN levels showed a stronger correlation with lack of immunity than age. These findings underscore the potential importance of OPN in malaria, particularly in non-immune individuals.

Background: Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access.

Aim: To determine the prevalence of hrHPV genotypes and cervical lesions' burden in women from the indigenous and marginalized communities of Botswana.

Methods: This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68.

Results: In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia.

Conclusions: Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.