Tropical Medicine &International Health, EarlyView.

Latent tuberculosis infectionQuantiFERONT-SOPT.TBpretransplant evaluationsolid organ transplantation…

Abstract Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

by Marco Carbonara, Erica Ferrari, Tatiana Birg, Veronica Punzi, Francesca Bichi, Beatrice Lazzari, Valentina Palmaverdi, Nicola Bottino, Fabrizio Ortolano, Tommaso Zoerle, Giorgio Conte, Nino Stocchetti, Elisa R. Zanier, The UOC Terapia Intensiva Presidio Temporaneo Fiera Milano Investigators group …

by Frederick Obeng-Boateng, Stephen Wilson Kpordze, Francis Addy Medical professionals continue to face a severe issue with the evolution of resistance to conventional antibiotics. The search for new novel compounds from plants has been proven to be the alternative solution. Morinda citrifolia is used traditionally for the treatment of infectious diseases. The present study investigates the antibacterial properties of M. citrifolia root, leaf, and fruit (fresh, dried, and fermented) extracts on three-gram-positive and five-gram-negative bacteria. The plant parts were processed and extracted in distilled water and ethanol (60%, 80%, and absolute (100%)). The antibacterial activities of the extracts were assessed in vitro using the agar well diffusion method, with Ciprofloxacin serving as the positive control. All the tests were conducted three times to obtain the average value of inhibition zones. Overall, root extracts showed the most significant antibacterial activity, followed by dried fruit, fermented fruit extract, fresh fruit, and the least leaf extract. Using one-way ANOVA and Tukey’s post-hoc tests, the statistical analysis revealed significant differences in antibacterial activity among the extracts and solvent concentrations. The 100% ethanol extracts had significantly higher zones of inhibition compared to the other solvents. The most inhibitory activity was against Campylobacter spp. (21.33±1.80) for the 80% ethanol root extract. All the extracts of M. citrifolia were found to exhibit moderate antibacterial activity against all the bacteria pathogens. However, Enterococcus faecium, Campylobacter spp., and Bacillus cereus were most sensitive to all the plant extracts while Shigella spp. and Klebsiella spp. showed resistance to most extracts. This observed difference is significant for each strain extract depending on the bacteria strain and the type of solvent extract (p < 0.001). The findings indicate a promising antimicrobial potential of M. citrifolia extracts.

by Chen Gao, Binni Yang, Yurong Li, Wenjuan Pei Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment.

by LaReine Yeoh, Luke Cogar, Mayes Barak, Lit Yeen Tan, Gavin Spargo, Jon Burdach Medical devices that contact non-intact skin or mucous membranes are considered semi-critical devices and must undergo high-level disinfection (HLD) before use. Studies have identified several potential limitations of UV-C for HLD of semi-critical medical devices, including a lack of data demonstrating that UV-C irradiance can be uniformly applied to complex surfaces that contain grooves, notches and imperfections. This study focused on ultrasound probes as commonly used medical devices to show the distribution of irradiance on these surfaces. An endocavity bi-plane probe and curved array surface probe with typical surface topology were 3D scanned and modelled and an array of UV-C light-emitting diodes (LEDs) irradiating the probe surfaces was simulated (simulated wavelength: 275nm [peak], power output: 50mW). The simulated chamber wall material was equivalent to highly reflective polished aluminum with a defined reflectance of 79% at 275nm. To calculate the cycle time required to achieve HLD on probe surfaces, a minimum effective dosage of 1500mJ/cm2 based on published research was used. The simulated irradiance distribution showed a large difference between the points of highest and lowest irradiance (maximum/minimum ratio: 14.70 for the surface probe and 12.74 for the endocavity probe). In addition, the presence of shadowing effects adjacent to notches or grooves was evident. By applying an effective UV-C dose from the literature, cycle times of up to 25 minutes would be required to achieve HLD in the minimally irradiated areas of the probes used in the simulation. These findings highlight the need to demonstrate the efficacy of UV-C radiation against worst case organisms in the areas of lowest irradiance on medical devices to provide assurance these devices are reliably high level disinfected.

by Motoki Imai, Fumitaka Kawakami, Takayuki Uematsu, Toshihide Matsumoto, Rei Kawashima, Yoshifumi Kurosaki, Shun Tamaki, Shotaro Maehana, Takafumi Ichikawa, Hideaki Hanaki, Hidero Kitazato, Makoto Kubo COVID-19, an infectious disease caused by SARS-CoV-2, was declared a pandemic by the WHO in 2020. Psychiatric symptoms including sleep disturbance, memory impairment, and depression are associated with SARS-CoV-2 infection. These symptoms are causes long-term mental and physical distress in recovering patients; however, the underlying mechanism is unclear. In this study, we determined the effects of SARS-CoV-2 infection on brain tissue using k18hACE2 mice. Using brain tissue from 18hACE2 mice infected with SARS-CoV-2 through intranasal administration, SARS-CoV-2 spike protein and RNA were analyzed by immunohistochemical staining and in-situ hybridization. Immunohistochemical analysis revealed that Tryptophan hydroxylase 2 (TPH2)-positive cells and SARS-CoV-2 spike protein were co-localized in the ventral tegmental area of SARS-CoV-2-infected mice. We observed decreased TPH2 expression and increased accumulation of phosphorylated tau protein and Phospho-Histone H2A.X (γH2AX) expression in the ventral tegmental region. In addition, activation of glycogen synthase kinase 3β (GSK3β) was induced by SARS-CoV-2 infection. Overall, our results suggest that SARS-CoV-2 infection of TPH2-positive cells in the ventral tegmental area induces neuronal cell death through increased accumulation of phosphorylated tau. Attenuation of the GSK3β pathway and decreased serotonin synthesis through suppression of TPH2 expression may contribute to the development of neurological symptoms.

by Shuo Liu, Jianwei Ren, Jiyuan Li, Detao Yu, Hang Xu, Fang He, Nianfeng Li, Ling Zou, Zhi Cao, Jianxin Wen This study aimed to comprehensively characterize the gut microbiota in diarrheal mink. We conducted Shotgun metagenomic sequencing on samples from five groups of diarrheal mink and five groups of healthy mink. The microbiota α-diversity and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology did not show significant differences between the groups. However, significant differences were observed in microbiota β-diversity and the function of carbohydrate-active enzymes (CAZymes) between diarrheal and healthy mink. Specifically, The relative abundance of Firmicutes was lower, whereas that of Bacteroidetes was higher in diarrheal mink. Fusobacteria were enriched as invasive bacteria in the gut of diarrheal mink compared with healthy mink. In addition, Escherichia albertii was identified as a new bacterium in diarrheal mink. Regarding functions, nicotinate and nicotinamide metabolism and glycoside hydrolases 2 (GH2) family were the enhanced KEGG orthology and CAZymes in diarrheal mink. Furthermore, the diversity and number of antibiotic-resistant genes were significantly higher in the diarrheal mink group than in the healthy group. These findings enhance our understanding of the gut microbiota of adult mink and may lead to new approaches to the diagnosis and treatment of mink diarrhea.

by Essra Youssef, Anna Calvert, Vanessa Greening, Dominique Pearce, Suzannah Wright, Emma Eccleston, Lolade Oshodi, Paul Heath, Tushna Vandrevala Background Vaccination during pregnancy is an important healthcare intervention for safeguarding the health of the mother and their infants. Ethnic disparities in recruitment to vaccine research studies during pregnancy potentially contribute to health inequalities. The aim of the current study was to explore the barriers and enablers influencing the willingness of pregnant women from ethnic minority backgrounds to participate in vaccine research studies. Methods and findings Semi-structured qualitative online interviews were conducted with 23 pregnant women from diverse ethnic backgrounds in the UK. Interviews were transcribed verbatim, and thematically analysed. Our findings suggest that participants perceived vaccines and vaccine research, in principle, to be beneficial to the individual and to society, and understood the value of vaccination in mitigating severity of disease and protecting the health of mothers and their infants. Apprehension over the safety of vaccination in pregnancy was common and reduced willingness to participate. For those that decided to participate in vaccine trials in pregnancy, this was seen as an act of solidarity, a way to contribute to a collective responsibility for the public health of the community. Personal and community connections and representation—seeing people from their own communities represented in in the recruitment process shapped decisions about vaccine trial participating. Trust and mistrust in health systems, shaped by past experiences of interacting with healthcare professionals were likely to inform whether they would consider participating. Practical considerations such as excessive time commitments related to study procedures, travel and organising childcare were barrier to participation. The level of invasiveness of trial procedures were also a concern, although increased monitoring during the trial was seen as a potential benefit, mitigating some safety concerns. Conclusions Our study reinforcing previously identified barriers to vaccine participation among pregnant women from diverse ethnic communities. This study underlines the need to develop tailored interventions that focus on fostering trust with the aid of community engagement to understand cultural contexts, establishing authentic representation, and address practical considerations, to contribute to enhancing vaccine trial participation in pregnancy in those from diverse ethnic communities. …

by Kelly W. Gagnon, Kaylee Burgan, Morgan Mulrain, Stefan Baral, Karen Cropsey, Michael Mugavero, Ellen Eaton People living with HIV are disproportionately affected by depression, anxiety, and substance use which impede engagement with HIV treatment services and can increase risks of HIV-related morbidity and mortality. Capturing timely, accurate patient data at point of care is recommended to inform clinical decision-making and retain patients on the HIV care continuum. Currently, there is limited use of validated screening tools for substance use and mental health at the point of care in HIV clinics, even though people with HIV (PWH) have a high prevalence of these comorbidities. Even fewer clinics screen in a manner that encourages disclosure of stigmatized substance use, depression, and anxiety. Electronic patient-reported outcomes (ePROs) are an evidence-based modality to overcome such limitations by eliciting responses directly from patients via tablet, smartphone, or computer. To date, there is limited consensus on how to implement ePROs into non-academic settings and enhance uptake. Our team sought to address this gap by examining the implementation of ePROs, previously implemented in an academic clinic, to enhance screening and treatment of mental health (MH) and substance use at five Ryan White HIV/AIDS Program-funded clinics in Alabama. The ePROs were delivered through a multi-component intervention titled HIV + Service delivery and Telemedicine through Effective Patient Reported Outcomes (+STEP), which also provides targeted training to frontline clinicians, and resources for MH and substance use treatment for PWH without access to care. The objective of this study is to provide an implementation blueprint that can be tested and utilized in other HIV clinics to integrate ePROs and increase evidence-based screening for depression, anxiety, and substance use among PWH, as well as outline lessons learned from implementation to date. The findings from this study provide practical steps and advice based on our experience in implementing electronic patient-reported outcomes in HIV clinics in the US Deep South.

by Lea Duesterwald, Marcus Nguyen, Paul Christensen, S. Wesley Long, Randall J. Olsen, James M. Musser, James J. Davis Over the last four years, each successive wave of the COVID-19 pandemic has been caused by variants with mutations that improve the transmissibility of the virus. Despite this, we still lack tools for predicting clinically important features of the virus. In this study, we show that it is possible to predict the PCR cycle threshold (Ct) values from clinical detection assays using sequence data. Ct values often correspond with patient viral load and the epidemiological trajectory of the pandemic. Using a collection of 36,335 high quality genomes, we built models from SARS-CoV-2 intrahost single nucleotide variant (iSNV) data, computing XGBoost models from the frequencies of A, T, G, C, insertions, and deletions at each position relative to the Wuhan-Hu-1 reference genome. Our best model had an R2 of 0.604 [0.593–0.616, 95% confidence interval] and a Root Mean Square Error (RMSE) of 5.247 [5.156–5.337], demonstrating modest predictive power. Overall, we show that the results are stable relative to an external holdout set of genomes selected from SRA and are robust to patient status and the detection instruments that were used. This study highlights the importance of developing modeling strategies that can be applied to publicly available genome sequence data for use in disease prevention and control.

by Samia S. Alkhalil, Taghreed N. Almanaa, Raghad A. Altamimi, Mohnad Abdalla, Amr Ahmed El-Arabey Microorganisms in the gut and other niches may contribute to carcinogenesis while also altering cancer immune surveillance and therapeutic response. However, determining the impact of genetic variations and interplay with intestinal microbes’ environment is difficult and unanswered. Here, we examined the frequency of thirteen mutant genes that caused aberrant gut in thirty different types of cancer using The Cancer Genomic Atlas (TCGA) database. Substantially, our findings show that all these mutated genes are quite frequent in uterine corpus endometrial cancer (UCEC). Further, these mutant genes are implicated in the infiltration of different subset of immune cells within the Tumor Microenvironment (TME) of UCEC patients. The top-ranking mutant genes that promote immune cell invasion into the TME of UCEC patients were PGLYRP2, OLFM4, and TLR5. In this regard, we used the same deconvolution of the TCGA database to analyze the microbiome that have a strong association with immune cells invasion with TME of UCEC patients. Several bacteria and viruses have been linked to the invasion of immune cells, such as B cell memory and T cell regulatory (Tregs), into the TME of UCEC patients. As a result, our findings pave the way for future research into generating novel immunizations against bacteria or viruses as immunotherapy for UCEC patients.

by Andrea K. Knittel, Gabriel Varela, Ella G. Ferguson, Hannah Hulshult, Jamie B. Jackson, James Moody, Adaora A. Adimora Background Many cisgender women in the US who have experienced incarceration are at substantial risk for HIV acquisition after they return to the community. Various network interventions have been leveraged for HIV prevention in this population. The objective of this study was to identify network and relationship determinants of influence on HIV prevention decisions, including PrEP. Methods We conducted interviews with a network mapping exercise with participants recruited from the social and sexual networks of women who had experienced incarceration. Participants enumerated important individuals in their lives from the past six months and provided demographic and relationship data as well as whether each relationship influenced their HIV prevention decisions. We abstracted network data from the interview transcripts and described the data set using descriptive statistics and network density graphs. To measure associations between characteristics at each level and whether a relationship was considered influential regarding PrEP decision-making, we use multiple logistic regression with random intercepts for each respondent. Results We interviewed 32 participants, average age 33.5 years (SD = 8.98), majority female (n = 28, 87.5%), white (n = 23, 71.8%), heterosexual/straight (n = 25, 78.1%), and with a personal history of incarceration (n = 29, 90%). They reported 253 relationships (119 family, 116 friend, 18 sexual relationships). Most adult network members had used drugs or alcohol (n = 182, 80.9%), and of those, 30.8% had used them with the participant (n = 53). The mean network size was 7 (SD = 4) and network density was 52.2%. In the full model, significant positive predictors of an influential relationship included participant non-heterosexual identity (OR 27.8), older average age in the network (OR 3.9 per standard deviation), and being a current or prior sexual partner (OR 10.1). Significant negative predictors included relationships with individuals who use or had used drugs (OR 0.28), longer average relationship duration in the network (OR 0.09) and being in a network with at least one sexual partner (OR 0.2). Conclusions There are significant positive and negative determinants of relationship influence related to PrEP at individual-, dyad-, relationship-, and network-levels. These support using nuanced network approaches to behavior change that respect and leverage the diversity of relationships that comprise the social networks of women who have experienced incarceration. …

by Xinghuang Liu, Bayasgalan Luvsandagva, Dongke Wang, Siran Zhu, Zhiyue Xu, Dan Zhou, Xiaotian Xie, Wei Qian, Xiaohua Hou, Tao Bai Objective This study focused on the gastrointestinal (GI) symptoms in the omicron variant infection and the related factors based on digestive health. Methods A cross-sectional study was conducted on individuals infected with the omicron variant. A structured questionnaire was developed to gather their demographic characteristics, preexisting digestive problems (diseases & symptoms), and clinical manifestations during the infection. Results 11,484 questionnaires were received from online platforms. 7,929 infected participants were selected based on inclusion and exclusion criteria. Among them, 4,225 (53.3%) were females, and the mean age was 36.0±8.8 years old. In general, the proportion of GI symptoms in the omicron variant infection was 31.4% (62.6% and 25.0% in participants with pre-existing digestive problems and those without, respectively). The participants with pre-existing digestive problems exhibited more severe clinical manifestations during infection compared to those without. Notably, participants with gastrointestinal symptoms during the infection had more severe clinical manifestations, regardless of basic digestive health. Upper, rather than lower GI symptoms were more closely associated with the severity of the clinical manifestations. NSAIDs may increase the occurrence of GI symptoms in participants with a healthy digestive system but not in those with preexisting digestive problems. Conclusion Patients infected with the omicron variant may experience more severe clinical symptoms if they have gastrointestinal issues. Digestive health strongly influences the occurrence of gastrointestinal symptoms and the severity of clinical manifestations. …

by Swagatika Panda, Lipsa Rout, Neeta Mohanty, Anurag Satpathy, Bhabani Sankar Satapathy, Shakti Rath, Divya Gopinath Background Streptococcus mutans is a major contributor to dental caries due to its ability to produce acid and survive in biofilms. Microbial resistance towards common antimicrobial agents like chlorhexidine and triclosan has shifted the research towards antimicrobial Photodynamic therapy (PDT). In this context, Toluidine Blue O (TBO) is being explored for its photosensitizing properties against Streptococcus mutans. There is a huge variation in the effective concentration of TBO among the current studies owing to the differences in source of and delivery system TBO as well as the time, power and energy densities of light. Objective The primary objectives of this study are to encapsulate improved Toluidine Blue O (ITBO) in nanoliposomes (NLITBO), characterize it, and evaluate its antibacterial photosensitizing potential against Streptococcus mutans suspensions in vitro. Method ITBO was synthesised as per Indian patent (number -543908). NLITBO was prepared using the thin-film hydration method. Dynamic light scattering experiment determined the vesicle size, polydispersity index (PDI), and zeta potential. Surface features were characterized by Scanning and Transmission Electron microscopy. ITBO release from NLITBO was assessed using the extrapolation method. The antibacterial activity of the NLITBO was determined by evaluating the zone of inhibition (ZOI) in the Streptococcus mutans culture and comparing with 2% chlorhexidine gluconate. The minimum inhibitory concentration (MIC) of NLITBO as a photosensitizer with red light (wavelength 650nm, power density 0.1 W/cm2, energy density 9–9.1 J/ cm2, 90seconds time) was evaluated against Streptococcus mutans cells by colorimetric method in 96 well plate. Results Percentage drug loading, loading efficiency, yield percentage, vesicle size, PDI, Zeta potential of NLTBO was reported as 9.3±0.4%, 84.4±7.6%, 73.5%, 123.52 nm, 0.57, -39.54mV respectively. Clusters of uni-lamellar nanovesicles with smooth non-perforated surfaces were observed in SEM and TEM. The size of the vesicle was within 100 nm. At 24 hours, a cumulative 79.81% of ITBO was released from NLITBO. Mean ZOI and MIC of NLITBO (1 μg /ml) were found to be 0.7±0.2 mm, 0.6μg/ml respectively. Conclusion We have synthesized and encapsulated improved Toluidine Blue O (ITBO) in nanoliposomes (NLITBO) and thoroughly characterized the formulation. The antibacterial efficacy of NLITBO without light was demonstrated by ZOI which is similar to 2% chlorhexidine gluconate. MIC of NLITBO as a photosensitiser along with the optimal light parameter was also proposed in this study. These findings suggested that NLITBO could serve as an effective alternative to conventional antibacterial treatments in managing Streptococcus mutans rich biofilms. It can have potential pharmaceutical application in oral health care. …

Abstract Background Reports on the impact of COVID-19 pandemic on the quality of malaria care and burden in sub Saharan Africa have provided a mixed picture to date. The impact of the 2nd (Delta) and 3rd (Omicron) COVID-19 waves on outpatient malaria indicators and case management practices was assessed at three public health facilities with varying malaria transmission intensities in Uganda. Methods Individual level data from all patients presenting to the out-patient departments (OPD) of the three facilities (Kasambya, Walukuba and Lumino) between January 2019 and February 2022 were included in the analysis. Outcomes of interest included total number of outpatient (OPD) visits, proportion of patients suspected to have malaria, proportion of suspected malaria cases tested with a malaria diagnostic test, test positivity rates (TPR) and proportion of malaria cases prescribed artemether-lumefantrine (AL). Using the pre-COVID-19 trends between January 2019 and February 2020, interrupted time series analysis was used to predict the expected trends for these study outcomes during the 2nd wave (May 2021–August 2021) and 3rd wave (November 2021–February 2022). The observed trends of the study outcomes were compared with the expected trends. Results There were no significant differences between the observed versus expected overall outpatient visits in the 2nd wave, however, a significant decline in OPD attendance was observed during the 3rd wave (15,101 vs 31,154; incidence rate ratio (IRR) = 0.48 [0.41–0.56]). No significant differences in the overall observed versus expected proportions of suspected malaria cases and test positivity rates in both COVID waves. However, a significant decrease in the overall proportion of suspected malaria cases tested with a malaria diagnostic test was observed during the 3rd wave (99.86% vs 99.99%; relative percent ratio [RPR] = 0.99 [0.99–0.99]). Finally, a significant decline in the overall proportion of malaria cases prescribed AL was observed during the 2nd wave (94.99% vs 99.85%; RPR = 0.95 [0.92–0.98]) but not the 3rd wave. Conclusion Significant declines in OPD attendance and suspected malaria cases tested with malaria diagnostic test were observed during the 3rd COVID-19 wave, while AL prescription significantly reduced during the 2nd COVID-19 wave. These findings add to the body of knowledge highlighting the adverse impact of COVID-19 pandemic on the malaria which could explain the increase in the malaria burden observed during this period. …

Abstract Background The use of insecticide-treated nets (ITNs) is a strategy recommended by the World Health Organization (WHO) for malaria prevention. In Nigeria, ITNs have been periodically distributed since 2007 through campaigns. Campaign activities and assets are typically tracked using either a paper-based or digital system. In 2017, a digital approach was introduced in Ondo state for tracking attendance at training sessions as part of the ITN campaign. Following the success of the 2017 introduction, subsequent campaigns planned to digitise other aspects of the campaign to improve accountability and efficiency of the ITN distribution. The COVID-19 pandemic posed additional challenges for the ITN distribution planned for 2021 and adaptations were made to the programme strategy to ensure the campaign could go ahead safely. This article presents lessons and experiences from the 2021 ITN distribution campaign in Ondo state, Nigeria. Methods The campaign used RedRose, a customised mobile application, to monitor the planning and delivery of the campaign, collect household information including training personnel and tracking the transfer of ITNs between distribution hubs and households. ITNs were delivered through a single-phase door-to-door distribution strategy. Results The campaign distributed 2,965,125 ITNs covering 1,057,577 households across Ondo state. The digital application was beneficial for monitoring the quality of implementation and tracking assets and staff to ensure safety.. The single-phase door-to-door approach was more convenient for households compared to fixed-point distribution but increased the workload for mobilization and distribution teams. Conclusions Single phase door-to-door strategy using digital tools was an effective method to increase coverage of ITNs while closely tracking the progress of distribution campaigns. High-quality population data are needed to further improve the planning and implementation of ITN campaigns and other health interventions. …

Abstract Purpose C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Methods Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150 h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Results Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4 mg/L in viral infections without antibiotics to 140.9 mg/L in Gram-negative bacteremia with antibiotics. Conclusions CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 11, November 2024.

Staphylococcus aureus is an important pathogen in many sites, including bloodstream, skin and soft tissue, bone and joints. When infection is caused by methicillin resistant S. aureus (MRSA) therapy is more difficult and outcomes are less favorable. Nasal colonization is associated with increased risk for MRSA infections. The nasal microbiome may play a role in risk for nasal colonization and infection.

Abstract Background Staphylococcus aureus clinical isolates with vancomycin MICs of 2 µg/ml have been associated with vancomycin therapeutic failure and the heterogenous vancomycin-intermediate S. aureus (hVISA) phenotype. While carriage of van genes has usually been associated with higher level of MIC and frank vancomycin resistance, the unrecognized risk of hetero-resistance is frequently underestimated. Methods used for assessing vancomycin susceptibility have also shown different concordance and variable performance and accessibility in routine clinical diagnostics posing a challenge to inform treatment selection in hospital settings. Methods A total of 195 clinical samples were obtained among which 100 S. aureus isolates were identified. Ninety-six MRSA isolates have been identified using cefoxitin disc and mecA gene detection. The vanA and vanB genes have been screened for in the studied isolates using conventional PCR amplification. Examination of reduced vancomycin susceptibility has been performed using vancomycin screen agar, Broth Micro Dilution method (BMD), and VITEK2. Blood isolates were screened for hVISA using PAP-AUC method. Results Vancomycin screening agar applied to 96 MRSA isolates revealed 16 isolates with reduced vancomycin susceptibility. Further MIC testing revealed that 7 isolates were VISA and only 1 isolate was identified as VRSA using both BMD MIC method and VITEK2. Among 24 tested blood isolates, 4 isolates (16.7%) revealed the hVISA phenotype as identified using PAP-AUC method. Using PCR, vanA gene was identified in 5 S. aureus isolates (5%). Three of them were VSSA while the other two isolates were VISA. Conclusion In this study, we report the very low prevalence of VRSA among the tested S. aureus clinical isolates (1%) and the existence of hVISA phenotype among studied S. aureus blood isolates at the rate of 16.7% in our setting. Fifty percent (8/16) of isolates that demonstrated reduced vancomycin susceptibility using vancomycin agar screen tested susceptible using both broth dilution method and VITEK2. These finding together with the concerning silent carriage of vanA gene among VSSA and VISA (5%) may underly hidden and uninvestigated factors contributing to vancomycin treatment failure that warrant cautious vancomycin prescription. …

Abstract Background Shigellosis continues to pose a significant public health problem in Africa; however, there is a lack of comprehensive knowledge regarding its prevalence, serogroup distribution, and antimicrobial resistance profiles. Therefore, the objective of this systematic review and meta-analysis was to determine the overall prevalence of Shigella, the distribution of species, and the patterns of antimicrobial resistance across Africa. Methods Following PRISMA guidelines, a systematic search strategy was conducted using the PubMed, Web of Science and Scopus databases from January 31, 2024 to February 10, 2024. The study quality was assessed using the Joanna Briggs Institute checklist, and data were analyzed using the R statistical language and the R package ‘meta’. The random effects model was employed to estimate the pooled prevalence, while heterogeneity was assessed using the I2 statistic and prediction interval. Results A total of 116 studies from 29 African countries were included in this meta-analysis, involving the examination of 99,510 samples. The overall pooled estimate of Shigella prevalence was determined to be 5.9% (95% CI: 4.9 – 7.0%). Regional prevalence showed prevalences of Southern Africa (6.9 [95% CI: 3.0 – 12.2%]), Northern Africa (6.7% [95% CI: 4.1 – 9.8%]), Eastern Africa (6.2% [95% CI: 4.9 – 7.6%]), Central Africa (4.5% [95% CI: 2.6 – 6.8%]) and Western Africa (4.0% [95% CI: 2.5 – 5.9%]). Shigella prevalence was found to be higher in children (6.6%, 95% CI: 3.2 – 11.1%) than in adults (3.6%, 95% CI: 1.6 – 6.3%). The most prevalent species was S. flexneri (53.6%, 95% CI: 46.1%—61.0%), followed by S. sonnei (11.5%, 95% CI: 7.7%—15.7%), S. dysenteriae (10.1%, 95% CI: 6.2 – 14.5%) and S. boydii (7.7%, 95% CI: 4.7 – 11.1%). Among the currently recommended first-line antibiotics, ciprofloxacin and ceftriaxone showed resistance prevalences of 10.0% (95% CI: 4.5%—16.9%) and 8.5% (95% CI: 2.4—16.9%) respectively. Conclusion This review highlights the burden of shigellosis in Africa. S. flexneri remains the most prevalent species associated with shigellosis cases with S. sonnei being the second most dominant. The antimicrobial resistance patterns observed in the study suggest local antimicrobial patterns in choosing antibiotics for the treatment of Shigellosis. Recommendation There is the need to explore alternative treatments for shigellosis with particular focus on vaccine development. There is also the need for more genomic epidemiology studies exploring the dissemination and risk of drug-resistant S. sonnei clones in Africa. …

Abstract Background Co-infection with Klebsiella pneumoniae presents a significant concern in hospitalized patients with coronavirus disease (COVID-19), increasing the risk of severe disease progression. Hypervirulent (hv) and hypermucoviscous (hm) K. pneumoniae (Kp) has gained prominence in Asia due to its capacity to cause invasive community-acquired infections. However, recognition of hvKp/hmKp co-infections in the context of COVID-19 remains limited. We report a severe case of rapidly progressing co-infection with hmKp exhibiting “difficult-to-diagnose” phenotypes in a hospitalized patient with COVID-19. Case presentation A 61-year-old woman with COVID-19 initially exhibited mild symptoms resembling the common cold. However, her condition rapidly deteriorated over 7 days, leading to hospital admission with the development of dyspnea. The patient required supplemental oxygen, antibiotic treatment, and mechanical ventilation. Gram-negative bacteria with atypical phenotypes were isolated from alveolar lavage fluid and blood cultures. Both strains formed small, glossy, non-lactose-fermenting colonies on clinically relevant media and were susceptible to ampicillin. Conventional biochemical tests failed to identify the Enterobacteriales strains owing to the urease-negative phenotype. Consequently, the identification of K. pneumoniae was difficult until matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis was performed. A positive string test indicated mucoviscosity, but with variability in the material used for stretching colonies. Whole-genome sequencing performed on the MiSeq and GridION platforms revealed the blood-derived strain JARB-RN-0063 as belonging to serotype K1 and sequence type (ST) 82. The hvKp-associated genes rmpA and iroCD were located on a 5.0-Mb chromosome, and iucABCD-iutA was identified on a 217.9-kb IncFIB(K)/IncR-type plasmid. Therefore, JARB-RN-0063 was genetically classified as hvKp with a Kleborate virulence score of 3. The intrinsic penicillinase gene blaSHV was defective owing to an IS1F element insertion, resulting in the strain being atypically susceptible to ampicillin. Conclusions This is the first case of severe COVID-19-associated co-infection with a difficult-to-diagnose K. penummoniae strain. Notably, co-infection by the hmKp K1-ST82 clone exhibited atypical phenotypes, including stunted growth, non-lactose fermentation, urease-negative reaction, ampicillin susceptibility, and abnormal mucoviscosity, posing diagnostic challenges for clinical laboratories and impedes the identification of hvKp/hmKp. Delayed identification may worsen patient outcomes, highlighting the need for increased clinical awareness of such difficult-to-diagnose clones to prevent deterioration. …

Abstract Background Ureaplasma spp. can be classified into different serovars. It is unknown whether distinct serovars are associated with clinical signs and symptoms. Methods We conducted a multicentre cross-sectional study. U. parvum serovars were identified on the basis of their multiple-banded antigen (MBA) genes. After adjusting for demographic variables and other reproductive tract infections, the odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the impact of U. parvum serovars on clinical symptoms. Results Among 5,277 individuals, U. parvum serovars 3 and 6 were the most prevalent serovars (17.9% and 16.0%, respectively). Potential confounders, such as age, body mass index (BMI), ethnicity, education level, contraceptive methods, number of sexual partners, gravidity, parity, and other sexually transmitted infections (STIs) that are associated with clinical symptoms (P 

Abstract Background Plasmodium falciparum merozoite surface proteins 1 (PfMSP1) and 2 (PfMSP2) are potential candidates for malaria vaccine development. However, the genetic diversity of these genes in the global P. falciparum population presents a significant challenge in developing an effective vaccine. Hence, understanding the genetic diversity and evolutionary trends in the global P. falciparum population is crucial. Methods This study analyzed the genetic variations and evolutionary changes of pfmsp1 and pfmsp2 in P. falciparum isolates from the Central Highland and South-Central regions of Vietnam. DNASTAR and MEGA7 programs were utilized for analyses. The polymorphic nature of global pfmsp1 and pfmsp2 was also investigated. Results A total of 337 sequences of pfmsp1 and 289 sequences of pfmsp2 were obtained. The pfmsp1 and pfmsp2 from Vietnam revealed a higher degree of genetic homogeneity compared to those from other malaria-endemic countries. Remarkably, the allele diversity patterns of Vietnam pfmsp1 and pfmsp2 differed significantly from those of neighboring countries in the Greater Mekong Subregion. Declines in allele diversity and polymorphic patterns of Vietnam pfmsp1 and pfmsp2 were observed. Conclusions The Vietnam P. falciparum population might be genetically isolated from the parasite populations in other neighboring GMS countries, likely due to geographical barriers and distinct evolutionary pressures. Furthermore, bottleneck effects or selective sweeps may have contributed to the genetic homogeneity of Vietnam pfmsp1 and pfmsp2. …

Abstract Background The role of combination therapies for serious methicillin-resistant Staphylococcus aureus (MRSA) infections is widely debated. Methods This retrospective cohort study included adults with MRSA bacteraemia treated between January 1, 2013, to December 31, 2022. Patients receiving combination therapy with vancomycin and ceftaroline were matched in a 2:1 ratio with those on vancomycin monotherapy based on bacteraemia source and illness severity. The primary outcome was frequency of bacteraemia recurrence. Secondary outcomes were all cause 30/90-day mortality, recurrence or mortality at 30/90 days and in hospital length of stay. Results Of 57 patients included, 37 (65%) were in the combination group. The overall intensive care unit admission rate was 63.2% (36/57) and the Pitt Bacteraemia Score was 1 [0–4] at the time of diagnosis. The most common source of infection was endovascular/endocarditis (n = 36, 63.2%). Demographic and clinical characteristics were similar between the monotherapy and combination group of patients, except for higher body mass index (32.5 [25.5–36.4] vs. 24.4 [20.9–29], p = 0.004) and a greater immunosuppression prevalence (3 (15%) vs. 0 (0%), p = 0.039) in monotherapy group. There was no significant difference in bacteraemia recurrence (3 (15%) vs. 4 (10.8%), p = 0.7) or all-cause 30-day mortality (3 (15%) vs. 4 (10.8%), p = 0.7) between the two groups. Conclusion The results of this study are limited by a retrospective observational design; however, combination of vancomycin and ceftaroline for MRSA bacteraemia was not associated with lower bacteraemia recurrence or mortality compared to vancomycin monotherapy. …

Abstract Background Fatty acid binding protein 1 (FABP1), a low molecular weight intracellular protein, has been proposed as a potential useful serum biomarker for liver injury. However, limited investigations have been conducted in chronic hepatitis B virus (HBV)-related liver disease. Objective To investigate the diagnostic potential of FABP1 in disease progression among patients with chronic HBV-related liver disease. Methods A prospective study was conducted on 293 patients with chronic HBV-related liver diseases, including chronic asymptomatic carrier (ASC), chronic hepatitis B (CHB). FABP1 was measured in serum samples collected at admission and some selected liver biopsies. Results Immunohistochemical analysis revealed abundant cytoplasmic expression of FABP1 in hepatocytes. A significant negative correlation was observed between FABP1 expression and inflammation grades in liver tissue (Spearman\'s r = -0.355, P = 0.017). However, no statistically significant correlation was found with fibrosis (P > 0.05). Serum FABP1 levels in the case group were significantly higher than in the healthy control (HC) group [median: 804.2 (687.8, 939.2) vs. 709.1 (626.2, 807.8) ng/ml, Z = -5.505, P 

Abstract Background Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited. Methods Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed. Results A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p 

Abstract Background Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline. …