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Enterococcus faecalis can adopt both a commensal as well as a nosocomial lifestyle, resisting numerous antibiotics. Here, we aim to investigate the relationship between cell wall (CW) thickness and decreased susceptibility to vancomycin in van-gene negative clinical isolates of E. faecalis (VD; nMIC 8=2, nMIC 4=3, ST30, ST40, ST59).

To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome.

Abstract Accurate DNA replication and transcription elongation are crucial for preventing the accumulation of unreplicated DNA and genomic instability. Cells have evolved multiple mechanisms to deal with impaired replication fork progression, challenged by both intrinsic and extrinsic impediments. The bacterium Bacillus subtilis, which adopts multiple forms of differentiation and development, serves as an excellent model system for studying the pathways required to cope with replication stress to preserve genomic stability. This review focuses on the genetics, single molecule choreography and biochemical properties of the proteins that act to circumvent the replicative arrest allowing the resumption of DNA synthesis. The RecA recombinase, its mediators (RecO, RecR, RadA/Sms) and modulators (RecF, RecX, RarA, RecU, RecD2, PcrA), repair licensing (DisA), fork remodelers (RuvAB, RecG, RecD2, RadA/Sms, PriA), Holliday junction resolvase (RecU), nucleases (RnhC, DinG), and translesion synthesis DNA polymerases (PolY1 and PolY2) are the key functions required to overcome a replication stress, provided that the fork does not collapse.

Abstract Small proteins comprising less than 100 amino acids have been often ignored in bacterial genome annotations. About 10 years ago, focused efforts started to investigate whole peptidomes, which resulted in the discovery of a multitude of small proteins, but only a number of them have been characterized in detail. Generally, small proteins can be either membrane or cytosolic proteins. The latter interact with larger proteins, RNA or even metal ions. Here, we summarize our current knowledge on small proteins from Gram-positive bacteria with a special emphasis on the model organism Bacillus subtilis. Our examples include membrane-bound toxins of type I toxin-antitoxin systems, proteins that block the assembly of higher order structures, regulate sporulation or modulate the RNA degradosome. We do not consider antimicrobial peptides. Furthermore, we present methods for the identification and investigation of such proteins.

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Bilateral renal agenesis is historically considered to be universally fatal, due to pulmonary hypoplasia resulting from failure to maintain adequate amniotic fluid from fetal urine production in the first half of pregnancy. This fundamental dictum from perinatal-neonatal medicine has been challenged by the RAFT trial in this issue of JAMA. The authors performed a multicenter nonrandomized clinical trial of pregnancies complicated by bilateral renal agenesis and anhydramnios due to fetal anuria to assess whether the infants of participants who agreed to serial amnioinfusions initiated prior to 26 weeks’ gestation to promote lung development would survive to 14 days of life or longer and receive placement of dialysis access. Even before the RAFT trial results were published, there was controversy about serial amnioinfusions for fetal bilateral renal agenesis. A key concern has been whether the goal for survival benefit is worth the risks (eg, complications associated with prematurity, dialysis, life-limiting kidney disease). In the RAFT trial, study participants were assessed, treated, delivered, and followed up at 1 of 9 US fetal therapy centers. Of the 18 participants who underwent serial amnioinfusions, all delivered preterm, and 82% of neonates met the primary outcome of survival to at least 14 days and receipt of access to dialysis. However, of the survivors, only 35% (n = 6) survived to discharge; 2 died after discharge of infectious complications and cardiac arrest, respectively, and 3 had a stroke. There were no surviving neonates among the 3 participants who selected expectant management. The authors conclude that they were able to mitigate pulmonary hypoplasia, but at what cost?…

To the Editor A recent Review recommended human papillomavirus (HPV) testing as the primary screening test for cervical cancer. However, the authors neglected to explore the consequences of endorsing HPV primary screening over cotesting, which includes cytological evaluation. The authors did not discuss the importance of HPV-negative neoplasms. These cases include cervical intraepithelial neoplasia grade 3 or worse (CIN3+) lesions (false-negative results as well as HPV subtypes not included in commonly used HPV testing kits) and neoplasms that are not caused by HPV, for example, about 20% of cervical adenocarcinomas. In addition, the salutary impact of HPV vaccination on the incidence of cervical cancer has the potential to be significant but must be forecast in the setting of the growing antivaccination movement in the US. Reducing death rates from cervical cancer, the long-standing goal of HPV vaccination, may not be achievable given the underwhelming vaccination rates.

To the Editor We have several comments about the recent randomized clinical trial (ACTIV-1) that investigated the effect of abatacept, cenicriviroc, or infliximab on COVID-19 pneumonia.

In Reply We thank Drs Mathew and Feldmann for their comments on the results of ACTIV-1. We agree that mortality is a very important clinical outcome, but designing a trial such as ACTIV-1 to have sufficient power to detect an effect on mortality was challenging in June 2020, when data on clinical outcomes of severe COVID-19 were in flux. Indeed, the design of ACTIV-1 was heavily influenced by the results of ACTT-1, the initial placebo-controlled trial of remdesivir, which showed evidence of improved time to recovery but not improved mortality.

An investigational messenger RNA (mRNA)–based vaccine designed to protect against both influenza and COVID-19 induced virus-specific immune responses in people who received it, manufacturers Pfizer and BioNTech announced in a press release.

A new analysis of genomic changes suggests that the mpox virus has been circulating in humans since 2016—several years before the international mpox epidemic began in 2022. Many of the changes to the virus’ genome were related to antiviral enzymes known as APOBEC3 deaminases.

This Medical News article is an interview with infectious disease physician Heather Yun, MD, cochair of this year’s Infectious Diseases Week meeting in Boston.

Divergent gene content among distinct probiotic strains contributes to varied or conflicting clinical efficacies. Zhang et al. unveils a novel bacterial gene signature, particularly the abfA gene cluster, offering a promising avenue for screening probiotics and advancing our understanding of strain-level activities in the context of gastrointestinal health.

by Rashidul Alam Mahumud, Khorshed Alam, Jeff Dunn, Jeff Gow …

by Petek Eylul Taneri, Jamie J. Kirkham, Eleanor J. Molloy, Linda Biesty, Richard A. Polin, James L. Wynn, Barbara J. Stoll, Niranjan Kissoon, Kondwani Kawaza, Mandy Daly, Aoife Branagan, Lívia Nagy Bonnard, Eric Giannoni, Tobias Strunk, Magdalena Ohaja, Kenneth Mugabe, Denise Suguitani, Fiona Quirke, Declan Devane Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients’ parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.

by Ramy E. El-Ansary, Samy Kasem, Mohamed A. M. El-Tabakh, Yassien Badr, Ahmed S. Abdel-Moneim Foot-and-mouth Disease (FMD) is a highly contagious viral disease affecting all hoof-cloven animals. Serotypes A, O and SAT 2 of the foot-and-mouth disease virus (FMDV) are circulating in Egypt. The present study aimed to identify and molecularly characterize the FMDV strains circulating in Northern Egypt during an epidemic that struck the nation in 2022. RNA was extracted from the epithelial specimens, vesicular fluid from affected cattle. The samples were screened using real-time reverse-transcription polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. Positive samples underwent individual serotype-specific amplification using primers designed for VP1 of O, A, and SAT 2 serotypes. Subsequently, direct sequencing was performed on the positive samples. The real-time RT-PCR detected positive samples from epithelial and vesicular fluid samples, but not in the blood of infected animals. Out of the 16 samples, seven tested positive for FMDV serotype A. Of these seven positive samples, six were categorized as serotype A-African topotype-G-IV, and these positive samples were isolated in BHK-21 cells, yielding an overt cytopathic effect caused by the virus. In conclusion, it is necessary to sustain continuous surveillance of the evolution of circulating FMDV strains to facilitate the assessment and aid in the selection of vaccine strains for the effective control of FMDV in Egypt.

by Byungseok Kang, Youngjae Jo Recently, Generative Adversarial Networks (GAN) has been greatly developed and widely used in image synthesis. A Style-Based Generator Architecture for Generative Adversarial Networks (StyleGAN) which is the foremost, continues to develop human face inversion domain. StyleGAN uses insufficient vector space to express more than one million pixels. It is difficult to apply in real business due to distortion-edit tradeoff problem in latent space. To overcome this, we propose a novel semantic segment encoder (SSE) with improved face inversion quality by narrowing the size of restoration latent space. Encoder’s learning area is minimized to logical semantic-segment units that can be recognized by humans. The proposed encoder does not affect other segments because only one segment is edited at a time. To verify the face inversion quality, we compared with the latest encoders both Pixel2style2Pixel and RestyleEncoder. Experimental result shows that the proposed encoder improved distortion quality around 20% while maintain editing performance.

by Desale Bihonegn Asmamaw, Yohannes Ayanaw Habitu, Eskedar Getie Mekonnen, Wubshet Debebe Negash Background World Health Organization (WHO) recommends that every pregnant woman receive quality care throughout pregnancy, childbirth, and the postnatal period. It is estimated that institutional delivery could reduce 16% to 33% of maternal deaths. Despite the importance of giving birth at a health institution, in Ethiopia, according to the Ethiopian Demographic Health Survey report, nearly half of the ANC-booked mothers gave birth at home. Therefore, this study aimed to determine the prevalence and associated factors of home delivery among antenatal care-booked women in their last pregnancy during the era of COVID-19. Methods A community-based cross-sectional study was conducted from March 30 to April 29, 2021. A simple random technique was employed to select 770 participants among women booked for antenatal care. Interviewer-administered questionnaires were used to collect the data. A binary logistic regression model was fitted. Adjusted odds ratios with its respective 95% confidence interval were used to declare the associated factors. Results The prevalence of home delivery was 28.8% (95% CI: 25.7, 32.2). Rural residence (AOR = 2.02, 95% CI: 1.23, 3.34), unmarried women (AOR = 11.16, 95% CI: 4.18, 29.79), husband education (AOR = 2.60, 95% CI: 1.72, 3.91), not being involved in the women’s development army (AOR = 1.64, 95% CI: 1.01, 2.65), and fear of COVID-19 infection (AOR = 3.86, 95% CI: 2.31, 6.44) were significantly associated factors of home delivery. Conclusion Even though the government tried to lower the rate of home delivery by accessing health institutions in remote areas, implementing a women’s development army, and introducing maternal waiting home utilization, nearly one in every three pregnant women gave birth at home among ANC booked women in their last pregnancy. Thus, improving the husband’s educational status, providing information related to health institution delivery benefits during antenatal care, and strengthening the implementation of the women’s development army, particularly among rural and unmarried women, would decrease home childbirth practices. …

by Ana Rubio-Garcia, Aldert L. Zomer, Ruoshui Guo, John W. A. Rossen, Jan H. van Zeijl, Jaap A. Wagenaar, Roosmarijn E. C. Luiken Animal rehabilitation centres provide a unique opportunity to study the microbiome of wild animals because subjects will be handled for their treatment and can therefore be sampled longitudinally. However, rehabilitation may have unintended consequences on the animals’ microbiome because of a less varied and suboptimal diet, possible medical treatment and exposure to a different environment and human handlers. Our study describes the gut microbiome of two large seal cohorts, 50 pups (0–30 days old at arrival) and 23 weaners (more than 60 days old at arrival) of stranded harbour seals admitted for rehabilitation at the Sealcentre Pieterburen in the Netherlands, and the effect of rehabilitation on it. Faecal samples were collected from all seals at arrival, two times during rehabilitation and before release. Only seals that did not receive antimicrobial treatment were included in the study. The average time in rehabilitation was 95 days for the pups and 63 days for the weaners. We observed that during rehabilitation, there was an increase in the relative abundance of some of the Campylobacterota spp and Actinobacteriota spp. The alpha diversity of the pups’ microbiome increased significantly during their rehabilitation (p-value…

by Bagdat Tekkus, Fatma Mutluay Objective This study investigates the impact of community-based exercises with action observation therapy (AOT) on the physical and cognitive performance of older adults experiencing social isolation during the COVID-19 pandemic. Methods One hundred participants aged 65–80 years were randomly divided into two groups: the AOT group, which engaged in balance, strengthening, and mobility exercises guided by 15-minute action observation videos before a 45-minute exercise session, and the control group, which performed the same exercises without action observation. Both groups underwent three sessions per week for eight weeks (24 sessions in total). The assessment tools used in this study included the following: For evaluating mobility and fall risk in older adults, the Timed Up-and-Go (TUG) Test was employed. To assess functional strength of lower extremities, balance, and fall risk, the Five Times Sit-to-Stand (5XSST) Test was administered. Balance and gait were measured using the Tinetti Balance and Gait Assessment (TBGA), utilizing the Tinetti Scale. Individuals’ confidence in performing daily activities without falling or losing balance was assessed using the Activities-Specific Balance Confidence Scale (ABC). Furthermore, cognitive functions across multiple domains, including attention-concentration, executive function, memory, language, visual construction skills, abstract thinking, calculation, and orientation, were evaluated using the Montreal Cognitive Assessment (MoCA) Tests. Results Results revealed significant improvements in both groups. Group I, which received Action Observation Therapy (AOT) in addition to exercise, demonstrated superior outcomes in the 5XSit-to-Stand test (Δ = -1.92, p < 0.0001, Cohen’s d = 0.77), Tinetti Balance and Gait Scale (Balance: Δ = 2.77, p < 0.0001, Cohen’s d = 0.91), and Timed Up and Go test (Δ = -1.98, p < 0.0005, Cohen’s d = 0.83). On the other hand, Group II, which received exercise only, exhibited substantial gains in the Tinetti Balance and Gait Scale (Walking: Δ = 0.52, p < 0.01, Cohen’s d = 0.27) and Activity-Specific Balance Confidence Scale (Δ = 5.77, p < 0.0001, Cohen’s d = 0.26). Conclusion These findings underscore the effectiveness of AOT-enhanced community-based exercises in enhancing both physical and cognitive performance among older adults facing social isolation during the pandemic, with Group I (AOT + exercise) showing particularly promising results. Trial registration This study was registered with ClinicalTrials.gov Identifier: NCT04759690, ClinicalTrials Protocol ID: p3957ghb. …

by Soeurette Policar, Alana Sharp, Joanne Isidor Hyppolite, Gérald Marie Alfred, Eva Steide, Leïnadine Lucien, Naiké Ledan, Matthew Kavanagh Background Failure to retain people living with HIV (PLHIV) in care remains a significant barrier to achieving epidemic control in Haiti, with as many as 30% lost from care within one year of starting treatment. Community-led monitoring (CLM) is an emerging approach of improving healthcare and accountability to service users, through a cycle of monitoring and advocacy. In 2020, a CLM program was launched in Haiti to identify barriers to retention and advocating for better health services. Methods Data from the community-led monitoring program in Haiti were analyzed, from a sample of 65 healthcare facilities in the Nord, Artibonite, and Ouest departments collected from April 2021 to February 2022. Qualitative data from six community-based focus groups and 45 semi-structured individual interviews were analyzed. Results Confidentiality and stigmatization emerged as barriers to care, particularly due to the separation of PLHIV from other patients in view of community members. To avoid identification, patients described traveling long distances, with the reimbursement of transportation costs described as being insufficient or unavailable. Costs of non-HIV clinical services were a frequent concern and respondents described a need for clinics to provide food during all patient visits. Stock-outs were a regular challenge; by contrast, treatment literacy did not emerge as a major barrier to retention. Conclusions These findings represent the first instance, to our knowledge, of original data from a community-led monitoring program being published in any country. These findings suggest that improving treatment retention for PLHIV is dependent on improving the acceptability and affordability of healthcare services. Ensuring confidentiality is critical, particularly where stigma is high. Retention could be improved by systematically strengthening patient confidentiality protections throughout the healthcare system, providing patients with sufficient travel compensation and other incentives, and delivering wraparound services provided for free. Addressing these challenges will require ongoing advocacy for community-developed recommendations and solutions. …

by Bingyu Zhang, Ruiling Zhang, Hongdu Deng, Ping Cui, Chunyan Li, Fan Yang, Mohammad Farris Iman Leong Bin Abdullah Background and aim Primarily, this study compares the efficacy of probiotic and acceptance and commitment therapy (ACT) in alleviating the severity of alcohol craving and alcohol use disorder (AUD) among patients who had undergo two weeks of in-patient detoxification. Secondarily, this study compares the efficacy of probiotic and ACT in mitigating the severity of comorbid depression and anxiety symptoms; decreasing serum level of pro-inflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); changing the event-related potential in electroencephalogram (EEG) and restoring microbiota flora in the gut of AUD patients. Methods and analysis Initially, during Phase I of the study, the serum level of IL-1β, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1β, IL-6 and TNF-α; changes in ERP and fecal microbiota content. Trial registration number NCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023. …

by Yuntao Bai, Lan Wang, Shuang Xu In 2020, COVID-19 became a global pandemic. Older people are less resistant to the novel coronavirus. In order to ensure the health of the elderly population, the governments of five Central Asian countries should provide home medical services for the elderly or provide \'green channel\' to medical services. This \'green channel\' means providing a special service and treatment for the elderly in the hospital to ensure that they can safely and easily access the medical services they need. In order to study the application scope of various modes, this article constructs three modes of differential game: no special care, home medical care and \'green channel\'. And the equilibrium results are compared and analyzed. Research shows that when the additional medical costs associated with house calls or \'green channel\' gradually increase, the social benefits to both the elderly and the government gradually decrease, and eventually it is less than the social benefits under the no-special care model. The greater the credibility of the government under the \'green channel\' service model, the greater the social benefits of the government. However, the greater the credibility of the government under the home medical service model, the smaller the social benefits of the government.

by Gabriel Morey-León, Paulina M. Mejía-Ponce, Juan Carlos Granda Pardo, Karen Muñoz-Mawyin, Juan Carlos Fernández-Cadena, Evelyn García-Moreira, Derly Andrade-Molina, Cuauhtémoc Licona-Cassani, Luisa Berná Introduction Tuberculosis (TB) is among the deadliest diseases worldwide, and its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, nonadherence to treatment and circulation of previously resistant isolates of Mycobacterium tuberculosis. In this study, we evaluated the performance and functionalities of web-based tools, including Mykrobe, TB-profiler, PhyResSE, KvarQ, and SAM-TB, for detecting resistance in 88 Ecuadorian isolates of Mycobacterium tuberculosis drug susceptibility tested previously. Statistical analysis was used to determine the correlation between genomic and phenotypic analysis. Our results showed that with the exception of KvarQ, all tools had the highest correlation with the conventional drug susceptibility test (DST) for global resistance detection (98% agreement and 0.941 Cohen’s kappa), while SAM-TB, PhyResSE, TB-profiler and Mykrobe had better correlations with DST for first-line drug analysis individually. We also identified that in our study, only 50% of mutations characterized by the web-based tools in the rpoB, katG, embB, pncA, gyrA and rrs regions were canonical and included in the World Health Organization (WHO) catalogue. Our findings suggest that SAM-TB, PhyResSE, TB-profiler and Mykrobe were efficient in determining canonical resistance-related mutations, but more analysis is needed to improve second-line detection. Improving surveillance programs using whole-genome sequencing tools for first-line drugs, MDR-TB and XDR-TB is essential to understand the molecular epidemiology of TB in Ecuador. Importance Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, most commonly affects the lungs and is often spread through the air when infected people cough, sneeze, or spit. However, despite the existence of effective drug treatment, patient adherence, long duration of treatment, and late diagnosis have reduced the effectiveness of therapy and increased drug resistance. The increase in resistant cases, added to the impact of the COVID-19 pandemic, has highlighted the importance of implementing efficient and timely diagnostic methodologies worldwide. The significance of our research is in evaluating and identifying a more efficient and user-friendly web-based tool to characterize resistance in Mycobacterium tuberculosis by whole-genome sequencing, which will allow more routine application to improve TB strain surveillance programs locally. …

by Gavin J. Fenske, Jane G. Pouzou, Régis Pouillot, Daniel D. Taylor, Solenne Costard, Francisco J. Zagmutt The serovars of Salmonella enterica display dramatic differences in pathogenesis and host preferences. We developed a process (patent pending) for grouping Salmonella isolates and serovars by their public health risk. We collated a curated set of 12,337 S. enterica isolate genomes from human, beef, and bovine sources in the US. After annotating a virulence gene catalog for each isolate, we used unsupervised random forest methods to estimate the proximity (similarity) between isolates based upon the genomic presentation of putative virulence traits We then grouped isolates (virulence clusters) using hierarchical clustering (Ward’s method), used non-parametric bootstrapping to assess cluster stability, and externally validated the clusters against epidemiological virulence measures from FoodNet, the National Outbreak Reporting System (NORS), and US federal sampling of beef products. We identified five stable virulence clusters of S. enterica serovars. Cluster 1 (higher virulence) serovars yielded an annual incidence rate of domestically acquired sporadic cases roughly one and a half times higher than the other four clusters combined (Clusters 2–5, lower virulence). Compared to other clusters, cluster 1 also had a higher proportion of infections leading to hospitalization and was implicated in more foodborne and beef-associated outbreaks, despite being isolated at a similar frequency from beef products as other clusters. We also identified subpopulations within 11 serovars. Remarkably, we found S. Infantis and S. Typhimurium subpopulations that significantly differed in genome length and clinical case presentation. Further, we found that the presence of the pESI plasmid accounted for the genome length differences between the S. Infantis subpopulations. Our results show that S. enterica strains associated with highest incidence of human infections share a common virulence repertoire. This work could be updated regularly and used in combination with foodborne surveillance information to prioritize serovars of public health concern.

Abstract Background Malaria is one of the most prominent illnesses affecting children, ranking as one of the key development concerns for many low- and middle-income countries (LMICs). There is not much information available on the use of anti-malarial drugs in LMICs in children under five. The study aimed to investigate disparities in anti-malarial drug consumption for malaria among children under the age of five in LMICs. Methods This study used recent available cross-sectional data from the Malaria Indicator Survey (MIS) datasets across five LMICs (Guinea, Kenya, Mali, Nigeria, and Sierra Leone), which covered a portion of sub-Saharan Africa. The study was carried out between January 2, 2023, and April 15, 2023, and included children under the age of five who had taken an anti-malarial drug for malaria 2 weeks before the survey date. The outcome variable was anti-malarial drug consumption, which was classified into two groups: those who had taken anti-malarial drugs and those who had not. Results In the study of LMICs, 32,397 children under five were observed, and among them, 44.1% had received anti-malarial drugs. Of the five LMICs, Kenya had the lowest (9.2%) and Mali had the highest (70.5%) percentages of anti-malarial drug consumption. Children under five with malaria are more likely to receive anti-malarial drugs if they are over 1 year old, live in rural areas, have mothers with higher education levels, and come from wealthier families. Conclusion The study emphasizes the importance of developing universal coverage strategies for anti-malarial drug consumption at both the national and local levels. The study also recommends that improving availability and access to anti-malarial drugs may be necessary, as the consumption of these drugs for treating malaria in children under the age of five is shockingly low in some LMICs. …

Abstract Background Children in sub-Saharan Africa (SSA) remain the most vulnerable to malaria and malaria mortality. This study estimated the disease burden and distribution of Plasmodium falciparum malaria among children with age categories (0 to

Abstract Background In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarized published full-text epidemiological data from the outbreaks. Methods A global evidence review (protocol: osf.io/j3kb7) with systematic literature search up to February 09, 2023. We focused on experimental/observational studies of laboratory confirmed Mpox, excluding case reports and case series of 

SARS-CoV-2 has infected over 620 million people and killed more than 6 million worldwide. [1] Since the beginning of the pandemic, Brazil has reported a disproportionately large number of infections and deaths of pregnant women attributed to COVID-19, [2] arguably caused by the disastrous response to the pandemic in its early months, with national policies contrary to scientific recommendations and against international infectious disease societies guidelines. [3]…

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background Opioid use disorder (OUD) has been associated with adverse health outcomes, and its potential impact on COVID-19 outcomes is of significant concern. This study aimed to assess the susceptibility and clinical outcomes of hospitalized COVID-19 patients with OUD using a propensity score-matched design. Methods A historical cohort study was conducted in Alborz province, Iran, during the early months of the COVID-19 pandemic. Patients aged 18 years and above with confirmed COVID-19 were included in the study. OUD was defined as a compulsive urge to use opioids or opioid-derivative drugs. Non-opioid abusers with COVID-19 were selected as the control group. Data on demographics, clinical characteristics, laboratory factors, comorbidities, and vital signs were collected. Propensity score matching (PSM) was used to balance the groups and assess the impact of OUD on ICU admission, mortality, the need for intubation, and the severity of pulmonary involvement on CT scans. Results A total of 442 patients were included in the study, with 351 discharged and 34 deceased. The PSM analysis showed that OUD was not significantly associated with ICU admission (OR: 1.87, 95% CI: 0.22–2.91, p = 0.631). However, opium users had an increased risk of mortality (OR: 2.38, 95% CI: 1.30–4.35, p = 0.005) and a higher likelihood of requiring intubation (OR: 3.57, 95% CI: 1.38–9.39, p = 0.009) compared to non-opioid abusers. The severity of pulmonary involvement on CT scans did not show a significant association with OUD. Conclusion OUD among hospitalized COVID-19 patients was associated with an increased risk of mortality and the need for intubation. These findings highlight the importance of addressing OUD as a potential risk factor in the management and treatment of COVID-19 patients. Further research is warranted to explore the underlying mechanisms and develop appropriate interventions to mitigate the impact of OUD on COVID-19 outcomes. …

Abstract Background Human mpox has increasingly been reported worldwide since May 2022, with higher incidence in men who have sex with men (MSM) and persons living with HIV (PLHIV) with presentation typical for generalized macules and papules. Case presentation We are describing a case of human mpox, which presented as widespread, atypical round verrucous lesions that went undiagnosed in the community for six months and was treated with antibacterials and antifungals given the similarity to skin manifestations associated with endemic mycoses. Conclusions Suspicion for human mpox should be high in young MSM and PLHIV who present with rash and mpox should be ruled out earlier. …

Volume 15, Issue 1, December 2024 .

Volume 15, Issue 1, December 2024 .

AbstractMultidrug-resistant(MDR) tuberculosis in Southern Africa is of great concern, exacerbated by the spread of a clone harboring a mutation missed by Xpert Ultra. In Southern Mozambique, the presence of such mutation and rising cases of non-MDR isoniazid resistance highlights the need to ensure accurate detection of antimicrobial-resistance in the country.

AbstractBackgroundMetallo-β-lactamases (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments and outcomes of infections by MBL-Enterobacterales.MethodsProspective observational study conducted in the Pisa University Hospital (Jan 2019-Oct 2022) including patients with MBL-producing Enterobacterales infections. The primary outcome measure was 30-day mortality. A multivariable Cox regression analysis was performed to identify factors associated with 30-day mortality. Adjusted hazard ratio (aHR) (95% confidence intervals, CI) were calculated.Results343 patients were included: 15 VIM- and 328 NDM-producing Enterobacterales infections. Overall, 199 (58%) were bloodstream infections, 60 (17.5%) hospital-acquired/ventilator-associated pneumonias, 60 (17.5%) complicated urinary tract infections, 13 (3.8%) intra-abdominal infections, 11 (3.2%) skin and soft tissue infections. Thirty-day mortality was 29.7%. Thirty-two patients did not receive in vitro active antibiotic therapy, 215/343 (62.7%) received ceftazidime-avibactam (CZA) plus aztreonam (ATM), 33/343 (9.6%) cefiderocol-containing regimens, 26/343 (7.6%) colistin-containing regimens and 37 (10.8%) other active antibiotics. On multivariable analysis, septic shock (aHR 3.57, 95% CI 2.05-6.23, p

AbstractBackgroundNeutropenia may limit use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir.MethodsIn this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks follow-up. Primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of non-inferiority margin of 7.0%). Key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8, through week 16. Treatment-emergent adverse events (TEAEs) were assessed.ResultsAmong patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of non-inferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference [95% confidence interval (CI)]: −7.7% [−14.98, −0.36]; lower limit of 95% CI of treatment difference exceeded −7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference [95% CI]: 4.4% [−3.91, 12.76]). With maribavir (versus valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%).ConclusionsAlthough non-inferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified non-inferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia.Clinical trials registrationNCT02927067 [AURORA]…

AbstractBackgroundTwo prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against respiratory syncytial virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines.MethodsWe developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the United States. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-year (QALY) gained as a measure of effectiveness and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective.ResultsUsing a willingness-to-pay of $95 000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD up to $127 with Arexvy and $118 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the United States, the budget impact of these programs at the maximum PPD ranged from $6.48 to $6.78 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $235 for Arexvy and $245 for Abrysvo, with 2-year budget impacts of $11.78 and $12.25 billion, respectively.ConclusionsVaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.

Abstract Background Plasmodium vivax has been more resistant to various control measures than Plasmodium falciparum malaria because of its greater transmissibility and ability to produce latent parasite forms. Therefore, developing P. vivax vaccines and therapeutic monoclonal antibodies (humAbs) remains a high priority. The Duffy antigen receptor for chemokines (DARC) expressed on erythrocytes is central to P. vivax invasion of reticulocytes. P. vivax expresses a Duffy binding protein (PvDBP) on merozoites, a DARC ligand, and the DARC: PvDBP interaction is critical for P. vivax blood stage malaria. Therefore, PvDBP is a leading vaccine candidate for P. vivax and a target for therapeutic human monoclonal antibodies (humAbs). Methods Here, the functional activity of humAbs derived from naturally exposed and vaccinated individuals are compared for the first time using easily cultured Plasmodium knowlesi (P. knowlesi) that had been genetically modified to replace its endogenous PkDBP orthologue with PvDBP to create a transgenic parasite, PkPvDBPOR. This transgenic parasite requires DARC to invade human erythrocytes but is not reticulocyte restricted. This model was used to evaluate the invasion inhibition potential of 12 humAbs (9 naturally acquired; 3 vaccine-induced) targeting PvDBP individually and in combinations using growth inhibition assays (GIAs). Results The PvDBP-specific humAbs demonstrated 70–100% inhibition of PkPvDBPOR invasion with the IC50 values ranging from 51 to 338 µg/mL for the 9 naturally acquired (NA) humAbs and 33 to 99 µg/ml for the 3 vaccine-induced (VI) humAbs. To evaluate antagonistic, additive, or synergistic effects, six pairwise combinations were performed using select humAbs. Of these combinations tested, one NA/NA (099100/094083) combination demonstrated relatively strong additive inhibition between 10 and 100 µg/mL; all combinations of NA and VI humAbs showed additive inhibition at concentrations below 25 µg/mL and antagonism at higher concentrations. None of the humAb combinations showed synergy. Invasion inhibition efficacy by some mAbs shown with PkPvDBPOR was closely replicated using P. vivax clinical isolates. Conclusion The PkPvDBPOR transgenic model is a robust surrogate of P. vivax to assess invasion and growth inhibition of human monoclonal Abs recognizing PvDBP individually and in combination. There was no synergistic interaction for growth inhibition with the humAbs tested here that target different epitopes or subdomains of PvDBP, suggesting little benefit in clinical trials using combinations of these humAbs. …

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

Colonization factors (CFs) are major virulence factors of enterotoxigenic Escherichia coli (ETEC). This pathogen is among the most common causes of bacterial diarrhea in children in low- and middle-income countries, travelers, and livestock. CFs are major candidate antigens in vaccines under development as preventive measures against ETEC infections in humans and livestock. Recent molecular studies have indicated that newly identified CFs on human ETEC are closely related to animal ETEC CFs. Increased knowledge of pathogenic mechanisms, immunogenicity, regulation, and expression of ETEC CFs, as well as the possible spread of animal ETEC to humans, may facilitate the future development of ETEC vaccines for humans and animals. Here, we present an updated review of CFs in ETEC.

Beneath the shimmering veneer of modern medicine exists an undeniable predicament—the fight against antimicrobial resistance (AMR). In what appears to be a documentary, Race against resistance: the life and death struggle to save antibiotics, the AMR Action Fund, a Venture Capitalists\' Fund that enables discoveries in the development of antimicrobials, brings us up to speed on the antimicrobial innovation pipeline. Premiered on 5 September on the YouTube channel of the BBC StoryWorks Commercial Productions, a BBC department making marketing materials on behalf of other organisations (in this case, the AMR Action Fund), this commercial content appears non-editorialised by the BBC.

“History has the power to shape not only what we remember, but what we forget.” In the final paragraph of the introduction to In Her Hands, Women\'s Fight Against AIDS in the United States, historian Emma Day perfectly sums up the message behind her book. Day seeks to readdress the narrative around women\'s fight against HIV/AIDS and the political systems that overlooked, mistreated, and maligned them during the 1980s epidemic of the disease. It is her intention to ensure that we remember the struggles that women faced with accuracy and in their entirety, as no one subgroup of sufferers should take precedence in the history books when we recall the scale and severity of this disease.

VAX-24 had a safety profile similar to PCV20 at all doses, with the 2·2 μg dose showing increased serotype coverage with decreased carrier suppression.

by Marc T. Valitutto, Ohnmar Aung, Kyaw Yan Naing Tun, Megan E. Vodzak, Dawn Zimmerman, Jennifer H. Yu, Ye Tun Win, Min Thein Maw, Wai Zin Thein, Htay Htay Win, Jasjeet Dhanota, Victoria Ontiveros, Brett Smith, Alexandre Tremeau-Bravard, Tracey Goldstein, Christine K. Johnson, Suzan Murray, Jonna Mazet …