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Cranberry products—including juice or capsules—reduced the risk of symptomatic, confirmed urinary tract infections (UTIs) in several groups, according to results published in the Cochrane Database of Systematic Reviews.

Although the bacille Calmette-Guérin (BCG) vaccine is used primarily to protect against tuberculosis, previous research has suggested it might also guard against other infections. At the start of the COVID-19 pandemic, researchers hypothesized that vaccination with BCG, which seems to cause epigenetic changes in immune cells that promote a stronger immune response against pathogens, might be effective against COVID-19.

Healthy children who were not infected with respiratory syncytial virus (RSV) during their first year of life were 26% less likely to have asthma by age 5 years than those who had been infected, according to results from an observational study that included 1946 participants. The researchers calculated that preventing RSV infections during infancy could avoid 15% of asthma cases in 5-year-olds.

Although a disproportionate number of mpox cases—between 35% and 47%, according to some studies—occur in people who also have HIV infection, research comparing the safety and outcomes of mpox treatments in patients with and without HIV is lacking.

In 2018, WHO formalised the term ‘Disease X’. Included in their list of priority diseases for research and development, Disease X represents the next unknown disease of epidemic potential. In Disease X: the 100 days mission to end pandemics, Kate Kelland explores how the world can possibly prioritise research and development on a disease that is not yet known, or perhaps not yet persisting in humans at all. An ambitious goal, but not unattainable.

COVID-19: surviving a pandemic is one of 19 titles part of The COVID-19 pandemic series, edited by J Michael Ryan. The series examines the impact of the COVID-19 pandemic on individuals, communities, and the larger global society from a social and scientific perspective. This edition, published in August 2022 offers critical insight into the various survival strategies adopted by those caught in the freefall of a world adapting to the threat of a deadly virus, economic recessions, and social isolation.

AbstractStreptococcus. pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium (SAVAC) mission is to accelerate the development of safe, effective and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance.

AbstractThe Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

AbstractThe World Health Organization recommends same-day initiation of antiretroviral therapy (ART) for all persons diagnosed with HIV and ready to start treatment. Evidence, mainly from randomized trials, indicates offering same-day ART increases engagement in care and viral suppression during the first year. In contrast, most observational studies using routine data find same-day ART to be associated with lower engagement in care. We argue that this discrepancy is mainly driven by different time points of enrolment leading to different denominators. While randomized trials enroll individuals when tested positive, most observational studies start at the time-point when ART is initiated. Thus, most observational studies omit those who are lost between diagnosis and treatment, thereby introducing a selection bias in the group with delayed ART. In this viewpoint, we summarize the available evidence and argue that the benefits of same-day ART outweigh a potential higher risk of attrition from care after ART initiation.

Science Advances, Volume 9, Issue 21, May 2023.

Science Advances, Volume 9, Issue 21, May 2023.

Science Advances, Volume 9, Issue 21, May 2023.

Science Advances, Volume 9, Issue 21, May 2023.

by Mário Songane, Célia C. Magaia, Aleny Couto, Nataniel Dengo, Abdul R. Cassamo, Rene Nhantumbo, Carlos Mahumane, Atanásio Mabote, Silvia Mikusova, Amâncio Nhangave, Nilesh Bhatt, Sushant S. Mukherjee Background In Mozambique, 38.7% of women and 60.4% of men ages 15–59 years old living with HIV do not know their HIV status. A pilot home-based HIV counseling and testing program based on index cases in the community was implemented in eight districts in Gaza province (Mozambique). The pilot targeted the sexual partners, biological children under 14 years old living in the same household, and parents (for pediatric cases) of people living with HIV. The study aimed to estimate the cost-efficiency and effectiveness of community index testing and compare the HIV testing outputs with facility-based testing. Methods Community index testing costs included the following categories: human resources, HIV rapid tests, travel and transportation for supervision and home visits, training, supplies and consumables, and review and coordination meetings. Costs were estimated from a health systems perspective using a micro-costing approach. All project costs were incurred between October 2017 and September 2018 and converted to U.S. dollars ($) using the prevailing exchange rate. We estimated the cost per individual tested, per new HIV diagnosis, and per infection averted. Results A total of 91,411 individuals were tested for HIV through community index testing, of which 7,011 were newly diagnosed with HIV. Human resources (52%), purchase of HIV rapid tests (28%) and supplies (8%) were the major cost drivers. The cost per individual tested was $5.82, per new HIV diagnosis was $65.32, and per infection averted per year was $1,813. Furthermore, the community index testing approach proportionally tested more males (53%) than facility-based testing (27%). Conclusion These data suggest that expansion of the community index case approach may be an effective and efficient strategy to increase the identification of previously undiagnosed HIV-positive individuals, particularly males. …

by Sara Prims, Xaveer Van Ostade, Miriam Ayuso, Martin Dom, Geert Van Raemdonck, Steven Van Cruchten, Christophe Casteleyn, Chris Van Ginneken Monitoring chronic stress in pigs is not only essential in view of animal welfare but is also important for the farmer, given that stress influences the zootechnical performance of the pigs and increases their susceptibility to infectious diseases. To investigate the use of saliva as a non-invasive, objective chronic stress monitoring tool, twenty-four 4-day-old piglets were transferred to artificial brooders. At the age of 7 days, they were assigned to either the control or the stressed group and reared for three weeks. Piglets in the stressed group were exposed to overcrowding, absence of cage enrichment, and frequent mixing of animals between pens. Shotgun analysis using an isobaric labelling method (iTRAQ) for tandem mass spectrometry performed on saliva samples taken after three weeks of chronic stress identified 392 proteins, of which 20 proteins displayed significantly altered concentrations. From these 20 proteins, eight were selected for further validation using parallel reaction monitoring (PRM). For this validation, saliva samples that were taken one week after the start of the experiment and samples that were taken at the end of the experiment were analysed to verify the profile over time. We wanted to investigate whether the candidate biomarkers responded fast or rather slowly to the onset of chronic exposure to multiple stressors. Furthermore, this validation could indicate whether age influenced the baseline concentrations of these salivary proteins, both in healthy and stressed animals. This targeted PRM analysis confirmed that alpha-2-HS-glycoprotein was upregulated in the stressed group after one and three weeks, while odorant-binding protein, chitinase, long palate lung and nasal epithelium protein 5, lipocalin-1, and vomeromodulin-like protein were present in lower concentrations in the saliva of the stressed pigs, albeit only after three weeks. These results indicate that the porcine salivary proteome is altered by chronic exposure to multiple stressors. The affected proteins could be used as salivary biomarkers to identify welfare problems at the farm and facilitate research to optimise rearing conditions.

by Jonathan Sserunkuuma, Mark Mohan Kaggwa, Moses Muwanguzi, Sarah Maria Najjuka, Nathan Murungi, Jonathan Kajjimu, Jonathan Mulungi, Raymond Bernard Kihumuro, Mohammed A. Mamun, Mark D. Griffiths, Scholastic Ashaba Background Students in sub-Saharan African countries experienced online classes for the first time during the COVID-19 pandemic. For some individuals, greater online engagement can lead to online dependency, which can be associated with depression. The present study explored the association between problematic use of the internet, social media, and smartphones with depression symptoms among Ugandan medical students. Methods A pilot study was conducted among 269 medical students at a Ugandan public university. Using a survey, data were collected regarding socio-demographic factors, lifestyle, online use behaviors, smartphone addiction, social media addiction, and internet addiction. Hierarchical linear regression models were performed to explore the associations of different forms of online addiction with depression symptom severity. Results The findings indicated that 16.73% of the medical students had moderate to severe depression symptoms. The prevalence of being at risk of (i) smartphone addiction was 45.72%, (ii) social media addiction was 74.34%, and (iii) internet addiction use was 8.55%. Online use behaviors (e.g., average hours spent online, types of social media platforms used, the purpose for internet use) and online-related addictions (to smartphones, social media, and the internet) predicted approximately 8% and 10% of the severity of depression symptoms, respectively. However, over the past two weeks, life stressors had the highest predictability for depression (35.9%). The final model predicted a total of 51.9% variance for depression symptoms. In the final model, romantic relationship problems (ß = 2.30, S.E = 0.58; p…

by Edgar Giovanhi Gómez-Domínguez, César Gabriel Toriz, Sirenia González-Pozos, Margarita González-del-Pliego, Elsa Liliana Aguirre-Benítez, Armando Pérez-Torres, Yazmin Monserrat Flores-Martinez, Carmen Solano-Agama, Verónica Rodríguez-Mata, Alejandro García-Godínez, Daniel Martínez-Fong, María Eugenia Mendoza-Garrido In humans, the pituitary gland is covered by a fibrous capsule and is considered a continuation of the meningeal sheath. However, in rodents some studies concluded that only the pars tuberalis (PT) and pars nervosa (PN) are enwrapped by the pia mater, while others showed that the whole gland is covered by this sheath. At PT the median eminence subarachnoid drains cerebrospinal fluid (CSF) to its cisternal system representing a pathway to the hypothalamus. In the present study we examined the rat pituitary capsule to elucidate its configuration, its physical interaction with the pituitary border and its relationship with the CSF. Furthermore, we also revisited the histology of the pituitary cleft and looked whether CSF drained in it. To answer such questions, we used scanning and transmission electron microscopy, intracerebroventricular infusion of Evan´s blue, fluorescent beads, and sodium fluorescein. The latter was measured in the pars distalis (PD) and various intracranial tissues. We found a pituitary capsule resembling leptomeninges, thick at the dorsal side of the pars intermedia (PI) and PD, thicker at the level of PI in contiguity with the PN and thinner at the rostro-ventral side as a thin membrane of fibroblast-like cells embedded in a fibrous layer. The capsule has abundant capillaries on all sides. Our results showed that the CSFs bathe between the capsule and the surface of the whole gland, and ciliate cells are present in the pituitary border. Our data suggest that the pituitary gland intercommunicates with the central nervous system (CNS) through the CSF.

by Steven P. Plesh, James R. Lovvorn, Micah W. C. Miller Arctic lowland tundra is often dominated by wetlands. As numbers and types of these wetlands change with climate warming, their invertebrate biomass and assemblages may also be affected. Increased influx of nutrients and dissolved organic matter (DOM) from thawing peat may alter the relative availability of organic matter (OM) sources, differentially affecting taxa with disparate dependence on those sources. In five shallow wetland types (150 cm), we used stable isotopes (δ13C, δ15N) to compare contributions of four OM sources (periphytic microalgae, cyanobacteria, macrophytes, peat) to the diets of nine macroinvertebrate taxa. Living macrophytes were not distinguishable isotopically from peat that likely contributed most DOM. Within invertebrate taxa, relative OM contributions were similar among all wetland types except deeper lakes. Physidae snails consumed substantial amounts of OM from cyanobacteria. However, for all other taxa examined, microalgae were the dominant or a major OM source (39–82%, mean 59%) in all wetland types except deeper lakes (20‒62%, mean 31%). Macrophytes and macrophyte-derived peat, likely consumed mostly indirectly as DOM-supported bacteria, ranged from 18‒61% (mean 41%) of ultimate OM sources in all wetland types except deeper lakes (38–80%, mean 69%). Invertebrate consumption of microalgal C may often have involved bacterial intermediates, or a mix of algae with bacteria consuming peat-derived OM. High production of periphyton with very low δ13C values were favored by continuous daylight illuminating shallow depths, high N and P levels, and high CO2 concentrations from bacterial respiration of peat-derived DOM. Although relative OM sources were similar across wetland types except deeper lakes, total invertebrate biomass was much higher in shallow wetlands with emergent vegetation. Impacts of warming on the availability of invertebrate prey to waterbirds will likely depend not on shifts in OM sources, but more on changes in overall number or area of shallow emergent wetlands.

by Yuta Miyazaki, Michiyuki Kawakami, Kunitsugu Kondo, Masahiro Tsujikawa, Kaoru Honaga, Kanjiro Suzuki, Tetsuya Tsuji Objectives Stepwise linear regression (SLR) is the most common approach to predicting activities of daily living at discharge with the Functional Independence Measure (FIM) in stroke patients, but noisy nonlinear clinical data decrease the predictive accuracies of SLR. Machine learning is gaining attention in the medical field for such nonlinear data. Previous studies reported that machine learning models, regression tree (RT), ensemble learning (EL), artificial neural networks (ANNs), support vector regression (SVR), and Gaussian process regression (GPR), are robust to such data and increase predictive accuracies. This study aimed to compare the predictive accuracies of SLR and these machine learning models for FIM scores in stroke patients. Methods Subacute stroke patients (N = 1,046) who underwent inpatient rehabilitation participated in this study. Only patients’ background characteristics and FIM scores at admission were used to build each predictive model of SLR, RT, EL, ANN, SVR, and GPR with 10-fold cross-validation. The coefficient of determination (R2) and root mean square error (RMSE) values were compared between the actual and predicted discharge FIM scores and FIM gain. Results Machine learning models (R2 of RT = 0.75, EL = 0.78, ANN = 0.81, SVR = 0.80, GPR = 0.81) outperformed SLR (0.70) to predict discharge FIM motor scores. The predictive accuracies of machine learning methods for FIM total gain (R2 of RT = 0.48, EL = 0.51, ANN = 0.50, SVR = 0.51, GPR = 0.54) were also better than of SLR (0.22). Conclusions This study suggested that the machine learning models outperformed SLR for predicting FIM prognosis. The machine learning models used only patients’ background characteristics and FIM scores at admission and more accurately predicted FIM gain than previous studies. ANN, SVR, and GPR outperformed RT and EL. GPR could have the best predictive accuracy for FIM prognosis. …

by Sofie J. Lorijn, Lydia Laninga-Wijnen, Maaike C. Engels, Gerine M. A. Lodder, René Veenstra The COVID-19 measures raised societal concerns about increases in adolescents’ loneliness. This study examined trajectories of adolescents’ loneliness during the pandemic, and whether trajectories varied across students with different types of peer status and contact with friends. We followed 512 Dutch students (Mage = 11.26, SD = 0.53; 53.1% girls) from before the pandemic (Jan/Feb 2020), over the first lockdown (March-May 2020, measured retrospectively), until the relaxation of measures (Oct/Nov 2020). Latent Growth Curve Analyses (LGCA) showed that average levels of loneliness declined. Multi-group LGCA showed that loneliness declined mostly for students with a victimized or rejected peer status, which suggests that students with a low peer status prior to the lockdown may have found temporary relief from negative peer experiences at school. Students who kept all-round contact with friends during the lockdown declined in loneliness, whereas students who had little contact or who did not (video) call friends did not.

by Aldo Córdova-Palomera, Csaba Siffel, Chris DeBoever, Emily Wong, Dorothée Diogo, Sandor Szalma As findings on the epidemiological and genetic risk factors for coronavirus disease-19 (COVID-19) continue to accrue, their joint power and significance for prospective clinical applications remains virtually unexplored. Severity of symptoms in individuals affected by COVID-19 spans a broad spectrum, reflective of heterogeneous host susceptibilities across the population. Here, we assessed the utility of epidemiological risk factors to predict disease severity prospectively, and interrogated genetic information (polygenic scores) to evaluate whether they can provide further insights into symptom heterogeneity. A standard model was trained to predict severe COVID-19 based on principal component analysis and logistic regression based on information from eight known medical risk factors for COVID-19 measured before 2018. In UK Biobank participants of European ancestry, the model achieved a relatively high performance (area under the receiver operating characteristic curve ~90%). Polygenic scores for COVID-19 computed from summary statistics of the Covid19 Host Genetics Initiative displayed significant associations with COVID-19 in the UK Biobank (p-values as low as 3.96e-9, all with R2 under 1%), but were unable to robustly improve predictive performance of the non-genetic factors. However, error analysis of the non-genetic models suggested that affected individuals misclassified by the medical risk factors (predicted low risk but actual high risk) display a small but consistent increase in polygenic scores. Overall, the results indicate that simple models based on health-related epidemiological factors measured years before COVID-19 onset can achieve high predictive power. Associations between COVID-19 and genetic factors were statistically robust, but currently they have limited predictive power for translational settings. Despite that, the outcomes also suggest that severely affected cases with a medical history profile of low risk might be partly explained by polygenic factors, prompting development of boosted COVID-19 polygenic models based on new data and tools to aid risk-prediction.

by Reyaz Ahmad Khan, Kangjam Rekha Devi, Manash Pratim Barman, Madhusmita Bhagawati, Rajeev Sarmah Food habits and oral hygiene are critical attributes for physiochemical environment of the oral cavity. Consumption of intoxicating substances such as betel nut (’Tamul’), alcohol, smoking and chewing tobacco may strongly influence the oral ecosystem including commensal microbes. Therefore, a comparative assessment of microbes in the oral cavity between individuals consuming intoxicating substances and non-consumers may indicate the influence of these substances. Oral swabs were collected from consumers of intoxicating substances and non- consumers of Assam, India, microbes were isolated by culturing on Nutrient agar and identified by phylogenetic analysis of their 16S rRNA gene sequences. The risks of consumption of intoxicating substance on occurrence of microbes and health conditions were estimated using binary logistic regression. Mostly pathogens and opportunistic pathogens were found in the oral cavity of consumers and oral cancer patients which included Pseudomonas aeruginosa, Serratia marcescens, Rhodococcus antrifimi, Paenibacillus dendritiformis, Bacillus cereus, Staphylococcus carnosus, Klebsiella michiganensis and Pseudomonas cedrina. Enterobacter hormaechei was found in the oral cavity of cancer patients but not in other cases. Pseudomonas sp. were found to be widely distributed. The risk of occurrence of these organisms were found in between 0.01 and 2.963 odds and health conditions between 0.088 and 10.148 odds on exposure to different intoxicating substances. When exposed to microbes, the risk of varying health conditions ranged between 0.108 and 2.306 odds. Chewing tobacco showed a higher risk for oral cancer (10.148 odds). Prolonged exposure to intoxicating substances conduce a favorable environment for the pathogens and opportunistic pathogens to colonize in the oral cavity of individuals consuming intoxicating substances.

by Bo-Guen Kim, Noeul Kang, Su-Young Kim, Dae Hun Kim, Hojoong Kim, O. Jung Kwon, Hee Jae Huh, Nam Yong Lee, Byung Woo Jhun Background The role of bacterial microbiota in the pathogenesis of nontuberculous mycobacterial pulmonary disease (NTM-PD) is unclear. We aimed to compare the bacterial microbiome of disease-invaded lesions and non-invaded lung tissue from NTM-PD patients. Methods We analyzed lung tissues from 23 NTM-PD patients who underwent surgical lung resection. Lung tissues were collected in pairs from each patient, with one sample from a disease-involved site and the other from a non-involved site. Lung tissue microbiome libraries were constructed using 16S rRNA gene sequences (V3–V4 regions). Results Sixteen (70%) patients had Mycobacterium avium complex (MAC)-PD, and the remaining seven (30%) had Mycobacterium abscessus-PD. Compared to non-involved sites, involved sites showed greater species richness (ACE, Chao1, and Jackknife analyses, all p = 0.001); greater diversity on the Shannon index (p = 0.007); and genus-level differences (Jensen-Shannon, PERMANOVA p = 0.001). Analysis of taxonomic biomarkers using linear discriminant analysis (LDA) effect sizes (LEfSe) demonstrated that several genera, including Limnohabitans, Rahnella, Lachnospira, Flavobacterium, Megamonas, Gaiella, Subdoligranulum, Rheinheimera, Dorea, Collinsella, and Phascolarctobacterium, had significantly greater abundance in involved sites (LDA >3.00, p…

Abstract Background Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether–lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed. Methods This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography–mass spectrometry (LC–MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90–110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher’s exact test of independence at 95% level of significance. Results A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being ‘Green leaf’. Overall prevalence of substandard quality artemether–lumefantrine was 18.9% (14/74; 95% CI: 11.4–29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (

Abstract Background Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep understanding of illness causation and prevention practices among at-risk communities remains limited. This study aims to document local knowledge on malaria causation and preventive practices of rural communities in Sabah, Malaysia, using photovoice—a participatory research method. Methods From January to June 2022, a photovoice study was conducted with rural communities in Matunggong subdistrict, Malaysia, to explore their experiences with and local knowledge of non-human primate malaria and prevention practices. The study included (1) an introductory phase in which participants were introduced to the photovoice method; (2) a documentation phase in which participants captured and narrated photos from their communities; (3) a discussion phase in which participants discussed photos and relevant topics through a series of three focus group discussions (FGDs) per village; and (4) a dissemination phase where selected photos were shared with key stakeholders through a photo exhibition. A purposively selected sample of 26 participants (adults > 18 years old, male, and female) from four villages participated in all phases of the study. The study activities were conducted in Sabah Malay dialect. Participants and the research team contributed to data review and analyses. Results Rural communities in Sabah, Malaysia possess local knowledge that attributes non-human primate malaria to natural factors related to the presence of mosquitoes that bite humans and which carry “kuman-malaria” or malaria parasite. Participants revealed various preventive practises ranging from traditional practises, including burning dried leaves and using plants that produce foul odours, to non-traditional approaches such as aerosols and mosquito repellents. By engaging with researchers and policymakers, the participants or termed as co-researchers in this study, showcased their ability to learn and appreciate new knowledge and perspectives and valued the opportunity to share their voices with policymakers. The study successfully fostered a balance of power dynamics between the co-researchers, research team members and policymakers. Conclusion There were no misconceptions about malaria causation among study participants. The insights from study participants are relevant because of their living experience with the non-human malaria. It is critical to incorporate rural community perspectives in designing locally effective and feasible malaria interventions in rural Sabah, Malaysia. Future research can consider adapting the photovoice methodology for further research with the community toward building locally tailored-malaria strategies. …

Abstract Background Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. Methods Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. Results All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate 

AbstractInnate Lymphoid Cells (ILCs) are tissue resident cells that are triggered through a relatively broad spectrum of alarmins, inflammatory cues, neuropeptides, and hormones. Functionally, ILCs are akin to subsets of helper T cells and are characterized by a similar effector cytokine profile. They also share a dependency on many of the same essential transcription factors identified for the maintenance and survival of T cells. The key distinguishing factor between the ILC family and T cells is the lack of antigen-specific T cell receptor (TCR) on ILCs and, thus, they can be considered the “ultimate invariant T cells”. ILCs, like T cells, orchestrate downstream effector inflammatory responses by adjusting the cytokine microenvironment in a fashion that promotes protection, health, and homeostasis at mucosal barrier sites. But also, like T cells, ILCs have recently been implicated in several pathological inflammatory disease states. This review focuses on the selective role of ILCs in the development of allergic airway inflammation (AAI) and fibrosis in the gut where a complex ILC interplay has been shown to either attenuate or worsen disease. Finally, we discuss new data on TCR gene rearrangements in subsets of ILCs that challenge the current dogma linking their origin to committed bone marrow progenitors and instead propose a thymic origin for at least some ILCs. In addition, we highlight how naturally occurring TCR rearrangements and the expression of major histocompatibility (MHC) molecules in ILCs provide a useful natural barcode for these cells and may prove instrumental in studying their origins and plasticity.

Abstract Background The Gambian Ministry of Health is supportive of HIV self-testing (HIVST) and HIVST initiatives are being piloted as an additional strategy to increase HIV testing for individuals not currently reached by existing services, particularly men. This study aimed to determine awareness of HIVST among Gambian men, and whether prior awareness of HIVST is associated with recent HIV testing uptake. Methods We used men’s cross-sectional data from the 2019–2020 Gambian Demographic and Health Survey. We employed design-adjusted multivariable logistic regression to examine the association between HIVST awareness and recent HIV testing. Propensity-score weighting was conducted as sensitivity analyses. Results Of 3,308 Gambian men included in the study, 11% (372) were aware of HIVST and 16% (450) received HIV testing in the last 12 months. In the design-adjusted multivariable analysis, men who were aware of HIVST had 1.76 times (95% confidence interval: 1.26–2.45) the odds of having an HIV test in the last 12 months, compared to those who were not aware of HIVST. Sensitivity analyses revealed similar findings. Conclusion Awareness of HIVST may help increase the uptake of HIV testing among men in Gambia. This finding highlights HIVST awareness-raising activities to be an important intervention for nationwide HIVST program planning and implementation in Gambia. …

Abstract Background Scedosporium is a lesser-known non-Aspergillus genus of mold that can present in unsuspecting ways. If overlooked, it may disseminate and cause high mortality in high-risk allogeneic stem cell transplant recipients. Case presentation This case report describes a 65-year-old patient with Acute Myeloid Leukemia who underwent an allogeneic hematopoietic stem cell transplant after a period of prolonged neutropenia with fluconazole prophylaxis. She suffered severe debility with altered mentation from a S. apiospermum infection which likely disseminated from a toe wound to the lung and central nervous system. She was successfully treated with liposomal amphotericin B and voriconazole, but faced a prolonged recovery from physical and neurologic sequela. Conclusions The case highlights the importance of adequate anti-mold prophylaxis in high-risk patients, and the value of a thorough physical examination in this patient population, with particular attention to skin and soft tissue findings. …

Abstract Background Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. Methods Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. Results Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p

Abstract Introduction Deep sternal wound infection is a rare but feared complication of median thoracotomies and is usually caused by microorganisms from the patient’s skin or mucous membranes, the external environment, or iatrogenic procedures. The most common involved pathogens are Staphylococcus aureus, Staphylococcus epidermidis and gram-negative bacteria. We aimed to evaluate the microbiological spectrum of deep sternal wound infections in our institution and to establish diagnostic and treatment algorithms. Methods We retrospectively evaluated the patients with deep sternal wound infections at our institution between March 2018 and December 2021. The inclusion criteria were the presence of deep sternal wound infection and complete sternal osteomyelitis. Eighty-seven patients could be included in the study. All patients received a radical sternectomy, with complete microbiological and histopathological analysis. Results In 20 patients (23%) the infection was caused by S. epidermidis, in 17 patients (19.54%) by S. aureus, in 3 patients (3.45%) by Enterococcus spp., in 14 patients (16.09%) by gram-negative bacteria, while in 14 patients (16.09%) no pathogen could be identified. In 19 patients (21,84%) the infection was polymicrobial. Two patients had a superimposed Candida spp. infection. Methicillin-resistant S. epidermidis was found in 25 cases (28,74%), while methicillin-resistant S. aureus was isolated in only three cases (3,45%). The average hospital stay for monomicrobial infections was 29.93 ± 13.69 days and for polymicrobial infections was 37.47 ± 19.18 (p = 0.03). Wound swabs and tissue biopsies were routinely harvested for microbiological examination. The increasing number of biopsies was associated with the isolation of a pathogen (4.24 ± 2.22 vs. 2.18 ± 1.6, p 

Abstract Objectives To make clear the roles of social interaction and social support in HIV infection among elderly men who visit female sex workers (FSW). Methods We conducted a case-control study: 106 newly HIV (+) vs. 87 HIV (-) elderly men who visited FSW with similar age, education levels, marital statuses, monthly expenses for entertainment and migration experiences. Experiences of visiting FSW, social interaction, and intimate social support were obtained. Backward binary logistic regression was applied. Results Cases’ first visit to FSW happened at the age of 44.01 ± 12.25, older than controls (33.90 ± 13.43). 23.58% cases had gotten HIV-related health education (HRHE) before, less than controls (57.47%). More cases (48.91%) “always” got material support than controls (34.25%). Less cases gave “close” (38.04%) comments toward daily life, “satisfied” (34.78%) with their sexual life, “agree” being emotional fulfilled (46.74%) than controls (71.23% ,64.38%, and 61.64%). Risky factors for HIV infection among elderly men were having 3000 YUAN and above monthly income, visiting teahouse with friends, living without spouses, visiting different FSW, visiting FSW for other reason, receiving material support from most intimate sexual partner, older age of first visit to FSW. The protective factors were receiving HRHE, visiting FSW due to loneliness, and giving positive comments toward daily life with most intimate sexual partner. Conclusions Elderly men’s social interactions are mainly visiting teahouse which is a potential sexual venue. Getting HRHE is formal protective social interactions but very rare for cases (23.58%). Social support from sexual partner is not enough. Emotional support is protective meanwhile material support only is risky for becoming HIV-positive. …

Abstract Background Intravenous artesunate (AS) is the first-line treatment for patients with severe imported malaria (SIM) worldwide. However, after 10 years of use in France, AS hasn’t yet received marketing authorization.The purpose of this study was to assess the real-life effectiveness and safety of AS in the treatment of SIM in two Hospitals in France. Methods We performed a bicenter retrospective and observational study. All patients treated with AS for SIM between 2014 and 2018 and 2016–2020 were included. The effectiveness of AS was evaluated by parasite clearance, number of deaths, and the length of hospital stay. The real-life safety was assessed by related adverse events (AE) and monitoring of biological blood parameters during the hospital stay and follow-up period. Results 110 patients were included during the six-year study period. 71.8% of patients were parasite-negative of their day 3 thick and thin blood smears after AS treatment. No patients discontinued AS due to an AE and no serious AE were declared. Two cases of delayed post-artesunate hemolysis occurred and required blood transfusions. Conclusion This study highlights effectiveness and safety of AS in non-endemic areas. Administrative procedures must be accelerated in order to obtain full registration and facilitate access to AS in France. …

Abstract Background Escherichia hermannii (E. hermanni) is always accompanied by other bacterial infections in humans. In previous reports, most E. hermannii-related infections were caused by sensitive strains. Here, for the first time, we report the case of a patient with New Delhi metallo-β-lactamase (NDM)-positive E. hermannii bloodstream infection. Case presentation The patient was a 70-year-old male admitted to our hospital due to a 4-day fever, with a history of malignant tumor, liver cirrhosis, and chronic obstructive pulmonary disease. After admission, his blood culture tested positive for E. hermannii. The drug resistance analysis showed positive for NDM resistance, with susceptibility to aztreonam, levofloxacin, and amikacin. The blood culture turned negative after 8 days of aztreonam treatment. The patient’s symptoms improved, and he was discharged after 14 days of hospitalization. Conclusions This is the first report of a bloodstream infection caused by an NDM-positive E. hermannii strain. The anti-infection regimen used in this case provides a new reference regimen for clinical practice. …

Abstract Background With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. Methods One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. Results Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 μg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). Conclusions Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality. …

Abstract Background Invasion of the corpus callosum by sparganosis is rare in children. After invading the corpus callosum, sparganosis has various migration modes, which can break through the ependyma and enter the ventricles, thus causing secondary migratory brain injury. Case presentation A girl aged 4 years and 7 months presented with left lower limb paralysis for more than 50 days. Blood examination showed that the proportion and absolute number of eosinophils in the peripheral blood were increased. Furthermore, enzyme-linked immunosorbent assay of serum and cerebrospinal fluid samples revealed positivity for IgG and IgM antibodies for sparganosis. Initial magnetic resonance imaging (MRI) revealed ring-like enhancements in the right frontoparietal cortex, subcortical white matter, and splenium of the corpus callosum. Within 2 months, a fourth follow-up MRI showed that the lesion had spread to the left parietal cortex, subcortical white matter, and deep white matter in the right occipital lobe and right ventricular choroid plexus, with left parietal leptomeningeal enhancement. Conclusion Migratory movement is one of the characteristics of cerebral sparganosis. When sparganosis invades the corpus callosum, clinicians should be aware that it may then break through the ependyma and enter the lateral ventricles, leading to secondary migratory brain injury. Short-term follow-up MRI is necessary to evaluate the migration mode of sparganosis and dynamically guide treatment strategies. …

Abstract Background Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM. Methods The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1–4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted. Results A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome. Conclusions Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention. …

Abstract Background Immigration is considered as a risk factor of tuberculosis (TB). Qom province receives millions of pilgrims and significant numbers of immigrants each year. Most of the immigrants to Qom, arrive from neighboring TB-endemic countries. This study aimed to identify the current circulating Mycobacterium tuberculosis genotypes in Qom province using 24-locus MIRU-VNTR genotyping. Methods Eighty six M. tuberculosis isolates were collected during 2018–2022 from patients referring to Qom TB reference laboratory. The DNA of isolates was extracted and followed by 24 loci MIRU-VNTR genotyping which performed using the web tools available on MIRU-VNTRplus. Results Of 86 isolates, 39 (45.3%) were of Delhi/CAS genotype, 24 (27.9%) of NEW-1, 6 (7%) of LAM, 6 (7%) of Beijing, 2 (2.3%) of UgandaII, 2 (2.3%) of EAI, 1 of S (1.2%) and 6 (7%) did not match with profiles present in MIRUVNTRplus database. Conclusions About half of the isolates belong to Afghan immigrants; which warns health policy makers about the future situation of TB in Qom. Also, the similarity of Afghan and Iranian genotypes provides evidence that immigrants partake in the circulation of M. tuberculosis. This study underpin the studies about the circulating M. tuberculosis genotypes, their geographical distribution, the association of TB risk factors with these genotypes and the impact of immigration on the situation of TB in Qom province. …

Abstract Background With the safety of blood transfusion being a major public health concern, the development of a rapid, sensitive, specific, and cost-effective multiplex PCR assay for simultaneous detection of hepatitis B virus(HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), and Treponema pallidum(T. pallidum) in blood is crucial. Methods Five primer pairs and probes were designed towards conserved regions of target genes and used to establish a one-step pentaplex real-time reverse transcription PCR(qRT-PCR) assay for simultaneous detection of HBV, HCV, HEV, T. pallidum, and RNase P(housekeeping gene), providing sample quality check. The clinical performance of the assay was further determined with 2400 blood samples from blood donors and patients in Zhejiang province, and compared the results with commercial singleplex qPCR and serological assays. Results The 95% limit of detection(LOD) of HBV, HCV, HEV, and T. pallidum were 7.11 copies/µL, 7.65 copies/µL, 8.45 copies/µL, and 9.06 copies/µL, respectively. Moreover, the assay has good specificity and precision. Compared to the singleplex qPCR assay, the novel assay for detecting HBV, HCV, HEV, and T. pallidum presented 100% clinical sensitivity, specificity, and consistency. Several discrepant results between serological and pentaplex qRT-PCR assays were found. Of 2400 blood samples, there were 2(0.08%) HBsAg positive samples, 3(0.13%) anti-HCV positive samples, 29(1.21%) IgM anti-HEV positive samples and 6(0.25%) anti-T. pallidum positive samples proven negative in nucleic acid detection. 1(0.04%) HBV DNA positive sample and 1(0.04%) HEV RNA positive sample were detected negative by serological testing. Conclusions The developed pentaplex qRT-PCR is the first assay on simultaneous, sensitive, specific, and reproducible detection of HBV, HCV, HEV, T. pallidum, and RNase P in a single tube. It could detect pathogens in blood during the window period of infection and is a good tool for effectively screening blood donors and early clinical diagnosis. …

Volume 12, Issue 1, December 2023 .

Volume 12, Issue 1, December 2023 .

Volume 12, Issue 1, December 2023 .

Volume 12, Issue 1, December 2023 .

Several mechanisms including reduced CCR5 expression, protective HLA, viral restriction factors, broadly neutralizing antibodies, and more efficient T-cell responses, have been reported to account for HIV cont...